ICCS e_Newsletter CSI Spring 2014 Suzanne Vercauteren MD, PhD, FRCPC Division of Hematopathology BC Children’s Hospital, Vancouver University of British Columbia
ICCS e_Newsletter CSI Spring 2014 Suzanne Vercauteren MD, PhD, FRCPC Division of Hematopathology BC Children’s Hospital, Vancouver University of British.
Dec 23, 2015
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ICCS e_Newsletter CSISpring 2014
Suzanne Vercauteren MD PhD FRCPCDivision of Hematopathology
BC Childrenrsquos Hospital VancouverUniversity of British Columbia
e-CSI - Clinical History
bull 4 year old boy with a 4 week history of unexplained fevers massive hepatosplenomegaly diffuse lymphadenopathy and bicytopenia
bull Differential Diagnosisndash Infectionndash Lymphomandash PrimarySecondary Hemophagocytic lympho-histiocytosis
(HLH)
e-CSI ndash Peripheral BloodCBC Reference Range
WBC 144 x 109L (53 - 160 x 109L)
RBC 351 x 1012L (390 - 530 x 1012L)
Hgb 89 gdL (105 ndash 135 gdL)
MCV 769 fl (750 ndash 870 fl)
RDW-CV 0149 (0117 ndash 0157)
Plts 46 x 109L (200 ndash 490 x 109L)
Differential Count Reference Range
Neutrophils 1046 x 109L (150 ndash 850 x 109L)
Lymphocytes 329 x 109L (200 ndash 800 x 109L)
Monocytes 061 x 109L (000 ndash 090 x 109L)
Eosinophils 002 x 109L (000 ndash 050 x 109L)
Basophils 002 x 109L (000 ndash 020 x 109L)
e-CSI ndash Biochemistry
Parameter Value Normal range
ALT 10 10 - 25 UL
AST 340 10 - 25 UL
G GT 127 10 - 25 UL
LDH 1227 470 - 900 UL
Ferritin 1190 9 ndash 30 ugL
bull Bone Marrowndash Normocellular marrow with trilineage hematopoiesisndash Mild hemophagocytosisndash Loose granulomasndash CD20 CD3 CD4 and CD8 immunohistochemistry non
contributoryndash Lymphoma screen panel ( see slide 18) by flow cytometry
rarr normal
bull Extensive infectious work up including TB as per patients recent travel to Cambodia
e-CSI ndashWork-Up
bull Work up for HLHndash Fever presentndash Splenomegaly presentndash Cytopenias presentndash Ferritin uarr uarrndash Triglycerides uarr uarrndash Soluble IL-2 receptor uarr uarrndash NK cell function rarr normalndash Mild hemophagocytosis in BM
rarr Criteria for HLH met (at least 58)
e-CSI ndashWork-Up
bull Infectious work up continuedndash Tuberculosis work up as granulomas seen in BM rarr
pertinently negativendash EBV and all other viruses rarr negative
bull Work up for primary immune deficiency rarr Flow cytometric immunophenotyping on peripheral blood
e-CSI ndashWork-Up
bull Acquisition Beckman Coulter Navios flow cytometerbull Data analysis Beckman Coulter Kaluza (software
version 12)bull T+B cell panel on peripheral blood
e-CSI ndash Flowcytometric Studies
FITC PC5 RD1 ECD
Tube 1 CD45 CD3 CD56 CD19
Tube 2 CD45 CD3 CD4 CD8
e-CSI ndash Flowcytometric StudiesTube 1
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI - Clinical History
bull 4 year old boy with a 4 week history of unexplained fevers massive hepatosplenomegaly diffuse lymphadenopathy and bicytopenia
bull Differential Diagnosisndash Infectionndash Lymphomandash PrimarySecondary Hemophagocytic lympho-histiocytosis
(HLH)
e-CSI ndash Peripheral BloodCBC Reference Range
WBC 144 x 109L (53 - 160 x 109L)
RBC 351 x 1012L (390 - 530 x 1012L)
Hgb 89 gdL (105 ndash 135 gdL)
MCV 769 fl (750 ndash 870 fl)
RDW-CV 0149 (0117 ndash 0157)
Plts 46 x 109L (200 ndash 490 x 109L)
Differential Count Reference Range
Neutrophils 1046 x 109L (150 ndash 850 x 109L)
Lymphocytes 329 x 109L (200 ndash 800 x 109L)
Monocytes 061 x 109L (000 ndash 090 x 109L)
Eosinophils 002 x 109L (000 ndash 050 x 109L)
Basophils 002 x 109L (000 ndash 020 x 109L)
e-CSI ndash Biochemistry
Parameter Value Normal range
ALT 10 10 - 25 UL
AST 340 10 - 25 UL
G GT 127 10 - 25 UL
LDH 1227 470 - 900 UL
Ferritin 1190 9 ndash 30 ugL
bull Bone Marrowndash Normocellular marrow with trilineage hematopoiesisndash Mild hemophagocytosisndash Loose granulomasndash CD20 CD3 CD4 and CD8 immunohistochemistry non
