Lymphoma - Non B cell neoplasms - Primary cutaneous CD30+ T cell lymphoproliferative disorders

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Lymphoma - Non B cell neoplasms

T/NK cell disorders

Primary cutaneous CD30+ T cell lymphoproliferative disorders

Reviewer: Dragos Luca, M.D. (see Reviewers page)
Revised: 30 October 2011, last major update August 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● Primary cutaneous CD30+ lymphoproliferative disorders are the second most common group of the cutaneous T cell lymphomas (CTCL), with 30% of cases (WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, Lyon 2008)

Terminology
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● Includes lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (C-ALCL)
● Spectrum with overlapping histopathologic and phenotypic features, therefore clinical features are critical for a definitive diagnosis
● Borderline cases exist despite clinicopathologic correlation

Primary cutaneous anaplastic large cell lymphoma (C-ALCL)

Definition
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● Cutaneous anaplastic large cell lym;homa is composed of large cells with an anaplastic, pleomorphic or immunoblastic cytomorphology that express the CD30 antigen by the majority (>75%) of the tumor cells (WHO 2008)

Terminology
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● Also called regressing atypical histiocytosis (European Organisation for Research and Treatment of Cancer)

Epidemiology
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● Second most common type of cutaneous T cell lymphoma
● Median age 60 years, M:F ratio 2-3:1, occasionally children
● Common form of cutaneous T cell lymphoma in HIV+ individuals

Sites
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● Trunk, face, extremities, buttocks

Clinical features
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● Solitary or localized nodules/tumors, sometimes papules, often ulcerated
● Multifocal lesions in 20% of cases
● Extracutaneous dissemination (mainly regional lymph nodes) in 10% of cases

Case reports
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● Three patients with eyelid lesions (Ophthalmology 2010;117:343)
● 63 year old man with scrotal tumor (Dermatol Online J 2009;15:9)
● 68 year old heart transplant patient (Acta Derm Venereol 2009;89:74)

Treatment and prognosis
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● Usually favorable prognosis (10-year disease-related survival of 90%)
● May show partial or complete spontaneous regression of skin lesions (10-40%)
● Frequent skin relapses
● Multifocality/nodal involvement have a similar prognosis as skin-only lesions
● No difference in behavior between anaplastic and non-anaplastic morphology

Postulated normal counterpart
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● Transformed/activated skin-homing T lymphocyte

Gross description
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● Solitary/multifocal papules/nodules/tumors

Gross images
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Shin

Gross and micro

With regression

Micro description
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● Diffuse, usually non-epidermotropic infiltrates of cohesive sheets of large CD30+ cells with anaplastic morphology (abundant cytoplasm, round / oval / irregular nuclei, prominent eosinophilic nucleoli)
● Non-anaplastic appearance (pleomorphic or immunoblastic) is less common (20-25%)
● Ulcerating lesions may show lymphomatoid papulosis-like histology with an inflammatory background (reactive T cells, histiocytes, eosinophils, neutrophils), relatively few CD30+ cells, prominent epidermal hyperplasia
● Rare neutrophil-rich (pyogenic) variant with extremely prominent inflammatory background

Micro images
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Various images (left: CD30 inset)

Positive stains
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● CD30 (>75% of cells), CD4, granzyme B, TIA1, perforin, CLA, CD56 (rare), CD25
● Variable loss of CD2, CD3, CD5
● Some cases are CD8+ (<5%)

Negative stains
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● EMA, ALK, CD15, CD8 (usually)

Genetics & molecular
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● Clonal TCR gene rearrangements in most cases (>90%), but no specific/consistent cytogenetic abnormalities
● No translocations involving the ALK gene at chromosome 2

Differential diagnosis
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● Mycosis fungoides with large cell transformation: clinical history, CD30 variable
● Systemic ALCL with cutaneous involvement: clinical history, ALK+

Lymphomatoid papulosis (LyP)

Definition
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● LyP is a chronic, self-healing skin disease composed of large, atypical, anaplastic, immunoblastic or Hodgkin-like cells in a marked inflammatory background (WHO 2008)

Epidemiology
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● Rare (0.1-0.2 cases per 100,000)
● Mostly adults (median age 45 years), but also children
● M:F ratio 2-3:1

Sites
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● Skin lesion but no known extracutaneous disease within 6 months of initial diagnosis
● Usually trunk, especially buttocks, and extremities, rarely oral mucosa

Etiology
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● Unknown, but endogenous retroviral elements have been identified

Clinical features
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● Self healing, recurrent, papular subcutaneous nodules less than 1 cm on extremities, trunk, face, genitals
● Papular, papulonecrotic or nodular skin lesions at different stages of development; may disappear in 3-12 weeks
● Clinically not considered malignant despite frequent monoclonality

Case reports
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● 12 year old boy with subsequent subcutaneous anaplastic large cell lymphoma (Ann Dermatol 2010;22:447)
● 21 year old man with Crohn's disease (Inflamm Bowel Dis 2009;15:965)
● 35 year old man with GI tract lesion / possible mucosal variant (Am J Surg Pathol 2000;24:296)
● 67 year old man with associated Paget disease of the nipple (J Med Case Reports 2011;5:43)

Treatment and prognosis
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● Probably benign, but 20% associated with lymphoma (mycosis fungoides, cutaneous anaplastic large cell lymphoma, Hodgkin lymphoma, up to 40 years later) and microscopically resembles lymphoma
● Generally excellent prognosis (only 2 of 118 patients 2 died of systemic disease, Blood 2000;95:3653)

Postulated normal counterpart
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● Activated skin-homing T lymphocyte

Gross description
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● Grouped or disseminated papules/nodules

Gross images
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Trunk

Face

Buttocks

Micro description
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● Large pleomorphic lymphoid cells with convoluted nuclei; some resemble Reed-Sternberg (RS) cells; also plasma cells and eosinophils
● Extremely variable histology that correlates in part with the age of the lesion (types, A, B and C, with overlapping features)
● Type A: small clusters of large, sometimes multinucleated or RS-like, CD30+ cells, admixed with numerous inflammatory cells (histiocytes, small lymphocytes, neutrophils, eosinophils)
● Type B: uncommon (<10%); epidermotropic infiltrate of of small atypical cells with cerebriform nuclei similar to Mycosis fungoides
● Type C: monotonous population or large clusters of large CD30+ T cells with relatively few admixed inflammatory cells
● Granulomatous eccrinotropic variant: Am J Clin Pathol 2003;119:731

Micro images
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Multiple images and review

Positive stains
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● CD3, CD30 (strong), CD4, granzyme B, perforin, TIA1, CLA (types A & C)
● CD3, CD4 (type B)
● Rare CD8+ (Am J Clin Pathol 2006;125:490) and NK-type LyP reported

Negative stains
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● CD15, EMA, ALK, CD8 (usually)
● CD30, CD8 (type B)

Genetics & molecular
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● Clonal rearrangement of T cell receptor genes in 60%; t(2,5) negative

Differential diagnosis
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● Arthropod bites, nonneoplastic disorders (usually have atypical CD30+ cells but polyclonal for T cell receptor rearrangements and polyclonal or oligoclonal for B cell immunoglobulin rearrangements, Am J Surg Pathol 2003;27:912)
● Mycosis fungoides: lymphomatoid papulosis type B

Additional references
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● WHO Classification of Skin Tumours, Lyon 2006
● Review articles: Haematologica 2004;89:1372

End of Lymphoma - Non B cell neoplasms > T/NK cell disorders > Primary cutaneous CD30+ T cell lymphoproliferative disorders

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