Renal cancer and Wegener's granulomatosis: a case report.

Wegener's granulomatosis (WG) is a systemic disorder characterized by necrotizing vasculitis involving the respiratory tract, and in most cases, the kidneys. The most common manifestation of WG in the kidneys is segmental necrotizing glomerulonephritis. The presence of a renal mass as a manifestation of WG is rare. We report a patient with WG in whom a CT scan revealed an infiltrating mass in the lower portion of the left kidney. After surgical exploration, we performed an open radical nephrectomy. Histopathology showed clear cell type renal cell carcinoma (RCC). RCC associated with WG has been reported in only a few cases, and in most of them, the diseases started simultaneously, suggesting common pathogenetic pathways. Long-term immunosuppressive treatment is a known risk factor in the development of malignancies, so occurrence of RCC in WG has been proposed as a side effect of cyclophosphamide treatment. Furthermore, it is important to make a differential diagnosis between RCC and pseudotumors in WG as they cannot be distinguished solely on basis of imaging findings. Due to the higher risk of urologic malignancies, more frequent checkups and screening of WG patients should be considered.

Primary non-hodgkin lymphoma of urinary bladder with nine years later renal involvement and absence of systemic lymphoma: a case report.

AIMS: Primary bladder non-Hodgkin lymphoma (PBNHL) is very rare, especially as extranodal B-small lymphocytic lymphoma (B-SLL). Also, late isolated renal manifestation of PBNHL is extremely unusual. We report a very rare type of extranodal B-SLL of bladder wall with extremely unusual late isolated renal involvement, clinically manifested by nephrotic syndrome and incipient renal failure. A CASE REPORT: A 56-year-old woman was presented with a solitary tumor of bladder wall, with history of dysuria and night sweating. A transvaginal needle biopsy of the tumor was performed, and diagnosis of primary extranodal B-SLL was made in the absence of bone marrow, lymph node, or blood involvement. She was treated with chemotherapy until the achievement of complete remission. Nine years later, she developed nephrotic syndrome. The renal biopsy revealed parenchymal lymphoma's involvement associated with glomerular lesion. Immunohistochemical analysis confirmed the same imunophenotype of lymphoma cells like in bladder wall nine years ago. Restaging procedure showed no evidence of disease elsewhere. CONCLUSION: To our knowledge, it is the first case of association of very rare primary bladder B-SLL with late isolated renal involvement.

Cytogenetics of agnogenic myeloid metaplasia: a study of 61 patients.

Agnogenic myeloid metaplasia (AMM) or idiopathic myelofibrosis is a chronic myeloproliferative disorder characterized by fibrotic bone marrow, extramedullar haematopoiesis, and a leukoerythroblastic picture in circulating blood. The cytogenetic data on AMM are scanty and no recurring chromosome abnormality has been associated with the natural course of this disease. Trisomy 1q, del(13q), del(20q), and trisomy 8, appear in about two thirds of patients with demonstrable chromosome aberrations. We report on the cytogenetic analyses of 61 consecutive patients with AMM studied at diagnosis. The metaphases could not be found in 10/61 (16.4%) patients, and chromosome studies were successful in 51 patients. Twenty-one patients (41%) had an abnormal clone, whereas 30 (59%) patients had a normal karyotype. Most frequent pathological findings included trisomy 8 (either alone or within a complex karyotype) in five patients, aberrations of chromosome 12 (translocation in two, monosomy in two, and trisomy in one patient), and aberrations of chromosome 20 (interstitial deletion in two, monosomy in two, and trisomy in one patient). We also detected aberrations of chromosome 13 (translocation in two and an interstitial deletion and trisomy in one patient each) and chromosome 18 (derivative 18 in two patients and a monosomy and deletion in one patient each). Three patients exhibited complex aberrations involving several chromosomes, sometimes with a mosaicisam. A near-tetraploid karyotype was observed in a single patient. Balanced translocations [t(2;16)(q31;q24), t(5;13)(q13;q32), t(12;13)(p12;q13), and t(12;16)(q24;q24)] were present in four patients. While the series of patients studied displayed chromosomal aberrations that are frequently observed in AMM, we found some new abnormalities (balanced translocations and polyploidy) that are rarely observed in AMM.

MUM-1 and bcl-2 Positive Primary Diffuse Large B Cell Non-Hodgkin's Lymphoma of the Colon.

