Introduction to Cutaneous Lymphomas

Diapositiva 1Dept. of Dermatology; Leiden University Medical Center Leiden, The Netherlands
ERN-EuroBloodNet Cutaneous Lymphomas May 18, 2020
Introduction to Cutaneous Lymphomas
• Mycosis Fungoides: Maarten Vermeer
• CD30+lymphoproliferations: Werner Kempf
• Indolent CBCL (PCFCL and PCMZL): Pablo Ortiz & Emmanuella Guenova
• Aggressive CBCL (PCDLBCL-LT): Marie Beylot Barry & Anne Pham-Ledard
• New therapeutic developments I: Julia Scarisbrick
• New therapeutic developments II: Rudolf Stadler
Cutaneous Lymphoma Webinars
To be discussed
Why are cutaneous lymphomas special (different from nodal NHL) ?
History of cutaneous lymphoma classification
• dictates the type of treatment
• provides information on clinical course and prognosis.
• incorrect classification → incorrect treatment
1806 Mycosis fungoides (MF)
1938 Sézary syndrome
proposed as an encompassing term for
above conditions.
described by Alibert (1806)
Edelson R. J Am Acad Dermatol 1980;2:89-106
History of cutaneous lymphoma classification: 1990
6
- classified by pathologist with schemes used
for nodal lymphomas and based on
morphology (histologic classification:
secondary cutaneous lymphomas.
lymphomas with secondary skin
7
- classified by pathologist with schemes used
for nodal lymphomas and based on
morphology (histologic classification:
secondary cutaneous lymphomas.
lymphomas with secondary skin
Primary ≠ secondary cutaneous lymphomas.
(histologic diagnosis ≠ final diagnosis).
clinicopathologic correlation essential.
Histology: CBCL, centroblastic = diagnosis
Therapy: multi-agent chemotherapy (consistent with centroblastic lymphoma) → CR
Follow-up: died of lymphoma 32 months after diagnosis.
Centroblastic lymphoma
Histology: CBCL, centroblastic = diagnosis
Follow-up: sustained CR (168 months).
Centroblastic lymphoma presenting with only skin lesions
Follicular: <5%
follicular and diffuse and diffuse growth pattern
Histologic growth pattern of PCFCL
Primary cutaneous ≠ nodal centroblastic lymphoma
• Solitary or localized lesions on trunk or face/scalp (85%)
• Therapy: radiotherapy
• Extracutaneous dissemination uncommon (<10%)
• Distinct clinicopathologic entity (derived from follicle center (germinal center) B-cells:
primary cutaneous follicle center cell lymphoma
before radiotherapy
after radiotherapy
Willemze R. et al, Am J Pathol 1987;126:325-333; Berti E. et al; J Am Acad Dermatol 1988;19:259-272
Primary Cutaneous Lymphoma (PCL):
• No evidence of extracutaneous disease at time diagnosis as
assessed by appropriate staging procedures.
Secondary CL (skin localizations of NHL)
• NHL with both cutaneous and extracutaneous localizations at
diagnosis
• Skin localizations in a patient with a history of a systemic NHL
Primary vs secondary cutaneous lymphomas
Primary cutaneous
immunocytoma (PCMZL)
(5-yr-survival: 99%)
Low grade (B-cell)
• Small lymphocytic (B-CLL)
Low grade (T-cell) = small cell
• Small lymphocytic (T-CLL)
• Small cerebriform (MF/SS)
• Lennert’s lymphoma
• Pleomorphic medium/large
18 Beljaards RC. Et al; Am J Pathol. 1989;135:1169-78.
PCL vs nodal NHL -/+ secondary cutaneous involvement
• Distinctive clinical features (disease entities)
• Other clinical behaviour and prognosis → different type of treatment.
• Other biologic features (e.g. genetic pathways; translocations;
adhesion molecules) → different pathogenesis.
• PCL should be included as separate entities in malignant lymphoma
classifications (to prevent unnecessarily aggressive therapies).
PCL vs nodal NHL -/+ secondary cutaneous involvement
Primary cutaneous lymphomas are visible and accessible:
• Different types of CTCL and CBCL have a characteristic clinical
presentation that may be helpful in diagnosis and classification.
