[Show abstract][Hide abstract] ABSTRACT: Introduction:
Primary adrenal non-Hodgkin's lymphoma (NHL) is a rare neoplasm with poor prognosis. On the other side, double-hit lymphomas with BCL2 and MYC translocation are characterized by advanced disease stage, extranodal and central nervous system involvements at presentation or disease progression.
We reported a 73-year-old male patient with double-hit primary adrenal lymphoma and preserved adrenal function, showing a favorable clinical course. Computed tomography of abdomen showed a 9 x 7 cm mass of the left adrenal gland. Laparatomy with left adrenalectomy was done and histological examination revealed diagnosis of a diffuse large B-cell NHL (DLBCL), non-GCB subtype. The patient was treated with 6 cycles of R-CHOP chemotherapy with reduced doses of doxorubicin because of the decreased left verticle ejection fraction. The patient was followed up regularly for 20 months with no evidence of tumor recurrence despite the inherently poor prognostic profile and double-hit phenotype of the disease.
R-CHOP chemotherapy in combination with adrenalectomy can be an effective first-line regimen for primary adrenal DLBCL, despite the inherently poor prognostic profile (non-GCB subtype, bulky disease, elevated lactate dehydrogenase and double-hit phenotype of the disease).
[Show abstract][Hide abstract] ABSTRACT: Apoptosis-related proteins might play an important role in the pathogenesis of lymphoma and sensibility to chemotherapy (CH) in patients with non-Hodgkin's lymphoma. We have analyzed the relationship between expression of two proapoptotic (CD95, caspase-3) and four antiapoptotic proteins (c-FLIP, bcl-2, survivin, and XIAP) and clinical outcome of patients with nodal diffuse large B-cell lymphoma (DLBCL).
We have analyzed lymph node biopsy specimens obtained from 78 patients with newly diagnosed nodal DLBCL. The expression of apoptotic parameters was analyzed using the standard immunohistochemical method (antibodies against caspase-3, CD95, c-FLIP, XIAP, survivin, and bcl-2) on formalin-fixed and routinely processed paraffin-embedded lymph node specimens. The expression of immunohistochemical parameters has been evaluated semiquantitatively as a percentage of tumor cells.
Immunoexpression of caspase-3, CD95, c-FLIP, survivin, XIAP, and bcl-2 has been found in 48 (61.5%), 39 (50%), 45 (57.7%), 41 (52.6%), 43 (55.12%), and 39 (50.0%) patients, respectively. The therapy response was achieved in 53 (67.9%) patients. Besides numerous clinical parameters, survivin and XIAP positivity along with CD95 negativity were found to be unfavorable factors for therapy response and shorter survival in univariate analysis. According to this finding, an 'apoptotic score' that includes unfavorable apoptotic parameters has been defined. In multivariate analysis, only International Prognostic Index (IPI) and apoptotic score remained independent prognostic predictors for the chance to reach the complete remission (P = 0.003 and P = 0.044, respectively) and longer overall survival (OS) (P = 0.002 and P = 0.046, respectively). Significantly, the better response to immunochemotherapy (ICH) in comparison with CH has been achieved in patients with expression of caspase-3, c-FLIP, and survivin and in patients without the immunoexpression of XIAP. In addition, ICH was superior to CH in both bcl-2-positive and bcl-2-negative patients.
The results of this study showed that the dysregulation of apoptosis can appear on different places of apoptotic cascade in DLBCL. Apoptotic score is a more useful tool in predicting therapy response and OS of patients with DLBCL than single apoptotic parameters and along with IPI could help to identify a high-risk group of newly diagnosed nodal DLBCL.
European Journal Of Haematology 03/2011; 86(3):246-55. DOI:10.1111/j.1600-0609.2010.01567.x · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Angiogenesis is an essential component in the growth and progression of multiple myeloma (MM). We studied the clinical significance of angiogenesis in patients with MM estimated by precise counting of the number of vessels (i.e. microvessel density, MVD) and compared these results with the results obtained using semi-quantitative grading of angiogenesis.
