engleski

Morphometry and Proliferation Parameters as Prognostic Indicators in Patients with Plasma Cell Neoplasms

Plasma cell neoplasms (PSN) are heterogeneous group of diseases that have a survival of a few months to several years depending on the type and stage of disease. The median survival of plasma cell leukemia is 10–12 months, monoclonal gammapathy of undetermined significance (MGUS) up to 10 years, and multiple myeloma (MM), 5–7 years. Morphological changes of plasma cells and proliferative parameters are significant predictors of survival in patients with PSN. Changes in the surface area, volume of plasma cells, and loss of circular shape and the size of the nucleus, increase in the number of nuclei in the cell, changes in the nucleus and cytoplasm ratio, are the characteristics of malignant cells that can be measured objectively by morphometry. Besides morphometric factors, proliferative parameters also have prognostic significance. Nuclear organizer regions (NOR) represent ribosomal DNA loop that is located in the nucleus. NOR’s are an easy way to distinguish the cells in the rest of those involved in cell cycle and are shown by the binding of Silver stained NORs (AgNORs) in the form of black dots of interphase nuclei. Increase in the number and size of the nuclei result in increased rRNA synthesis due to increased level of protein in tumor cells. Morphometric analysis was performed on standard smears stained with May Gru¨ nwald Giemsa and AgNOR silver staining, in 90 patients. Morphometric analyzes included the following parameters: cell volume, total area, minimum and maximum radius, length and width of the cells, the factor ofcompleteness and cell elongation and nucleocitoplasmic ratio, nucleus size, range, minimum and maximum radius of the nucleus and the number of nuclei in the cell. Proliferating cells were evaluated by measuring the AgNOR. We measured the number of AgNORs in the nucleus, the total area of AgNORs, and the relations between nucleus and AgNOR’s. The obtained parameters were compared with clinical, laboratory and cytogenetic parameters. Patients with a lower surface and diameter of plasma cells and smaller nucleocytoplasmic ratios have a better prognosis and longer survival. Also, patients with smaller nucleolar area, a small volume, more regular shape of nuclei and a smaller number of nuclei live longer. Number of nuclei in human cells correlates with clinical stage Durie and Salmon and International Scoring System (DS and ISS), the degree of plasma cell differentiation and cytogenetic analysis of chromosome deletion 13. AgNOR counts and total area AgNOrR were significantly associated with several recognized prognostic factors DS and ISS clinical stage, hemoglobin, creatinine, lactate dehydrogenase, C-reactive protein, calcium, albumin, total protein, erythrocyte sedimentation rate, degree of differentiation PC, percentage of PCs in the bone marrow, and cytogenetic detection of del 13, t(4.14). Patients with a greater number and total area of AgNORs had worse survival. AgNOR is an important prognostic parameter in patients with PSN. Morphological characteristics and proliferation of tumor plasma cells could be used by agreement and the proposed criteria as prognostic parameters in the time of diagnosis and select those patients who need more aggressive treatment.

morphometry; proliferation parameters; prognosis; plasma cell neoplasms

DOI: 10.1111/cyt.12004