Gastrointestinal Tract Lymphoma Dr. Shad Salim Akhtar MBBS, MD, MRCP(UK), FRCP(Edin), FACP(USA), Member AUICC Fellows Consultant Medical Oncologist Medical Director Prince Faisal Oncology Center & KFSH Prof. of Clinical Medicine, Qassim Medical University Buraidah, Al-Qassim, KSA
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Gastrointestinal Tract Lymphoma
Dr. Shad Salim AkhtarMBBS, MD, MRCP(UK), FRCP(Edin), FACP(USA), Member AUICC Fellows
Consultant Medical OncologistMedical DirectorPrince Faisal Oncology Center & KFSHProf. of Clinical Medicine, Qassim Medical UniversityBuraidah, Al-Qassim, KSA
Non Hodgkin's Lymphoma Heterogeneous collection of lympho-proliferative
diseases Is it the same disease at all sites??? Major divisions
Nodal Extra nodal
Around 33-40% are extra nodal GIT is the commonest extra- nodal site
Around 50%
Henessey BT et al. Lancet Oncol 2004;5:341
Extra nodal NHL Clinically dominant (>75%) extra nodal
component with No or Minor nodal involvement (25%) Tonsils / Waldeyer’s ring??
Zucca E et al: Ann Oncol 1997; 8:727
GI NHL-Definition Localized disease to the GIT
Stage IE, IIE disease
Lymphoma patients exhibiting GI symptoms or have a predominant lesion in GI
Dawson IMP et al: Br. J Surg 1961; 49:80
Lewin KJ et al: Cancer 1978; 42:693
Haber DA et al: Semin Oncol 1988; 15:154
All patients who present with NHL that apparently originated at an extra nodal site even in the presence of disseminated disease, as long as the extra nodal component is dominant”
GI NHL-Definition
Krol ADG et al: Ann Oncol 2003; 14:131
NHL-Increasing incidence 1970 10.2/100,000 1990 18.5/100,000 81% increase or 3.6% per year Extra nodal NHL 3-6.9%/year Nodal NHL 1.7-2.5%/year
Vose JM et al: Hematology 2002; 242
Ries LAG et al: National Cancer Institute 2002`
GI NHL-Sites of involvementAuthor Total Gastric IntestKoch P 371 277 70Liang R 442 238 184Radaszkiewicz T 307 264 59Morton JE 175 78 95Azab MB 106 55 43Amer MH 185 94 91El Foudeh M 215 185 66Nakamura S 455 342 96Ducreux M 78 42 13
GI NHL-Major symptomsPainNausea vomitingBleedingWeight lossDiarrheaAcute abdomen
GI NHL-Symptoms versus site
Stomach Small intestine
Colorectal
Pain Pain PainNausea & Vomiting
Obstruction Bleeding
Weight loss Weight loss DiarrheaBleeding Malabsorption
Crump M et al: Semin Oncol 1999; 26:324
GI NHL-Staging system TNMI Single nodal region
Localized single extra lymphatic organ/site IEII 2 or more node regions same side of diaphragm
Localized single extra lymphatic organ/site with its regional nodes+/- other nodes on the same side of diaphragm
IIE
III Node regions both sides of diaphragm+/- localized single extra lymphatic organ/siteSpleen / Both
IIIEIIISIIIES
IV Diffuse or multi focal involvement of extra lymphatic organs+/- regional nodes; isolated extra lymphatic organ and non regional lymph nodes
Sobin LH et al: TNM Manual 6th Edition 2002; 238
GI NHL-Staging systemStage I
Tumor confined to the GI tract Single primary site or multiple non contiguous
lesionsStage II
Tumor extending into abdomen from a primary GI siteNodal involvement
Stage IIE Penetration of serosa to involve adjacent
organs or tissuesStage IV
Disseminated extra nodal involvement or GIT lesion with supradiaphragmatic nodal
involvement
GI NHL-Staging system
Rohatiner A et al: Ann Oncol 1994; 5:397
? X to denote the organ of origin X [stomach] II (gastric NHL with local nodes
involved) X [stomach, colon] II
Addition of IP index as in AJCC Cancer Staging Manual 6th Edition?
GI NHL- StagingSuggested modifications
Armitage JO; N Engl J Med 2005; 352:1250Grothus-Pinke B et al: Ann Oncol 1996; 7:S126
GI NHL-Work up History & physical examination Weight loss not recorded as a B symptom Waldeyer’s ring assessment especially with
limited GI involvement Routine bloods Endoscopic examination CT Barium studies Bone marrow examination!!! Endoscopic USG
GI NHL-Do they need laparotomy for diagnosis?