Fifty-nine newly diagnosed cases of MM were analyzed with respect to clinical features, laboratory findings, histological features, angiogenesis parameters, and response to treatment. Bone marrow microvessels were examined using immunohistochemical staining for CD34. Bone marrow angiogenesis was estimated by two different methods. The mean number of vessels per area in each sample was characterized as the MVD. Microvessels were counted manually on light microscopy in 3 hot spots at ×400 magnification. Semiquantitative estimation of angiogenesis was based on visual assessment of slides at ×100 magnification. Each slide was assigned as low, intermediate or high intensity of angiogenesis.
The median MVD was 15 vessels per 3 hot spots (range 1-89). Intensity of angiogenesis was assigned as low in 24 (40.7%) patients, intermediate in 17 (28.8%) and high in 18 (30.5%). Significant correlation between intensity of angiogenesis (estimated using both methods) and histological grade, extent of bone marrow infiltration, proliferative activity of myeloma cells and poor survival was found. Semiquantitatively assessed intensity of angiogenesis additionally correlated with clinical stage. There was a statistically highly significant correlation between MVD and semi-quantitatively estimated intensity of angiogenesis (p <0.001).
Tumor-associated angiogenesis is an important prognostic feature in MM and should be routinely done on bone marrow biopsies of these patients. Simple semiquantitative grading of angiogenesis can be recommended for daily practice, as an alternative method for complicated and time-consuming estimation of MVD.
Journal of B.U.ON.: official journal of the Balkan Union of Oncology 01/2011; 16(1):98-103. · 0.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary amyloidosis belongs to a group of monoclonal plasma cell disorders, characterized by extracellular deposition of immunoglobulin light chain fibrils in various tissues and subsequent multiorgan dysfunction.
We present a 51-year-old female with 2-years history of fatigue on exertion, oedema of face, abdomen and legs, bone pain and obstipation. After diagnostic procedures such as electrophoresis and immunoelectrophoresis of serum and urine proteins, immunohistohemical staining of bone marrow biopsy specimens and Congo red staining of rectal biopsy specimens, the patient received misdiagnosis of multiple myeloma and was referred to our hospital for further treatment. We reevaluated and complemented diagnostic procedures (ehocardiosonography and biopsy of subcutaneaus tissue with Congo red staining), and established diagnosis of primary amyloidosis. The therapy had started with intravenous (i.v.) melphalan and dexamethasone (totally eight cycles) and continued with peroral melphalan and i.v. dexamethasone. Stabilization of the disease was achieved after 35 months of the treatment.
The case of this rare and often fatal disease emphasizes significance of early diagnosis and, consequently, initiation of specific therapies which are indispensable to improve the disease prognosis.
[Show abstract][Hide abstract] ABSTRACT: The conflicting data are reported on the clinical significance of VEGF deregulation and intensity of angiogenesis in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of VEGF expression and microvessel density (MVD) in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of VEGF and MVD was analyzed using standard immunohistochemical method (antibodies against VEGF and CD34, respectively) on B5-fixed and routinely processed paraffin-embedded bone marrow specimens. MVD was estimated by counting the number of microvessels in three "hot spots" at 400x magnification. VEGF immunoreactivity was estimated on the basis of intensity and percentage of positive plasma cells. VEGF was expressed in 47/59 (79.7%) specimens. There was no significant correlation between VEGF overexpression and age, clinical stage, the extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, and albumins, the extent of bone marrow infiltration, histological grade, and proliferative activity index (measured with Ki-67 immunoreactivity). No significant difference was observed regarding the overall survival between VEGF-positive and VEGF-negative patients (29 vs. 34 months, P = 0.8). Median MVD was 15, ranging from 1 to 89 microvessels per three "hot spots". There was significant correlation between MVD and histological grade, the extent of bone marrow infiltration, and proliferative activity. Significant difference was observed regarding the overall survival between patients with low MVD (<15) and patients with high MVD (> or = 15) (46 vs. 22 months, P = 0.009; univariate analysis). The results of this study did not reveal clinical significance of VEGF overexpression in multiple myeloma. On the contrary, the extent of bone marrow angiogenesis is an indicator of biological potency of malignant clone and a predictor of poor survival in newly diagnosed myeloma.
