Li-Fraumeni syndrome presenting as precursor B lymphoblastic leukemia mimicking intravascular large B-cell lymphoma

A 25-year-old man presented with abdominal pain and 15-kg weight loss over the course of 6 months. Computed tomography imaging showed hepatomegaly with diffuse heterogenous densities. A liver biopsy demonstrated intermediate to large cells within sinusoids with irregular nuclei, dispersed chromatin, occasional nucleoli, and scant cytoplasm (panel A; hematoxylin and eosin stain, original magnification ×400). The infiltrate was positive for CD45, CD79a, PAX5 (brown)/CD34 (red) double-stain (panel B; original magnification ×400), TdT, CD10, BCL6, MUM1, BCL2, MYC, and subset CD20 (panel C; original magnification ×400). Fluorescence in situ hybridization was negative for MYC, IGH-BCL2, or BCR-ABL1 rearrangements. Although the bone marrow was involved (panel D; hematoxylin and eosin stain, original magnification ×400), there was minimal blood involvement by flow cytometry. Bone marrow karyotype showed no evidence of hypodiploidy: 46,XY[cp15]. Next-generation sequencing of the marrow aspirate identified a TP53 p.R282W mutation (47.0% of reads) without copy number variants. Molecular testing on cultured fibroblasts confirmed the mutation as germline, indicative of Li-Fraumeni syndrome. A family history obtained through a translator revealed unknown cancers in the father (deceased aged 32 years) and paternal aunt.

This case illustrates precursor B lymphoblastic leukemia as the presenting neoplasm in Li-Fraumeni syndrome, mimicking intravascular diffuse large B-cell lymphoma. Although more than 90% of cases of precursor B lymphoblastic leukemia with low-hypodiploid cytogenetics will have mutations in TP53, almost half of which are germline, the hypodiploid karyotype was not identified in this case.