What is mantle cell lymphoma?

Mantle Cell Lymphoma: Diagnosis and Characteristics

Mantle cell lymphoma (MCL) is a relatively uncommon subtype of lymphoid malignancy representing 5-7% of malignant lymphomas in Western Europe, with an annual incidence of 1-2/100,000 that has increased in recent decades. 1

Epidemiology and Clinical Features

• MCL is significantly more common in males than females with a 3:1 ratio 1
• Typically affects older patients and is often chemotherapy-resistant 2
• Presents with heterogeneous clinical behavior ranging from indolent to very aggressive forms 3

Pathophysiology and Molecular Biology

Defining Genetic Features

• The hallmark genetic abnormality is the t(11;14)(q13;q32) translocation 3
  • Results in fusion of cyclin D1 gene (CCND1) and immunoglobulin heavy chain gene (IGH)
  • Leads to overexpression of cyclin D1 protein

Diagnostic Markers

• Cyclin D1 overexpression is mandatory for diagnosis in most cases 1
• In rare cyclin D1-negative cases, detection of SOX11 may help establish diagnosis 1
• Immunophenotype typically includes:
  • CD5+, CD19/20+ expression
  • Detection of t(11;14)(q13;q32) translocation
  • FMC7 positivity (typically with CD5 positivity and CD23 negativity) 4

Diagnostic Approach

Preferred Specimen Collection

• Diagnosis should be based on a surgical specimen, preferably a lymph node biopsy 1
• Core biopsies should only be performed in patients without easily accessible lymph nodes
• Fine needle aspirations are inappropriate for reliable evaluation of risk factors 1
• In rare cases with leukemic manifestation only, bone marrow biopsy may be sufficient with additional diagnostic measures 1

Essential Diagnostic Workup

• Histological report according to WHO classification
• Ki-67 assessment (most established histomorphological risk factor) 1
• Immunohistochemistry for cyclin D1 overexpression
• FISH for t(11;14) translocation

Morphological Variants

• Most tumors have classic morphology of small-medium sized cells with irregular nuclei 1
• Variants include:
  • Small round cells (resembling chronic lymphocytic leukemia)
  • Blastoid variant (associated with poorer prognosis) 5

Staging and Risk Assessment

• Thorough initial staging is crucial, particularly in rare non-bulky stages I and II 1
• Initial workup should include:
  • CT scan of neck, thorax, abdomen, and pelvis
  • Bone marrow aspirate and biopsy
  • PET-CT scan (especially recommended in limited stages I/II)
  • Gastrointestinal endoscopy in limited stages or symptomatic patients 1

Prognostic Factors

• Poor prognostic factors include:
  • Blastoid morphology
  • TP53 aberrancy
  • Ki-67 >30% 5
  • Elevated lactate dehydrogenase (LDH)
  • Impaired performance status 1

Treatment Approaches

• Treatment strategies are variable and dependent on symptoms and patient fitness 6
• Frontline treatment often involves:
  • Anti-CD20 antibody (rituximab) with chemotherapy backbone
  • Consideration of autologous stem cell transplantation in eligible patients 7, 6
• For previously untreated MCL, acalabrutinib in combination with bendamustine and rituximab is indicated for patients ineligible for autologous hematopoietic stem cell transplantation 7
• For relapsed/refractory disease:
  • Targeted therapies like BTK inhibitors (e.g., acalabrutinib) 7
  • CAR-T therapies are established treatment options 3

Recent Advances and Future Directions

• Treatment paradigm is shifting away from primarily cytotoxic agents toward targeted therapies 2
• Emerging approaches include:
  • Non-covalent BTK inhibitors
  • Bispecific antibody therapy 3
  • Therapies targeting NF-κB signaling pathways 8

Common Pitfalls in Diagnosis

• Relying solely on classical histology without expert hematopathologist review 1
• Failing to perform immunohistochemistry for cyclin D1 overexpression
• Inadequate specimen collection (e.g., fine needle aspiration instead of excisional biopsy)
• Missing CNS involvement in high-risk cases 1