contributoryndash Lymphoma screen panel ( see slide 18) by flow cytometry
rarr normal
bull Extensive infectious work up including TB as per patients recent travel to Cambodia
e-CSI ndashWork-Up
bull Work up for HLHndash Fever presentndash Splenomegaly presentndash Cytopenias presentndash Ferritin uarr uarrndash Triglycerides uarr uarrndash Soluble IL-2 receptor uarr uarrndash NK cell function rarr normalndash Mild hemophagocytosis in BM
rarr Criteria for HLH met (at least 58)
e-CSI ndashWork-Up
bull Infectious work up continuedndash Tuberculosis work up as granulomas seen in BM rarr
pertinently negativendash EBV and all other viruses rarr negative
bull Work up for primary immune deficiency rarr Flow cytometric immunophenotyping on peripheral blood
e-CSI ndashWork-Up
bull Acquisition Beckman Coulter Navios flow cytometerbull Data analysis Beckman Coulter Kaluza (software
version 12)bull T+B cell panel on peripheral blood
e-CSI ndash Flowcytometric Studies
FITC PC5 RD1 ECD
Tube 1 CD45 CD3 CD56 CD19
Tube 2 CD45 CD3 CD4 CD8
e-CSI ndash Flowcytometric StudiesTube 1
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Peripheral BloodCBC Reference Range
WBC 144 x 109L (53 - 160 x 109L)
RBC 351 x 1012L (390 - 530 x 1012L)
Hgb 89 gdL (105 ndash 135 gdL)
MCV 769 fl (750 ndash 870 fl)
RDW-CV 0149 (0117 ndash 0157)
Plts 46 x 109L (200 ndash 490 x 109L)
Differential Count Reference Range
Neutrophils 1046 x 109L (150 ndash 850 x 109L)
Lymphocytes 329 x 109L (200 ndash 800 x 109L)
Monocytes 061 x 109L (000 ndash 090 x 109L)
Eosinophils 002 x 109L (000 ndash 050 x 109L)
Basophils 002 x 109L (000 ndash 020 x 109L)
e-CSI ndash Biochemistry
Parameter Value Normal range
ALT 10 10 - 25 UL
AST 340 10 - 25 UL
G GT 127 10 - 25 UL
LDH 1227 470 - 900 UL
Ferritin 1190 9 ndash 30 ugL
bull Bone Marrowndash Normocellular marrow with trilineage hematopoiesisndash Mild hemophagocytosisndash Loose granulomasndash CD20 CD3 CD4 and CD8 immunohistochemistry non
contributoryndash Lymphoma screen panel ( see slide 18) by flow cytometry
rarr normal
bull Extensive infectious work up including TB as per patients recent travel to Cambodia
e-CSI ndashWork-Up
bull Work up for HLHndash Fever presentndash Splenomegaly presentndash Cytopenias presentndash Ferritin uarr uarrndash Triglycerides uarr uarrndash Soluble IL-2 receptor uarr uarrndash NK cell function rarr normalndash Mild hemophagocytosis in BM
rarr Criteria for HLH met (at least 58)
e-CSI ndashWork-Up
bull Infectious work up continuedndash Tuberculosis work up as granulomas seen in BM rarr
pertinently negativendash EBV and all other viruses rarr negative
bull Work up for primary immune deficiency rarr Flow cytometric immunophenotyping on peripheral blood
e-CSI ndashWork-Up
bull Acquisition Beckman Coulter Navios flow cytometerbull Data analysis Beckman Coulter Kaluza (software
version 12)bull T+B cell panel on peripheral blood
e-CSI ndash Flowcytometric Studies
FITC PC5 RD1 ECD
Tube 1 CD45 CD3 CD56 CD19
Tube 2 CD45 CD3 CD4 CD8
e-CSI ndash Flowcytometric StudiesTube 1
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Biochemistry
Parameter Value Normal range
ALT 10 10 - 25 UL
AST 340 10 - 25 UL
G GT 127 10 - 25 UL
LDH 1227 470 - 900 UL
Ferritin 1190 9 ndash 30 ugL
bull Bone Marrowndash Normocellular marrow with trilineage hematopoiesisndash Mild hemophagocytosisndash Loose granulomasndash CD20 CD3 CD4 and CD8 immunohistochemistry non
contributoryndash Lymphoma screen panel ( see slide 18) by flow cytometry
rarr normal
bull Extensive infectious work up including TB as per patients recent travel to Cambodia
e-CSI ndashWork-Up
bull Work up for HLHndash Fever presentndash Splenomegaly presentndash Cytopenias presentndash Ferritin uarr uarrndash Triglycerides uarr uarrndash Soluble IL-2 receptor uarr uarrndash NK cell function rarr normalndash Mild hemophagocytosis in BM
