Lymphoma & related disorders
Mature B cell neoplasms
Splenic B cell lymphomas and leukemias
Splenic B cell leukemia / lymphoma, unclassifiable
Authors: Maria Paz Gray, M.D., Anamarija M. Perry, M.D.
Editorial Board Member: Roberto N. Miranda, M.D.
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Last author update: 19 November 2024
Last staff update: 19 November 2024
Copyright: 2020-2024, PathologyOutlines.com, Inc.
PubMed Search: Splenic B cell leukemia / lymphoma, unclassifiable
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Peripheral smear description | Peripheral smear images | Positive stains | Negative stains | Flow cytometry description | Flow cytometry images | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Gray MP, Perry AM. Splenic B cell leukemia / lymphoma, unclassifiable. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomaspleniBcellunclassifiable.html. Accessed November 28th, 2024.
Definition / general
- Low grade B cell lymphoma involving the spleen, bone marrow and peripheral blood
- Comprises 2 entities: splenic diffuse red pulp small B cell lymphoma (SDRPL) and splenic B cell lymphoma / leukemia with prominent nucleoli (SBLPN)
Essential features
- This review is based on the 5th edition of the World Health Organization (WHO HAEM5) classification of hematolymphoid tumors
- SDRPL
- Involves spleen, bone marrow and peripheral blood
- Usually causes massive splenomegaly
- Characterized by diffuse infiltrate of splenic red pulp with atrophic white pulp
- Lymphoma cells are round, hyperchromatic with clumped chromatin and pale cytoplasm
- Expresses pan B cell markers, DBA-44, IgG and cyclin D3
- SBLPN
- Designated as hairy cell leukemia variant in WHO HAEM4
- Involves spleen, bone marrow and peripheral blood
- Splenomegaly with red pulp involvement, prominent lymphocytosis and coupled with anemia or thrombocytopenia, without monocytopenia
- Medium sized lymphoid cells with prominent nucleoli
- Negative for hairy cell leukemia markers (CD25, annexin A1, TRAP)
Terminology
- Splenic B cell lymphoma / leukemia, unclassifiable (NOS) in WHO HAEM4
- WHO HAEM5 includes: splenic diffuse red pulp small B cell lymphoma (SDRPL) and splenic B cell lymphoma / leukemia with prominent nucleoli (SBLPN)
- 2022 International Consensus Classification (ICC): splenic diffuse red pulp small B cell lymphoma and hairy cell leukemia variant
- The ICC maintains the name of HCLv, while the WHO HAEM5 nomenclature is SBLPN (Blood 2022;140:1229)
ICD coding
- ICD-O
- ICD-11
- 2A82.Y & XH99V9 - other specified mature B cell neoplasm with leukemic behavior & splenic diffuse red pulp small B cell lymphoma
- 2A82.3 - splenic B cell lymphoma or leukemia, unclassifiable
Epidemiology
- SDRPL
- Rare; < 1% of all non-Hodgkin lymphomas (Leuk Lymphoma 2017;58:666)
- 10% of lymphomas diagnosed in spleen
- Most patients are men, < 75 years of age
- SBLPN
- Rare; < 1% of chronic lymphoid malignancies (Cancer Treat Rev 2011;37:3, J Cancer Res Ther 2024;20:315)
- Median age is ~70 years
- M:F = 1.6:1
Sites
- SDRPL and SBLPN
- Spleen, bone marrow and peripheral blood are involved
- Lymphadenopathy outside the splenic hilum is uncommon
Etiology
- Unknown
Clinical features
- SDRPL
- Frequently massive splenomegaly and mild lymphocytosis
- B symptoms are infrequent (Haematologica 2010;95:1122, Discov Med 2012;13:253)
- SBLPN
- Splenomegaly
- High lymphocytosis
- No monocytopenia
- Hepatomegaly in < 33% of cases (J Cancer Res Ther 2024;20:315, Leukemia 2001;15:184)
Diagnosis
- SDRPL (Curr Oncol 2021;28:5148)
- Spleen diffusely infiltrated by monomorphic small B cells with atrophic white pulp
- Peripheral blood involved with lymphoma cells
- CD5- / CD10- / CD25- immunophenotype
