Lymphoma and plasma cell neoplasms
Mature B cell neoplasms: Mantle cell lymphoma
Leukemic nonnodal mantle cell lymphoma

Editor-in-Chief: Debra Zynger, M.D.
Nicholas Nowacki, M.D.

Topic Completed: 18 October 2019

Revised: 22 October 2019

Copyright: 2019, PathologyOutlines.com, Inc.

PubMed Search: Nonnodal mantle cell lymphoma "loattrfree full text"[sb]


Nicholas Nowacki, M.D.
Page views in 2019 to date: 268
Cite this page: Nowacki N. Leukemic nonnodal mantle cell lymphoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/lymphomanonnodalmantlecell.html. Accessed December 10th, 2019.
Definition / general
  • Mantle cell lymphoma involving the peripheral blood, bone marrow, occasionally spleen and gastrointestinal tract but not lymph nodes
Essential features
  • Must lack significant lymphadenopathy (< 1 cm on physical exam and not detected via imaging / CT scans)
  • t(11;14)(q13;q32) = fusion of CCND1 and IGH genes
  • Positive for Cyclin D1 (also known as BCL1) and negative for SOX11
Terminology
  • Leukemic mantle cell lymphoma
  • Nonnodal leukemic mantle cell lymphoma (NN-L-MCL)
  • Monoclonal asymptomatic lymphocytosis, cyclin D1 positive (MALD1)
ICD coding
  • ICD-10: C83.10 - mantle cell lymphoma, unspecified site
Epidemiology
  • M > F = ~2:1
  • Mean age = ~60 years old
Sites
  • Peripheral blood, bone marrow and occasionally spleen or gastrointestinal tract
  • Circulating cells may reversibly infiltrate extranodal sites and typically remain in the mantle zones of follicles, overlapping with in situ mantle cell lymphoma
Pathophysiology
  • t(11;14)(q13;q32), fusion of CCND1 gene and IGH promoter increases production of the Cyclin D1 protein, regulator of cyclin dependent kinase (CDK4) and CDK6 which controls the G1 / S cell cycle transition (J Clin Invest 2012;122:3416)
Etiology
  • Cell of etiology thought to be peripheral B cell of inner mantle zone
Clinical features
  • Typically asymptomatic at presentation
Laboratory
  • Mild leukocytosis and mild absolute lymphocytosis
  • 10 - 20% patients will have a monoclonal protein
Prognostic factors
Case reports
Treatment
  • May be observed until progression, then treated as typical mantle cell lymphoma with combination chemotherapy, rituximab and subsequent stem cell transplant depending on age and performance status (Curr Oncol Rep 2018;20:79)
Microscopic (histologic) description
  • Diffuse interstitial infiltrate or small scattered nonparatrabecular lymphoid aggregates
  • Small to intermediate size lymphoid cells with scant cytoplasm, round to slightly irregular nuclear contours and mature chromatin
  • Some cases will show dispersed chromatin and indistinct nucleoli
Microscopic (histologic) images

Contributed by Nicholas Nowacki, M.D.

Lymphoid infiltrate

Small lymphoma cells


CD3 highlights T cells

CD5 positive

CD20 positive

Cyclin D1 positive

SOX11 negative

Cytology description
  • Variable morphologic appearance
    • Majority (~70%) show chronic lymphocytic leukemia-like morphology = small with scant cytoplasm, round nuclear contours and condensed chromatin (Cancer Res 2010;70:1408)
    • Fewer (~30%) with typical mantle cell lymphoma, centrocyte-like morphology = small to medium sized lymphoid cells with scant cytoplasm, irregular nuclear contours, dispersed chromatin and indistinct nucleoli
Cytology images

Contributed by Nicholas Nowacki, M.D.

Marrow aspirate

Peripheral smear description
  • Same as cytology description
Peripheral smear images

Contributed by Nicholas Nowacki, M.D.

Peripheral blood

Positive stains
Negative stains
Flow cytometry description
  • Typical immunophenotype:
    • Positive: CD20 (moderate to bright), surface light chain restriction (moderate to bright), CD5 (subset), CD79b, FMC7
    • Negative: CD10, CD103, CD123, CD11c
Flow cytometry images

Contributed by Nicholas Nowacki, M.D.

Aberrant CD5 co-expression

CD20 moderate expression

Surface light chain restriction

Molecular / cytogenetics description
  • t(11;14)(q13;q32), fusion of CCND1 and IGH genes
  • Most cases have somatic hypermutation / IgVH gene hypermutated (Clin Cancer Res 2014;20:1007)
  • Typically few additional cytogenetic abnormalities and much less likely to have a complex karyotype than classic mantle cell (Leukemia 2012;26:1895)
Sample pathology report
  • Bone marrow, biopsy, aspirate and peripheral blood smear:
    • Mantle cell lymphoma involving a normocellular marrow with preserved trilineage hematopoiesis (see comment)
    • Comment: The overall findings are consistent with marrow involvement by mantle cell lymphoma. Given the lack of SOX11 staining, the possibility of the leukemic nonnodal mantle cell lymphoma variant should be considered. By definition, patients with this variant must lack significant lymphadenopathy (< 1 cm). The presence of lymphadenopathy would argue for the classic variant of mantle cell lymphoma. Clinical correlation and correlation with cytogenetic / FISH studies, including t(11;14)(q13;q32) IGH-CCND1, is recommended.
Differential diagnosis
Board review question #1
What is the most likely immunophenotype for leukemic nonnodal mantle cell lymphoma?



  1. CD20+, CD5+, CD10+, CD103-, CD123-, Cyclin D1+, SOX11+
  2. CD20+, CD5+, CD10-, CD103+, CD123+, Cyclin D1+, SOX11-
  3. CD20+, CD5+, CD10-, CD103-, CD123-, Cyclin D1+, SOX11+
  4. CD20+, CD5+, CD10-, CD103-, CD123-, Cyclin D1+, SOX11-
  5. CD20+, CD5-, CD10-, CD103-, CD123-, Cyclin D1-, SOX11+
Board review answer #1
D. CD20+, CD5+, CD10-, CD103-, CD123-, Cyclin D1+, SOX11-

Reference: Lymphoma and plasma cell neoplasms - Nonnodal mantle cell lymphoma

Comment here
Board review question #2
A 60 year old woman was noted to have a mild absolute lymphocytosis on routine labs. A bone marrow biopsy was performed and based on the morphologic and immunophenotypic features a diagnosis of leukemic nonnodal mantle cell lymphomais is suspected. If this is correct, which cytogenetic abnormality should be detected on cytogenetic / FISH analysis?

  1. deletion 17p and t(8;14)(q24;q32) IGH-MYC
  2. t(8;14)(q24;q32) IGH-MYC
  3. t(11;14)(q13;q32) IGH-CCND1
  4. t(14;18)(q32;q231) IGH-BCL2
  5. trisomy 12
Board review answer #2
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