rarr Criteria for HLH met (at least 58)
e-CSI ndashWork-Up
bull Infectious work up continuedndash Tuberculosis work up as granulomas seen in BM rarr
pertinently negativendash EBV and all other viruses rarr negative
bull Work up for primary immune deficiency rarr Flow cytometric immunophenotyping on peripheral blood
e-CSI ndashWork-Up
bull Acquisition Beckman Coulter Navios flow cytometerbull Data analysis Beckman Coulter Kaluza (software
version 12)bull T+B cell panel on peripheral blood
e-CSI ndash Flowcytometric Studies
FITC PC5 RD1 ECD
Tube 1 CD45 CD3 CD56 CD19
Tube 2 CD45 CD3 CD4 CD8
e-CSI ndash Flowcytometric StudiesTube 1
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Bone Marrowndash Normocellular marrow with trilineage hematopoiesisndash Mild hemophagocytosisndash Loose granulomasndash CD20 CD3 CD4 and CD8 immunohistochemistry non
contributoryndash Lymphoma screen panel ( see slide 18) by flow cytometry
rarr normal
bull Extensive infectious work up including TB as per patients recent travel to Cambodia
e-CSI ndashWork-Up
bull Work up for HLHndash Fever presentndash Splenomegaly presentndash Cytopenias presentndash Ferritin uarr uarrndash Triglycerides uarr uarrndash Soluble IL-2 receptor uarr uarrndash NK cell function rarr normalndash Mild hemophagocytosis in BM
rarr Criteria for HLH met (at least 58)
e-CSI ndashWork-Up
bull Infectious work up continuedndash Tuberculosis work up as granulomas seen in BM rarr
pertinently negativendash EBV and all other viruses rarr negative
bull Work up for primary immune deficiency rarr Flow cytometric immunophenotyping on peripheral blood
e-CSI ndashWork-Up
bull Acquisition Beckman Coulter Navios flow cytometerbull Data analysis Beckman Coulter Kaluza (software
version 12)bull T+B cell panel on peripheral blood
e-CSI ndash Flowcytometric Studies
FITC PC5 RD1 ECD
Tube 1 CD45 CD3 CD56 CD19
Tube 2 CD45 CD3 CD4 CD8
e-CSI ndash Flowcytometric StudiesTube 1
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Work up for HLHndash Fever presentndash Splenomegaly presentndash Cytopenias presentndash Ferritin uarr uarrndash Triglycerides uarr uarrndash Soluble IL-2 receptor uarr uarrndash NK cell function rarr normalndash Mild hemophagocytosis in BM
rarr Criteria for HLH met (at least 58)
e-CSI ndashWork-Up
bull Infectious work up continuedndash Tuberculosis work up as granulomas seen in BM rarr
pertinently negativendash EBV and all other viruses rarr negative
bull Work up for primary immune deficiency rarr Flow cytometric immunophenotyping on peripheral blood
e-CSI ndashWork-Up
bull Acquisition Beckman Coulter Navios flow cytometerbull Data analysis Beckman Coulter Kaluza (software
version 12)bull T+B cell panel on peripheral blood
e-CSI ndash Flowcytometric Studies
FITC PC5 RD1 ECD
Tube 1 CD45 CD3 CD56 CD19
Tube 2 CD45 CD3 CD4 CD8
e-CSI ndash Flowcytometric StudiesTube 1
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Infectious work up continuedndash Tuberculosis work up as granulomas seen in BM rarr
pertinently negativendash EBV and all other viruses rarr negative
bull Work up for primary immune deficiency rarr Flow cytometric immunophenotyping on peripheral blood
e-CSI ndashWork-Up
bull Acquisition Beckman Coulter Navios flow cytometerbull Data analysis Beckman Coulter Kaluza (software
version 12)bull T+B cell panel on peripheral blood
e-CSI ndash Flowcytometric Studies
FITC PC5 RD1 ECD
Tube 1 CD45 CD3 CD56 CD19
Tube 2 CD45 CD3 CD4 CD8
e-CSI ndash Flowcytometric StudiesTube 1
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Acquisition Beckman Coulter Navios flow cytometerbull Data analysis Beckman Coulter Kaluza (software
version 12)bull T+B cell panel on peripheral blood
e-CSI ndash Flowcytometric Studies
FITC PC5 RD1 ECD
