Primary Author(s)*
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
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)
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
Other Information
Links
References
(use "Cite" icon at top of page)
↑ 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 )
↑ 2.0 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 .
↑ 3.00 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 )
↑ 4.0 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 .
↑ 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 .
↑ 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 )
↑ 7.0 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
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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