Diagnosis: Mantle Cell Lymphoma (MCL)
The immunophenotypic profile of CD19+, CD20+, dim CD5+, CD23-, CD38+, CD200-, FMC7+, and lambda-restricted light chain expression in the thyroid is diagnostic of mantle cell lymphoma, not chronic lymphocytic leukemia. 1
Key Diagnostic Features Distinguishing MCL from CLL
The immunophenotype presented represents the classic signature that distinguishes MCL from CLL:
- CD23 negativity is the most critical discriminator, as CLL characteristically expresses CD23 while MCL does not 2, 1
- CD200 negativity strongly argues against CLL and favors MCL, since CLL is typically CD200+ with bright expression in 100% of cases 1, 3, 4
- Dim CD5 expression is characteristic of MCL rather than the bright CD5 seen in CLL 1, 5
- FMC7 positivity supports MCL, as CLL is typically FMC7 negative or dim 2, 5
- Lambda light chain restriction is seen in 85% of MCL cases, whereas CLL more commonly shows kappa restriction 5
Mandatory Confirmatory Testing
Before finalizing the diagnosis, the following tests are essential:
- Cyclin D1 expression by immunohistochemistry or flow cytometry to confirm MCL, as cyclin D1 overexpression is mandatory for diagnosis 2, 1
- FISH for t(11;14)(q13;q32) to detect the hallmark translocation of MCL 2, 1
- SOX11 immunohistochemistry if cyclin D1 is negative but clinical suspicion remains high, to identify rare cyclin D1-negative MCL 2, 1
- Ki-67 proliferation index as this is a critical prognostic marker in MCL 2, 1
Complete Staging Workup Required
The following staging procedures must be performed:
- CT chest/abdomen/pelvis to evaluate for lymphadenopathy, splenomegaly, and hepatomegaly 2, 1
- Bone marrow aspirate and biopsy with flow cytometry and FISH 2, 1
- Complete blood count with differential to assess absolute lymphocyte count and cytopenias 1
- Gastrointestinal endoscopy is recommended given the thyroid involvement (stage III disease by Lugano classification) to detect asymptomatic GI involvement 2
- PET-CT scan for accurate staging 2
- LDH, uric acid, liver and renal function tests 2
- Hepatitis B and C serology before initiating therapy 2
Management Approach
MCL is an aggressive lymphoma requiring prompt treatment in most cases, unlike CLL which can often be observed. 1
Treatment Initiation
- Observation is rarely appropriate for MCL, even in asymptomatic patients, given its aggressive natural history 1
- Treatment should be initiated for stage III/IV disease or symptomatic stage I/II disease 2
Standard Treatment Regimens
For fit patients, intensive induction regimens include:
- R-HyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate and cytarabine) 1
- Bendamustine-rituximab as an alternative for patients unable to tolerate intensive chemotherapy 1
- VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone) 1
Consolidation and Maintenance
- Autologous stem cell transplant consolidation should be considered in younger, fit patients achieving remission 1
- Maintenance rituximab improves progression-free survival and should be administered 1
Critical Pitfalls to Avoid
- Do not mistake this for CLL based on CD5 positivity alone—the CD23-negative, CD200-negative, FMC7-positive profile excludes CLL 2, 1, 3
- Do not delay treatment with a "watch and wait" approach as appropriate for CLL, since MCL requires prompt intervention 1
- Be aware that aberrant CD20 expression can occur in thyroid carcinoma (seen in <10% of papillary thyroid cancers), but the complete B-cell immunophenotype with light chain restriction confirms this is a true B-cell lymphoma, not aberrant epithelial expression 6
- Ensure cyclin D1 or t(11;14) confirmation before finalizing MCL diagnosis, as this is mandatory 2, 1