Tube 1 CD45 CD3 CD56 CD19
Tube 2 CD45 CD3 CD4 CD8
e-CSI ndash Flowcytometric StudiesTube 1
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Flowcytometric StudiesTube 1
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Flowcytometric StudiesTube 2
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
This is strange(Repeat specimen showed same results)
Aberrant CD3 dim-negCD4+CD8+ population
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Differential Diagnosis of aberrant T cell immunophenotype in this childbull Hemophagocytic Lymphohistiocytosis (aberrant
immunophenotype of CD8+ T cell (described)bull Pediatric T cell Lymphoma
bull T cell lymphoblastic Lymphomabull Anaplastic Large Cell Lymphomabull EBV positive T cell lymphoproliferative disorders of childhood
e-CSI ndash Differential Diagnosis
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Lymphoma panel on peripheral blood
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 IgG1 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD34
Tube 3 CD45 CD30 CD25 CD3 CD5
Tube 4 IgG1 Cont PE Cont FITC IgG1 IgG1
Tube 5 CD45 Lambda Kappa CD10 CD19
Tube 6 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 7 CD45 cCD79a cTdT CD3 CD19
cIgG1 = cytoplasmic IgG1
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Flowcytometric Studies
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
Tube 2
Tube 3
some CD30 no CD25 Normal T cells
CD4+CD8+
e-CSI ndash Flowcytometric Studies
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
Tube 5
Tube 7
e-CSI ndash Flowcytometric Studies
no TdT No B or T cells aberrant population
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Blood specimen send for T and B cell clonality studies by PCR rarr CLONAL T cell population
bull Lymph node biopsy suggested but surgeons wary about low platelet count (lt20 x 109L at this time)
e-CSI ndashWork-Up
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Lymphoma screen panel on cells from supraclavicular cervical lymph node biopsy
e-CSI ndash Flowcytometric Studies
PC5 PE FITC ECD PC7
Tube 1 CD45 IgG1 IgG1 IgG1 IgG1
Tube 2 CD45 CD4 CD8 CD20 CD2
Tube 3 CD45 Lambda Kappa CD10 CD19
Tube 4 IgG1 cIgG1 cIgG1 IgG1 IgG1
Tube 5 CD45 cCD79a cTdT CD3 CD19
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Flowcytometric Studies Lymph Node
CD4+CD8+ Bright CD2+
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Flowcytometric Studies Lymph Node
Dim CD3+
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Sinus extended by large cells with convoluted nucleibull Immunohistochemistry stainsndash CD30 positivendash ALK positivendash CD3 CD4 CD8 CD68 CD1a and S100 negativendash Brisk mitotic activity
bull FISH shows NPM-ALK translocation
e-CSI ndash Lymph Node Results
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Aberrant T cell population detected in blood and lymph node but not bone marrow of this patient suggestive of mature T cell lymphoproliferative disorder
bull CD3 expression on aberrant population in lymph node brighter compared to blood
bull Immunohistochemistry studies differ from flow cytometry studies in that the aberrant cells are CD4 and CD8 negative by immunohistochemistry and CD30 positive in contrast to flow cytometry studies
bull Circulating cells of this case of Anaplastic Large Cell Lymphoma were negative for CD30 and CD25 by flow cytometry (unfortunately these markers were not run on the lymph node)
e-CSI ndash Case Conclusions
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull T cell lymphoblastic Lymphomabull 15 of childhood ALLbull BM always involvedbull CD3+ CD2+ CD5+ CD7+ CD4 and CD8 often coexpressed
bull BUT BONE MARROW NEGATIVE AND NO PERIPHERAL BLASTS SEEEN
bull EBV positive T cell lymphoproliferative disorders of childhoodbull Mostly in Asiabull Sites of involvement Liver Spleen LN Bone marrowbull CD2+ CD3+ CD8+ (some CD4 and CD8 positive cases reported)
