Lymphoma & related disorders
Mature B cell neoplasms
Splenic B cell lymphomas and leukemias
Splenic marginal zone
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PubMed Search: Splenic marginal zone B cell lymphoma[TIAB]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Pathophysiology | Clinical features | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Peripheral smear images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Kaseb H, Hudnall S. Splenic marginal zone. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomasplenicmzl.html. Accessed December 24th, 2024.
Definition / general
- Splenic marginal zone lymphoma (SMZL) is a low grade B cell neoplasm composed of small lymphocytes that originate from the splenic white pulp germinal centers
- Marginal zone: light zone surrounding splenic follicles which contains post follicular memory B cells derived after stimulation of recirculating cells from T cell dependent antigen
Essential features
- Splenic marginal zone lymphoma is a low grade B cell neoplasm composed of small lymphocytes that originate from the splenic white pulp germinal centers
- The spleen and bone marrow are infiltrated by a micronodule that replaces the pre-existing lymphoid follicles and show marginal zone differentiation
- Patients usually present with splenomegaly and no lymphadenopathy
- The clinical, immunophenotypic, and genetic features of splenic marginal zone lymphoma are different from other marginal zone lymphomas, indicating that splenic marginal zone lymphoma is a distinct clinicopathologic entity, unrelated to mucosa associated lymphoid tissue or nodal marginal zone lymphomas (Jaffe: Hematopathology, 2nd Edition, 2017)
Terminology
- Splenic B cell marginal zone lymphoma; splenic lymphoma with villous lymphocytes; splenic lymphoma with circulating villous lymphocytes
ICD coding
- ICD-10: C83.07 - small cell B cell lymphoma, spleen
Epidemiology
- Splenic marginal zone lymphoma is a rare disorder, accounting for 20% of marginal zone lymphomas and < 2% of lymphoid neoplasms
- Affects middle aged and elderly patients (most patients > 50 years, median age 69 years, female predominance) (Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017)
Pathophysiology
- Splenic marginal zone lymphoma pathogenesis involves antigen or superantigen stimulation and molecular deregulation of different genes (including NOTCH2 and KLF2) involved in normal lymphocyte differentiation (Blood 2016;127:2072)
- Some splenic marginal zone lymphoma patients with hepatitis C seem to have better disease control with hepatitis C treatment, suggesting a possible role for hepatitis C in disease
Clinical features
- Splenic marginal zone lymphoma patients are usually asymptomatic (Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017)
- Symptomatic patients usually present with (Jaffe: Hematopathology, 2nd Edition, 2016, Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017):
- Splenomegaly (75%)
- Symptoms related to bone marrow infiltration: autoimmune thrombocytopenia, anemia and leukocytosis (25%)
- Other signs and symptoms:
- Hepatomegally
- Splenic hilar lymphadenopathy
- 1/3 of the patients may present with paraprotein; however, hyperviscosity and hypergammaglobulinemia are uncommon
- Peripheral blood involvement with atypical lymphocytes
- Peripheral lymphadenopathy and extranodal infiltration are extremely uncommon
- Usually indolent but 13% transform, possibly related to 7q deletion
- Association with hepatitis C virus has been reported
Prognostic factors
- The prognosis of splenic marginal zone lymphoma is overall favorable with a 5 year survival of approximately 70% and median survival: > 10 years (Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017)
- Adverse prognosis is seen in patients with high tumor burden or poor performance status
- 10% transform to high grade large B cell lymphoma
Case reports
- 46 year old woman presenting with rituximab induced acute thrombocytopenia as a complication of splenic marginal zone lymphoma treatment (Am J Case Rep 2019;20:1394)
- 68 year old man presenting with splenic marginal zone lymphoma and angioedema (Am J Case Rep 2019;20:1476)
- 71 year old man presenting with splenic marginal zone lymphoma and myelofibrosis (Case Rep Oncol 2019;12:834)
- 73 year old woman treated with laparoscopic splenectomy (Int J Surg Case Rep 2019;65:288)
- 73 year old man presenting with cold agglutinin disease and splenic marginal zone lymphoma (Clin Nucl Med 2019;44:e372)
Treatment
- Close observation (watch and wait) is advisable for asymptomatic patients (Blood 2016;127:2072)
- Symptomatic
- Rituximab:
- Rituximab monotherapy is treatment of choice
- Rituximab with or without splenectomy has been found to be an effective treatment modality (Blood 2018;132:666)
- Resistant or relapsed patients
- Chemotherapy: fludarabine or chlorambucil
- Splenectomy
- Indicated in patients refractory to immunochemotherapy
- Is associated with a better disease outcome
- HCV patients: appropriate viral eradication is associated with splenic marginal zone lymphoma remission
- Rituximab:
Gross description
- Multiple small, grayish-white nodules due to marked expansion of the white pulp and infiltration of the red pulp
Microscopic (histologic) description
- Spleen (Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017)
- Micronodular lymphoid infiltrate in which white pulp follicles
- Infiltration by two cells types: small lymphocytes and marginal zone cells
- The cells are often more admixed, leading to mixed mantle zone and marginal zone involvement pattern
- Infiltration of small atypical lymphocytes in mantle zone and medium lymphocytes with pale cytoplasm and oval clear nucleus in marginal zone
- Infiltration by two cells types: small lymphocytes and marginal zone cells
- The red pulp is usually infiltrated in both the cords and the sinuses; the pattern of infiltration is usually diffuse
- Variable follicular colonization but definite increase in white pulp
- Cells are centrocyte-like, monocytoid or lymphoplasmacytic
- < 20% immunoblasts; involves red pulp also
- Micronodular lymphoid infiltrate in which white pulp follicles
- Bone marrow (Jaffe: Hematopathology, 2nd Edition, 2016)
- Combination of nodular, interstitial and intrasinusoidal is the most common pattern
- Intrasinusoidal and interstitial infiltrate
- Common in early stage
- Intrasinusoidal infiltration of bone marrow is relatively specific finding
- Nodular pattern is typical encountered with disease progression
- In advanced disease, a combination of intrasinusoidal, interstitial and nodular infiltration is seen
- Peripheral smear
- Cells with scant cytoplasm and cleaved nucleus; confirm neoplastic with flow cytometry
Microscopic (histologic) images
Contributed by Hatem Kaseb, M.D., Ph.D., M.P.H.
