Cytopathology and diagnostics of Warthin's tumour.

Warthin's tumour (WT) is a benign epithelial salivary tumour, one type of salivary adenoma. Histologically, WT is structured of two components, epithelial tissue that often lines cystic formations and lymphoid tissue in the tumour stroma. FNA is a reliable diagnostic approach in the diagnosis of salivary gland lesions allowing a highly accurate categorization of benign tumour-like lesions, benign tumours and malignant tumours. In the proposed Milan reporting system of salivary gland lesions, WT is categorized in the IVA group of benign neoplasms. Accurate cytological diagnosis is straightforward when three characteristic components are present: oncocytes, either isolated or associated in clusters, lymphocytes and lymphoid cells and often an inflammatory/necrotic-like substance. Also, specific features of scintigraphy and radiological imaging contribute to the diagnosis of WT. WT is categorized according to Seifert G. et al in 4 types, depending on the proportions of the epithelial component and lymphoid stroma. Differential cytopathological and pathohistological diagnosis include other salivary gland lesions with lymphoid, oncocytic epithelial and cystic components. In some cases, such as the metaplastic WT variant, there are additional cytopathological and histological diagnostic difficulties. Moreover, bilateral, multicentric or multiple and infrequently seen extra-salivary localizations of WT are associated with further cytopathological diagnostic difficulties. Also, a rare possibility of malignant transformation of the epithelial or lymphoid component of WT as well as possible association with other primary tumours remains a challenge in accurate cytopathological and histological diagnosis of WT.

Immunoexpression of 5-methylcytosine (5mc) in Bone Marrow Haematopoietic Cells in Patients with Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are biologically and clinically heterogenous groups of clonal haematopoietic stem cell diseases characterized by ineffective haematopoiesis and peripheral blood cytopenia, with a variable tendency to transform within acute leukaemia (AL). DNA hypermethylation and hypo-methylation are associated with cancer. Thus, the hypermethylation of DNA is essential for the molecular pathophysiology of MDS by inactivating genes involved in cell growth, differentiation and apoptosis. It was documented that the 5-methylcytosine (5mc) immunostaining score of BM haematopoietic mononuclear cells is higher in MDS patients than in a normal control group, and that the prognosis of the disease significantly correlated with global DNA methylation, age and IPSS score. In our study, we analysed the immunocytochemical expression of 5mc in bone marrow (BM) mononuclear cells from 13 MDS patients and a control group consisting of 13 patients with anaemia of chronic disease. The immunopositivity of 5mc BM mononuclear cells was statistically significantly higher in our MDS patients than in patients with anaemia of chronic disease. In most MDS patients (11 out of 13), a higher 5mc immunopositivity of BM mono-nuclear cells (above 10%) was found. Our results are in concordance with data from literature observing that a higher percentage of 5mc immunopositive BM mononuclear cells is documented in MDS patients.

A patient with prostate cancer and multiple myeloma-diagnostics and possible association of both diseases.

In this report, we describe a case of a patient with prostate cancer and multiple myeloma as the second metachronous malignant disease. To our knowledge, synchronous occurrence of bone marrow prostate cancer metastases and multiple myeloma-as it was found in the clinical disease course of our patient-has not been documented in the literature. Among other diagnostic procedures, cytomorphology and immunocytochemistry analyses contribute to detection of metastases of epithelial cells and synchronous plasma cell proliferation in bone marrow. Occurrence of multiple myeloma and prostate cancer in our patient adds to other similar reports and points to possible association between both diseases and also to other factors involved in the development of a second malignant disease. Further studies are needed to confirm and clarify this association, because prostate cancer is a relatively common malignant disease.

[Isolated central nervous system relapse of diffuse large B-cell lymphoma in the era of immunochemotherapy]. / Izolirani relaps difuznog B-limfoma velikih stanica u CNS u eri imunokemoterapije.

Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin's lymphoma. Standard chemotherapy is CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone). Addition of rituximab to standard chemotherapy regimen significantly increased the success of treatment and overall survival in DLBCL patients. The incidence of isolated relapse of lymphoma in the central nervous system (CNS) occurs in 1.2% to 10.4% of patients, and the outcome is almost always fatal. In this paper, we report the clinical course in a patient with advanced large B-cell lymphoma, who had been treated with immunochemotherapy but developed isolated CNS relapse of lymphoma shortly after achieving complete remission. There is still no consensus regarding the administration of prophylaxis for CNS relapse of lymphoma in patients with DLBCL, hence the question when and how to conduct the prophylaxis remains unresolved. The risk of CNS relapse of lymphoma in young patients with a low risk of death is decreased and it is classified as score 0 and 1 according to the International Prognostic Index (IPI), while the risk is increased in patients with score 2 to 5 according to the same classification. The risk of CNS relapse of lymphoma is increased if the disease is found in the head, neck, bone marrow or testicle. According to the results of some studies, the addition of rituximab to standard chemotherapy as well as intrathecal methotrexate CNS prophylaxis or prophylactic head irradiation do not reduce the risk of relapse of lymphoma in the CNS. Some studies suggest that high-dose intravenous methotrexate may help reduce the risk of CNS relapse in high-risk patients, but it needs to be confirmed in future researches.

