Lymphoma and plasma cell neoplasms
B cell lymphoma subtypes
Mantle cell lymphoma

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 3 April 2017, last major update February 2011

Copyright: (c) 2001-2017, PathologyOutlines.com, Inc.

PubMed Search: mantle cell lymphoma

Cite this page: Mantle cell lymphoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/lymphomaMCL.html. Accessed June 23rd, 2017.
Definition / general
  • Intermediate grade B cell lymphoma characterized by CD5+ CD23-, cyclin D1+ and t(11;14)(q13;q32)
Terminology
Etiology
  • Cell of origin appears to be naïve pregerminal center B lymphocyte present in primary lymphoid follicles and mantle zones of secondary follicles with nonmutated Vh region genes
Clinical features
  • 3 - 10% of non-Hodgkin lymphomas in Western countries
  • Usually 60+ years with stage III / IV disease; 80% men
  • Lymphadenopathy, bone marrow involvement in 2/3 (lymphoid aggregates, often paratrabecular), splenomegaly in 50% with white pulp involvement, periportal hepatic infiltration, lymphomatoid polyposis of small bowel and other extranodal involvement
  • CNS involvement in 10% (Mod Pathol 2002;15:1073)
  • B symptoms (fever, night sweaters, weight loss) in 30%
  • Peripheral blood involvement (leukemic phase) in 20 - 60% at diagnosis; usually < 20,000 absolute lymphocytes, associated with worse outcome
  • More aggressive than SLL / CLL or marginal zone lymphoma
  • Median survival 3 years, may transform to blastoid variant, but blastic transformation is uncommon
  • Does not transform to large cell lymphoma
  • Most patients relapse
  • Complete remission in less than 35%
  • Cutaneous cases associated with disseminated disease at diagnosis or shortly thereafter
Prognostic factors
  • Longer survival: nodular or mantle zone pattern (5 years)
  • Shorter survival: blastic variant (3 years), high mitotic count, high proportion of Ki67+ cells, trisomy 12, 3q+, 9q-, p53 mutation / overexpression / loss
  • International Prognostic Index not useful because most patients present with high stage disease with multiple foci of extranodal involvement
Case reports
Treatment
  • No standard or curative treatment - various chemotherapy regimens are used, with rituximab
  • Proteasome inhibitor bortezomib may be helpful
Microscopic (histologic) description
  • Three patterns of tumor infiltration: (1) diffuse replacement of entire lymph node, (2) infiltration into expanded mantle zone or (3) vague nodular pattern
  • Tumor cells are monotonous small lymphocytes resembling centrocytes / mantle cells with scant cytoplasm, cleaved, slightly irregular or round nuclei; condensed chromatin
  • Tumor cells have no nucleoli; no large cells, no proliferation centers
  • May have prominent hyalinized vessels or scattered epithelioid histiocytes
  • Rarely platelet satellitism around atypical lymphocytes (Am J Clin Pathol 2001;115:567)
  • Cases with prominent nucleoli resemble AML-M3 (Am J Clin Pathol 2002;117:246)
  • Bone marrow involvement: most of these patients relapse - only 35% attain complete remission; focal paratrabecular and nonparatrabecular patterns; may have benign germinal centers; cells are pleomorphic with variation in size and irregular nuclear contours
  • Cutaneous: dermal and subcutaneous aggregates of small to medium lymphocytes, often perivascular or periadnexal; Grenz zone present with sparing of the epidermis; often blastoid (Am J Surg Pathol 2002;26:1312)
Microscopic (histologic) images

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Presenting as breast mass

Axillary node: tumor cells have scant cytoplasm, irregular nuclei, small nucleoli


With synchronous colonic adenocarcinoma

CD20+

Cyclin D1+

CD43+ (cytoplasmic staining)

Cytology images

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Various images

Peripheral smear description
  • Cells (if present) have scant cytoplasm and cleaved nuclei; confirm neoplastic with flow cytometry
  • Differential diagnosis is SLL / CLL, prolymphocytic leukemia, follicular lymphoma
Positive stains
  • CD5, CD19 (strong), CD20 (strong), cyclin D1 / BCL1 (variable nuclear staining since cells are at different stages of cell cycle); also CD22, CD43, CD79a, FMC7, surface IgM or IgD, kappa or lambda, BCL2
  • In situ hybridization for cyclin D1 / BCL1 is more sensitive / specific than immunostains (Mod Pathol 2001;14:62)
  • Cyclin D1 helpful to identify "in situ MCL," when the involvement is restricted to the inner mantle zones
  • Rare cases have all morphologic features of MCL but are negative for cyclin D1, may be positive for cyclin D2 / D3 (great caution required for diagnosis, Blood 2005;106:4315, Blood 2006;108:1109)
Negative stains
Molecular / cytogenetics description
  • t(11;14)(q13;q32): fusion of cyclin D1 (also called BCL1, PRAD1, CCND1) and IgH in 90% (same translocation present in some B cell prolymphocytic leukemia, myeloma and CLL)
  • Cyclin D1 regulates G1 to S phase transition, but the cell cycle suppressive effect of RB1 and p27 kip1 is overcome by deregulated expression of cyclin D1, leading to development of mantle cell lymphoma
  • t(11;14) is not specific for mantle cells - it is also found in normal patients
  • Leukemic cases often have chromosome 17 abnormalities associated with p53; also additional cytogenetic breakpoints at 8q24, 9p22-24 and 16q24 (Am J Clin Pathol 2001;116:886)
  • Clonal IgH rearrangements are present in 100% of cases by PCR
  • Real time RT-PCR for quantifying cyclin D1 may be useful for diagnosis (Mod Pathol 2002;15:556)
  • Insertion of CCDN1 gene at IgH locus may be microscopic, causing fusion gene with BCL1 overexpression on an apparently normal chromosome 14 (J Clin Pathol 2003;56:798)
  • FISH: 57 - 90% of interphase nuclei have 3 or more 11q13 signals (Am J Clin Path 2000;114:248); may be more sensitive than immunostains (Mod Pathol 2002;15:517)
Molecular / cytogenetics images

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PCR / Southern blot image

Peripheral blood single and double fusion of cyclin D1 / IgH cells

ISH for cyclin D1

Differential diagnosis