- SBLPN (Best Pract Res Clin Haematol 2015;28:253, Leukemia 2001;15:184)
- Circulating medium sized lymphoid cells moderate to abundant amount of cytoplasm and central nuclei with prominent nucleoli
- Some cells may show poorly defined cytoplasmic projections but not circumferential fine villous as seen in HCL
- Absence of HCL phenotype (CD25, annexin A1, cyclin D1 and TRAP expression) but share CD11c and CD103 with HCL
- For both entities, it is desirable to have absence of BRAF mutation
Laboratory
- SDRPL
- Leukopenia and thrombocytopenia, secondary to bone marrow involvement
- Mild lymphocytosis
- Anemia is rare or absent (Curr Oncol 2021;28:5148)
- SBLPN
- Initially leukocytosis followed by leukopenia (Cureus 2023;15:e47085)
- Moderate to marked lymphocytosis
- Anemia and thrombocytopenia are common
- No monocytopenia
Radiology description
- SDRPL and SBLPN (Curr Oncol 2021;28:5148)
- Ultrasound or PET / CT scan shows splenomegaly without distinct splenic lesions
- Small lymph nodes (< 1 cm) beyond splenic hilum
- Increased homogeneous 18F-fluorodeoxyglucose (FDG) avidity may be seen
Prognostic factors
- SDRPL (Curr Oncol 2021;28:5148)
- Studies limited
- Cases with mutations in NOTCH1, TP53 or MAP2K1 may show aggressive behavior (Am J Surg Pathol 2016;40:192)
- SBLPN (Best Pract Res Clin Haematol 2015;28:253, Leukemia 2001;15:184)
- Medial survival time is ~9 years (Cancer Treat Rev 2011;37:3, J Cancer Res Ther 2024;20:315)
- More aggressive than classic hairy cell leukemia (HCL)
Case reports
- 25 year old man with abdominal swelling and generalized weakness (Blood Res 2018;53:74)
- 58 year old woman with pain in abdomen and loss of weight (J Clin Diagn Res 2013;7:358)
- 68 year old man with heaviness in the left upper side of the abdomen for a year (Cureus 2023;15:e47085)
Treatment
- SDRPL (Curr Oncol 2021;28:5148)
- Initial treatment options include watchful waiting, splenectomy and rituximab
- SBLPN (Best Pract Res Clin Haematol 2015;28:253)
- Combination of 2-chlorodeoxyadenosine and rituximab
- Refractory to purine analogues in 50% of cases (unlike uniform response with HCL)
- Ibrutinib is a promising treatment in relapsed / refractory disease (Clin Case Rep 2019;7:1161)
Gross description
- SDRPL and SBLPN: enlarged spleen with diffuse involvement and no distinct or nodular lesions
Gross images
Contributed by Maria Paz Gray, M.D.
Massively enlarged spleen with SBLPN
Microscopic (histologic) description
- SDRPL
- Spleen
- Monomorphic infiltrate of small to medium sized B cells in red pulp cords and sinusoids
- Atypical cells are round, hyperchromatic with clumped chromatin and pale cytoplasm; plasmacytoid features
- So called blood lakes lined with lymphoma cells
- Atrophic or absent white pulp; better determined with immunohistochemistry for B and T cell markers (Curr Oncol 2021;28:5148)
- Bone marrow
- Variable cellularity
- Most typical pattern of infiltration is intrasinusoidal
- Interstitial and nodular (rarely) infiltration can also be seen (Curr Oncol 2021;28:5148)
- Spleen
- SBLPN
- Spleen
- Diffusely involved red pulp, with intrasinusoidal involvement
- Atrophic or absent white pulp; better determined with immunohistochemistry for B and T cell markers
- Neoplastic cells are medium to large size with abundant cytoplasm, round nucleus and prominent nucleolus
- Bone marrow
- Variable degree of lymphoid infiltration and usually some fibrosis
- Most common patterns of infiltration are interstitial and intrasinusoidal (Leukemia 2001;15:184, Best Pract Res Clin Haematol 2015;28:253, Hematol Oncol Clin North Am 2006;20:1051)
- Spleen
Microscopic (histologic) images
Contributed by Dennis O’Malley, M.D. and Maria Paz Gray, M.D.