bull BUT EBV serology NEGATIVE
e-CSI ndash Pediatric T cell lymphomas
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Pediatric T cell lymphomas
bull Anaplastic Large Cell Lymphomabull 10-20 of childhood lymphomasbull Often advanced disease with B symptomsbull ALK+ in all pediatric casesbull CD3 often negativebull CD2 CD5 and CD4 often positive
BUT almost always CD8 negative
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Anaplastic Large Cell Lymphoma (ALCL) most common mature T-cell neoplasm in children and adolescents
bull approximately 15 of all non-Hodgkin lymphomas (NHL) in children and adolescents
bull commonly present with advanced systemic diseasebull nearly universally anaplastic large cell lymphoma kinase (ALK)
positivebull event free survival (EFS) rates of 65-75
e-CSI ndash Pediatric ALCL
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Flow Cytometric Findings in ALCL
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 15 cases of pediatric ALCLbull High forward and side scatter (monocyte or granulocyte
region)bull Frequently expressed antigens CD4 (85) CD2 (77) CD7
(62) CD3 (54) and CD5 (38)bull CD3 often dimly expressedbull No CD8 expression
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull HLH is a hyperinflammatory syndromebull Impaired cytotoxic T cells and NK cellsbull Rarebull Primary (familial inherited) and secondary (infection
hematological malignancy rheumatological diseases)bull Often fatalbull Aberrant immunophenotype of T cells reported
e-CSI ndash Hemophagocytic LymphoHistiocytosis
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
e-CSI ndash Flow Cytometric Findings in HLH
McCall CM et al Am J Clin Pathol 2012 May137(5)786-94
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull 1315 patients (87) expressed activation marker HLA-DR on cytotoxic T cells
bull 69 (67)EBV associated HLH had aberrant expansion of CD8+ T cells with variable loss of CD3 CD5 and CD7
bull 58 (63) of non EBV associated HLH had expansion of CD8+ T cells but only one (familial HLH) had aberrant loss of markers CD3 or CD5 or CD7
rarr Care must be taken with diagnosing T cell lymphomas based on aberrant CD8+ T cells in the setting of HLH
e-CSI ndash Flow Cytometric Findings in HLH
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
bull Aberrant CD8+ T cells are a common finding in HLH
Thereforebull HLH can mask an underlying CD8+ T cell
lymphomabull Although rare CD8 expression can be seen on
ALCL
e-CSI ndash Conclusions
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
Referencesbull Pediatr Blood Cancer 2013 Nov60(11)1916-7 doi 101002pbc24638 Epub 2013 Jul 19 Pediatric
subcutaneous panniculitis-like T-cell lymphoma with features of hemophagocytic syndromeMerritt BY1 Curry JL Duvic M Vega F Sheehan AM Curry CV
bull Pediatr Hematol Oncol 2013 Sep30(6)509-19 doi 103109088800182013805347 Epub 2013 Jun 12 Anaplastic large cell lymphoma in children and adolescents Lowe EJ1 Gross TG
bull Am J Clin Pathol 2012 May137(5)786-94 Flow cytometric findings in hemophagocytic lymphohistiocytosisMcCall CM1 Mudali S Arceci RJ Small D Fuller S Gocke CD Vuica-Ross M Burns KH Borowitz MJ Duffield AS
- ICCS e_Newsletter CSI Spring 2014
- e-CSI - Clinical History
- e-CSI ndash Peripheral Blood
- e-CSI ndash Biochemistry
- PowerPoint Presentation
- Slide 6
- Slide 7
- Slide 8
- Slide 9
- Slide 10
- This is strange (Repeat specimen showed same results)
- Slide 12
- Slide 13
- Slide 14
- Slide 15
- Slide 16
- Slide 17
- Slide 18
- Slide 19
- Slide 20
- Slide 21
- Slide 22
- e-CSI ndash Pediatric T cell lymphomas
- e-CSI ndash Pediatric T cell lymphomas
- Slide 25
- Slide 26
- Slide 27
- Slide 28
- Slide 29
- Slide 30
- References
-
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