• Different types of cutaneous lymphoma can show an identical histology
→ classification on the basis of histology alone impossible.
• Histologic diagnosis = differential diagnosis ≠ final diagnosis →
clinicopathologic correlation essential
Centroblastic lymphoma presenting with only skin lesions
Localized skin lesions on trunk (back) or scalp (>80%)
Primary cutaneous marginal zone lymphoma
Preferential localization on arms and upper trunk (65%)
Primary cutaneous DLBCL, leg type
Preferential localization on leg(s) in elderly patients (>80%)
Early stage mycosis fungoides
Folliculotropic mycosis fungoides
Petrella T. et al. Am J Surg Pathol. 2007;31:1887-9
PCL vs nodal NHL -/+ secondary cutaneous involvement
Primary cutaneous lymphomas are visible and accessible:
• Different types of CTCL and CBCL have a characteristic clinical
presentation that may be helpful in diagnosis and classification.
• Different types of cutaneous lymphoma can show an identical histology
→ classification on the basis of histology alone impossible.
• Histologic diagnosis = differential diagnosis ≠ final diagnosis →
clinicopathologic correlation essential
Epidermotropic atypical infiltrate: MF?
dermatologists
pathologists
mycosis fungoides pagetoid reticulosis LyP, type D aggressive CD8+ CTCL
CD3 CD30
DD. Diffuse CD30-positive skin infiltrate
Examination: nodules and ulcerating tumors on left upper leg for 2 months.
Histology: (C-)ALCL = diagnosis ?
Skin infiltrates with clusters of CD30+ cells:
• Cutaneous anaplastic large cell lymphoma (C-ALCL)
• Lymphomatoid papulosis (type C)
• Skin localizations of Hodgkin lymphoma.
• MTX-associated B-cell lymphoproliferative disorder
DD. Diffuse CD30-positive skin infiltrate
Examination: nodules and ulcerating tumors on left upper leg for 2 months.
Histology: (C-)ALCL = diagnosis ? ?
Therapy: ?
Man, 74 yrs. Nodules and ulcerating tumors on left upper leg for 2 months. Diagnosis: transformed MF (CD30+)
CD3 CD30 CD3
DD. Diffuse CD30-positive skin infiltrate
Examination: nodules and ulcerating tumors on left upper leg for 2 months.
Histology: Diffuse CD30+ dermal infiltrate; DD: (C-)ALCL; transformed MF
Staging: no extracutaneous disease
Therapy: RT (tumor); topical steroids (patches)
Follow-up: nodal and pleura lesions 4 years after diagnosis.
DD. Diffuse CD30-positive skin infiltrate
PCL vs nodal NHL -/+ secondary cutaneous involvement
Primary cutaneous lymphomas are visible and accessible:
• Different types of CTCL and CBCL have a characteristic clinical
presentation that may be helpful in diagnosis and classification.
• Different types of cutaneous lymphoma can show an identical histology
→ classification on the basis of histology alone impossible.
• Histologic diagnosis = differential diagnosis ≠ final diagnosis →
clinicopathologic correlation essential
PCL vs nodal NHL -/+ secondary cutaneous involvement
Primary cutaneous lymphomas are visible and accessible:
• Different types of CTCL and CBCL have a characteristic clinical
presentation that may be helpful in diagnosis and classification.
• Different types of cutaneous lymphoma can show an identical histology
→ classification on the basis of histology alone impossible.
• Histologic diagnosis = differential diagnosis ≠ final diagnosis →
clinicopathologic correlation essential
C-ALCL
MF LyP PCSM-TCLPD
C-ALCL
MF LyP PCSM-TCLPD
• Different types of CTCL and CBCL have a characteristic clinical
presentation that may be helpful in diagnosis and classification.
• Different types of cutaneous lymphoma can show an identical histology
→ classification on the basis of histology alone impossible.
• Histologic diagnosis = differential diagnosis ≠ final diagnosis →
clinicopathologic correlation essential
• CTCL is not a diagnosis → Do not use the term without further specification.
