Splenic marginal zone lymphoma 5633928 225708318 2008-07-15T00:38:30Z WhatamIdoing 1998764 Make a proper lead. Some clean up. Some ref formatting. Needs more clean up. Why is there no treatment information? {{Infobox_Disease | Name = {{PAGENAME}} | Image = | Caption = | DiseasesDB = | ICD10 = | ICD9 = | ICDO = 9689/3 | OMIM = | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | MeshID = | }} '''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]] [[lymph follicle|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.<ref name="who1">[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</ref> ==Synonyms== Under older classification systems, the following names were used:<ref name="who1"/> {| class="wikitable" |- ! '''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 |- |} ==Cause== The cell of origin is postulated to be a post-germinal center B-cell with an unknown degree of differentiation.<ref name="who1"/> ==Diagnosis== With splenic involvement a requirement for a diagnosis of SMZL, [[splenomegaly]] is seen in almost all patients, commonly without lymphadenopathy.<ref name="who1"/> Aside from the uniform involvement of the [[spleen]], the [[bone marrow]] is frequently positive in patients with SMZL. Nodal and extranodal involvement are rare.<ref name="who1"/> Circulating [[lymphoma]] cells are sometimes present in peripheral [[blood]], and they occasionally show short villi at the poles of cells and plasmacytoid differentiation.<ref name="mel1">{{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}}</ref> [[Autoimmune thrombocytopenia]] and [[anemia]] sometimes seen in patients with SMZL. Circulating [[villous lymphocytes]] are sometimes observed in peripheral [[blood]] samples.<ref name="who1"/> A [[monoclonal]] [[paraprotein]] is detected in a third of patients without [[hypergammaglobulinemia]] or [[hyperviscosity]].<ref name="ber1"/><ref name="mol1">{{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=}}</ref> [[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]].<ref name="mol1"/><ref name="jaf1"> [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.</ref> 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 (anatomy)|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.<ref name="who1"/> SMZL in [[bone marrow]] displays a nodular pattern with morphology similar to what is observed in the splenic [[hilar]] [[lymph nodes]].<ref name="fra1"> [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.</ref> ==Molecular Findings== ===Immunophenotype=== {| class="infobox bordered" style="width: 20em; text-align: left; font-size: 100%;" |- ! '''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 table to the right.<ref name="isa1"> [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.</ref><ref name="mat1"> [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.</ref> 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.<ref name="sav1"> [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.</ref> ===Genetics=== Clonal rearrangements of the [[immunoglobulin]] genes (heavy and light chains) are frequently seen.<ref name="dun1">[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.</ref> The deletion 7q21-32 is seen in 40% of SMZL patients, and translocations of the CDK6 gene located at 7q21 have also been reported.<ref name="cor1"> [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.</ref> ==Epidemiology== Less than 1% of all lymphomas are splenic marginal zone lymphomas<ref name="arm1">{{cite 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}}</ref> and it is postulated that SMZL may represent a large fraction of unclasssifiable CD5- chronic lymphocytic leukemias.<ref name="who1"/> The typical patient is over the age of 50, and gender preference has been described.<ref name="ber1">{{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}}</ref> ==References== {{reflist|2}} {{Hematological malignancy histology}} [[Category:Hematology|Splenic marginal zone lymphoma]] [[Category:Types of cancer|Splenic marginal zone lymphoma]] [[Category:Blood disorders|Splenic marginal zone lymphoma]]