Classical mantle cell lymphoma (MCL) and 2 aggressive variants exhibited similar rates of negativity for the CD5 marker, with differentiation achieved by finding a classical type component and/or CD5 positivity, according to a new study.
However, authors of the study, published in Human Pathology, demonstrated through 2 case studies that cases of an MCL variant may be misdiagnosed as diffuse large B-cell lymphoma (DLBCL) unless certain types of additional testing are performed routinely.
MCL is a mature B-cell neoplasm that accounts for 3%-10% of non-Hodgkin lymphoma. It is considered highly aggressive and incurable, predominantly affecting middle-aged to elderly males. Not only are blastoid and pleomorphic variants challenging to diagnose from among classical MCL cases, but they can also be mistaken for DLBCL in instances of CD5 negativity, the authors said. Proper diagnosis is crucial for appropriate care.
Researchers from Japan decided to investigate the proportion of CD5 negativity in MCL and assess the diagnosis of aggressive MCL after encountering 2 rare cases of CD5 negativity in the blastoid variant.
They found that among 117 patients diagnosed with MCL, CD5 negativity was observed in 13% of cases with classical MCL (13 of 104) and in a similar percentage (15%, 2 of 13) for those with either the blastoid or pleomorphic variant.
Six patients required a differential diagnosis between the blastoid variant and classical MCL; classical MCL cells were found in the background of aggressive variant tumors or in other sites.
The researchers also assessed 1534 patients diagnosed with DLBCL, determining that 92% (1,413) were CD negative. However, the diagnoses of 2 patients (0.1%) were amended to the CD5-negative blastoid variant of MCL during relapses.
One case involved a 22-year-old female diagnosed with primary mediastinal large B-cell lymphoma who suffered 2 different relapses. The second time, which occurred 5 years later after initial diagnosis, suggested a transformation of low-grade B-cell lymphoma. Immunohistological (IHC) staining was used to determine if large lymphoid cells in a bone marrow biopsy were cyclin D1 positive since MCL is characterized by the t(11;14) translocation, implicating cyclin D1 (CCND1) in its pathogenesis. They were cyclin D1 positive, and small lymphoid cells were shown to be CD3-positive T cells.
A stomach biopsy resulted in diagnosis of blastoid variant MCL with CCND1 split by fluorescence in situ hybridization (FISH) analysis. Reexamination of earlier biopsies confirmed the presence of blastoid variant MCL as well. Chemotherapy and cord blood transplantation led to complete remission lasting 5 months.
The other case was a 72-year-old male with persistent sore throat and enlarged tonsils. After a relapse, he was diagnosed as classical MCL instead of CD5-negative DLBCL. An initial biopsy was later re-examined to find cyclin D1 and SOX11 positivity, and FISH demonstrated IGH/CCND1 fusion. The diagnosis was amended to blastoid variant MCL. Remission was achieved through bendamustine therapy.
Since the incidence in the study of CD5-negative variant MCL was close to the expected 0.6%-2.2% range, the researchers indicated it is unlikely there are many cases misdiagnosed as DLBCL. However, they called for cyclin D1 testing in all new DLBCL cases, with subsequent testing by IHC to determine the true incidence.
If IHC staining is performed in all DLBCLs, the authors said, 2.1% of cyclin D1-postiive cases may be detected, requiring further testing to exclude MCL.
Yamamoto N, Maeshima AM, Taniguchi H, et al. CD5-negative blastoid variant mantle cell lymphoma: A diagnostic dilemma, Hum Pathol. 2021. Epub ahead of print. doi:10.1016/j.humpath.2021.03.005.