Splenic Diffuse Red Pulp Small B-cell Lymphoma

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editPREVIOUS EDITION
This page from the 4th edition of Haematolymphoid Tumours is being updated. See 5th edition Table of Contents.

Primary Author(s)*

  • Snehal Patel, MD, PhD

Cancer Category/Type

Cancer Sub-Classification / Subtype

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][2][3]

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

Clinical Features[1][4]

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

Sites of Involvement[1]

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

Morphologic Features[1]

  • 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

Immunophenotype[1][2][4][5][6]

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.

Chromosomal Rearrangements (Gene Fusions)

  • No consistent gene fusion

Characteristic Chromosomal Aberrations / Patterns

  • BCOR copy number loss in 10% and often with BCOR point mutations[3]
  • Copy number alterations in 69%[7]
  • Complex karyotypes in 13%[3]

Genomic Gain/Loss/LOH

  • 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[7]
  • In a study of 24 cases, 7q deletion in 6 cases; trisomy 3 and 18 in 1 case; trisomy 12 in 3 case[3]

Gene Mutations (SNV/INDEL)

Gene* Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence[3]
CCND3 Oncogene GOF 21%
BCOR Tumor Suppressor LOF 14%

‡Specific mutations in these genes can be found in cBioPortal, COSMIC, and elsewhere[3]

Epigenomics (Methylation)

  • Not studied

Genes and Main Pathways Involved

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

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[3] 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

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

Alteration Significance Note
BRAF p.Val600Glu Possible role in diagnosis (exclusion) Prevalent in HCL but rare/absent in SDRPL[3]
MAP2K1 Possible role in diagnosis (exclusion) Prevalent in HCL-v and a subset of cases classified as HCL but uncommon in SDRPL[3]
KLF2 and TNFAIP3 Possible role in diagnosis (exclusion) Prevalent in SMZL but rare/absent in SDRPL[3]
MYD88 Possible role in diagnosis (exclusion) Prevalent in LPL and SMZL but rare/absent in SDRPL[3]
BCOR Possible role in diagnosis (inclusion) Prevalent in SDRPL but rare/absent in HCL, HCL-v, and SMZL[3]

Familial Forms

  • Not described

Other Information

  • None

Links

References

(use "Cite" icon at top of page)

  1. ↑ 1.0 1.1 1.2 1.3 1.4 T, Vig; et al. (2018). "A Rare Case of Splenic Diffuse Red Pulp Small B-cell Lymphoma (SDRPL): A Review of the Literature on Primary Splenic Lymphoma With Hairy Cells". doi:10.5045/br.2018.53.1.74. PMC 5898999. PMID 29662866.CS1 maint: PMC format (link)
  2. ↑ 2.0 2.1 J, Tóth-Lipták; et al. (2015). "A Comprehensive Immunophenotypic Marker Analysis of Hairy Cell Leukemia in Paraffin-Embedded Bone Marrow Trephine Biopsies--A Tissue Microarray Study". PMID 24903677.
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 L, Jallades; et al. (2017). "Exome Sequencing Identifies Recurrent BCOR Alterations and the Absence of KLF2, TNFAIP3 and MYD88 Mutations in Splenic Diffuse Red Pulp Small B-cell Lymphoma". doi:10.3324/haematol.2016.160192. PMC 5622860. PMID 28751561.CS1 maint: PMC format (link)
  4. ↑ 4.0 4.1 Wy, Cheng; et al. (2018). "Development of B-cell Prolymphocytic Leukemia in a Patient With Splenic Diffuse Red Pulp Small B-cell Lymphoma". PMID 29199492.
  5. ↑ Y, Yamada; et al. (2018). "[Splenic Diffuse Red Pulp Small B-cell Lymphoma Diagnosed by Splenectomy Initially Mimicking Hairy Cell leukemia-Japanese Variant]". PMID 29618685.
  6. ↑ G, Kanellis; et al. (2010). "Splenic diffuse red pulp small B-cell lymphoma: revision of a series of cases reveals characteristic clinico-pathological features". doi:10.3324/haematol.2009.013714. PMC 2895036. PMID 20220064.CS1 maint: PMC format (link)
  7. ↑ 7.0 7.1 D, Martinez; et al. (2016). "NOTCH1, TP53, and MAP2K1 Mutations in Splenic Diffuse Red Pulp Small B-cell Lymphoma Are Associated With Progressive Disease". PMID 26426381.

EXAMPLE Book

  1. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.

Notes

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