Mantle cell lymphoma

Overview

•Mature B-cell non-Hodgkin lymphoma - aggressive but rarely curable with conventional chemotherapy

•5-7% of all NHL; median age 60-65 years; male:female ~3:1

•Most present at advanced stage (Ann Arbor III-IV)

Pathophysiology

•Defined by t(11;14)(q13;q32) - juxtaposes CCND1 (cyclin D1) next to IGH enhancer → constitutive cyclin D1 overexpression → uncontrolled G1-to-S phase entry

•Ki-67 >30% = aggressive disease with significantly worse prognosis

•TP53 mutation - chemotherapy resistant, very poor prognosis

•Blastoid variant - lymphoblast-like morphology, high Ki-67, worst prognosis among morphological subtypes

Presentation

•Painless generalised lymphadenopathy (cervical, axillary, inguinal)

•Splenomegaly - present in majority

•B symptoms - fever >38°C, drenching night sweats, weight loss >10% over 6 months (~50%)

•Peripheral blood involvement - lymphocytosis (leukaemic phase); may mimic CLL

•Bone marrow infiltration - anaemia, thrombocytopenia, neutropenia

•GI involvement - multiple lymphomatous polyposis of the colon (pathognomonic)

💡

If a patient presents with multiple colonic polyps on colonoscopy plus lymphocytosis, consider MCL (lymphomatous polyposis).

Investigations

•FBC/blood film - lymphocytosis, anaemia, thrombocytopenia; medium-sized lymphoid cells with irregular/notched nuclei; elevated LDH

•Flow cytometry - immunophenotype: CD5+, CD19+, CD20+, CD22+, CD23-, FMC7+, cyclin D1+

•FISH/cytogenetics - detects t(11;14)(q13;q32)

•CT chest/abdomen/pelvis - staging; PET-CT increasingly used

•Bone marrow trephine biopsy - almost universally positive

•Ki-67 on biopsy - critical prognostic marker; >30% = aggressive

🏆 Gold standard

•lymph node excision biopsy with histology/IHC - confirms cyclin D1 overexpression and architecture

Differential diagnosis

MCL vs key differentials

Feature	MCL	CLL	Follicular lymphoma
CD5	Positive	Positive	Negative
CD23	Negative	Positive	Negative
Cyclin D1	Positive	Negative	Negative
Translocation	t(11;14)	None	t(14;18)
Course	Aggressive, incurable	Indolent	Indolent

Management

•Indolent/leukaemic non-nodal MCL - watch and wait appropriate (treatment does not improve survival in asymptomatic disease)

•Fit for intensive therapy: induction with R-CHOP/R-DHAP (high-dose cytarabine-containing) → autologous stem cell transplant (ASCT)

•Unfit for intensive therapy: R-bendamustine or R-CHOP → rituximab maintenance

•Post-ASCT maintenance: rituximab 375 mg/m² every 2 months for up to 3 years - prolongs progression-free survival

•Relapsed/refractory: ibrutinib (BTK inhibitor), venetoclax (BCL-2 inhibitor), acalabrutinib (next-generation BTK inhibitor)

•TP53-mutated MCL - direct towards clinical trials/novel agents rather than conventional chemotherapy

⚠️

Monitor patients on ibrutinib for atrial fibrillation (recognised class effect), bleeding, and infections.

Prognosis

•Incurable with conventional chemotherapy in the majority; median OS historically 3-5 years

•Risk stratified by MIPI score (age, ECOG, LDH, WCC):

•Low MIPI - median OS >5 years

•Intermediate MIPI - median OS ~3-4 years

•High MIPI - median OS <2 years

•Ki-67 >30% - independently worse regardless of MIPI

•TP53 mutation - median OS often <1-2 years

•Blastoid variant - worst prognosis among morphological subtypes