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Created page with "==Primary Author(s)*== *Snehal Patel, MD, PhD __TOC__ ==Cancer Category/Type== *Mature B-Cell Neoplasm ==Cancer Sub-Classification / Subtype==..."

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==Primary Author(s)*==

*Snehal Patel, MD, PhD
__TOC__

==Cancer Category/Type==

*[[Mature B-Cell Neoplasms|Mature B-Cell Neoplasm]]

==Cancer Sub-Classification / Subtype==

*[[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<ref name=":0">{{Cite journal|last=T|first=Vig|last2=Ta|first2=Kodiatte|last3=Mt|first3=Manipadam|last4=Fn|first4=Aboobacker|date=2018|title=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|url=https://pubmed.ncbi.nlm.nih.gov/29662866/|language=en|doi=10.5045/br.2018.53.1.74|pmc=PMC5898999|pmid=29662866}}</ref><ref name=":1">{{Cite journal|last=J|first=Tóth-Lipták|last2=K|first2=Piukovics|last3=Z|first3=Borbényi|last4=J|first4=Demeter|last5=E|first5=Bagdi|last6=L|first6=Krenács|date=2015|title=A Comprehensive Immunophenotypic Marker Analysis of Hairy Cell Leukemia in Paraffin-Embedded Bone Marrow Trephine Biopsies--A Tissue Microarray Study|url=https://pubmed.ncbi.nlm.nih.gov/24903677/|language=en|pmid=24903677}}</ref><ref name=":3">{{Cite journal|last=L|first=Jallades|last2=L|first2=Baseggio|last3=P|first3=Sujobert|last4=S|first4=Huet|last5=K|first5=Chabane|last6=E|first6=Callet-Bauchu|last7=A|first7=Verney|last8=S|first8=Hayette|last9=Jp|first9=Desvignes|date=2017|title=Exome Sequencing Identifies Recurrent BCOR Alterations and the Absence of KLF2, TNFAIP3 and MYD88 Mutations in Splenic Diffuse Red Pulp Small B-cell Lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28751561/|language=en|doi=10.3324/haematol.2016.160192|pmc=PMC5622860|pmid=28751561}}</ref>==

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

==Clinical Features<ref name=":0" /><ref name=":2">{{Cite journal|last=Wy|first=Cheng|last2=Ym|first2=Zhu|last3=S|first3=Cheng|last4=Ys|first4=Chen|last5=Y|first5=Shen|date=2018|title=Development of B-cell Prolymphocytic Leukemia in a Patient With Splenic Diffuse Red Pulp Small B-cell Lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/29199492/|language=en|pmid=29199492}}</ref>==

'''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<ref name=":0" />==

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

==Morphologic Features<ref name=":0" />==

*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<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref>{{Cite journal|last=Y|first=Yamada|last2=M|first2=Miura|last3=M|first3=Tagari|last4=K|first4=Oshimi|last5=T|first5=Shiragata|last6=W|first6=Suga|last7=T|first7=Takahashi|last8=K|first8=Shimizu|last9=K|first9=Ohshima|date=2018|title=[Splenic Diffuse Red Pulp Small B-cell Lymphoma Diagnosed by Splenectomy Initially Mimicking Hairy Cell leukemia-Japanese Variant]|url=https://pubmed.ncbi.nlm.nih.gov/29618685/|language=en|pmid=29618685}}</ref><ref>{{Cite journal|last=G|first=Kanellis|last2=M|first2=Mollejo|last3=S|first3=Montes-Moreno|last4=Sm|first4=Rodriguez-Pinilla|last5=Jc|first5=Cigudosa|last6=P|first6=Algara|last7=C|first7=Montalban|last8=E|first8=Matutes|last9=A|first9=Wotherspoon|date=2010|title=Splenic diffuse red pulp small B-cell lymphoma: revision of a series of cases reveals characteristic clinico-pathological features|url=https://pubmed.ncbi.nlm.nih.gov/20220064/|language=en|doi=10.3324/haematol.2009.013714|pmc=PMC2895036|pmid=20220064}}</ref>==

