Sevasti Kamina

Increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas.

There is increasing evidence that bcl6 and CD10 expression may be related to apoptosis and cell cycle progression. Therefore, 79 cases of de novo diffuse large B-cell lymphomas were studied for the expression of bcl6 and CD10 proteins in relation to 1) the apoptotic index; 2) the proliferation-associated proteins Ki67, cyclin A, and cyclin B1; and 3) the expression of the bcl2, p53, Rb, p16, and p27 proteins. Expression of bcl6, CD10, and bcl2 proteins was found in 54/79 (68%), 28/79 (35%), and 47/74 (63%) cases, respectively. The bcl6/CD10 patterns were as follows: bcl6+/CD10+ (26 cases, 32%), bcl6+/CD10- (28 cases, 33%), bcl6−/CD10− (23 cases, 31%), and bcl6−/CD10+ (2 cases, 4%). Significant positive correlations were found between bcl6/Ki67 (r = .328, P = .003), bcl6/cyclin A (r = .265, P = .018), bcl6/apoptotic index (r = .327, P = .010), CD10/Ki67 (r = .296, P = .008), and CD10/apoptotic index (r = .397, P = .001). In addition, high expression of bcl6 showed significant correlation with negative (null/low) bcl2 expression (χ2 test, P = .002). The above findings indicate that increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas. The association between increased bcl6 expression and enhanced apoptosis might be due, at least in part, to the null/low bcl2 expression because previous in vitro data showed that bcl6 overexpression induces apoptosis accompanied by bcl2 and bcl-xl downregulation. Moreover, significant correlation was found between increased apoptotic index and the bcl6+/CD10+ pattern (t test: P = .014, Mann-Whitney test: P = .046). This finding and the positive correlation of the apoptotic index with bcl6 and CD10 expression may be related to previous results showing that the expression of these proteins has favorable effects on the clinical outcome of diffuse large B-cell lymphomas.

Diffuse large B-cell lymphomas with germinal center B-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl

The aim of this study was to analyze the relations between differentiation immunophenotypes and the status of apoptosis and proliferation in diffuse large B-cell lymphomas. Therefore, the bcl6/CD10/MUM1/CD138 differentiation immunophenotypic profiles were studied in relation to (a) the apoptotic index, (b) the apoptosis-associated bcl2 family proteins bcl2, bcl-xl, bax, bak, bad and bid, (c) the proliferation index (Ki67) and (d) the cell cycle proteins cyclin A, cyclin B1, cyclin D3, cyclin E, p53, Rb, p16 and p27 in 79 cases of diffuse large B-cell lymphomas. Two major differentiation immunophenotypic profiles were distinguished: the germinal center B-cell-like profile; 31 cases (bcl6+/CD10±/MUM1−/CD138−: 29 cases and bcl6−/CD10+/MUM1−/CD138−: two cases) and the nongerminal center B-cell-like profile (bcl6±/CD10−/MUM1+/CD138−); 48 cases. The expression of bax, bak and bid and the apoptotic index were significantly higher in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.045, 0.018, 0.003 and 0.034, respectively). In contrast, the expression of bcl-xl was significantly lower in the germinal center B-cell-like profile than in the nongerminal center B-cell-like profile (P=0.026). The expression of bcl6 and CD10 showed significant positive correlation with the expression of bax (r=0.659, P<0.001 and r=0.240, P=0.033, respectively), bak (r=0.391, P<0.001 and r=0.233, P=0.039, respectively) and bid (r=0.652, P<0.001 and r=0.238, P=0.035, respectively) and significant negative correlation with the expression of bcl-xl (r=−0.536, P<0.001 and r=−0.250, P=0.029, respectively). The expression of MUM1 showed significant negative correlation with the expression of bax (r=−0.276, P=0.014) and bid (r=−0.266, P=0.018) and significant positive correlation with the expression of bcl-xl (r=0.238, P=0.037). The above findings indicate that diffuse large B-cell lymphomas with germinal center B-cell-like immunophenotypic profile are associated with increased apoptosis status, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl.

Proliferation profile of classical Hodgkin's lymphomas. Increased expression of the protein cyclin D2 in Hodgkin's and Reed-Sternberg cells

There is accumulating evidence that Hodgkins and Reed–Sternberg cells of classical Hodgkins lymphomas (cHL) display multiple and concurrent alterations in different pathways and checkpoints of the cell cycle. However, the expression of cyclin D2 and its relation to other major cell cycle proteins has not been analyzed in cHL. The aim of the present study was to assess expression of cyclin D2, Ki67, cyclin A, cyclin B1, cyclin D1, cyclin D3, cyclin E, p53, Rb, p16 and p27 proteins in order to gain further insight into the proliferation profile of cHL. Overexpression of cyclin D2 in Hodgkins and Reed–Sternberg cells was detected in 64/89 (72%) cases of cHL. This finding, in view of recent in vitro data showing that constitutive activation of nuclear factor (NF)-kB could upregulate cyclin D2 expression in part via signal transducer and activator of transcription (STAT)-5a, suggests that induction of cyclin D2 expression may support the proliferation of Hodgkins and Reed–Sternberg cells. In addition, the present study showed that (1) increased p27 expression status was significantly correlated with higher levels of cyclin A expression (P=0.048) and (2) increased p53 expression status was significantly correlated with higher levels of cyclin A (P<0.001) and cyclin B1 (P=0.040) expression. The association between increased p27 and p53 expression status and higher expression levels of G2/M cyclins suggests that the impairment of the growth inhibitory activity of the p27 and p53 tumor suppressor pathways may promote the proliferation of Hodgkins and Reed–Sternberg cells.