Lymphoid aggregate
Peripheral smear images
Contributed by Hatem Kaseb, M.D., Ph.D., M.P.H.
Atypical lymphocytes
Positive stains
- CD19, CD20, CD22, CD45RA, CD79a, BCL2 (Jaffe: Hematopathology, 2nd Edition, 2016, Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017)
- Tumor cells are IgM+ and IgD (dim) but there is no IgD positive mantle area
Negative stains
Molecular / cytogenetics description
- Splenic marginal zone lymphoma lacks recurrent chromosomal translocations (Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017)
- Clonal rearrangements of IgH and IgL are common
- Other reported genetic changes (Jaffe: Hematopathology, 2nd Edition, 2016)
- Deletions 7q (in up to 40%)
- p53 alterations
- NOTCH2 mutation
- 14q aberrations
- Deletion of 7q and NOTCH2 mutations are specific for splenic marginal zone lymphoma (Blood 2016;127:2072)
- Complex karyotype, 14q aberrations, NOTCH2 mutations, and TP53 mutations are poor prognostic indicators
Sample pathology report
- Bone marrow, biopsy and aspirate:
- Low grade non-Hodgkin B cell lymphoma, with features most suggestive of splenic marginal zone lymphoma (see comment)
- Comment: Given the pattern of infiltration (nodular and intrasinusoidal) as well as cytomorphology of some lymphocytes with villous cytoplasmic projections and radiographic history of mild splenomegaly, features are most suggestive of a splenic marginal zone lymphoma. Correlation with clinical, cytogenetic and laboratory findings is recommended.
- CBC (3/14/18) by report: HGB: 12.1 g/dL, MCV: 84.9 fL, WBC: 24.8 K/uL, PLT: 109 K/uL
- Bone marrow biopsy:
- Variably cellular overall normocellular marrow for age (30% cellular). Approximately 40% of the cellularity is comprised of large paratrabecular lymphoid aggregates and scattered interstitial lymphoid aggregates composed of small lymphocytes. Megakaryocytes are normal in number and morphology; the myeloid:erythroid (M:E) ratio is normal. Erythroid elements exhibit normal maturation; myeloid elements exhibit normal maturation. Granulomas are not seen; reticulin stain reveals that reticulin is mildly increased in association with the lymphoid aggregates. Trabecular bone is unremarkable.
- Immunostains:
- CD20 and CD19 highlight B cell comprising the majority of lymphocytes within the lymphoid aggregates with intrasinusoidal infiltration. Scattered CD3 positive T cells are present.
- Bone marrow aspirate:
- The marrow aspirate smears are spicular and paucicellular; scattered lymphocytes with occasional fine cytoplasmic projections present. Megakaryocytes are rare; the myeloid:erythroid (M:E) ratio is approximately 1:1; erythroid maturation is present.
- Myeloid maturation is present. Prussian blue iron stain shows trace storage iron and no significant increase in ring sideroblasts.
- Aspirate cell count: a 202 cell count reveals < 1% blasts, 6% promyelocytes / myelocytes, 32% maturing granulocyte forms, 16% erythroid forms, 38% lymphocytes, 3% plasma cells, 3% eosinophils and 2% monocytes.
Differential diagnosis
- Other small B cell lymphoma
- B-CLL:
- Mantle cell lymphoma:
- Absence of cyclin D1 and LEF1 is useful in excluding mantle cell lymphoma and CLL
- Hairy cell leukemia (HCL):
- Lack of nodular pattern of infiltration on bone marrow biopsy absence of annexin A1 excludes HCL
- Follicular lymphoma:
- Lymphoplasmacytic lymphoma:
- No pale corona surrounding reactive or colonized germinal centers and no monocytoid B cells in marginal zone
- Persistent polyclonal B cell lymphocytosis:
Board review style question #1
- What is the most common cytogenetic abnormality in splenic marginal zone lymphoma (SMZL)?
- Amp 22
- Del 7q
- Del 11q
- t (8;14)
Board review style answer #1
B. Deletion 7q is identified in up to 40% of splenic marginal zone lymphoma patients.
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Reference: Splenic marginal zone B cell lymphoma
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Reference: Splenic marginal zone B cell lymphoma
Board review style question #2
- What is the immunophenotypic pattern of splenic marginal zone lymphoma (SMZL)?
- CD19+, CD20+, CD5-, CD23-
- CD19+, CD20+, CD5+, CD23+
- CD19+, CD20+, CD10+, BCL6+
- CD19+, CD20+, CD10+, BCL6+
Board review style answer #2
A. CD19+, CD20+, CD5-, CD23- is consistent with splenic marginal zone lymphoma.
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Reference: Splenic marginal zone B cell lymphoma
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Reference: Splenic marginal zone B cell lymphoma