{| class="wikitable sortable"
|-
!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%
|}
<nowiki>*</nowiki>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<ref name=":3" />
*Copy number alterations in 69%<ref name=":4">{{Cite journal|last=D|first=Martinez|last2=A|first2=Navarro|last3=A|first3=Martinez-Trillos|last4=R|first4=Molina-Urra|last5=B|first5=Gonzalez-Farre|last6=I|first6=Salaverria|last7=F|first7=Nadeu|last8=A|first8=Enjuanes|last9=G|first9=Clot|date=2016|title=NOTCH1, TP53, and MAP2K1 Mutations in Splenic Diffuse Red Pulp Small B-cell Lymphoma Are Associated With Progressive Disease|url=https://pubmed.ncbi.nlm.nih.gov/26426381/|language=en|pmid=26426381}}</ref>
*Complex karyotypes in 13%<ref name=":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<ref name=":4" />
*In a study of 24 cases, 7q deletion in 6 cases; trisomy 3 and 18 in 1 case; trisomy 12 in 3 case<ref name=":3" />

==Gene Mutations (SNV/INDEL)==

{| class="wikitable sortable"
|-
!Gene*!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence<ref name=":3" />
|-
|CCND3
|Oncogene
|GOF
|21%
|-
|BCOR||Tumor Suppressor||LOF||14%
|}
<sup>‡</sup>Specific mutations in these genes can be found in [https://www.cbioportal.org/ cBioPortal], [https://cancer.sanger.ac.uk/cosmic COSMIC], and elsewhere<ref name=":3" />

==Epigenomics (Methylation)==

*Not studied

==Genes and Main Pathways Involved==
{| class="wikitable"
!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: [[Hairy Cell Leukemia|HCL]], [[Hairy Cell Leukemia Variant|HCL-v]], [[Splenic Marginal Zone Lymphoma|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<ref name=":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)==
{| class="wikitable"
!Alteration
!Significance
!Note
|-
|BRAF p.Val600Glu
|Possible role in diagnosis (exclusion)
|Prevalent in [[Hairy Cell Leukemia|HCL]] but rare/absent in SDRPL<ref name=":3" />
|-
|MAP2K1
|Possible role in diagnosis (exclusion)
|Prevalent in [[Hairy Cell Leukemia Variant|HCL-v]] and a subset of cases classified as [[Hairy Cell Leukemia|HCL]] but uncommon in SDRPL<ref name=":3" />
|-
|KLF2 and TNFAIP3
|Possible role in diagnosis (exclusion)
|Prevalent in [[Splenic Marginal Zone Lymphoma|SMZL]] but rare/absent in SDRPL<ref name=":3" />
|-
|MYD88
|Possible role in diagnosis (exclusion)
|Prevalent in [[Lymphoplasmacytic Lymphoma|LPL]] and [[Splenic Marginal Zone Lymphoma|SMZL]] but rare/absent in SDRPL<ref name=":3" />
|-
|BCOR
|Possible role in diagnosis (inclusion)
|Prevalent in SDRPL but rare/absent in [[Hairy Cell Leukemia|HCL]], [[Hairy Cell Leukemia Variant|HCL-v]], and [[Splenic Marginal Zone Lymphoma|SMZL]]<ref name=":3" />
|}

==Familial Forms==

*Not described

==Other Information==

*None

==Links==

*[[Hairy Cell Leukemia]]
*[[Hairy Cell Leukemia Variant]]
*[[Splenic B-cell Lymphoma/Leukemia, Unclassifiable]]
*[[Splenic Marginal Zone Lymphoma]]

==References==
(use "Cite" icon at top of page)
<references />
===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==
<nowiki>*</nowiki>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.

HAEM4Backup:Splenic Diffuse Red Pulp Small B-cell Lymphoma - Revision history

Bailey.Glen: Created page with "==Primary Author(s)*== *Snehal Patel, MD, PhD __TOC__ ==Cancer Category/Type== *Mature B-Cell Neoplasm ==Cancer Sub-Classification / Subtype==..."

Bailey.Glen: Created page with "==Primary Author(s)== Snehal Patel, MD, PhD TOC ==Cancer Category/Type== *Mature B-Cell Neoplasm ==Cancer Sub-Classification / Subtype==..."