An Unusual Case of Splenic B‐cell Lymphoma/leukemia

A 76-year-old man with a history of relapsed/refractory splenic marginal zone lymphoma (SMZL) underwent splenectomy for cytoreduction (WBC 133.7 109/L) after failing rituximab, ibrutinib, bendamustine, obinutuzumab, and cyclophosphamide. The spleen (3470 grams) had a homogeneous cut surface on gross examination (Panel A). Microscopically, the infiltrate is composed of small to medium sized lymphoid cells involving chiefly the red pulp. (Panel B: Diff-Quik stain, original magnification ×1000; Panel C-D: H&E, original magnification ×20 and ×400, respectively). Flow cytometry detected monotypic B-cells positive for CD5 (partial), CD103 (dim), and negative for CD25 and CD200. By immunohistochemistry, the lymphoma cells were positive for PAX-5, CD5 (partial/weak) (Panel E: PAX-5/CD5 dual stain, original magnification ×400), IgD (Panel F, original magnification ×400), DBA.44 (Panel G, original magnification ×400), and negative for Cyclin D1, SOX11, IgG, and BRAF V600E. The proliferation rate was approximately 50% (Panel H, Ki67 stain, original magnification ×400). Karyotyping showed complex aberrations including i(17q). FISH studies confirmedTP53 deletion (Panel I). Next generation sequencing revealed TP53 E56*, a nonsense mutation in transactivation domain (TAD), and no BRAFV600E or MAP2K1 mutations. The patient passed away shortly after splenectomy. Though originally diagnosed with SMZL, the diffuse red pulp involvement in the case favors more a diagnosis of splenic red pulp lymphoma/leukemia, a provisional entity in the 2017 World Health Organization classification characterized by proliferation of predominately small mature B cells and an indolent clinical course. The highly aggressive clinical course and the unusual morphology (increased medium sized, high Ki67) in the current case are most likely related to a “null” TP53 status, an early nonsense mutation in TAD in one allele and deletion of another allele, that is, bi-allelic inactivation of TP53 gene. The case also illustrates the diagnostic challenge in distinguishing SMZL from splenic red pulp lymphoma/leukemia in the absence of a splenectomy specimen as the two share common immunophenotypic profile.