Medical Oncology 05/2008; 25(4):451-7. DOI:10.1007/s12032-008-9066-y · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Carcinosarcomas are rare, malignant, biphasic tumors. We report the case of a 62-year-old man with gastric carcinosarcoma, along with its clinical, macroscopic and histopathological features. Macroscopically, a specimen of deformed stomach was obtained that measured 200 mm x 150 mm x 100 mm. A 150 mm x 100 mm x 50 mm exophytic tumoral mass (Borrmann type I) was found, which involved the posterior wall from the cardia to the antrum. Histopathologically, a mixed type of malignancy was revealed: an adenocarcinoma with intestinal metaplasia, with interposed fascicles of fusiform atypical cells and numerous large, rounded and oval cells. The tumor showed positive histochemistry for cytokeratin 18, epithelial membrane antigen, carcinoembryonic antigen, chromogranin A and vimentin. Liver metastases were diagnosed 8 mo postoperatively, and the patient died 4 mo later. A review of the available literature is also presented.
World Journal of Gastroenterology 12/2007; 13(41):5533-6. DOI:10.3748/wjg.v13.i41.5533 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although mutations of p53 are one of the most often acquired genetic changes in malignant tumors, these mutations are rare events in patients with newly diagnosed multiple myeloma (MM). Moreover, there are a few literature data about clinical significance of p53 overexpression in multiple myeloma.
The aim of our study was to evaluate the clinical significance of p53 immunoexpression in multiple myeloma.
A total of 58 patients with newly diagnosed MM (26 females and 32 males, mean age 62 years) were enrolled in the study. The diagnosis of MM was made according to criteria of Chronic Leukemia-Myeloma Task Force. Clinical staging was done according to Durie and Salmon classification (4 patients had disease stage 1, 15 patients stage II and 39 patients stage III). The histological grade and histological stage were determined according to predominant plasma cell morphology and volume of myeloma infiltration, respectively. Standard immunohistochemical analysis with p53 antibody in B5-fixed and paraffin-embedded bone marrow specimens was used to evaluate the expression of p53 in myeloma cells. The specimens were considered positive when 25% of plasma cells exhibited clear nuclear positivity.
Out of 58 patients, p53 expression was detected in 9 (15.52%). No significant correlation was found between p53 expression and clinical stage (I+II vs. III), beta2-microglobulin level (< or =6 mg/L vs. > 6 mg/L), histological grade (I vs. II+III), histological stage (<20% vs. 21-50% vs. >50%) and the extent of osteolytic lesions (< or =3 vs. >3 lesions). Median survival of patients with p53 immunoreactivity in =>5% of plasma cells was 10 months, whilst median survival of patients with p53 immunoreactivity in <5% of plasma cells was 36 months. However, such difference was not significant (p = 0.2).
The frequency of p53 immunoexpression in our group of newly diagnosed MM was relatively low. Although p53 immunoexpression was not associated with clinical and histological features of more aggressive disease, or with shorter survival, further investigations of larger group of patients will lead to final conclusions.
Srpski arhiv za celokupno lekarstvo 01/2007; 135(1-2):43-7. DOI:10.2298/SARH0702043M · 0.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoetic stem cell characterized by the presence of the Philadelphia (Ph) chromosome in more than 90% of patients. Cryptic or "masked" BCR/ABL gene rearrangements may be found in cases with a normal karyotype and in cases with the complex karyotype, in which typical t(9;22) is not visible at the microscopic level. Those rearrangements can now be detected by fluorescence in situ hybridization. Here, we report on a novel and complex Ph chromosome-negative CML case with a t(6;9)(p21;q34.1) in which the BCR/ABL fusion gene is located at 6p21.
