Primary Cutaneous Anaplastic Large Cell Lymphoma

C. Cameron Yin, MD, PhD

Key Facts

Terminology

Cutaneous lymphoma composed of large T cells that express CD30 (> 75%)

Clinical Issues

Common sites: Face, trunk, and extremities
Solitary nodule or localized nodules/papules; ± ulceration
Multifocal lesions occur in ˜ 20% of patients
Extracutaneous dissemination in ˜ 10% of patients
Spontaneous regression can occur; relapse is common
Favorable prognosis with 10-year survival of ˜ 90%

Microscopic Pathology

Diffuse infiltrates of large neoplastic cells mainly located in dermis; can extend into subcutaneous tissue
Variable inflammatory cell infiltrate in background
Anaplastic cells in most cases; ˜ 20% nonanaplastic

Ancillary Tests

> 75% of neoplastic large cells CD30(+)
CD4(+), cytotoxic proteins(+), cutaneous lymphocyte antigen (+/-)
CD56(-/+), EMA(-), CD15(-), ALK(-)
No specific cytogenetic abnormalities identified
Monoclonal T-cell receptor rearrangements

Top Differential Diagnoses

Systemic ALK(-) ALCL with cutaneous involvement
Large cell transformation of mycosis fungoides
Lymphomatoid papulosis, type C
Peripheral T-cell lymphoma, NOS

Excisional skin biopsy specimen shows cutaneous anaplastic large cell lymphoma (C-ALCL) composed of sheets of intermediate and large anaplastic lymphoid cells with frequent mitoses

Skin biopsy specimen of C-ALCL. Immunohistochemistry showed that the neoplastic cells are uniformly and strongly CD30(+).

TERMINOLOGY

Abbreviations

Primary cutaneous anaplastic large cell lymphoma (C-ALCL)

Synonyms

Primary cutaneous CD30(+) T-cell lymphoproliferative disorder
- This term also includes lymphomatoid papulosis

Definitions

Cutaneous lymphoma composed of large T cells that express CD30 (> 75%)

ETIOLOGY/PATHOGENESIS

Unknown

CD30/TRAF1/IRF-4 activation induced upregulation of NF-κB is implicated
Other suggested factors
- Viral infection, reduced immunosurveillance
- Chronic antigenic stimulation, direct oncogenic effect of immunosuppressive drugs
Gene expression profiling has failed to show genes that clearly distinguish C-ALCL from ALK(-) systemic ALCL
- Increased expression of skin-homing chemokine receptors may play a role in confining C-ALCL to skin

CLINICAL ISSUES

Epidemiology

Age
- Median: 60 years
Gender
- M:F = 2-3:1

Site

Common sites: Face, trunk, and extremities

Presentation

Solitary nodule or localized nodules or papules; ± ulceration
Multifocal lesions occur in ˜ 20% of patients
Extracutaneous dissemination in ˜ 10% of patients
- Regional lymph nodes; rarely viscera
Partial or complete spontaneous regression can occur; relapse is common

Treatment

Irradiation for localized nodules
Low-dose methotrexate for multifocal lesions
Extracutaneous tumors require systemic chemotherapy

Prognosis

Favorable, with 10-year survival of ˜ 90%
Similar prognosis for patients with localized vs. multifocal skin lesions

MICROSCOPIC PATHOLOGY

Histologic Features

Diffuse infiltrates of large neoplastic cells mainly located in dermis; can extend into subcutaneous tissue
- Epidermal involvement ± ulcer
Variable degree of inflammatory infiltrate consisting of reactive T-cells, histiocytes, eosinophils, and neutrophils
- Biopsy lesions can be eosinophil-rich or neutrophilrich (pyogenic)

Cytologic Features

Anaplastic cells with round to irregular nuclei, prominent eosinophilic nucleoli, and abundant cytoplasm
˜ 20% of cases appear nonanaplastic (pleomorphic or immunoblastic)

ANCILLARY TESTS

Immunohistochemistry

> 75% of neoplastic large cells are CD30(+)
Activated CD4(+) T-cell phenotype
Rarely show CD8(+) T cell or null CD4(-)/CD8(-) immunophenotype
Variable loss of pan-T-cell antigens: CD2, CD3, CD5, T-cell receptor (βF1)
Cytotoxic proteins(+), cutaneous lymphocyte antigen (+/-)
CD56(-/+), EMA(-), CD15(-), ALK(-)

Cytogenetics

No specific cytogenetic abnormalities identified
No translocations involving ALK gene at chromosome 2p23
Array-based comparative genomic hybridization has revealed chromosomal imbalances
- Gains in 7q, 17q, 21; losses in 3p, 6q, 8p, 13q

Molecular Genetics