Splenic diffuse red pulp small B-cell lymphoma

Haematolymphoid Tumours (5th ed.)

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This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Splenic Diffuse Red Pulp Small B-cell Lymphoma.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

• Snehal Patel, MD, PhD

Cancer Category / Type

• Mature B-Cell Neoplasm

Cancer Sub-Classification / Subtype

• HAEM4:Splenic B-cell Lymphoma/Leukemia, Unclassifiable

Definition / Description of Disease

• Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is an extremely rare indolent B-cell neoplasm of adults (provisional WHO entity)
• Name derives from diffuse involvement of the splenic red pulp by small mature-appearing B-cells
• Marked splenomegaly and marrow infiltration result in left flank discomfort, fatigue, and susceptibility to infections

Synonyms / Terminology

• Splenic marginal zone lymphoma, diffuse variant
• Splenic red pulp lymphoma with numerous basophilic villous lymphocytes
• Splenic lymphoma with villous lymphocytes

Epidemiology / Prevalence

• <1% of all non-Hodgkin lymphomas
• Median age ~ 66 to 80 years
• M:F 1.8:1 to 2.4:1

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Clinical Features

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Signs and Symptoms	EXAMPLE Asymptomatic (incidental finding on complete blood counts) EXAMPLE B-symptoms (weight loss, fever, night sweats) EXAMPLE Fatigue EXAMPLE Lymphadenopathy (uncommon)
Laboratory Findings	EXAMPLE Cytopenias EXAMPLE Lymphocytosis (low level)

editv4:Clinical Features

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Signs & Symptoms

• Splenic enlargement and/or discomfort
• Fatigue
• B-symptoms - weight loss, fever, night sweats (variable)
• Lymphadenopathy (uncommon)

Laboratory findings

• Cytopenias (uncommon)
• Lymphocytosis (moderate)
• No monocytopenia

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Sites of Involvement

• Spleen (red pulp)
• Bone marrow (sinusoidal > interstitial)
• Blood
• Liver
• Lymph node (uncommon)

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Morphologic Features

• Monomorphic small lymphocytes
• Villous projections
• Scant cytoplasm
• Condensed chromatin
• Smooth nuclear contours
• Inconspicuous nucleoli
• Involvement of red pulp (cords & sinusoids)
• Residual white pulp
• No/minimal reticulin fibrosis

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Immunophenotype

Finding	Marker
Positive (B-cell lineage markers)	CD19, CD20 (bright), CD22, CD79a, CD79b, PAX5, FMC7, sIg (monotypic), IgG
Positive	DBA-44, BCL2 (weak), CD11c*
Negative	CD5, CD10, CD23, BCL1, BCL6
Negative (HCL markers)	CD25, CD43, CD103 (variable), CD123, CD138, CD200, annexin A1, TRAP
MIB-1 proliferative index	2-4%

*Reports of CD11c expression are conflicting in the literature.

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Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE t(9;22)(q34;q11.2)	EXAMPLE 3'ABL1 / 5'BCR	EXAMPLE der(22)	EXAMPLE 20% (COSMIC) EXAMPLE 30% (add reference)	Yes	No	Yes	EXAMPLE The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

editv4:Chromosomal Rearrangements (Gene Fusions)

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• No consistent gene fusion

editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

Please incorporate this section into the relevant tables found in:

• Chromosomal Rearrangements (Gene Fusions)
• Individual Region Genomic Gain/Loss/LOH
• Characteristic Chromosomal Patterns
• Gene Mutations (SNV/INDEL)

Alteration	Significance	Note
BRAF p.Val600Glu	Possible role in diagnosis (exclusion)	Prevalent in HCL but rare/absent in SDRPL
MAP2K1	Possible role in diagnosis (exclusion)	Prevalent in HCL-v and a subset of cases classified as HCL but uncommon in SDRPL
KLF2 and TNFAIP3	Possible role in diagnosis (exclusion)	Prevalent in SMZL but rare/absent in SDRPL
MYD88	Possible role in diagnosis (exclusion)	Prevalent in LPL and SMZL but rare/absent in SDRPL
BCOR	Possible role in diagnosis (inclusion)	Prevalent in SDRPL but rare/absent in HCL, HCL-v, and SMZL