Primary diffuse large B cell lymphoma (DLBCL) presents as a nodal and extranodal disease. The most common extranodal site is the gastrointestinal tract (GI), with the stomach most frequently involved, followed by the small bowel. Primary DLBCL of the large bowel accounts for 0.2%-1.2% of all colonic tumors. We present two patients who underwent radical resections of right colonic tumors. They were diagnosed with primary colonic DLBCL following histological and immunohistochemical testing of the excised tissues, and were determined as being in stage IIE of the disease. The tumors expressed CD20 markers. Both received multi-agent chemotherapy with combined immunotherapy and remain in complete remission at 4 and 5 years.

THE CASE OF T-CELL LARGE GRANULAR LYPHOCYTE LEUKEMIA PRESENTED AS TRANSFUSION DEPENDENT ANEMIA WITH SUSTAINED RESPONSE TO CYC- LOSPORINE A THERAPY: CASE REPORT.

CASE REPORT: A 41-year-old man presented with anemia, lymphocytosis and splenoniegaly. T-cell large granular lymphocyte leukemia was diagnosed based on lymphocytosis of T-cell large granular lymphocytes, characteristic inimunophenotype (CD)3⁺ CD8⁺, CD16⁺, CD57⁺) of the lymphocytes and clonally rearranged T-cell receptor genes. Therapy indication was transfusion-dependent anemia. Initial cyclosporine therapy and low-dose oral methotrexate failed to control anemia and lymphocytosis. Yet, a complete clinical and hematological. response (without molecuIlar remission) was achieved and sustained when cyclosporine was reintroduced into the therapy. CONCLUSION: Our case confirms that cyclosporine therapy is effective in treating T-celI large granular lymphocyte leukemia and suggests that indefinite treatment may not be needed to maintain the response.

JAK2V617F Mutation in a Patient with B-cell Chronic Lymphocytic Leukemia and Prefibrotic Primary Myelofibrosis.

INTRODUCTION: Secondary malignancies, particularly solid tumors, are common in patients with chronic lymphocytic leukemia (CLL), but association of myeloproliferative neoplasms and chronic lymphocytic leukemia in the same patient is very rare. CASE OUTLINE: We report of a 67-year-old man with B-cell chronic lymphoid leukemia (B-CLL) who developed primary myelofibrosis (PMF) nine years after initial diagnosis. Patient received alkylation agents and purine analogue, which can be a predisposing factor for the development of myeloproliferative neoplasms. JAK2V617F mutation was not present initially at the time of CLL diagnosis, but was found after nine years when PMF occurred, which indicates that B-CLL and PMF represent two separate clonal origin neoplasms. CONCLUSION: Pathogenic mechanisms for the development of myeloproliferative and lymphoproliferative neoplasms in the same patient are unknown. Further research is needed to determine whether these malignancies originate from two different cell clones or arise from the same pluripotent hematopoietic stem cell.

ALK-negative T-cell anaplastic large cell lymphoma associated with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) appear to have an increased risk of developing malignancies, especially lymphomas. We report the development of a systemic ALK-negative T-cell anaplastic large cell lymphoma, stage IIB, in a 53-yr-old Caucasian female with a 12-yr history of stable SLE. The patient responded poorly to chemotherapy and died 2 yr after diagnosis. Lymphomas that develop in patients with SLE and other autoimmune diseases are virtually always of B-cell origin. To our knowledge this is the first report of a T-cell anaplastic large cell lymphoma in a patient with SLE. This article discusses the association of SLE and lymphoma, with an emphasis on T-lymphoproliferative states.

c-FLIP does not correlate with response to immunochemotherapy treatment and outcome of patients with nodal diffuse large B-cell lymphoma.

UNLABELLED: Cellular FLICE-inhibitory protein (c-FLIP) is a critical anti-apoptotic regulator that inhibits apoptosis-inducing ligand, (TRAIL)-induced apoptosis as well as chemotherapy-triggered apoptosis in malignant cells. The present study was designed to investigate the clinical and prognostic significance of c-FLIP expression in patients with nodal diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy. METHODS: We have analyzed lymph node biopsy specimens, obtained from 60 patients with newly diagnosed nodal DLBCL treated with immunochemotherapy (R-CHOP or R-EPOCH). The expression of c-FLIP was analyzed using the standard imunohistochemical method on formalin-fixed and routinely processed paraffin-embedded lymph node specimens and evaluated semi quantitavely as a percentage of tumor cells. RESULTS: c-FLIP immunoexpression (>50% positive tumor cells) has been found in 28 (46.7%) patients, and observed as cytoplasmic staining. There was not significant difference in c-FLIP immunoexpression between GCB and non-GCB subtype of DLBCL (P=0.639). Besides, c-FLIP immunoexpression had no significant association with IPI, "bulky" disease, extranodal localization, haemoglobin, Ki-67 immunoexpression or other clinico-pathological parameters. c-FLIP positivity has no significant influence on therapy response and survival in patients with DLBCL (P=0.562 and P=0.093, respectively). Patients with c-FLIP overexpression did not relapse more often that patients without expression of this apoptotic protein (P=0.365). CONCLUSION: Our results suggest that c-FLIP immunoexpression can not be used as a prognostic factor in patients with nodal DLBCL treated with immunochemotherapy.