SDRPL infiltrating the spleen
SBLPN infiltrating the spleen
SBLPN infiltrating spleen sinusoids
SBLPN infiltrating the bone marrow
SBLPN
infiltrating
spleen sinusoids,
CD20 immunostain
SBLPN
infiltrating the
bone marrow,
CD20 immunostain
Peripheral smear description
- SDRPL
- Small to medium sized cells with clumped chromatin
- Cytoplasm is basophilic and in variable amount, usually scant
- Cells contain broad based cytoplasmic villous projections with a polar distribution
- Nucleolus is small or inconspicuous
- SBLPN
- Medium to large cells with intermediate in size round to oval nucleus with single prominent nucleolus and abundant cytoplasm with variably defined projections
- In contrast to HCL, the lymphoma cells do not have circumferential villous processes
Peripheral smear images
Contributed by Dennis O’Malley, M.D.
Peripheral blood with SBLPN
Positive stains
- SDRPL
- SBLPN
Negative stains
Flow cytometry description
- SDRPL
- CD180 distinguishes it from HCL and splenic marginal zone lymphoma
- CD200 positivity increases sensitivity and specificity (Blood 2017;129:1042)
- CD103 expression in up to 33% of cases (Curr Oncol 2021;28:5148)
- SBLPN
- CD20, CD11c and CD103 expression (J Cancer Res Ther 2024;20:315)
Flow cytometry images
Contributed by Anamarija M. Perry, M.D.
SBLPN: CD19 and CD20
SBLPN: kappa light chain
SBLPN: CD22 and CD11c
SBLPN: CD103 and CD25
Molecular / cytogenetics description
- SDRPL
- Atypical cells express B cell receptor immunoglobulin with somatically hypermutated immunoglobulin heavy chain genes (IGHV) with predominance of IGHV3-23 and IGHV4-34
- Cytogenetic abnormalities including chromosome 7q deletion, trisomy 18 and partial trisomy 3q can be detected in 33% of cases (Curr Oncol 2021;28:5148)
- NOTCH1, NOTCH2, MYD88 mutations are rare (Haematologica 2017;102:1758)
- CCND3 (21 - 24%), BCOR (24%) mutations and copy number variations have been reported (Blood 2017;129:1042, Haematologica 2017;102:1758)
- Absence of BRAF p.V600E mutation (associated with HCL in > 95% of cases) (Leuk Lymphoma 2017;58:666)
- SBLPN
- Mutations of IGVH in 67% of cases (Best Pract Res Clin Haematol 2015;28:253)
- Complex karyotypes have been described: abnormalities of 8q24 / MYC, 14q32 / IGH, del 17p / TP53 (J Cancer Res Ther 2024;20:315)
- Gains of chromosome 5, losses on 7q and 17p
- Absence of BRAF p.V600E mutation (J Cancer Res Ther 2024;20:315)
Sample pathology report
- Spleen, splenectomy:
- Spleen (3,200 g) with diffuse involvement of red pulp by small B cell lymphoma (see comment)
- Comment: Sections show spleen with expanded red pulp, diffusely involved by small monomorphic lymphoid cells with round nuclei, inconspicuous nucleoli and pale cytoplasm. White pulp is almost completely absent or atrophic. Immunophenotype of the cells (positive for CD19, CD20, DBA-44 and BCL2 and negative for CD5, CD10, CD11C, CD25 and CD103), in conjunction with morphology, is consistent with diagnosis of splenic diffuse red pulp small B cell lymphoma.
