Breast MALT lymphomas: a clinicopathological and cytogenetic study of 9 cases.

Primary breast mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon and restricted diagnostic criteria should be used to exclude breast involvement by systemic lymphomas. The molecular pathogenesis of primary breast MALT lymphomas is not clear because of the rarity of the disease. Generally the molecular studies of MALT lymphoma in extranodal sites have shown the presence of different chromosomal aberrations, mutually exclusive with substantial differences in their frequency relatively to topographic localization. Few cases of breast MALT lymphomas in the literature have been assessed for MALT lymphoma-associated translocations and BCL10 expression, underlying their rarity in primary breast MALT lymphomas. In our study, we analyzed a series of nine cases of primary breast MALT lymphomas. FISH results showed evidence of MALT1 gene rearrangements in four primary breast lymphomas, in particular three cases with t(11;18)(q21;q21) and one case with t(14;18)(q32;q21). In addition, BCL10 gene rearrangement was not observed. There was no evidence of BCL10 gene translocation in any of the neoplasms assessed. Our data indicate that MALT1 gene rearrangements are not rare in primary breast MALT lymphoma in contrast with results of previous series. Finally, t(11;18) has been observed to be significantly associated with high intensity cytoplasmic BCL10 expression underlying cross-talk between MALT1 and BCL10 pathways in the pathogenesis of MALT lymphomas.

"CXCR4-CXCL12 and VEGF correlate to uveal melanoma progression".

Despite improvements in early diagnosis of uveal melanoma, prognosis is still poor due to metastases development. Neoangiogenesis and migration are requisites to metastasis promotion. Cross-talking between CXCR4-CXCL12 axis and the VEGF pathway was shown to favours tumour progression. CXCR4-CXCL12-VEGF expression was evaluated by immunohistochemistry in 53 selected cases of primary uveal melanoma and in liver melanoma metastases. CXCR4 protein was detected in 41.4 per cent cases, CXCL12 in 43.4 per cent cases and VEGF expression in 39.6 per cent cases. A significant correlation was found between CXCR4 and VEGF expression (p=0.011), CXCL12 and both tumour dimension and (p=0.006) and epithelioid-mixed cytotype (p=0.012). The two cases of uveal melanoma liver metastases in our series showed CXCR4 expression, weak immunoreactivity for CXCL12 and absent VEGF immunostaining. These data indicate that CXCR4-CXCL12 axis and its cross-talking with VEGF plays a role in uveal melanoma metastases and may be new prognostic markers in UMM. Moreover, these results suggest that targeted inhibition of CXCR4 could be introduced to control metastasis development in UMM.

Hepatic angiomyolipoma and intramural small intestinal schwannoma: a coincidence or a relationship?

We report a case of hepatic angiomyolipoma associated to a small bowel schwannoma in a 40-years old woman. Both lesions were asyntomatic. Histologically, hepatic angiomyolipoma showed oncocytic features and scanty adipose tissue, the tumor cells expressed desmin, smooth muscle actin, S-100 protein and HMB45. The tumor cells of intramural small intestinal mass were positive for S-100 protein and GFAP and negative for CD117, CD34 and desmin. To the best of our knowledge, no case of hepatic angiomyolipoma has been previously reported in association with intestinal schwannoma.

Concomitant occurrence of facial cutaneous and parotid gland metastases from rectal cancer after preoperative chemoradiotherapy.

BACKGROUND: Unusual sites of metastasis to the parotid gland and face are reported in patients with colorectal cancer, but the localization to both sites at the same time has never been described so far. CASE REPORT: Here, we describe the case of a 76-year-old woman with a T3N1M0 G2 rectal adenocarcinoma, treated with preoperative chemoradiotherapy performed at suboptimal dosages due to unacceptable toxicity. At the end of the program, the re-staging demonstrated the presence of metastasis in both the left parotid gland and subcutaneously on the frontal region of her face while the primary locoregional tumour manifestation was radiologically down-staged (reduction in N staging from N1 to N0). The patient did not respond to any other treatment and died due to disease progression 15 months after the diagnosis. CONCLUSIONS: Metastatic tumours in the parotid gland are uncommon with a higher incidence of primary sites of the head and neck. Parotid involvement of rectal adenocarcinoma is also extremely rare, and concomitant involvement of both the parotid gland and the face was not previously described. In this case, we cannot rule out the hypothesis that the delay of surgical removal of the primary tumour and/or a specific action of concomitant chemoradiotherapy on the tumour cell phenotype could promote cancer cell spreading to unusual sites.