Individual Region Genomic Gain / Loss / LOH

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Chr #	Gain / Loss / Amp / LOH	Minimal Region Genomic Coordinates [Genome Build]	Minimal Region Cytoband	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE 7	EXAMPLE Loss	EXAMPLE chr7:1- 159,335,973 [hg38]	EXAMPLE chr7	Yes	Yes	No	EXAMPLE Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
EXAMPLE 8	EXAMPLE Gain	EXAMPLE chr8:1-145,138,636 [hg38]	EXAMPLE chr8	No	No	No	EXAMPLE Common recurrent secondary finding for t(8;21) (add reference).

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• In a study of 13 cases, 10q23, 14q31-q32, and 17p13 deletions in 3 cases; 9p21 deletions in 2 cases; 7q31.3-q32.3 deletion in 1 case; no trisomies 3 or 18
• In a study of 24 cases, 7q deletion in 6 cases; trisomy 3 and 18 in 1 case; trisomy 12 in 3 case

Characteristic Chromosomal Patterns

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Chromosomal Pattern	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE Co-deletion of 1p and 18q	Yes	No	No	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

editv4:Characteristic Chromosomal Aberrations / Patterns

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• BCOR copy number loss in 10% and often with BCOR point mutations
• Copy number alterations in 69%
• Complex karyotypes in 13%

Gene Mutations (SNV / INDEL)

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Gene; Genetic Alteration	Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)	Prevalence (COSMIC / TCGA / Other)	Concomitant Mutations	Mutually Exclusive Mutations	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: TP53; Variable LOF mutations EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations	EXAMPLE: TSG	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add Reference)	EXAMPLE: IDH1 R123H	EXAMPLE: EGFR amplification				EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

editv4:Gene Mutations (SNV/INDEL)

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Gene*	Oncogene/Tumor Suppressor/Other	Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)	Prevalence
CCND3	Oncogene	GOF	21%
BCOR	Tumor Suppressor	LOF	14%

^‡Specific mutations in these genes can be found in cBioPortal, COSMIC, and elsewhere

Epigenomic Alterations

• Not studied

Genes and Main Pathways Involved

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Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations	EXAMPLE: MAPK signaling	EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations	EXAMPLE: Cell cycle regulation	EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations	EXAMPLE:  Histone modification, chromatin remodeling	EXAMPLE:  Abnormal gene expression program

editv4:Genes and Main Pathways Involved

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Molecular feature	Pathway
BCOR LoF alterations (point mutations & copy number loss; 24% of SDRPL)	germinal center formation & apoptosis
CCND3 GoF alterations (point mutations; 21% of SDRPL)	cell cycle regulation

Genetic Diagnostic Testing Methods

• SDRPL is a provisional WHO entity and definitive diagnostic criteria have not been determined
  • Diagnosis of exclusion
    • Differential of splenic lymphomas with cytoplasmic projections: HCL, HCL-v, SMZL
  • Distinction is by clinical history, morphology, and immunohistochemistry
    • No pathognomonic diagnostic markers (molecular or otherwise)
    • Mutations seen in other entities in DDx are absent/rare in SDRPL and vice versa and may be diagnostically useful (see Clinical Significance below)
      • Next-generation sequencing with targeted lymphoid malignancy panels or exome sequencing may be considered in challenging cases

Familial Forms

• Not described

Additional Information

• None

Links

• HAEM5:Hairy cell leukaemia
• HAEM5:Hairy cell leukaemia Variant
• HAEM4:Splenic B-cell Lymphoma/Leukemia, Unclassifiable
• HAEM5:Splenic marginal zone lymphoma

References

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Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome. *Citation of this Page: “Splenic diffuse red pulp small B-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/13/2023, https://ccga.io/index.php/HAEM5:Splenic_diffuse_red_pulp_small_B-cell_lymphoma.