Secondary CNS involvement of ALK‐negative anaplastic large cell lymphoma
Authors: Ajay Major, Zenggang Pan, Manali Kamdar
Journal: American Journal of Hematology (2017)

A 42-year-old previously healthy male presented with a six-month history of B symptoms and new onset fever, nausea, and vomiting. Laboratory evaluation demonstrated anemia (8.0 g/dL), thrombocytopenia (18 × 109/L), neutropenia (1.0 × 109/L), abnormal liver function (total bilirubin 3.3 mg/dL), coagulopathy (INR 1.9, PTT 111.3 sec, d-dimer 23 000 FEU, fibrinogen 143 mg/dL), elevated ferritin (>375 000 ng/mL), elevated LDH (3729 U/L), and acute renal insufficiency (serum creatinine 7.5 mg/dL). He met the clinical diagnostic criteria for hemophagocytic lymphohistiocytosis. HIV antibody, EBV PCR, and HHV8 PCR testing were negative. A computerized tomography (CT) scan of chest, abdomen, and pelvis demonstrated splenomegaly and multiple mesenteric and retroperitoneal lymph nodes. Bone marrow biopsy showed a high-grade T-cell lymphoma with abundant large pleomorphic and anaplastic tumor cells with interstitial and nodular infiltrative patterns. There was an increase in gamma delta T cells. Tumor cells were positive for clonal T-cell receptor gene rearrangement. Tumor cells also exhibited expression of CD3 as well as diffuse and strong expression of CD30. Granzyme B and TIA-1 were also positive in the tumor cells. However, the tumor cells did not exhibit expression of ALK, CD4, CD5, CD8, CD15, CD43, or CD56, most consistent with ALK-negative anaplastic large cell lymphoma (ALCL). The patient was diagnosed with stage IV BES ALK-negative ALCL and expeditiously started on CHOEP (cyclophosphamide, doxorubicin, etoposide, vincristine, and prednisone) chemotherapy. After two cycles, he attained complete remission. The CSF cytospin shows frequent large and pleomorphic lymphoma cells, and they have large irregular nuclei with open chromatin and one or several prominent nucleoli. The cytoplasm is abundant and dense-blue staining. (Diff-Quick, 1000×) However, after four cycles of CHOEP, the patient presented with fevers, slurred speech, left facial droop, and confusion. Magnetic resonance imaging (MRI) of the brain demonstrated multiple focal T2/FLAIR hyperintense lesions in the right frontal operculum, left cerebellar hemisphere, and right parietal cortex, most likely related to secondary CNS lymphoma. Lumbar puncture revealed numerous large atypical cells (Image 1) and flow cytometry detected a large CD45-positive lymphoma population with a high side scatter with tumor cells positive for CD3, CD7, CD30, CD45, and TCR-gamma/delta, but negative for CD4 and CD5. Tumor cells in the CSF were positive for clonal T-cell receptor gene rearrangement. The immunophenotype was similar to that detected from the lymphoma cells in the bone marrow and was consistent with central nervous system involvement of ALCL. High-dose systemic methotrexate was initiated with near resolution of neurological deficits. Subsequent lumbar puncture was negative for lymphoma. Unfortunately, the patient presented one month later with fevers and was found to be in septic shock with rapid development of multiple organ failure and refractory ARDS, ultimately resulting in his death from cardiac arrest. This case is an exceptionally rare presentation of secondary CNS involvement of ALK-negative ALCL, of which only five cases in adults have been reported in the literature.1 A. Major performed the chart review, collected all of the patient information, wrote the manuscript, and revised the manuscript. Z. Pan and M. Kamdar edited the manuscript. M. Kamdar has been a speaker for Seattle Genetics.