<aside> 💡 CD5+, CD20+, CD43+, cyclin D1+, FMC7+, CD23**-/+, CD10-**/+ t(11;14)(q13,q23) → CCND1- IGH translocation (90~99%) SOX11+ (>90%); SOX11- → better prognosis

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Epidemiology

• ~5% of NHL in Western populations.
• Predominantly in the elderly (median age 60-68 years).
• 2- to 3-fold male predominance.

Clinical Manifestations

• The majority of patients present at an advanced stage (III or IV) with lymphadenopathy, hepatomegaly, splenomegaly (40%), and involvement of bone marrow and extranodal sites, especially the gastrointestinal tract.
  • B symptoms are present in 25% to 50% of patients.
  • 15% to 30% have or will develop a unique gastrointestinal presentation with multiple lymphomatous polyposis.
  • Bone marrow involvement is detected in 60% to 90% of patients, and up to 25% will have an overt leukemic phase, although most patients have a small circulating clone detectable by FC.
    • Cytopenias are typically present secondary to bone marrow involvement.
  • During the progression of the disease the tumor may infiltrate any tissue, including the central nervous system (9%), respiratory tract, breast, or orbit.
    • Involvement of the CNS is relatively more common with blastoid MCL and relapsed disease.
• Elevated LDH, uric acid and β2-microglobulin, and rarely hypogammaglobulinemia or monoclonal gammopathy.

Immunophenotype

• Most expressing CD5 and negative for CD10 and CD23, which helps distinguish MCL from follicular and small lymphocytic lymphomas.
  • Some cases of MCL may be CD5- or CD23+. LEF1 may help distinguish from variant CLL.
• Expression of nuclear cyclin D1 protein is found in >90% of cases and is considered the most reliable immunophenotypic marker in the diagnosis of MCL, although variant MCL with cyclin D2 or cyclin D3 expression also occur.
  • The cyclin D1 overexpression can also be seen in a subset of patients with ALL, Burkitt lymphoma, hairy cell leukemia and multiple myeloma.
  • In patients with cyclin D1-negative MCL, overexpression of cyclin D2, cyclin D3, or SOX11 can help in establishing the diagnosis.
  • Overexpression of SOX11, present in more than 90% of the patients with MCL, can also be seen in ALL, T-cell prolymphocytic leukemia, and Burkitt lymphoma.

Morphology

• Classical: a monomorphic proliferation of small-to medium-sized lymphoid cells with an irregular nuclear border, dispersed chromatin, and inconspicuous nucleoli.
• Blastoid variant: lymphoma cells have a high mitotic rate (20–30 per 10 high-power fields) and dispersed chromatin; frequently resembles lymphoblasts.
• Pleomorphic variant: cells have different forms including frequent large cells, pale cytoplasm, oval to irregular nuclear border, and often prominent nucleoli.
• Small cell variant: cells are small and round with clumped chromatin; frequently resembles small lymphocytic lymphoma (SLL).
• Marginal zone-like variant: this variant has clusters of marginal zone-like or monocytoid B cells with abundant pale cytoplasm.

<aside> 💡 Histologic transformation to large B-cell lymphoma does not occur.

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Subtypes