The patient is a 83-year old man who presented with a rapidly growing mass on his scalp. An excisional biopsy was performed.
Histological sections reveal a dense infiltrate of large atypical lymphoid cells arranged as nodules, sparing the epidermis. Neoplastic cells feature moderate amounts of pale-staining cytoplasm, large irregular nuclei with conspicuous nucleoli and brisk mitotic activity. By immunohistochemistry, tumor cells express CD45 and are negative for melanocytic markers, pan-cytokeratin, CD43 and CK20. CD30 is strongly diffusely positive in a membranous and Golgi pattern. The neoplastic cells have an immunophenotype of CD4+ activated helper T lymphocytes with an aberrant loss of other T cells markers CD3, CD5, and CD8. Graenzyme B and EMA are negative. Alk-1 is not expressed. Ki-67 proliferative index is approaching 100%.
DIAGNOSIS: PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA
Anaplastic large cell lymphoma (ALCL) is a neoplasm composed of large atypical lymphocytes with pleomorphic, anaplastic or immunoblastic features and expression of CD30 by most tumor cells. Cutaneous ALCL (C-ALCL) usually occurs on the head and neck and extremities of older men and is particulary prevalent in HIV-infected patients, although it can also affect children. It presents a solitary firm nodule that grows rapidly. C-ALCL has an activated T-cell phenotype with variable loss of some T cell antigen and expression of activation markers CD25, CD30 and HLA-DR. C-ALCL is a part of the spectrum of primary cutaneous CD30-positive T-cell lymphoproliferative disorders, along with lymphomatoid papulosis. By definition, CD30 must be expressed by over 75% of cells. The tumor cells may also be positive for cytotoxic markers graenzyme B and perforin.
Primary cutaneous form (C-ALCL) must be distinguished from the primary nodal CD30+ ALCL as they have different prognosis. The two entities can have a similar morphologic and immunophenotypic features. Moreover, the cutaneous disease may secondarily involve the regional lymph nodes, and the systemic ALCL may have skin presentation. In this case, ALK-1 (anaplastic lymphoma related tyrosine kinase) negativity suggests either primary cutaneous involvement or aggressive systemic variant. Absence of epithelial membrane antigen (EMA) expression favors primary cutanous ALCL. Another characteristic feature of systemic ALCL that is uaully absent in C-ALCL is the presence of t(2;5) (p23;q35) translocation leading to expression of NPM-ALK protein. Despite the anaplastic morphology, C-ALCL has an excellent prognosis with over 90% 5-year survival and up to 40% of the tumor showing spontaneous regression.
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