Prolymphocytic progression of splenic marginal zone lymphoma

A 64-year-old woman was diagnosed with splenic marginal zone lymphoma following evaluation of lymphocytosis (lymphocytes, 4.6 × 10⁹/L). At diagnosis, a computed tomography scan showed a 15-cm spleen but no lymphadenopathy. Twenty-four months later, she first complained of fatigue, left upper quadrant discomfort, and B symptoms (profuse evening sweating and a weight loss of 5 kg). Physical examination revealed a massive splenomegaly, measuring 23 × 18.7 × 9.1 cm on total body computed tomography scan (panel A, coronal view). A complete blood count revealed marked lymphocytosis of 284.13 × 10⁹/L, severe anemia, and thrombocytopenia. Blood film showed 87% prolymphocytes of intermediate size, with a mature appearance and prominent nucleolus, some with pink cytoplasmic inclusions (panel B: May-Grünwald-Giemsa stain, original magnification ×1000). Flow cytometry confirmed a clonal B-cell population, CD19⁺, CD5^+weak, CD10⁻, CD20⁺, CD22⁺, CD79b⁺, CD11c^+weak, CD103⁻, similar to the findings at diagnosis. Molecular testing detected a TP53 mutation associated with deletion of the other allele, both absent at diagnosis. These findings are consistent with a prolymphocytic progression of her lymphoma. Treatment with rituximab and bendamustine was not effective. A partial response to zanabrutinib is ongoing at 9 months after progression.

Prolymphocytic progression is a rare and aggressive evolution of splenic marginal zone lymphoma. It should be suspected in the presence of rapidly progressive lymphocytosis and massive splenomegaly. The diagnosis is confirmed by a peripheral blood smear that reveals more than 55% prolymphocytes.

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