Primary Central Nervous System ALK-negative Anaplastic Large Cell Lymphoma, with TP53 Deletion

Abstract

Abstract Introduction/Objective ALK-negative anaplastic large cell lymphoma (ALCL) primary to the central nervous system (CNS), is a sporadic and rare lymphoma, characterized by neoplastic T-cells which are CD30 positive and ALK negative. It has a male predominance, mostly affects old adults and usually displays supratentorial, single or multiple lesions. Methods/Case Report We report the case of a 57-year-old woman with medical history of breast cancer, S/P lumpectomy and radiation therapy, who came to our institution with confusion, partial aphasia and headache. MRI showed a thick-walled, irregular, ring enhancing mass in the periventricular white matter of the occipital and temporal horns of the lateral ventricle with surrounding vasogenic edema and mass effect. It was isointense to cortex on T1- and heterogeneously hyperintense on T2-weighted images with mild diffusion restriction in the enhancing portion. A left parieto-occipital decompressive craniotomy was performed and tissue was procured for diagnosis. The biopsy showed an infiltrating, angiocentric neoplasm, composed of large anaplastic cells, including hallmark cells with "horseshoe" nuclei, abundant eosinophilic cytoplasm and occasional perinuclear clearing. Large areas of necrosis and pericellular reticulin deposits of the vascular walls were also noted. On immunohistochemistry, the neoplastic cells diffusely expressed CD45, CD2, CD3, CD25, CD43, MUM1, and CD30, and were negative for ALK, CD20, CD79a, PAX-5, CD15, CD5, BCL-6, BCL-2, Granzyme B, GFAP, Pancytokeratin. In situ hybridization for EBER was negative. The proliferative index (Ki-67), while variable, was as high as 80%. TP53 deletion was detected by FISH in 100% of the cells analyzed. No rearrangements in the ALK or MYC genes was noted by FISH. Additional studies revealed a complex karyotype including loss of chromosomes 9 and 10, gain of chromosome 17 and a marker chromosome, and structural rearrangements involving chromosomes 4, 10, and 13. Previously reported rearrangements involving DUSP22 (6p25) and TP63 (3q28) were not identified. TCR gene rearrangement was also identified by PCR. High dose Cytarabine/Methotrexate, and radiation were not successful in controlling disease progression and home hospice was recommended. Results (if a Case Study enter NA) N/A Conclusion This is an infrequent type of primary CNS lymphoma with a poor prognosis and, while TP53 has been reported in sporadic, and cutaneous ALCL, to our knowledge, this is the first report of primary CNS ALK-negative anaplastic large cell lymphoma with TP53 deletion.