Analysis of the influence of various factors on anemia in patients with lymphoid malignancies.

Anemia is a frequent complication of lymphoid neoplasms as a result of the disease and myelotoxic chemotherapy, and has a significant impact on treatment outcome, survival and quality of life. The aim of this study was to investigate clinical characteristics of anemia in lymphoid malignancies and to assess the need of anemia treatment in the context of modern therapeutic possibilities. Fifty-five patients (32 female and 23 male) with non-Hodgkin's lymphoma (NHL, n = 30), chronic lymphocytic leukemia (CLL, n = 8) and multiple myeloma (MM, n = 17) were included in the study. The influence of age, sex, type of malignancy and chemotherapy on the prevalence, severity and type of anemia before and after chemotherapy was analyzed. The prevalence of anemia was 51.02% before (A1) and 55.31% after (A2) chemotherapy. Women had a higher prevalence of anemia than men (63% vs. 43%), but the severity was higher in men at the beginning (103 vs. 99 g/L Hb) and at the end of treatment (101 vs. 89 g/L Hb). The highest prevalence of anemia was found in MM (69%), followed by NHL (44.4%) and CLL (40%) before chemotherapy, and in MM (68.7%), CLL (42.9%) and NHL (20.8%) after chemotherapy. The prevailing anemia was anemia of chronic disease (53.8%), followed by anemia due to multiple causes (anemia of chronic disease + iron deficiency anemia or anemia of chronic disease + hemolytic anemia; 30.7%), anemia due to iron deficiency (11.5%) and hemolytic anemia (7.6%). The prevalence of anemia as a consequence of the disease is high in lymphoproliferative disease, but there was no significant rise under chemotherapy, even showing a decline in NHL patients (44% vs. 21%), however, the severity of anemia increased. Since stage 1 anemia according to the WHO prevailed, only a small number of patients required transfusion therapy. About 27% of all patients had hemoglobin values <100 g/L during chemotherapy and could be candidates for erythropoiesis-stimulating agent treatment.

Klinefelter syndrome and acute basophilic leukaemia--case report.

Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia. We report a patient with acute basophilic leukaemia with 47, XXY karyotype in both the tumour and constitutional cells. Acute basophilic leukaemia is very rare disease comprising less than 1% of all acute myeloid leukaemias. Morphological characteristic of leukaemic blast cells is moderately basophilic cytoplasm containing a variable number of coarse basophilic granules. The most characteristic cytochemical reaction is metachromatic positivity with toluidine blue. Blast are myeloperoxidase negative. Also leukemic blasts express myeloid and monocyte markers. There is no consistent chromosomal abnormality identified in this leukaemia. This is the first reported case of acute basophilic leukaemia in patient with Klinefelter syndrome. In this article the medical history of the patient is given and the possible connection between Klinefelter syndrome and acute myeloid leukaemia is discussed.

Cytological detection of lymphoma in Douglas aspirate.

Except in primary effusion lymphoma (PEL), serous effusions with lymphomatous cells in non-Hodgkin lymphoma (NHL) are not frequently seen as first manifestation of disease. In NHL lymphoplasmacytic lymphoma (LPL) the spleen, lymph nodes, and bone marrow are frequently sites of disease and this type of NHL is usually associated with a serum paraprotein of IgM type accompanied by the clinical syndrome of Waldenström macroglobulinemia. Our patient with NHL LPL type presented in this report had less frequently seen involvement of gastrointestinal tract and clinically was first manifested as effusion in Douglas space. Cytological evaluation as well immunoanalyses of effusion in such cases is essential, and various ancillary studies, because of differential diagnostic problems of lymphomas in serous effusions, first include reactive lymphocytoses and small round-cell tumors (SRCT). In our patient, cytology of effusion revealed cytomorphologically atypical lymphomatous cells with plasmocytoid differentiation. Immunocytochemical and flow cytometry analysis confirmed lymphoid cell differentiation and pathohistological diagnosis of CD20(+) LPL was set after pathohistological analysis of resected ileum.