MCL is diagnosed based upon detailed patient history, thorough clinical evaluation and a variety of specialised tests, including a biopsy of an affected lymph node or the bone marrow. Such testing is necessary to:
Because treatment may differ depending on disease stage, in-depth evaluation should occur at initial staging.
The risk assessment can help plan the next steps for treatment of MCL by dividing it into:
Indolent disease – watch and wait
A way to predict the outlook for patients with MCL was developed – The Mantle Cell International Prognostic Index (MIPI). It is a classification tool that enables patients to be grouped as low, medium or high risk.
Adapted from Vose et al. 2017.
The independent prognostic factors for shorter OS identified by MIPI were higher age, worse ECOG performance status, higher LDH, and a higher white blood cell count at diagnosis.
For each prognostic factor, 0–3 points were given to each patient to a maximum of 11.
Another strong predictor for the survival of patients with MCL is the Ki-67 proliferation index. It is the most important prognostic factor used in routine clinical practice. Ki–67 is a protein linked to cell proliferation, thus measuring Ki-67 provides an indication on the rate of cellular growth. The Ki-67 proliferation index is the percentage of mantle cell lymphoma cells that express Ki-67.
Ki-67 proliferation index (%).
Median survival (months).
The Ki-67 proliferation index is the % of mantle cell lymphoma cells that express Ki-67.
MIPI and Ki-67 can be combined to create the combined MIPI (MIPI-c). The MIPI-c provides a more accurate representation of the predicted survival for patients with MCL compared with MIPI and divides patients into four groups: low, low-intermediate, high-intermediate or high risk.
MIPI risk group (weights in MIPI-c)
Ki-67 index (weight in MIPI-c)
MIPI-c risk group (sum of weights)
|Low (0)||<30% (0)||Low (0)|
|Low (0)||≥30% (1)||Low-intermediate (1)|
|Intermediate (1)||<30% (0)||Low-intermediate (1)|
|Intermediate (1)||≥30% (1)||High-intermediate (2)|
|High (2)||<30% (0)||High-intermediate (2)|
|High (2)||≥30 (1)||High (3)|
For treatment purposes, MCL has been categorised into two major subgroups, which were included in the WHO 2016 update of lymphoid malignancies. The subgroups of MCL are distinct in clinical presentation and molecular features.
Patients with MCL may initially present in a primary care setting with persistent but non-specific symptoms, including swelling of lymph nodes, unintentional weight loss or night sweats. It should be noted that asymptomatic presentation accounts for around 10–20% of MCL cases.
At this stage, the primary care physician should take the patient’s medical history, perform a physical examination and request initial blood tests, including complete blood count and blood film. If lymphoma is suspected, a referral will then be made.
Unintentional weight loss
To confirm an MCL diagnosis, a biopsy or analysis of a sample may undergo a few tests.
A biopsy or sample can be taken from
Microscopic examination of involved lymph node or tissue is a key part of the diagnosis of MCL.
A diagnosis of MCL requires histopathological confirmation of lymph node infiltration. A part, or all, of an easily accessible, enlarged lymph node is removed.
The histological report should give the diagnosis according to the WHO classification and Ki-67, a proliferation marker, the most established histomorphological risk factor.
Most tumours have a classic structure of small-medium sized cells with irregular nuclei. However, malignant lymphocytes may present in a variety of forms.
In some cases, MCL cells can resemble other forms of B-cell malignancy in appearance, making diagnosis more challenging. Examples include
Smouldering nodal/extra-nodal MCL
Asymptomatic purely leukaemic non-blastoid MCL
Diagnosis should be based on a surgical specimen, preferably a lymph node biopsy. Core biopsies should only be carried out in patients without easily accessible lymph nodes (e.g. retroperitoneal bulk), keeping in mind the heterogeneity of MCL.
In rare cases with leukaemic manifestation only, a bone marrow biopsy may be sufficient if additional diagnostic measures are applied, immunophenotype (CD5+, CD19/20+), detection of t(11;14)(q13;q32) and overexpression of cyclin D1. Fine needle aspirations are inappropriate for a reliable evaluation of additional risk factors (cytology, cell proliferation).
A histological report should give the diagnosis according to the WHO classification and Ki-67 as the most established histomorphological risk factor.
Most tumours have a classic morphology of small-medium sized cells with irregular nuclei. However, the malignant lymphocytes may present with a spectrum of morphological variants, including small round (resembling chronic lymphocytic leukaemia), marginal zone-like, pleomorphic and blastoid cells.
In the updated WHO classification, a leukaemic non-nodal subtype has been characterised based on the clinical presentation usually with a more indolent clinical course. As only the minority of these cases is correctly diagnosed based on classical histology only, review by an expert haematopathologist is advised. In particular, additional immunohistochemistry for detection of cyclin D1 overexpression is mandatory.
In the rare cyclin D1–negative cases, detection of SOX11 may help to establish the diagnosis.
CBC=complete blood count; CT=computerised tomography; DNA=deoxyribonucleic acid; ECOG=Eastern Cooperative Oncology Group; ESMO=European Society for Medical Oncology; FACS=fluorescence-activated cell sorting; FISH=fluorescence in situ hybridisation; LDH=lactate dehydrogenase; NHL=non-Hodgkin lymphoma; PET=positron emission tomography; SUV=standardised uptake value; WBC=white blood cell; WHO=World Health Organization.
This site has been developed by Janssen-Cilag International NV. Janssen-Cilag International NV is the responsible editor of this document.
ITEM CODE: CP-233134 | DATE OF PREPARATION: June 2021