Angiogenesis and survival in patients with myelodysplastic syndrome.

Angiogenesis has been implicated in the pathogenesis and prognosis of myelodysplastic syndrome (MDS). In this study, we investigated the relationship between microvessel density (MVD), vascular endothelial growth factor (VEGF) expression, common morphological and clinical factors, and survival in patients with MDS. We examined the MVD of paraffin-embedded bone marrow sections from 70 MDS patients and 31 controls. VEGF expression was determined in 50 patients and 20 controls. The median MVD in MDS patients was significantly higher than that in controls (p = 0.025), whereas there was no difference in VEGF expression between MDS patients and controls. In univariate analysis, increased MVD was associated with a shorter survival time (p = 0.023). However, in multivariate analysis, MVD was not an independent predictor of survival. The VEGF expression did not influence survival in univariate analysis. Survival was independently influenced by platelet count (p = 0.0073), cytogenetic risk category (p = 0.022), and transfusion dependence (p = 0.0073). Neither MVD nor VEGF expression were predictors for progression to acute myeloid leukemia in univariate analysis. Progression to acute myeloid leukemia was independently influenced only by the cytogenetic risk category (p = 0.022). This study confirmed increased MVD in MDS. It does not support an independent prognostic role of angiogenesis in MDS.

[Diffuse large cell lymphoma and colon adenocarcinoma in patient with Waldenström's macroglobulinaemia].

INTRODUCTION: Waldenström's macroglobulinaemia is a rare B cell lymphoproliferative disorder characterized by lymphoplasmocyte bone marrow infiltration and monoclonal IgM gammopathy. In the majority of cases, Waldenström's macroglobulinaemia is a chronic disease with variable course. Therapy consists of alkylating agents, purine analogs and antiCD20 monoclonal antibody. In the literature, there have been descriptions of rare cases of progression of Waldenström's macroglobulinaemia to aggressive lymphoma, as well as secondary carcinoma in the patients after treatment of macroglobulinaemia. CASE OUTLINE: A 63-year-old patient was diagnosed with serum monoclonal IgM kappa gammopathy (Waldenström's macroglobulinaemia). Chemotherapy was applied and a good clinical and haematological response had been achieved. Ten years later, the patient was diagnosed with colon adenocarcinoma as a secondary malignancy, and operated on. Within one month, the patient rapidly developed a large neck tumour mass. Tumour biopsy revealed the diagnosis of diffuse large B-cell lymphoma with the expression of monoclonal lambda chain, which more likely pointed out to coexistence of two different B cell lymphoproliferative disorders, rather than the transformation of Waldenström's macroglobulinaemia to aggressive lymphoma. The patient was treated with chemotherapy following R-CHOP protocol, and clinical remission was achieved. Seven months later, despite the successful treatment of lymphoproliferative disorder, dissemination of adenocarcinoma led to the lethal outcome. CONCLUSION: The patient was diagnosed with a rare occurrence of three neoplastic diseases: Waldenstrom's macroglobulinaemia, colon adenocarcinoma and diffuse large B cell lymphoma. The possible mechanisms of the combined appearance of lymphoproliferative and other malignant diseases include the previous treatment with alkylating agents, genetic, immunomodulatory and environmental factors.

Immunohistochemical study of pathological alterations of peritoneum in patients with terminal renal insufficiency and on peritoneal dialysis.

