Primary Anaplastic Large Cell Lymphoma of the Central Nervous System

Abstract

Anaplastic large cell lymphoma (ALCL) rarely occurs in the central nervous system. Although defined by its composition of large, pleomorphic, CD30-positive lymphocytes, ALCL is heterogeneous. Most are T cell but some are null cell. Most but not all have a characteristic 2:5 translocation producing the fusion protein ALK-1, which is reliably detected by immunohistochemistry. In systemic ALCL, ALK-1 expression correlates with young patient age and a favorable prognosis. Herein we report four new cases of primary central nervous system ALCL from the Mayo Clinic and incorporate additional data from five previously published cases. ALK-1 expression was determined in all nine tumors. Patient age was 4-66 years (mean 29 years) with a bimodal distribution: 6 < or = 22 years, 3 > or = 50 years. Six were female. Tumors were mostly supratentorial, five were multifocal, and seven had involvement of dura or leptomeninges. Seven tumors were T cell, two were null cell, and five of nine were ALK-1 immunopositive. Total mortality was six of nine. Three patients, 4-18 years of age (mean 13 years), were alive at 4.8-6.1 years postdiagnosis; these tumors were all ALK positive. Five patients, 13-66 years of age (mean 43 years), died of tumor 4 days to 11 weeks postdiagnosis; four of five of these tumors were ALK negative. One 10-year-old child with an ALK-positive tumor died of sepsis, but in remission. Central nervous system ALCL is aggressive. Our study suggests that a better outcome may be associated with young age and ALK-1 positivity, prognostic parameters similar to systemic ALCL.

Results of AIEOP LNH‐97 protocol for the treatment of anaplastic large cell lymphoma of childhood

“…However, when comparing results of these two protocols, we should consider the higher percentage of CNS positive patients (22% vs. 0%) and of the lymphohistiocytic variant (13% vs. 3%) in the LNH-97 protocol compared to the LNH-92 protocol, both characteristics being correlated to unfavorable prognosis [15,31]. The AIEOP LNH-97 protocol used higher doses of chemotherapy compared to the ALCL99 protocol, but achieved comparable outcome (5-year EFS 68% vs. 2-year EFS 71%).…”

“…The central nervous system (CNS) is rarely involved [14]. In the literature, few cases of primary CNS ALCL have been described, but in those cases the tumor-associated mortality seemed to be lower in patients with ALK-positive ALCL and young age [15]. The secondary spread of primary nodal or systemic ALCL to the CNS is a rare event [7][8][9][10][11][12][16][17][18].…”

Pathology of primary central nervous system lymphoma

“…An ALCL may have a worse prognosis than other types of PCNSL. 15 Tumor necrosis and multifocal disease may indicate a worse prognosis. Dural and leptomeningeal involvement, although common, appear to have no impact on prognosis.…”

“…Although the number of tumors investigated is small, ALCL primary to the CNS, like its nodal counterpart, often shows immunopositivity with antibody to the anaplastic lymphoma kinase gene (ALK-1). 15 Immunopositivity is specific for the fusion of the ALK gene on chromosome 2 with the nucleophosmin gene (NPM) on chromosome 5, which yields the fusion transcript protein p80. Positive findings for ALK-1 appear to correlate with a young patient age and a favorable prognosis.…”

Primary Cerebral ALK-1-Positive Anaplastic Large Cell Lymphoma in a Child

“…ALCL rarely occurs in the central nervous system (CNS) and metastasis of primary nodal or systemic ALCL to the CNS is an uncommon event [5]. A thorough review of the literature of primary CNS ALCL reveals that this case represents the 3rd case in a pediatric patient and 14th documented case overall [7,8,9,10,11,12,13,14,15]. In this report, we describe the case of primary ALCL in the brain of a 4-year-old boy and review the current literature of this neoplastic entity in the CNS.…”