cyclin-d1 and Bone-Marrow-Neoplasms

Distinguishing mantle cell lymphoma (MCL), from low-grade B-cell lymphoma is important because MCL is clinically more aggressive and is treated differently. Though most MCL overexpress cyclinD1 (CCND1) and have a t(11;14)(q13;q32), MCL that are negative for CCND1 exist. Some have translocations involving cyclinD2 (CCND2) and either the immunoglobulin heavy chain or kappa light chain locus. We present a CD5-positive, CCND1-negative B-cell lymphoma with a novel translocation involving CCND2 and the immunoglobulin lambda (IGL) gene. A 64-year-old male underwent resection of a polypoid mass of the ileum. Histology showed atypical, medium-sized lymphoid cells positive for CD20, CD5, CD43, and CCND2 by immunohistochemistry, and negative for CCND1, CCND3, and p27. Fluorescence in situ hybridization was negative for CCND1 abnormalities, but demonstrated a CCND2/IGL fusion. Clinical workup revealed stage IV disease. Current diagnostic criteria are insufficient for subclassifying this case, highlighting the need for additional studies on CCND2-translocated B-cell lymphomas to guide therapy appropriately.

Topics: Bone Marrow Neoplasms; CD5 Antigens; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 22; Cyclin D1; Cyclin D2; Diagnosis, Differential; Gastrointestinal Neoplasms; Humans; Immunoglobulin lambda-Chains; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Male; Middle Aged; Translocation, Genetic

Mantle cell lymphoma (MCL) is recognized as a well-defined B cell neoplasm characterized by overexpression of cyclin D1 (CCND1), with "classical" and "aggressive" variant subtypes. A small-cell variant of MCL (small-MCL), resembling small lymphocytic lymphoma/chronic lymphocytic lymphoma (CLL/SLL), has been added to the World Health Organization classification. However, to the best of our knowledge, there have been no studies focusing on this neoplasm. In the present study, we analyzed 15 cases of CCND1-positive small-MCL, including immunohistochemical analysis of Ki-67 and CCND1 expression, and compared our findings with those of 151 cases of classical MCL. Morphologically, most small-MCL showed a diffuse growth pattern (76.9%), whereas others featured a very thin mantle zone pattern resembling a reactive follicle (23.1%). Bone marrow involvement and splenomegaly occurred significantly more frequently in small-MCL than in classical MCL (P < 0.05). Ki-67 expression in small-MCL was lower than in classical MCL (mean [± 2 SD] 12.5 ± 17.3% and 25.2 ± 25.5%, respectively; P < 0.001), but there was no significant difference in CCND1 expression (P = 0.2445). The 5-year survival rate in small-MCL was 83.3%. Although there was no significant difference in outcome between small-MCL and classical MCL (P = 0.287), only one small-MCL patient died of the disease. Thus, small-MCL constitutes a specific subset of indolent lymphoma with distinguishing features, possibly making a major contribution to the accuracy of therapeutic decisions. In addition, clinicians should be aware of the possible presence of small-MCL to avoid making a misdiagnosis of follicular hyperplasia or CLL/SLL.

Topics: Aged; Bone Marrow Neoplasms; Cyclin D1; Female; Humans; Ki-67 Antigen; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Male; Middle Aged; Splenomegaly

We report the case of a 62-year-old man who presented with splenomegaly, leukocytosis, anemia, and thrombocytopenia. Examination of the peripheral blood, bone marrow, and spleen revealed involvement by mantle cell lymphoma, with some blastoid features and an atypical phenotype. Spleen and bone marrow classical chromosome analysis followed by fluorescence in situ hybridization revealed a novel and unusual unbalanced variant of the t(11;14)(q13;q32) translocation, resulting in a complex derivative chromosome harboring the IGH/CCND1 fusion gene. This chromosome was designated as der(14)t(11;14)(q13;q32)t(11;14)(p11.1;p11.2).

Topics: Allelic Imbalance; Bone Marrow Neoplasms; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Cyclin D1; Genetic Variation; Humans; Immunoglobulin Heavy Chains; Lymphoma, Mantle-Cell; Male; Middle Aged; Oncogene Proteins, Fusion; Splenic Neoplasms; Translocation, Genetic

The distinction between mantle cell lymphoma (MCL) and other low-grade B-cell neoplasms is important because MCL has a more aggressive clinical course. In bone marrow biopsy specimens, this distinction can be especially difficult. We examined 70 bone marrow biopsy specimens involved by various B-cell lymphoid neoplasms to assess the utility of cyclin D1 immunostaining in distinguishing MCL from other B-cell lymphoproliferative disorders. We used a cocktail of two monoclonal anti-cyclin D1 antibodies and a heat- and sonication-induced epitope retrieval procedure. The neoplasms assessed included MCL (32 cases), small lymphocytic lymphoma/chronic lymphocytic leukemia (18 cases), follicular lymphoma (11 cases), hairy cell leukemia (5 cases), splenic marginal zone lymphoma (2 cases), and small lymphocytic lymphoma with plasmacytoid differentiation (2 cases). The diagnosis of MCL in bone marrow was confirmed by review of the original diagnostic biopsy specimens along with additional data, such as immunophenotypic or molecular studies. Most MCL (23/32; 72%) cases expressed cyclin D1 protein. In contrast, one case of small lymphocytic lymphoma/chronic lymphocytic leukemia (1/18; 6%) and one case of hairy cell leukemia (1/5; 20%) expressed cyclin D1 protein. These findings demonstrate that immunostaining for cyclin D1 protein expression is useful in distinguishing MCL from other B-cell lymphoid neoplasms in the bone marrow.

Topics: Antibodies, Monoclonal; Base Sequence; Bone Marrow; Bone Marrow Neoplasms; Cyclin D1; Cyclins; Diagnosis, Differential; DNA Primers; DNA, Neoplasm; Humans; Immunohistochemistry; Immunophenotyping; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Oncogene Proteins; Pathology, Clinical; Polymerase Chain Reaction