Cancer Genetics and Cytogenetics 05/2006; 166(2):180-5. DOI:10.1016/j.cancergencyto.2005.11.008 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 63 years old male patient with systemic extranodal marginal zone lymphoma, most probably originating from mucosa associated lymphoid tissue (MALT) involving central nervous system (CNS) is presented. The usual site of origin of this type of lymphoma was not identified. The diagnosis was stated after neurosurgery according to histopathology, immunohistochemistry and additional haematologic examination. Postoperative therapy included local irradiation (30Gy) of rest tumor, combined by Rituximab-CHOP (R-CHOP) protocol, which resulted in complete remission lasting three years up to now.
Journal of neurosurgical sciences 04/2006; 50(1):9-12. · 1.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purine analogs, particularly pentostatin and cladribine, are highly effective in hairy cell leukemia (HCL). Both of these drugs induce responses in approximately 80-95% of patients. However, it is not yet determined if treatment with these drugs can induce second malignancies. Hodgkin's lymphoma is very rare as a second malignancy and there are only 3 reported cases concerning the association of this lymphoma with HCL. We describe a patient with longstanding HCL in complete remission after cladribine, in whom extranodal Hodgkin's lymphoma appeared 8 years after the diagnosis of HCL. Magnetic resonance imaging revealed diffuse intra-osseal neoplastic infiltration of the corpora of the whole spinal column and extra-osseal propagation from the fifth thoracic vertebra into the spinal canal with spinal cord compression. Histological and immunohistochemical analysis of the extradural tumor, which was completely excised, disclosed nodular sclerosis Hodgkin's lymphoma with typical Reed-Sternberg cells that were positive for CD30, CD15, bcl-6, Ki67, p53, EBV LPM-1 and IgG, and negative for CD45, CD20, DBA44, kappa, lambda light chains and IgM. In addition, immunohistochemical analysis of the bone marrow in 1999 showed infiltration with positivity for IgM and negative for kappa light chains and IgG. These findings (expression of different immunoglobulins and light chains on the cells) suggest an independent origin of these 2 B-cell neoplasms. After neurosurgery the patient received 6 courses of the MP-ABVD protocol and achieved a complete remission, which has lasted 16 months thus far.
Leukemia and Lymphoma 06/2005; 46(5):765-9. DOI:10.1080/10428190400027845 · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The article is concerned with incidence, clinical features, response to therapy, and prognosis of patients with hypocellular myelodysplastic syndromes. Bone marrow (BM) cellularity <30% (or <20% in patients >70 yr) was found in 24 of 236 (10.2%) trephine biopsies. Median age was 61 yr, with significant male predominance (M/F=3.0) At diagnosis, median hemoglobin was 83 g/L, median platelet and neutrofil counts were 31x109/L and 1.2x109/L, respectively. According to FAB classification, 17 patients had RA, 6 had RAEB, and only 1 had RAEB-t. Beside marrow hypoplasia, the most prominent PH finding was megakaryocyte hypoplasia and dysplasia, found in two-thirds of cases, each. Comparison between hypocellular and normo/hypercellular MDS cases regarding clinicopathological features showed younger age, more severe cytopenia, less blood and BM blast infiltration, MK hypoproliferation, and more pronounced stromal reactions in former cases. Karyotypic abnormalities were present in 12.5% hypocellular cases, in contrast to 44.6% normo/hypercellular cases (p=0.0025). Eleven patients were treated with supportive therapy alone, six with danazol or androgens, six with immunosuppressive therapy, and one with LDARAC. However, complete or partial response was achieved in only four patients treated with danazol or androgens. None of the patients developed leukemia. Eleven patients died, so marrow insufficiency was the main cause of death. Median survival was 33 mo for hypocellular MDS, and 19 mo for normo/hypercellular MDS (p=0.09). The results confirm the existence of hypocellular variant of MDS, which seems to have better prognosis than those patients with normo/hypercellular disease.
