Splenic marginal zone lymphoma

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Splenic marginal zone lymphoma (SMZL) is a lymphoma comprised 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 blasts, 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 villious lymphocytes due to their characteristic appearance. [http://www.iarc.fr/WHO-BlueBooks/BBwebsite/bb3.html] Jaffe E.S., Harris N.L., Stein H., Vardiman J.W. (eds): World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues. IARC Press: Lyon 2001]

ynonyms

Under older classification systems, the following names were used:

Cause

The cell of origin is postulated to be a post-germinal center B-cell with an unknown degree of differentiation.

Diagnosis

With splenic involvement a requirement for a diagnosis of SMZL, splenomegaly is seen in almost all patients, commonly without lymphadenopathy. Aside from the uniform involvement of the spleen, the bone marrow is frequently positive in patients with SMZL. Nodal and extranodal involvement are rare.

Circulating lymphoma cells are sometimes present in peripheral blood, and they occasionally show short villi at the poles of cells and plasmacytoid differentiation.cite journal |author=Melo JV, Hegde U, Parreira A, Thompson I, Lampert IA, Catovsky D |title=Splenic B cell lymphoma with circulating villous lymphocytes: differential diagnosis of B cell leukaemias with large spleens |journal=J. Clin. Pathol. |volume=40 |issue=6 |pages=642–51 |year=1987 |month=June |pmid=3497180 |pmc=1141055 |doi= |url=http://jcp.bmj.com/cgi/pmidlookup?view=long&pmid=3497180]

Autoimmune thrombocytopenia and anemia sometimes seen in patients with SMZL. Circulating villous lymphocytes are sometimes observed in peripheral blood samples. A monoclonal paraprotein is detected in a third of patients without hypergammaglobulinemia or hyperviscosity.cite journal |author=Mollejo M, Menárguez J, Lloret E, "et al" |title=Splenic marginal zone lymphoma: a distinctive type of low-grade B-cell lymphoma. A clinicopathological study of 13 cases |journal=Am. J. Surg. Pathol. |volume=19 |issue=10 |pages=1146–57 |year=1995 |month=October |pmid=7573673 |doi= |url=]

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. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=6638043&query_hl=11&itool=pubmed_ExternalLink] Jaffe ES, Costa J, Fauci AS, Cossman J, Tsokos M. "Malignant lymphoma and erythrophagocytosis simulating malignant histiocytosis." Am J Med. 1983 Nov;75(5):741-9. PMID 6638043.] The red pulp is always involved, with both nodules of larger neoplastic cells and sheets of the small neoplastic lymphocytes. Other features that may been 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.

SMZL in bone marrow displays a nodular pattern with morphology similar to what is observed in the splenic hilar lymph nodes. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8971565&query_hl=13&itool=pubmed_ExternalLink] Franco V, Florena AM, Campesi G. "Intrasinusoidal bone marrow infiltration: a possible hallmark of splenic lymphoma." Histopathology. 1996 Dec;29(6):571-5. PMID 8971565.]

Molecular Findings

Immunophenotype

The relevant markers that define the immunophenotype for SMZL are shown in the table to the right. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=7949139&query_hl=17&itool=pubmed_ExternalLink] Isaacson PG, Matutes E, Burke M, Catovsky D. "The histopathology of splenic lymphoma with villous lymphocytes." Blood. 1994 Dec 1;84(11):3828-34. PMID 7949139.] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8123845&query_hl=20&itool=pubmed_ExternalLink] Matutes E, Morilla R, Owusu-Ankomah K, Houlihan A, Catovsky D. "The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders."Blood. 1994 Mar 15;83(6):1558-62. PMID 8123845.] 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. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9688179&query_hl=22&itool=pubmed_ExternalLink] Savilo E, Campo E, Mollejo M, Pinyol M, Piris MA, Zukerberg LR, Yang WI, Koelliker DD, Nguyen PL, Harris NL. "Absence of cyclin D1 protein expression in splenic marginal zone lymphoma."Mod Pathol. 1998 Jul;11(7):601-6. PMID 9688179.]

Genetics

Clonal rearrangements of the immunoglobulin genes (heavy and light chains) are frequently seen. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9635678&query_hl=24&itool=pubmed_ExternalLink] Dunn-Walters DK, Boursier L, Spencer J, Isaacson PG. "Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation." Hum Pathol. 1998 Jun;29(6):585-93. PMID 9635678.] The deletion 7q21-32 is seen in 40% of SMZL patients, and translocations of the CDK6 gene located at 7q21 have also been reported. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10597225&query_hl=28&itool=pubmed_ExternalLink] Corcoran MM, Mould SJ, Orchard JA, Ibbotson RE, Chapman RM, Boright AP, Platt C, Tsui LC, Scherer SW, Oscier DG. "Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations." Oncogene. 1999 Nov 4;18(46):6271-7. PMID 10597225.]

Epidemiology

Less than 1% of all lymphomas are splenic marginal zone lymphomascite journal |author=Armitage JO, Weisenburger DD |title=New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project |journal=J. Clin. Oncol. |volume=16 |issue=8 |pages=2780–95 |year=1998 |month=August |pmid=9704731 |doi= |url=http://www.jco.org/cgi/pmidlookup?view=long&pmid=9704731] and it is postulated that SMZL may represent a large fraction of unclasssifiable CD5- chronic lymphocytic leukemias. The typical patient is over the age of 50, and gender preference has been described.cite journal |author=Berger F, Felman P, Thieblemont C, "et al" |title=Non-MALT marginal zone B-cell lymphomas: a description of clinical presentation and outcome in 124 patients |journal=Blood |volume=95 |issue=6 |pages=1950–6 |year=2000 |month=March |pmid=10706860 |doi= |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=10706860]

References