Splenic marginal zone lymphoma

Splenic marginal zone lymphoma (SMZL) is a type of cancer (specifically a lymphoma) made up of B-cells that replace the normal architecture of the white pulp of the spleen. The neoplastic cells are both small lymphocytes and larger, transformed lymphoblasts, and they invade the mantle zone of splenic follicles and erode the marginal zone, ultimately invading the red pulp of the spleen. Frequently, the bone marrow and splenic hilar lymph nodes are involved along with the peripheral blood. The neoplastic cells circulating in the peripheral blood are termed villous lymphocytes due to their characteristic appearance.[1]

Splenic marginal zone lymphoma
SpecialtyHematology, oncology

Cause

The cell of origin is postulated to be a post-germinal center B-cell with an unknown degree of differentiation.[1] SMZL is a form of cancer known to be associated with Hepatitis C virus infection.

Diagnosis

Enlargement of the spleen is a requirement for the diagnosis of SMZL and is seen in nearly all people affected by SMZL (often without lymphadenopathy).[1] Aside from the uniform involvement of the spleen, the bone marrow is frequently positive in patients with SMZL. Nodal and extranodal involvement are rare.[1]

Circulating lymphoma cells are sometimes present in peripheral blood, and they occasionally show short villi at the poles of cells and plasmacytoid differentiation.[2]

Autoimmune thrombocytopenia and anemia sometimes seen in patients with SMZL. Circulating villous lymphocytes are sometimes observed in peripheral blood samples.[1] A monoclonal paraprotein is detected in a third of patients without hypergammaglobulinemia or hyperviscosity.[3][4]

Reactive germinal centers in splenic white pulp are replaced by small neoplastic lymphocytes that efface the mantle zone and ultimately blend in with the marginal zone with occasional larger neoplastic cells that resemble blasts.[4][5] The red pulp is always involved, with both nodules of larger neoplastic cells and sheets of the small neoplastic lymphocytes. Other features that may be seen include sinus invasion, epithelial histocytes, and plasmacytic differentiation of neoplastic cells.

Involved hilar lymph nodes adjacent to the spleen show an effaced architecture without preservation of the marginal zone seen in the spleen.[1]

SMZL in bone marrow displays a nodular pattern with morphology similar to what is observed in the splenic hilar lymph nodes.[6]

Prognosis

Three-quarters of patients survive five or more years; more than half of patients with SMZL survive more than a decade after diagnosis.[7]

Patients who have a hemoglobin level of less than 12 g/dL, a lactate dehydrogenase level higher than normal, and/or a blood serum albumin levels of less than 3.5 g/dL are likely to have more an aggressive disease course and a shorter survival.[7] However, even high-risk patients have even odds of living for five years after diagnosis.[7]

Some genetic mutations, such as mutations in NOTCH2, are also correlated with shorter survival.

Molecular findings

Immunophenotype
Antigen Status
CD20 Positive
CD79a Positive
CD5 Negative
CD10 Negative
CD23 Negative
CD43 Negative
cyclin D1 Negative

The relevant markers that define the immunophenotype for SMZL are shown in the adjacent table.[8] [9] The lack of CD5 expression is helpful in the discrimination between SMZL and chronic lymphocytic leukemia/small lymphocytic lymphoma, and the lack of CD10 expression argues against follicular lymphoma. Mantle cell lymphoma is excluded due to the lack of CD5 and cyclin-D1 expression.[10]

Genetics

Clonal rearrangements of the immunoglobulin genes (heavy and light chains) are frequently seen.[11] The deletion 7q21-32 is seen in 40% of SMZL patients, and translocations of the CDK6 gene located at 7q21 have also been reported.[12]

Epidemiology

Less than 1% of all lymphomas are splenic marginal zone lymphomas[13] and it is postulated that SMZL may represent a large fraction of unclassifiable CD5- chronic lymphocytic leukemias.[1] The typical patient is over the age of 50, and gender preference has been described.[3]