Rectal Epstein-Barr virus-positive Hodgkin's lymphoma in a patient with Crohn's disease: case report and review of the literature.

We present the case of a 35-year-old man with Crohns disease diagnosed at the age of 27, several months after an operation for small-bowel adenocarcinoma. Seven years after the adenocarcinoma diagnosis, the patient presented with severe continuous anal pain and diarrhea. In parallel with antibiotic administration, the patient was given treatment with Infliximab, but without clinical symptom amelioration. Sigmoidoscopy and subsequent biopsies from an ulcerated rectal area supported the diagnosis of Epstein-Barr virus-positive (EBV(+)) primary Hodgkins lymphoma. Infliximab administration was immediately discontinued and the patient underwent oncological follow-up and began a course of chemotherapy. Only a few cases with primary gastrointestinal Hodgkins lymphoma in Crohns disease patients have so far been reported, including a variety of scenarios on the causal relationship including disease duration, presence of EBV, long-term immunosuppressive treatment and, recently, anti-TNFα administration.

Primary mantle cell lymphoma of the conjunctiva: a case report.

Primary non-Hodgkin’s lymphomas of the conjunctiva are uncommon. They are almost exclusively extranodal marginal zone B-cell lymphomas/mucosa-associated lymphoid tissue lymphomas. In this study, we report an extremely rare case of conjunctival mantle cell lymphoma in a 78-year-old man, presenting as a unilateral epibulbar mass.

Multiple brown tumors of the ribs simulating malignancy

Bone disease associated with primary hyperparathyroidism, known as osteitis fibrosa cystica, is now very rarely encountered, since the parathyroid disorder is most often diagnosed at the early stage of asymptomatic hypercalcemia. Here, we report the case of a patient with multiple pleural-based masses and hypercalcemia. which led to the presumptive diagnosis of malignancy. However, histological and laboratory data were consistent with the development of brown tumors of the ribs due to underlying severe hyperparathyroidism.

An unusual presentation of a patient with advanced prostate cancer, massive ascites and peritoneal metastasis: Case report and literature review.

We describe the case of a patient with prostate cancer, ascites, omental and bone metastases, an extremely rare clinical variant that warrants further investigation, and review the relevant literature.

Incidence of apoptosis and cell proliferation in multiple myeloma: correlation with bcl-2 protein expression and serum levels of interleukin-6 (IL-6) and soluble IL-6 receptor.

Abstract: We evaluated the in vivo incidence of apoptosis and cell proliferation in multiple myeloma (MM) and investigated the correlation of both cellular events with histological tumour stage and grade, bcl‐2 protein expression, serum IL‐6 and sIL‐6R. Material and methods: The TUNEL method was used to assess apoptosis and immunohistochemistry to assess the expression of proliferating cell nuclear antigen (PCNA) and bcl‐2 protein in 30 bone marrow biopsy specimens. The apoptotic index (AI) and proliferative index (PI) were defined as the percentage of TUNEL and PCNA positive plasma cells, respectively. Results: The mean AI was 0.162% and the mean PI 27.44%. A positive correlation between AI and PI was found (r = 0.44, P = 0.017). PI was also correlated with tumour grade (P = 0.015). The mean bcl‐2 protein expression was 70% and did not correlate with AI or PI, but was higher in specimens taken at first diagnosis than in specimens taken after response to treatment (P = 0.035). The mean serum IL‐6 and sIL‐6R values were 9.43 pg mL−1 and 47.27 ng mL−1, respectively. These parameters did not correlate with AI or PI. Conclusions: The results indicate that MM might be among the malignancies with very low incidence of apoptosis. Proliferative activity increased in parallel with tumour histological grade. A positive correlation between apoptosis and proliferation was observed, but the incidence of these two cellular events seems not to be related to the bcl‐2 protein expression and the serum levels of IL‐6 and sIL‐6R.

Diagnosis and endoscopic treatment of esophago-bronchial fistula due to gastric heterotopy

Heterotopic gastric mucosa patches are congenital gastrointestinal abnormalities and have been reported to occur anywhere along the gastrointestinal tract from mouth to anus. Complications of heterotopic gastric mucosa include dysphagia, upper gastrointestinal bleeding, upper esophageal ring stricture, adenocarcinoma and fistula formation. In this case report we describe the diagnosis and treatment of the first case of esophago-bronchial fistula due to heterotopic gastric mucosa in mid esophagus. A 40-year old former professional soccer player was referred to our department for treatment of an esophago-bronchial fistula. Microscopic examination of the biopsies taken from the esophageal fistula revealed the presence of gastric heterotopic mucosa. We decided to do a non-surgical therapeutic endoscopic procedure. A sclerotherapy catheter was inserted through which 1 mL of ready to use synthetic surgical glue was applied in the fistula and it closed the fistula opening with excellent results.

Immunohistochemical expression of cell cycle proteins in multiple myeloma

Despite advances in the basic understanding and development of novel agents, multiple myeloma (MM) remains incurable, with survival varying due to biological heterogeneity. Unlike normal plasma cells, myeloma cells retain their self-renewing potential, and although impaired apoptosis accounts for their accumulation in the bone marrow