- Bone marrow, aspirate smear, core biopsy, clot section and peripheral blood smear:
- Mildly hypercellular bone marrow for age and peripheral blood with involvement by B cell lymphoproliferative disorder, best classified as splenic B cell lymphoma / leukemia with prominent nucleoli (see comment)
- Comment: Per clinical history and imaging findings, the patient has moderate splenomegaly. Bone marrow is involved by atypical lymphoid cells (comprising ~25% of bone marrow cellularity) in mainly interstitial and focally intrasinusoidal pattern. Neoplastic cells are medium sized with round nucleus, prominent nucleolus and abundant cytoplasm. Peripheral blood shows lymphocytosis, mainly medium sized to large atypical cells with single prominent nucleolus, abundant cytoplasm and occasional cytoplasmic projections. Morphology and immunophenotype (positive for CD19, CD20, DBA-44, CD11c, CD103; negative for CD25, annexin A1, BRAF V600E, CD123 and TRAP), presence of splenomegaly and lymphocytosis are most consistent with splenic B cell lymphoma / leukemia with prominent nucleoli (formerly designated as hairy cell leukemia variant in the WHO HAEM4).
Differential diagnosis
- Splenic marginal zone lymphoma:
- Cytological and immunophenotypically similar to SDRPL in peripheral blood and bone marrow
- Involves white pulp with a nodular pattern and secondary red pulp involvement as small aggregates in the Billroth cords and sinusoids
- White pulp is expanded and nodular; better appreciated with B cell markers
- In bone marrow, the growth pattern is often nodular, paratrabecular in addition to interstitial and less prominent is intrasinusoidal
- Mutations in NOTCH2 and KLF2 are frequent in SMZL and rarely seen in SDRPL
- Hairy cell leukemia (HCL):
Additional references
Board review style question #1
Which of the following features is characteristic of splenic diffuse red pulp small B cell lymphoma (SDRPL)?
- Commonly involves lymph nodes outside the splenic hilum
- High frequency of BRAF p.V600E mutation
- Neoplastic cells with a single large nucleolus
- Often associated with monocytopenia
- Presence of cyclin D3 in ~70% of cases
Board review style answer #1
E. Presence of cyclin D3 in ~70% of cases. Answer E is correct becauise in SDRPL, cyclin D3 is seen in ~70% of cases. Answer C is incorrect because this feature is characteristic of splenic B cell lymphoma / leukemia with prominent nucleoli (SBLPN), not SDRPL. Answer A is incorrect because SDRPL typically does not associate with lymphadenopathy outside the splenic hilum. Answer B is incorrect because this mutation is more commonly associated with classic hairy cell leukemia (HCL). Answer D is incorrect because monocytopenia is a characteristic of classic hairy cell leukemia, not SDRPL.
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Reference: Splenic B cell leukemia / lymphoma, unclassifiable
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Reference: Splenic B cell leukemia / lymphoma, unclassifiable
Board review style question #2
A 70 year old man presents with left upper quadrant discomfort and was found to have massive splenomegaly. Complete blood count shows WBC = 32 x 109/L; RBC = 4.28 x 1012/L; HGB = 11.5 g/dL; and PLT = 59 x 109/L. Differential count showed 80% lymphocytes, most of which are atypical with round nuclei, prominent central nucleoli and variably abundant cytoplasm. Which of the following is characteristic for this lymphoma?
- Commonly associated with monocytopenia
- High frequency of BRAF p.V600E mutation
- Lymphoma cells usually express CD25
- Primarily affects young adults under the age of 40
- Typically presents with splenomegaly, moderate to marked lymphocytosis and cytopenias without monocytopenia
Board review style answer #2
E. Typically presents with splenomegaly, moderate to marked lymphocytosis and cytopenias without monocytopenia. This is an example of SBLPN. Answer E is correct because SBLPN typically presents with splenomegaly, moderate to marked lymphocytosis and cytopenias (anemia and thrombocytopenia) without monocytopenia. Answer A is incorrect because monocytopenia is a characteristic of classic hairy cell leukemia, not SBLPN. Answer C is incorrect because in SBLPN, the neoplastic cells are typically negative for CD25. Answer B is incorrect because BRAF p.V600E mutation is more commonly associated with classic hairy cell leukemia. Answer D is incorrect because SBLPN primarily affects older adults, with a median age of 70 years, not young adults under the age of 40.
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Reference: Splenic B cell leukemia / lymphoma, unclassifiable
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Reference: Splenic B cell leukemia / lymphoma, unclassifiable
