The t(11;14) translocation that juxtaposes the Cyclin D1 (CCND1) gene to the immunoglobulin heavy chain gene is considered a hallmark of mantel cell lymphoma (MCL).1 Immunohistochemical (IHC) analysis of CCND1 expression in formalin-fixed paraffin-embedded (FFPE) tissue sections of material from patients with suspected MCL is therefore the most obvious and effective diagnostic tool.2 We identified two cases of MCL based on morphology, expression of CD20, CD5 and SOX11 and absence of CD23 expression. Notably, both cases were negative for nuclear CCND1 staining by IHC (Figure 1G,J), despite being positive for the t(11;14)(q13;q32) translocation using fluorescence in situ hybridization (FISH, Figure 1H,L). Patient A was a 81-year-old female presenting with Ann Arbor stage IIIA. After six cycles of R-CHOP (rituximab, clorambucil, vincristine, prednisolone) and two additional cycles of rituximab, she achieved complete remission until last follow up 15 months after initial diagnosis. Patient B was an 87-year-old female with lymphadenopathy on both sides of the diaphragm, but staging remained incomplete. Due to comorbidities and patients' refusal of chemotherapy, rituximab mono-therapy was initiated until last follow up after two months. Surgical excision biopsies of an inguinal (patient A) and cervical (patient B) lymph node were submitted for consultation. In order to investigate if the lack of CCND1 immunostaining was due to low CCND1 expression, we performed quantitative PCR analysis of CCND1 expression in total RNA from patient A and patient B compared to CCND1 expression observed in two classical CCND1-positive MCL cases and two normal lymph nodes. The expression of CCND2 was also investigate as it is known that CCND2 can compensate for CCND1 in some cases.3 As shown in Figure 2A, both patients have CCND1 expression levels similar or higher to that observed in classical MCL samples and much higher than the expression observed in normal lymph nodes. These data are in line with the presence of a t(11;14) translocation in biopsies of the two patients and suggest that the lack of CCND1 immunostaining in patient A and patient B is not due to a defect in mRNA expression.
T(11;14)-positive mantle cell lymphomas lacking cyclin D1 (CCND1) immunostaining because of a CCND1 mutation or exclusive expression of the CCND1b isoform
Iaccarino I;
2018
Abstract
The t(11;14) translocation that juxtaposes the Cyclin D1 (CCND1) gene to the immunoglobulin heavy chain gene is considered a hallmark of mantel cell lymphoma (MCL).1 Immunohistochemical (IHC) analysis of CCND1 expression in formalin-fixed paraffin-embedded (FFPE) tissue sections of material from patients with suspected MCL is therefore the most obvious and effective diagnostic tool.2 We identified two cases of MCL based on morphology, expression of CD20, CD5 and SOX11 and absence of CD23 expression. Notably, both cases were negative for nuclear CCND1 staining by IHC (Figure 1G,J), despite being positive for the t(11;14)(q13;q32) translocation using fluorescence in situ hybridization (FISH, Figure 1H,L). Patient A was a 81-year-old female presenting with Ann Arbor stage IIIA. After six cycles of R-CHOP (rituximab, clorambucil, vincristine, prednisolone) and two additional cycles of rituximab, she achieved complete remission until last follow up 15 months after initial diagnosis. Patient B was an 87-year-old female with lymphadenopathy on both sides of the diaphragm, but staging remained incomplete. Due to comorbidities and patients' refusal of chemotherapy, rituximab mono-therapy was initiated until last follow up after two months. Surgical excision biopsies of an inguinal (patient A) and cervical (patient B) lymph node were submitted for consultation. In order to investigate if the lack of CCND1 immunostaining was due to low CCND1 expression, we performed quantitative PCR analysis of CCND1 expression in total RNA from patient A and patient B compared to CCND1 expression observed in two classical CCND1-positive MCL cases and two normal lymph nodes. The expression of CCND2 was also investigate as it is known that CCND2 can compensate for CCND1 in some cases.3 As shown in Figure 2A, both patients have CCND1 expression levels similar or higher to that observed in classical MCL samples and much higher than the expression observed in normal lymph nodes. These data are in line with the presence of a t(11;14) translocation in biopsies of the two patients and suggest that the lack of CCND1 immunostaining in patient A and patient B is not due to a defect in mRNA expression.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
