Abstract

Intravascular large B-cell lymphoma (IVLBL) is a rare, aggressive non-Hodgkin lymphoma characterized by intraluminal neoplastic cells without peripheral circulating cells or extravascular tumor. The diverse systemic manifestations, often neurological and cutaneous, resulting from the occlusion of small vessels pose diagnostic challenges. A 65-year-old male with recurrent CVAs was readmitted for acute encephalopathy after a stroke code at an outside facility. After extensive workup, a brain MRI raised concerns for acute disseminated encephalomyelitis, CNS lymphoma, or IVL. Clinically, no obvious locations for biopsy or explicit signs of IVL were present. Three standard 4mm punch biopsies of normal-appearing skin were performed, all of which revealed no evidence of neoplasm. Given the persistent encephalopathy, further decompensation, and ongoing suspicion of IVL, another 6mm telescoping biopsy was performed to sample the deep subcutaneous fat. Histology revealed atypical large lymphocytes with frequent mitoses within the vascular spaces of the deeper portions of the subcutis. Immunohistochemical staining revealed these cells were positive for CD20 and Mum-1, with a subset also expressing Bcl-6, while being negative for CD3, CD10, Bcl-2, and EBV by in-situ hybridization. CD31 immunostaining highlighted the intravascular location of these cells, confirming the diagnosis of IVLBL. Diagnosis can be made with lesional skin or, ideally, at least three random biopsies of normal-appearing skin. Incisional or telescoping punch biopsies are favored for greater diagnostic yield as the more frequently involved vessels are deeper (>5mm). This case underscores biopsy depth in diagnosing IVLBL, especially in the absence of skin lesions and when initial superficial biopsies are negative.