Medical Oncology 02/2005; 22(2):169-75. DOI:10.1385/MO:22:2:169 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diffuse large-cell B lymphoma of the pancreas is a rare disease, representing less than 1% of all non-Hodgkin's lymphomas and less than 0.9% of all malignant tumours of the pancreas. About 150 cases of the disease have been observed so far. The tumours are more frequent in the head of the pancreas then in other parts of the organ. They are usually larger (average size of 8 cm) and are non-resectionable. As a rule, exact diagnosis is based on the histology and the immunohistology of the specimen taken during open surgery performed for general diagnosis of the pancreatic tumour. Very rarely can a very reliable and experienced cytopathologist establish a proper diagnosis based on material obtained from a fine needle biopsy. The disease usually responds positively to immunochemotherapy according to protocol R-CHOP. Occasionally, additional radiotherapy may be required. We present two women, 66 and 49 years old, in whom a diagnosis of large-cell B lymphoma of the pancreas was established, based on the histology and the immunohistochemistry of a specimen taken during open surgery performed in order to remove pancreatic tumours, which turned out to be non-resectionable. After immunochemotherapy, the symptoms disappeared and the tumours shrank, in one patient after additional radiotherapy. The authors would like to point out the importance of a proper histological diagnosis, which permitted the application of immunochemotherapy alone or together with additional radiotherapy with at least temporarily favourable results.
Srpski arhiv za celokupno lekarstvo 01/2005; 133(5-6):276-9. DOI:10.2298/SARH0506276C · 0.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study we analyzed proliferative activity of myeloma cells and a possible correlation with selected clinical data, histological features and survival in 59 patients with newly diagnosed multiple myeloma (27 females and 32 males, mean age 62 years). Imunohistochemical method was applied using Ki-67 antibody on B5-fixed and paraffin-embedded bone marrow specimens to evaluate growth fraction of myeloma cells. Clinical staging was done according to the Durie-Salmon classification (4 patients had stage I disease, 16 patients stage II and 39 patients stage III). The number of Ki-67+ myeloma cells ranged from 1% to 36% (mean value 7%). In 39 of 59 patients (66.1%) number of Ki-67+ cells was less than 10% (cases with low proliferative index). Ki-67 expression significantly correlated with the clinical stage, beta2-microglobulin level, plasma cell morphology, volume of myeloma infiltration and the extent of osteolytic lesions. Patients with increased proliferative index (Ki-67+ cells > or = 10%) showed a significantly shorter survival compared to those with low proliferative index (14 months vs. 36 months, p = 0.023). However, this difference was not shown in multivariate analysis, particularly due to the high correlation between proliferative activity and plasma cell morphology and the volume of myeloma infiltration.
[Show abstract][Hide abstract] ABSTRACT: Pathohistological (PH) analysis is recommended as basic diagnostic procedure during the investigation of myelodysplastic syndromes (MDS).
The aim of this paper was to investigate diagnostic and prognostic significance of bone marrow PH features in patients with MDS, and its relation to cytological characteristics of bone marrow aspirate.
Cellularity, disorder of marrow histotopography, quantity of hematopoiesis lineages, cellular atypia, the amount of myeloblasts, and stromal changes were particularly analyzed in trephines of 236 patients with primary MDS.