BACKGROUND/AIM: During peritoneal dialysis (PD) an exchange of substances between blood and dialysate takes place through specific histological structures of peritoneum. Peritoneal double-layered serous membrane has, so far, mostly been studied with electron microscopy on experimental animals. The aim of this study was to assess integrity of peritoneal tissue in end-stage renal disease (ESRD) and PD patients using standard light microscopy and immunohistochemical methods. METHODS: Peritoneal tissue biopsies were performed on 25 persons: 8 healthy donors during nephrectomy, 9 ESRD patients upon insertion of PD catheter, and 8 PD patients upon removal of the catheter for medical indications. The samples were fixed and prepared routinely for immunocytochemical staining by standardized streptavidin biotin AEC method using a LSAB2 HRP kit (Dako, Denmark) for collagen IV and analyzed by light microscopy. RESULTS: We observed mesothelial detachment from lamina propria, duplicated basement membrane and much thicker blood vessel walls in ESRD and PD patients, compared to healthy subjects. Differences in histological structure, emphasized with immunostaining, indicated pathological alterations of peritoneal tissue in the renal patients. CONCLUSIONS: Imunohistochemistry can be used in studying histological alterations of peritoneal tissue in ESRD and PD patients. This method may indicate possible problems in filtration and secretion processes in this tissue.

[Clinical and prognostic significance of CD34 expression in bone marrow biopsies in myelodysplastic syndrome].

INTRODUCTION: The expression of CD34 antigen is increased in a substantial portion of MDS patients, particularly in high risk patients, which was associated with unfavorable survival in some studies. The aim of this study was to determine the CD34 expression in bone marrow biopsies and its prognostic significance in MDS patients and to analyze it in the context of different clinical, laboratory and prognostic parameters. MATERIAL AND METHODS: The study was conducted in 53 MDS patients and 20 controls with normal bone marrow. The CD34 expression was determined by CD34 monoclonal antibody and labelled streptovidin biotin peroxidase method. The positivity was determined by counting the 500 cells and it was expressed as percentage. RESULTS: Among the 53 MDS patients there were 37 males and 16 females with average age of 62. The average CD34 expression in the MDS group was 1.37%, the range being 0-8.8%, and in the control group 0.78%, the range being 0-1.60%. The difference was statistically significant (p < 0.05). There was a statistically significant difference in the CD34 expression comparing RA and CMML group and high risk and low risk MDS (p < 0.02). The median survival in the patients with the CD34 expression with less than 2% was 22 months, while it was 6 months in the patients with the CD34 expression over 2% (p < 0.05). In a multivariate analysis the CD34 expression together with the karyotype and transfusion dependence had a statistical significance (p < 0.05). CONCLUSION: The CD34 expression in bone marrow biopsies is higher in the MDS patients comparing with the controls as well as in high risk comparing with low risk patients. The cutoff 2% seems to have a prognostic significance.

[Prognostic factors in patients with diffuse large B-cell lymphoma].

Diffuse large B-cell lymphoma is an aggressive type of lymphoma, potentially curable, with heterogeneous prognosis. The aim of this study was to determine prognostic significance of clinical, laboratory and immunohystochemical factors. The retrospective study was done in 50 patients with diffuse large B-cell lymphoma. The following parameters were investigated: demographic (age, sex), clinical (time to diagnosis, B symptoms, clinical stage), laboratory (erythrocyte sedimentarion rate, haemoglobin, lactate dehydrogenase, albumine), standard and revised international prognostic index, and immunohystochemical parameters, cluster designation 20, B-cell-2, and Ki67 expression. There were 20 females and 30 males, their average age being 54 (22-83) years. The majority of patients had advanced disease: B symptoms in 76%, III and IV stage in 78%, increased lactate dehydrogenase in 74%, high risk standard international prognostic index in 62% of patients. B-cell leukemia/lymphoma 2 expression was found in 57%, and high Ki67 in 62% of patients. Rituximab-Cyclophosphamnide, Hydroxydaunorubicin, Vincristine, Prednisolone and Rituximab-Cyclophosphamide, Hydroxydaunorubicin, Vincristine, Etoposide, Prednisolone were conducted in 72% (36), and Cyclophosphamide, Hydroxydaunorubicin, Vincristine, Prednisolone and Cyclophosphamide, Hydroxydaunorubicin, Vincristine, Prednisolone-like treatment in 28% (14) of patients. The complete remission rate was 74%, and the partial remission rate was 9%. A significant difference in survival was found between low intermediate and high intermediate S-IPI risk groups, good and bad risk R-IPI, and patients with complete remission and patients with other treatment responses. The other parameters, including Bcl-2 and Ki67 expression, and type of treatment did not show significant influence on survival. The expected five-year survival was 69%. Our results have shown that international prognostic index, and complete remission status have prognostic significance in diffuse large B-cell lymphomas.

[Significance of the initial cytomorphological and immunocytochemical findings and the correlation with the International Prognostic Index for the survival in patients with non-Hodgkin's lymphoma].

