(SRY-related HMG-box), which regulates multiple cellular transcriptional events, including
cell proliferation and differentiation, apoptosis,
and angiogenesis. 11 MCL expressing SOX 11
behaves more aggressively than MCL variants
lacking SOX 11 expression, and tends to accumulate more genetic alterations. 12 Moreover, lack
of SOX 11 expression characterizes a subset of
MCL that does not carry the t( 11; 14) translocation.
DIAGNOSIS AND STAGING
A 62-year-old man with a history of diabetes
mellitus and hypertension presents with cervical lymphadenopathy, fatigue, and early satiety
over the past several months. He is otherwise in
good health. His Eastern Cooperative Oncology
Group (ECOG) performance status is 1. On
physical examination, 3-cm lymphadenopathy
in the bilateral cervical chain is noted. Bilateral
axillary lymph nodes measure 2 to 4 cm. His
spleen is enlarged and is palpable at approximately 5 cm below the costal margin. A complete blood count reveals a total white blood cell
(WBC) count of 14,000 cells/µL, with 68% lymphocytes and a normal distribution of neutrophils.
Hemoglobin is 11 g/dL, and platelet count is
112,000/µL. The lactate dehydrogenase (LDH)
level is 322 U/L (upper limit of normal: 225 U/L).
Diagnosis of MCL requires review by expert
hematopathologists. 13 Whenever possible, an excisional biopsy should be performed for the
adequate characterization of lymph node architecture and evaluation by immunohistochemistry.
Aside from the characteristic expression of CD5
and CD20 and absence of CD23, MCL should
express cyclin D1, which reflects t( 11; 14). If cyclin
D1 is inconclusive or unavailable, fluorescent
in situ hybridization (FISH) for t( 11; 14) should
be performed. 8 Patients often have circulating
malignant lymphocytes, or leukemic phase MCL.
Flow cytometry of the peripheral blood can detect
traditional surface markers, and FISH can also be
performed on circulating abnormal lymphocytes.
For disease staging, bone marrow biopsy and
aspiration are required. Radiographic staging
using computed tomography (CT) scans and/or
positron emission tomography (PET) scans had
traditionally followed the Ann Arbor staging
system, but recently the Lugano classification
has emerged, which delineates only early or
advanced stage. 14 Gastrointestinal evaluation
of MCL with endoscopy and colonoscopy with
blind biopsies has been recommended to evaluate for the presence of lymphomatous polyps,
but this is not an absolute requirement. 15
At diagnosis, patients should undergo risk
stratification in order to understand prognosis
and possibly guide treatment. In MCL, the MCL
international prognostic index (MIPI) is used.
The MIPI is a prognostic tool developed exclusively for patients with MCL using data from 455
patients with advanced-stage MCL treated within
3 European clinical trials. 16 The MIPI classified
patients into risk groups based on age, ECOG
performance status, LDH level, and WBC count.
Patients were categorized into low-risk (44% of
patients, median OS not reached), intermediate-risk (35%, median OS 51 months), and high-risk
groups (21%, median OS 29 months). This is
done through a logarithmic calculation, which
can be accessed through online calculators (a
prototype example can be found at www.qxmd.
com/calculate-online/hematology/prognosis-mantle-cell-lymphoma-mipi). Cell proliferation
using the Ki-67 index was evaluated in an exploratory analysis (the biologic [“B”] MIPI), and also
demonstrated strong prognostic relevance. 16 Currently, treatment of MCL patients is not stratified
by MIPI outside of a clinical trial, but this useful
tool assists in assessing patient prognosis and has
been validated for use with both conventional
chemoimmunotherapy and in the setting of
autologous stem cell transplant (autoSCT). 16, 17