Synonyms

Under older classification systems, the following names were used:[1]

Classification system Name
Rappaport well-differentiated lymphocytic lymphoma
Lukes-Collins small lymphocytic lymphoma
Working Formulation small lymphocytic lymphoma
FAB splenic lymphoma with circulating villous lymphocytes

See also

References
  1. Elaine Sarkin Jaffe, Nancy Lee Harris, World Health Organization, International Agency for Research on Cancer, Harald Stein, J.W. Vardiman (2001). Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumors. 3. Lyon: IARC Press. ISBN 978-92-832-2411-2.CS1 maint: multiple names: authors list (link)
  2. Melo JV, Hegde U, Parreira A, Thompson I, Lampert IA, Catovsky D (June 1987). "Splenic B cell lymphoma with circulating villous lymphocytes: differential diagnosis of B cell leukaemias with large spleens". J. Clin. Pathol. 40 (6): 642–51. doi:10.1136/jcp.40.6.642. PMC 1141055. PMID 3497180.
  3. Berger F, Felman P, Thieblemont C, et al. (March 2000). "Non-MALT marginal zone B-cell lymphomas: a description of clinical presentation and outcome in 124 patients". Blood. 95 (6): 1950–6. doi:10.1182/blood.V95.6.1950. PMID 10706860.
  4. Mollejo M, Menárguez J, Lloret E, et al. (October 1995). "Splenic marginal zone lymphoma: a distinctive type of low-grade B-cell lymphoma. A clinicopathological study of 13 cases". Am. J. Surg. Pathol. 19 (10): 1146–57. doi:10.1097/00000478-199510000-00005. PMID 7573673.
  5. Jaffe ES, Costa J, Fauci AS, Cossman J, Tsokos M (November 1983). "Malignant lymphoma and erythrophagocytosis simulating malignant histiocytosis". Am. J. Med. 75 (5): 741–9. doi:10.1016/0002-9343(83)90402-3. PMID 6638043.
  6. Franco V, Florena AM, Campesi G (December 1996). "Intrasinusoidal bone marrow infiltration: a possible hallmark of splenic lymphoma". Histopathology. 29 (6): 571–5. doi:10.1046/j.1365-2559.1996.d01-536.x. PMID 8971565.
  7. Arcaini, L. (2006). "Splenic marginal zone lymphoma: a prognostic model for clinical use" (PDF). Blood. 107 (12): 4643–4649. doi:10.1182/blood-2005-11-4659. hdl:11380/584206. ISSN 0006-4971. PMID 16493005.
  8. Isaacson PG, Matutes E, Burke M, Catovsky D (1 December 1994). "The histopathology of splenic lymphoma with villous lymphocytes". Blood. 84 (11): 3828–34. doi:10.1182/blood.V84.11.3828.bloodjournal84113828. PMID 7949139.
  9. Matutes E, Morilla R, Owusu-Ankomah K, Houlihan A, Catovsky D (15 March 1994). "The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders". Blood. 83 (6): 1558–62. doi:10.1182/blood.V83.6.1558.1558. PMID 8123845.
  10. Savilo E, Campo E, Mollejo M, et al. (July 1998). "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma". Mod. Pathol. 11 (7): 601–6. PMID 9688179.
  11. Dunn-Walters DK, Boursier L, Spencer J, Isaacson PG (June 1998). "Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation". Hum. Pathol. 29 (6): 585–93. doi:10.1016/S0046-8177(98)80007-5. PMID 9635678.
  12. Corcoran MM, Mould SJ, Orchard JA, et al. (November 1999). "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations". Oncogene. 18 (46): 6271–7. doi:10.1038/sj.onc.1203033. PMID 10597225.
  13. Armitage JO, Weisenburger DD (August 1998). "New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project". J. Clin. Oncol. 16 (8): 2780–95. doi:10.1200/JCO.1998.16.8.2780. PMID 9704731. Archived from the original on 2013-04-15.
Classification
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