BACKGROUND/AIM: Fine-needle aspiration biopsy is a quick, economical, and safe initial method in managing a patient with suspected lymphoma. According to a few reports on this preoblem, the aim of this study was to compare histological findings to cytomorphological ones in needle aspirates. We also compared these findings to the overal survival (OS) time. METHODS: We analyzed the fine-needle aspiration biopsies of peripheral lymph nodes, and the International Prognostic Index (IPI) in 81 patients with non-Hodgkin's lymphoma (NHL). We put these findings into correlation with OS time. RESULTS: According to the International Working Formulation (IWF) criteria, the dominant cell population was asfollows: 18 patients had the small cell population, 21 patients had small cleaved cells, 18 patients had the mixed cell population, 21 patients had large cell population, 2 patients had Burkitt lymphoma type, and 1 patient had the dominant lymphoblasts. On presentation, 32 patients had a low IPI index, 32 patients had a low intermediate, and 17 patients had a high intermediate IPI. We confirmed the statistical significance (Kaplan-Mayer) of cytomorphology (p = 0.013) and IPI index (p = 0.016) for survival time. During a 48-month follow-up, OS was 37.2 months for the patients with the dominant small cells, and 32 months for the patients with small cleaved cells (PH equivalent to indolent NHL). For the patients with the dominant mixed cell population, large cell population and Burkitt limphoma cell, OS were 17, 14.4, and 9.3 months, respectively (PH equivalent to aggressive NHL). Patients with low IPI had the highest OS, 36 months for the low intermediate and only 11.6 months for the high intermediate IPI index. CONCLUSION: We concluded that an initial cytological and clinical profile of patients with NHL, might give a quick and relevant information for planning an adequate therapy.

[Hemangioma of the spleen].

Although the most frequent benign tumors of the spleen, hemangiomas are very rare, much rarer than hemangiomas of the liver. They manifest as localized (either single or multiple) or diffuse lesions, vary from solid to cystic, histologically from capillary to cavernous. Usually, they are small in size (1-3 cm), rarely larger and very rarely of large size. A 67-year old woman admitted to Institute of Hematology, CCS, for investigation of the left upper abdominal pain, loss of appetite, loss in weight and malaise. As the investigation showed a number of hypoechogenic lesions within the enlarged, diffusely non-homogenic spleen, splenectomy was indicated. The spleen weighing 2600 grams was removed, in which the number of lesions histologically corresponded to hemangioma of the spleen. Postoperative recovery was uneventful. The patient has remained symptom free more than two years after surgery.

[Hodgkin's and Reed-Sternberg cells in the peripheral blood of a patient with advanced stage Hodgkin's disease]. / Hockinove i Red-Sternbergove celije u perifernoj krvi bolesnika sa odmaklim stadijumom Hockinove bolesti.

The occurrence of abnormal Hodgkin's and Reed-Sternberg cells in the peripheral blood in a patient suffering from Hodgkin's disease has been noticed exceptionally rare in a previous period, and especially rare in last ten years primarily due to successful treatment of this disease. The presence of atypical mononuclear cells in peripheral blood which cytomorphologically resembled Reed-Sternberg cells was registered in 8 patients till 1966. During the last decade, the presence of atypical mononuclear cells in the peripheral blood was used for their isolation, cultivation, and detailed immunophenotypic and genetic analysis. The analysis of mononuclear cells in rare patients with Hodgkin's disease was established that they belong to the B-lymphoid cells with expression of CD30 and CD15 antigens. The examination of presence of Hodgkin's cells in the peripheral blood of patients with Hodgkin's disease is important for patients with advanced stage of the disease in which autologous stem cell transplantation and high dose chemotherapy is planned. The authors present a 33-year-old patient, who noticed enlarged neck lymph nodes in September 2000, high temperature and loss in weight. On physical examination enlarged neck lymph nodes 5 x 8 cm and hepatosplenomegaly were found. There was anemia and thrombocytopenia, and normal WBC count with 24% of lymphoid elements in differential formula. On histologic examination of lymph nodes, Hodgkin's disease, type nodular sclerosis with mixed cellularity was found. Histology of bone marrow showed nodal lymphomatous infiltration. Immunohistochemistry with monoclonal antibodies of concentrate of peripheral blood cells showed expression of CD30+ and CD15+, immunophenotypically and morphologically matching Reed-Sternberg cells. Cytogenetic analysis of mononuclear cells of the bone marrow showed normal karyotype. The patient was in clinical stage IV/V of the disease and chemotherapy with 9 cycles of ABVD + Mp protocol was applied. He is still in remission.