In most cases (78.4%) hypercellular bone marrow was observed, although in 10.2% patients hypocellular subtype of MDS was diagnosed. Erythropoiesis dislocation was present in 64.7% patients, dislocation of MK-poiesis in 50.9% patients, while 61.3% had dislocation of granulopoesis (so-called ALIP phenomenon). In most cases three lineage hyperplasia was present, while relative hypoplasia of E- and MK-lineage was found in 1/4 cases, each, particularly in advanced MDS. Morphological features of dyseritropoiesis and dysmegakaryocytopoiesis were present in 42.5% and 75.7% cases, respectively. Different stages of reticulin and collagen fibrosis were observed in 55.5% patients, while 7.6% had hyperfibrotic subtype of MDS. Comparative analysis of cytological and histological features of MDS bone marrow showed positive correlation between two methods only in respect of estimation of eritropoiesis quantity, presence of dismegakaryocytopoiesis and "reactive" cells. The univariate analysis showed that MK- and G-lineage dislocation, quantity of E- and G-lineage, and presence of dysmegakaryocytopoiesis, were prognostic indicators for short survival and evolution of the disease in MDS patients. However, multivariate analysis showed that only G-lineage dislocation was independent prognostic variable for survival in MDS cases.
PH analysis is irreplaceable diagnostic procedure during MDS investigation, since it provides reliable information of cellularity, architectural disorganization, number of megakaryocytes and alterations of marrow stroma. In addition, PH analysis provides numerous important prognostic information.
Srpski arhiv za celokupno lekarstvo 01/2005; 133(3-4):162-9. DOI:10.2298/SARH0504162M · 0.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To present a patient diagnosed with pancreatic carcinoid that was extremely rare and produced an atypical carcinoid syndrome. We reported a 58-year old male patient who presented with long standing, prominent cervical lymphadenopathy and occasional watery diarrhea. Pathohistological and immunohistochemical examination of lymph node biopsy showed a metastatic neuroendocrine tumor, which was histological type A of carcinoid (EMA+, cytokeratin+, CEA-, NSE+, chromogranin A+, synaptophysin+, insulin-). Bone marrow biopsy showed identical findings. Primary site of the tumor was pancreas and diagnosis was made according to cytological and immunocytochemical analysis of the tumor cells obtained with aspiration biopsy of pancreatic mass (12 mm in diameter) under endoscopic ultrasound guidance. However, serotonin levels in blood and urine samples were normal. It is difficulty to establish the precise diagnosis of a "functionally inactive" pancreatic carcinoid and aspiration biopsy of pancreatic tumor under endoscopic ultrasound guidance can be used as a new potent diagnostic tool.
World Journal of Gastroenterology 11/2004; 10(19):2919-21. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumor is a form of mesenchimal neoplasm that may be present in all parts of gastrointestinal system. We are reviewing diagnostic and therapeutic algorithms for patient with diagnosed gastrointestinal neoplasm of small intestine, experiencing repeated episodes of painful bleeding from gastrointestinal trackt.
[Show abstract][Hide abstract] ABSTRACT: In a retrospective study of 236 patients with primary myelodysplastic syndromes (MDS), 130 cases (55.1%) revealed myelofibrosis in bone marrow biopsies. It was observed that fibrosis mostly occurs focally or patchy, and collagen deposits were found very rarely (only four patients). The histopathology of bone marrow biopsies revealed several differences between fibrotic and non-fibrotic MDS: cellularity is significantly higher, dysmegakaryopoiesis is more pronounced, plasmocytes and mast cells are more often increased, and disturbance of marrow topography (particularly of the MK- and G-line) can be found more frequently in MDS with myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelomonocytic leukemia. The frequency of abnormal growth of GM-progenitors was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly higher WBC, more frequent presence of immature granulocytes, and higher percentage of myeloblasts in peripheral blood and bone marrow in MDS with myelofibrosis compared to cases without myelofibrosis. Life expectancy was reduced to 13 mo, compared with 35 mo in MDS without fibrosis (p=0.00055). Time to leukemic transformation was 32 mo in MDS with fibrosis, compared with >56 mo in MDS without fibrosis (p=0.015). Myelofibrosis therefore seems to herald a poor prognosis.
Medical Oncology 02/2004; 21(4):325-31. DOI:10.1385/MO:21:4:325 · 2.63 Impact Factor