PCL vs nodal NHL -/+ secondary cutaneous involvement
Primary cutaneous lymphomas are visible and accessible:
• Different types of CTCL and CBCL have a characteristic clinical
presentation that may be helpful in diagnosis and classification.
• Different types of cutaneous lymphoma can show an identical histology
→ classification on the basis of histology alone impossible.
• Histologic diagnosis = differential diagnosis ≠ final diagnosis →
clinicopathologic correlation essential
• CTCL is not a diagnosis → Do not use the term without further specification.
• Therapeutic consequences: importance of skin-directed therapes (topical
steroids; topical cytostatics; phototherapy; radiotherapy).
New concepts in cutaneous lymphoma classification
Primary ≠ secondary cutaneous lymphomas.
• Histologic diagnosis ≠ final diagnosis.
• Clinicopathologic correlation essential in diagnosis and classification
New types of CTCL and CBCL
New classifications (EORTC; WHO-EORTC; WHO-EORTC 2018)
New types of CTCL and CBCL: 1985 - 1996
1987 primary cutaneous follicle center cell lymphoma
1989 primary cutaneous CD30+ large T-cell lymphoma (C-ALCL) vs
1989 primary cutaneous CD30 - large T-cell lymphoma
1991 primary cutaneous immunocytoma (PCMZL)
1992 spectrum primary cutaneous CD30+ LPD
1993 CD30-negative CTCL (non-MF) [small vs large]
1996 primary cutaneous large B-cell lymphoma of the leg
Should be, but were not included as distinct disease entities in malignant lymphoma
classifications to prevent unnecessarily aggressive treatment: → EORTC classification (1997)
EORTC classification for cutaneous lymphomas
Cutaneous T-cell Lymphoma
Cutaneous B-cell Lymphoma
Intermediate behaviour • large B-cell lymphoma of the leg
Provisional entities • plasmacytoma • intravascular large B-cell lymphoma
Willemze R et al: BLOOD 1997;90: 354-371
• First classification for primary cutaneous
lymphomas.
• Distinction between indolent, intermediate
• Clinical relevance validated on more than
1300 patients.
WHO-EORTC classification for cutaneous lymphomas 2005
Willemze R. et al, Blood 2005; 105: 3768-3785
Classification for primary cutaneous
and hematologists
Classification DER PA HEM
1988 Updated Kiel classification - (+) +
2005 WHO-EORTC classification + (+) -
2016 WHO classification (revised 4th ed.) + + +
2018 update WHO-EORTC classification + + +
Classification DER PA HEM Treatment PCFCL and
C-ALCL with RT
2005 WHO-EORTC classification + (+) - -
2016 WHO classification (revised 4th ed.) + + + +
2018 update WHO-EORTC classification + + + +
Cutaneous T-cell lymphomas
– Folliculotropic MF
- Primary cutaneous γ/δ T-cell lymphoma
- Aggressive cytotoxic epidermotropic CD8+ CTCL
- Primary cutaneous CD4+ small/medium T-cell LPD
- Primary cutaneous acral CD8+ T-cell lymphoma
Cutaneous B-cell lymphomas
• EBV-positive mucocutaneous ulcer
75%
25%
• CTCL (75%) much more common than CBCL (25%)
• CTCL is not a diagnosis, but refers to a group of diseases with different
treatment and prognosis.
phenotypical, genetic and clinical criteria (clinicopathologic entities).
• Clinical presentation (localization !!) often is a major diagnostic adjunct.
• If the clinician fails to provide the appropriate clinical information, a
definite diagnosis can often not be made.
Summary
approach form the basis of cutaneous lymphoma diagnosis
and classification and are a prerequisite for correct
management and treatment.
• Mycosis Fungoides: Maarten Vermeer
• CD30+lymphoproliferations: Werner Kempf
• Indolent CBCL (PCFCL and PCMZL): Pablo Ortiz & Emmanuella Guenova
• Aggressive CBCL (PCDLBCL-LT): Marie Beylot Barry & Anne Pham-Ledard
• New therapeutic developments I: Julia Scarisbrick
• New therapeutic developments II: Rudolf Stadler
Discussion