cyclin-d1 and Lymphatic-Diseases

The increasing use of immunophenotypic and molecular analysis in the routine evaluation of patients with lymphocytosis, lymphadenopathy, or other hematologic disorders has led to the identification of unexpected small clonal lymphoid populations. These clones, sometimes with disease-specific markers, such as the t(14;18), are especially challenging for the clinician because of their unknown biologic potential and uncertain clinical behavior. Study of these early lymphoid lesions is providing important clues to the process of lymphomagenesis, and may provide the rationale for preemptive therapy in the future. More and more, the hematologist/oncologist is consulted regarding otherwise healthy individuals with lymphadenopathy and/or lymphocytosis, and pathology reports that confound the referring internist or surgeon. The report does not name a malignant lymphoproliferative disorder, but is not completely "normal". Does the patient have a benign or malignant condition? How should they be evaluated? Is treatment indicated? These patients prove challenging for the consulting hematologist as well as the referring physician. In this review, we will focus on some of these scenarios and attempt to provide guidance for their management.

Topics: B-Lymphocytes; Bone Marrow Cells; Cell Transformation, Neoplastic; Cyclin D1; Disease Progression; Hematology; Humans; Immunophenotyping; Lymph Nodes; Lymphatic Diseases; Lymphocytosis; Lymphoma; Lymphoproliferative Disorders; Risk; Translocation, Genetic; Treatment Outcome

Topics: Adult; Antigens, CD20; Biomarkers, Tumor; Biopsy; CD5 Antigens; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Cyclin D1; Diagnosis, Differential; Early Diagnosis; Gene Expression Regulation, Neoplastic; Genes, bcl-1; Humans; Incidental Findings; Lymph Nodes; Lymphatic Diseases; Lymphoma, Mantle-Cell; Male; Translocation, Genetic

Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over-expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the effect of its expression on clinical behavior and outcome in B-cell Non-Hodgkin lymphoma (NHL). In this study, we investigated the expression of cyclin Dl in group of patients with NHL and correlated the results with the clinical and laboratory data. The degree of expression of cyclin Dl protein was evaluated by flow cytometry in a group of NHL patients (n = 46) and in normal control group (n = 10). Cyclin Dl over expression was detected in 10 out of 46 (21.7%) patients; they were 5/5-mantle cell lymphoma (MCL) (100%) and 5/28 large B-cell lymphoma (17.8%). All other NHL subtypes showed normal cyclin D1 expression. The clinical signs (hepatomegaly, splenomegaly and B-symptoms, clinical staging) and laboratory data (hemoglobin, white cell count (WBCs), platelet count, and bone marrow infiltration) were not significantly different between NHL subgroup with cyclin Dl over expression and that with normal cyclin Dl expression. Serum lactic dehydrogenase (LDH) levels and lymphadenopathy were significantly higher in NHL group with cyclin D1 over expression as compared to those without. Also, cyclin D1 over expression is associated with poor outcome of NHL patients. Cyclin Dl over expression was evident among all cases of MCL and few cases of large B-cell lymphoma. Cyclin Dl over expression might be used as adjuvant tool for diagnosis of MCL; has role in NHL biology and is bad prognostic index in NHL.

Topics: Adult; Aged; Case-Control Studies; Cyclin D1; Female; Gene Expression Regulation, Neoplastic; Humans; Lymphatic Diseases; Lymphoma, B-Cell; Male; Middle Aged; Prognosis; Up-Regulation

Mantle cell lymphoma (MCL) is a B-cell neoplasm with a relatively aggressive clinical course. There is a very small subgroup of patients who present with atypical lymphocytes in peripheral blood, with or without lymphocytosis, lymphadenopathy, or splenomegaly, and with an indolent clinical course. They frequently show mutated IgV(H) genes and CD5 negativity. We report an asymptomatic elderly patient who presented with a single submandibular lymphadenopathy. The biopsy showed immunophenotype and t(11;14)(q13;q32) consistent with MCL. The abnormal lymphoid population was also detected in peripheral blood and bone marrow. The patient has remained asymptomatic for 5 years without receiving any therapy. It is uncertain whether these cases represent an early-stage event in the development or an indolent form of MCL. The existence of such asymptomatic patients with an indolent clinical course should induce a strict clinical judgment in terms of therapeutic decisions.

Topics: Aged; Bone Marrow; Chromosome Aberrations; Cyclin D1; Diagnosis, Differential; Female; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lymph Nodes; Lymphadenitis; Lymphatic Diseases; Lymphocytes; Lymphoma, Mantle-Cell; Polymerase Chain Reaction

Chronic lymphoproliferative disorders sometimes can be difficult to classify. We report 4 cases characterized by large cells with distinct central nucleoli, reminiscent of prolymphocytic leukemia, but shown on further workup to represent mantle cell lymphoma. At initial examination, the patients had generalized lymphadenopathy, splenomegaly, and a leukemic blood picture. The peripheral blood showed many large cells with round to slightly irregular nuclei, single central nucleoli, and a fair amount of pale cytoplasm. The picture was not typical of prolymphocytic leukemia because of the presence of generalized lymphadenopathy and the large size of the circulating abnormal cells. Immunophenotypic study showed that the large lymphoid cells were CD5+ CD23- mature B cells with overexpression of cyclin D1, and cytogenetic study demonstrated the translocation t(11;14)(q13;q32) in 3 patients. Lymph node biopsy confirmed a diagnosis of mantle cell lymphoma, pleomorphic variant, in all 4 patients. This study documents the existence of an unusual leukemic form of mantle cell lymphoma with prominent nucleoli; the clinicopathologic features that distinguish it from other chronic lymphoproliferative disorders are discussed.

Topics: Aged; Bone Marrow; CD5 Antigens; Cell Nucleolus; Cyclin D1; Diagnosis, Differential; Fatal Outcome; Female; Humans; Immunohistochemistry; Immunophenotyping; Leukemia, Hairy Cell; Leukemia, Prolymphocytic; Lymph Nodes; Lymphatic Diseases; Lymphoma, Mantle-Cell; Male; Splenomegaly; Translocation, Genetic

Inflammatory myofibroblastic tumor (IMT) is composed of myofibroblasts, plasma cells, and lymphocytes. Cytokines are possibly involved in its pathogenesis. Human herpesvirus-8 (HHV-8) encodes cell cycle regulatory and signaling proteins. A combination of nested PCR with several negative controls and Southern blot methods showed the presence of HHV-8 DNA in seven cases of IMT. Additionally, strong expression was demonstrated by in situ hybridization in many tumoral nuclei. Most of the myofibroblasts in all of the cases were immunoreactive for human IL-6 and cyclin D1. These cytokines probably have a paracrine action and may sustain myofibroblastic growth. HHV-8 could play an essential role in triggering IMT development by a local reactivation of viral lytic replication. The relationship between HHV-8 and immunosuppression status as the only associated cause for tumorigenesis should be revised.

Topics: Adult; Aged; Cyclin D1; DNA, Viral; Female; Granuloma, Plasma Cell; Herpesvirus 8, Human; Humans; Interleukin-6; Leg; Lung Neoplasms; Lymph Nodes; Lymphatic Diseases; Male; Middle Aged; Soft Tissue Neoplasms