PRIMARY KI-1-POSITIVE ANAPLASTIC LARGE-CELL LYMPHOMA - A DISTINCT CLINICOPATHOLOGICAL ENTITY

The morphology of anaplastic large-cell lymphoma (ALCL) is associated with a clinical syndrome of peripheral lymphadenopathy (> 80%) and frequent extranodal disease (>40%) in children and young adults (median age <40 yrs.). Skin lesions occur in more than 20% of patients; other extranodal sites are bone, soft tissue, gastro-intestinal tract, lung, and pleura. Marrow involvement is infrequent (<10%). Features that distinguish ALCL from Hodgkin's disease (HD) are noncontiguous nodal disease (>50%), infrequent mediastinal mass (<20%), and frequent inguinal lymphadenopathy (>40%). Most patients present with stage III/IV disease. Stage is highly predictive of achieving complete remission, disease-free survival, and overall survival. Localized skin lesions have an excellent prognosis and occasional spontaneous regressions are noted. Distinctive histopathologic features of ALCL are partial lymph node involvement with sinus infiltration, sparing of B-cell regions, and tumor cell pleomorphism. Other features are high mitotic rate, necrosis, fibrosis, and plasma cell infiltrates. Morphologic variants of ALCL resemble carcinoma, syncytial variant of nodular sclerosing HD, true histiocytic lymphoma or interdigitating cell sarcoma, and mycosis fungoides. ALCL can be distinguished from these morphologically similar disorders by immunophenotype (CD30+, CD45+, CD15-, EMA+, BNH9+, keratin-, lysozyme-). A recurrent cytogenetic translocation, t(2; 5) (p23; q35), has been observed among morphologic variants, including a small-cell-predominant variant and tumor cell line which contains a spectrum of small cerebriform and large anaplastic CD30+ cells. 70% of ALCL cases are of T-cell lineage, 15% B, 5% T/B, and 10% undefined. ALCL appears to be distinct from peripheral T-cell lymphomas such as HTLV-1+ adult T-cell leukemia, angioimmunoblastic lymphadenopathy, angiocentric T-cell lymphoma, and mycosis fungoides, which occur mainly in older patients. These combined clinical, pathologic, immunophenotypic, and cytogenetic observations support the concept that ALCL is a distinct clinicopathologic entity.