In 30-50% of intestinal NHL who may present as an emergency
Endoscopic biopsy from accessible lesions Diagnostic accuracy 62% to 98.5% First attempt diagnosis 80% of
above May miss areas of transformation
Al Akwaa AM et al: Worl J Gastroenterol 2004; 10:5
FNAC Laparoscopic biopsy
Frozen section facility Bone marrow in the same sitting
All tissues must be sent for Histological Immunohistochemistry Cytogenetic studies
GI NHL-Diagnosis?
Kaleem Z et al: Am J Clin Pathol 2001; 115:136Koniaris LG et al: J Am Coll Surg 2003; 197:127
GI NHL-Histological types Diffuse B cell large cell
Secondary DLBCL Extra nodal marginal zone lymphoma (MALT) Follicular lymphoma Mantle cell lymphoma Burkitt’s lymphoma Enteropathy type T cell lymphoma Peripheral T cell lymphoma NOS Majority of cases seen in KSA are DLBCL type
Risk of relapse from complete response according to the primarysite of the lymphoma. GI, gastrointestinal.
Kniaris LG :J Am Coll Surg2003;197:127 Koch P :JCO 2001;19:3861
Intestinal DLBCL Surgical intervention is less controversial
Acute presentation more common Completely resected patients do better Generally poorer prognosis as compared to
gastric Survival
Early stage disease better Surgery+CT+RT 50-70% Single modality 30-50%
Koniaris LG et al: J Am Coll Surg 2003; 197:127Daum S et al: J Clin Oncol 2003; 21:2740
Marginal Zone
Mantle ZoneGerminal Centre
(Contains post germinal centre B cells, monocytoid B cells, plasma cells and centrocyte like cells)
Normal MALT
Rooney N et al: Curr Diag Pathol 2004; 10:69
Calam J etal. BMJ 2001;323:980
Relation of H pylori infection to UGI conditions
H pylori and Malt lymphoma ~90% have H pylori in gastric mucosa~90% have H pylori in gastric mucosa Case control studies confirm relationship Case control studies confirm relationship
between previous infection and lymphomabetween previous infection and lymphoma Clonal B cell detection in chronic gastritis Clonal B cell detection in chronic gastritis
which precedes lymphomawhich precedes lymphoma H pylori strain specific T cells promote H pylori strain specific T cells promote
lymphoma growth in culturelymphoma growth in culture Eradication of H pylori causes regression in Eradication of H pylori causes regression in
75% of caces75% of caces
Gastric MALT lymphoma MALT reacts with the antigen
present within the lumen An Pr Cells +H pyhlori
antigen+CD4+ T cells stimulate peoliferation of B cells
B cells synthesize immunoglobulins
Immunoglobulins react with autoantigens
Parsonnet J et al: N Engl J Med 2004; 350:213
Rooney N et al: Curr Diag Pathol 2004; 10:69
Rooney N et al: Curr Diag Pathol 2004; 10:69
Gastric MALT typesA low grade classical
<5% blasts and clusters of <10 cells
B 10-20% transformed cells Clusters of >20 cells
C high grade transformation with sheets of transformed cells
D no MALT component is recognizableIsaacson PG: Hematology 2001; 241
MALT lymphoma management Careful imaging
CT scan Endoscopic ultrasonography
Sufficient tissue to Differentiate from
Mantle cell lymphoma Follicular lymphoma
Confirm presence of more transformed clone Immunohistochemical studies (bcl2 expression)
Gastric MALT management Antibiotic therapy
Regression in approximately 75% cases Time to regression may be as long as 18 months Predictors of failure of antibiotic therapy
t(14:18) do not respond to antibiotics Node positive disease Depth of invasion muscularis mucosa
Lymphoma clone persists Therefore it becomes dormant rather than disappearIsaacson PG; Best Prac & Res 2005; 18:57
Cavalli F et al: Hematology 2001; 241
Surgical resection Antrectomy usually adequate
Radiotherapy Chemotherapy Alone or in combinations 5 yr DFS
>95% in IE 75% in IIE
Gastric MALT management antibiotic failure or advanced
Koniaris LG: J Am Coll Surg 2003; 197:127
IPSID MALT type B cell lymphoma Proximal small intestine involved Geographical distribution
Mediterranean Middle East Africa Far East
Children & young adults Monotypic truncated immunoglobulin α heavy
chainLecuit M et al: N Engl J Med 2004; 350:239
IPSID Campylobacter jejuni
Small group of patients (4/6) FISH, PCR, DNA sequencing and
immunohistochemistry Early stages respond to antibiotics Non responsive pts progress to lymphoma
Lymphoplasmacytic & immunoblastic Locally invasive and metastatic