CD5 Negative Mantle Cell Lymphomas: a trivial aberration or a variation of significance?

Introduction:
Mantle cell lymphomas are a category of B-cell Non-Hodgkins lymphomas which have an aggressive clinical course. On Immunohistochemistry (IHC) evaluation, these usually show positivity for CD5, Cyclin D1 and SOX 11. The pathognomic cytogenetic abnormality seen in most cases (upto 95%) is the t(11;14)(q13;q32), leading to the fusion of IGH and CCND1 genes which is considered a primary event. CCND2 rearrangements are detected in cases which are negative for Cyclin D1. On IHC, a very small proportion (upto 5%) of cases show negativity for CD5. With more information being brought to forefront about the prognostic subtypes of Mantle cell lymphomas, we evaluated the subgroup showing negativity for CD5 on IHC, to decipher it's cytogenetic profile and wherever possible, clinical behaviour.
Methods:
5 cases of CD5 negative Mantle cell lymphomas were assessed for their IHC and Cytogenetic profile. IHC staining was performed on Formalin Fixed Paraffin Embedded (FFPE) blocks following standard operating procedure (SOP) on Ventana BenchMark XT platform with satisfactory controls. This was followed by Fluorescence in situ hybridization (FISH) studies on the FFPE, as per manufacturer's protocol and SOP.
Results:
Cyclin D1 was positive in 4 of the 5 cases, while all showed positive expression for SOX11 on IHC. FISH studies detected IGH/CCND1 fusion product in 4 of 5 cases with the case which showed negativity for Cyclin D1 on IHC, also showing negativity for t(11;14). All cases harbored significant variation from standard fusion pattern, with most suggesting a complex clonal evolution.
Discussion:
With many recent studies suggesting prognostic variation for Mantle cell lymphoma cases especially those showing negativity for CD5 and SOX11, we aimed to evaluate the CD5 negative cases in detail for their cytogenetic patterns. In all our cases the cytogenetic profile of these tumors showed complex variations, in many instances hinting towards a divergent clonal evolution of a common precursor. While the clinical management of these cases was based on current standard protocol, it would be imperative to evaluate this subgroup more in the future given the regular nature of genetic complexity detected, for its biological behaviour and if needed, a different approach to management.