Splenic B‐Cell Lymphoma/Leukemia With Prominent Nucleoli Presenting With Characteristic Peripheral Blood and Bone Marrow Findings

1.

An 81‐year‐old man was referred for further examination of fever and pancytopenia. He had been diagnosed with splenic marginal zone lymphoma (SMZL) three years prior to presentation, but had not undergone regular follow‐up. Computed tomography revealed splenomegaly and lymphadenopathy involving cervical, supraclavicular, para‐aortic, and mesenteric regions. Complete blood count on admission showed the following: hemoglobin, 7.5 g/dL; platelet count, 60 × 10⁹/L; and white blood cell count, 1.9 × 10⁹/L with 20% abnormal lymphoid cells. Peripheral blood smear showed medium‐sized atypical lymphoid cells with irregular, hairy cytoplasmic borders, abundant pale cytoplasm, and prominent nucleoli (Figure 1A). Flow cytometry analysis revealed that the abnormal lymphoid cells presented CD11c⁻, CD19⁺, CD20⁺, partially CD25⁺, CD45⁺, CD103⁻, CD123⁻, CD200⁺, and IgGλ⁺. Clonal rearrangements of IgH and IgL genes were confirmed. A bone marrow sample was normocellular, containing 4.6% abnormal lymphocytes with similar characteristics to peripheral blood (Figure 1B). Immunohistochemical staining revealed that the cells were negative for BRAF V600E. The BRAF V600E mutation was negative.

FIGURE 1.

Morphological findings of splenic B‐cell lymphoma/leukemia with prominent nucleoli (SBLPN). (A) Peripheral blood smear shows medium‐sized atypical lymphoid cells presenting with irregular hairy cytoplasmic borders (black arrows), abundant pale cytoplasm (yellow arrows), and prominent nucleoli (red arrows) (May‐Giemsa stain, ×100). (B) Bone marrow smear reveals abnormal lymphocytes exhibiting characteristics like those seen in the peripheral blood (May–Giemsa stain, ×100).

These findings supported a diagnosis of splenic B‐cell lymphoma/leukemia with prominent nucleoli (SBLPN). The patient was administered bendamustine and rituximab (BR). After undergoing three cycles of this therapy, the patient demonstrated improvement in splenomegaly, lymphadenopathy, and cytopenia. These findings were consistent with a partial response, which was maintained after the completion of six cycles of BR therapy.

SBLPN is a newly defined entity in the fifth edition of the World Health Organization (WHO) classification of hematolymphoid tumors [1, 2]. It functions as a provisional entity for splenic B‐cell neoplasms, typically comprised of medium‐to‐large cells showing abundant basophilic or pale cytoplasm, variable cytoplasmic projections, and a prominent single nucleolus [2]. These morphological features distinguish SBLPN from other splenic B‐cell lymphoma/leukemia, including HCL and SMZL. SBLPN typically lacks HCL markers such as CD25, ANXA1, and TRAP, and the absence of the BRAF V600E mutation further differentiates it from classic HCL [1, 2, 3]. The key distinctions between classic HCL and SBLPN are summarized in Table 1. In this case, the findings were consistent with SBLPN. Despite diagnostic overlaps among splenic B‐cell neoplasms, the diagnosis was supported by prominent nucleoli, CD123 negativity, and the absence of the BRAF V600E mutation.

TABLE 1.

Comparison of clinicopathological features: Classic HCL vs. SBLPN.

	Classic HCL	SBLPN
Morphology
Cell size	Small to medium	Medium to large
Nucleoli	Inconspicuous or absent	Prominent, single
Cytoplasm	Abundant cytoplasm with fine villous (hairy) projections	Abundant cytoplasm with fine to poorly defined projections
Immuno‐phonotype (flow cytometry/IHC)
Pan‐B cell markers CD19, CD20, CD79a, and PAX5	Positive	Positive
Shared B‐cell markers CD11c and CD103	Usually positive	Usually positive (negative in this case)
Discriminatory HCL markers CD25, CD123, ANXA1, and TRAP	Positive	Negative (partially CD25+ in this case)
Genetic abnormalities
BRAF V600E mutations	> 95%	Negative
MAP2K1 mutations	Negative	∼40%

Note: The table summarizes the key diagnostic distinctions between classic hairy cell leukemia (HCL) and splenic B‐cell lymphoma/leukemia with prominent nucleoli (SBLPN).

Abbreviations: ANXA1, Annexin A1; BRAF, B‐Raf proto‐oncogene; CD, cluster of differentiation; FCM, flow cytometry; HCL, hairy cell leukemia; IHC, immunohistochemistry; MAP2K1, mitogen‐activated protein kinase kinase 1; PAX5, paired box 5; SBLPN, splenic B‐cell lymphoma/leukemia with prominent nucleoli; TRAP, tartrate‐resistant acid phosphatase.

SBLPN is defined primarily by morphology; its cytogenetic data remain limited. Complex karyotypes involving 14q32, 8q24, 7p deletion, and trisomy 12 are frequently observed, and MAP2K1 mutations are detected in approximately 40% of cases [2, 3]. In this case, the karyotype was normal, and the BRAF V600E mutation was negative. We could not assess the MAP2K1 mutation, which is an important limitation of this case study.

No standard treatment of SBLPN has been established. In our case, BR therapy was selected following the strategy for indolent B‐cell lymphomas [4]. Targeted agents such as Bruton's tyrosine kinase (BTK) inhibitors and MEK inhibitors are anticipated to be effective therapeutic options [3, 5]. Recognition of this newly defined SBLPN classification and accurate morphological diagnosis are key steps toward accumulating cases and establishing its definitive cytogenetic profile and treatment standards.

Funding

The authors have nothing to report.

Ethics Statement

The authors have nothing to report.

Consent

Written informed consent was obtained from the patient for the publication of this case report and accompanying images.

Conflicts of Interest

The authors declare no conflicts of interest.

Son K., Shimomura Y., Yamashita D., and Kondo T., “Splenic B‐Cell Lymphoma/Leukemia With Prominent Nucleoli Presenting With Characteristic Peripheral Blood and Bone Marrow Findings.” eJHaem 7, no. 2 (2026): e70286. 10.1002/jha2.70286

Data Availability Statement

Data from this study are not deposited in a publicly accessible database.