CXC chemokine receptor 4 is expressed in uveal malignant melanoma and correlates with the epithelioid-mixed cell type.

PURPOSE: Although relatively rare, uveal melanoma is the most common ocular tumor of adults. Up to half of uveal melanoma patients die of metastatic disease. CXCR4, a chemokine receptor, is a prognostic factor in cutaneous melanoma involved in angiogenesis and metastasis formation. The aim of this study was to evaluate the expression of CXCR4 in uveal melanoma. METHODS: CXCR4 was detected by immunohistochemistry in 44 samples of uveal melanoma. Staining was categorized into three semiquantitative classes based on the rate of stained (positive) tumor cells: absence of staining, <50% of cell (+) and >50% (++). Correlations between CXCR4 expression, data on patient and tumor features were studied by contingency tables and the chi2 test. Time-to-event curves were studied using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test. Ninety-five percent confidence intervals (95% CI) of hazard ratios were also reported. RESULTS: Staining for CXCR4 protein was absent in 18 tumors (40.9%), present in <50% of cells in 19 (43.2%) and in >50% of cells in 7 (15.9%) tumors. CXCR4 expression correlated to the epithelioid-mixed cell type (P=0.030). No statistically significant relation emerged between CXCR4 expression, largest tumor diameter (LTD) and extracellular matrix patterns as evaluated through histological patterns stained with periodic acid-Schiff (PAS). Events occurred in 2 out of 18 patients (11.1%) with negative tumors (2 deaths), in 3 out of 19 patients (15.8%) with <50% of positive tumor cells (2 deaths and 1 occurrence of metastases) and in 1 out of 7 patients (14.3%) with >50% of positive tumor cells (1 occurrence of metastases). The cell type (P=0.0457) but not CXCR4 showed prognostic value at univariate analysis. CONCLUSION: This study shows that CXCR4 is commonly expressed in uveal melanoma and correlates with cell type a well-established prognostic factor.

Isolated hepatic involvement of cat scratch disease in immunocompetent adults: Enhanced magnetic resonance imaging, pathological findings, and molecular analysis--two cases.

Visceral involvement in absence of lymphadenopathy is a rare manifestation in cat scratch disease; hepatic granulomas are rare, representing 0.3% of systemic manifestations of cat scratch disease, and gallbladder extension is a singular case. The present article refers to 2 rare cases of visceral cat scratch disease in immunocompetent adults with hepatic granulomatous inflammation, caused by Bartonella henselae infection, with gallbladder involvement in 1 case and no lymphadenopathy. Histological features demonstrated the presence of inflammatory necrotizing granulomatous nonneoplastic process. Molecular studies (polymerase chain reaction) were performed to confirm the infectious etiology.

Prognostic significance of epidermal growth factor receptor expression in colon cancer patients undergoing curative surgery.

BACKGROUND: To investigate the role of epidermal growth factor receptor (EGFR) expression as a prognostic marker for prediction of cancer behavior and clinical outcomes in colon cancer patients undergoing potentially curative surgery. METHODS: EGFR determination using a commercially available immunohistochemistry kit was performed in tissues from 149 colon cancer patients receiving primary surgical treatment and in 25 normal colon mucosa specimens from noncancer patients. EGFR positivity was correlated in univariate and multivariate analyses with disease recurrence and survival. In addition, p27, p53, and vascular endothelial growth factor expression were assessed by immunohistochemistry in 104 patients and correlated with EGFR tumor expression and clinical outcome. RESULTS: EGFR expression was detected in approximately one third of colon cancer patients (53 of 149; 35.6%). In 126 curatively treated patients, EGFR expression was correlated with disease recurrence and worse survival in both univariate and multivariate analyses. In a multivariate model for predicting recurrence and survival, Dukes' staging, p27, and EGFR expression were the only independent covariates. In particular, in Dukes' A and B patients the 5-year survival probability was 96% for EGFR-negative and high p27 expression cases and was 30.7% for EGFR-positive and low p27 expression cases. CONCLUSIONS: EGFR expression was an independent prognostic indicator of disease recurrence and poor survival in colon cancer patients undergoing curative surgery. In the context of novel therapeutic options such as molecularly targeted therapies, these findings suggest that anti-EGFR drugs could be evaluated in the adjuvant treatment of EGFR-positive colon cancer patients.

p27 downregulation and metallothionein overexpression in gastric cancer patients are associated with a poor survival rate.

BACKGROUND AND OBJECTIVES: As a significant number of curatively treated gastric cancer patients will ultimately relapse, there is an urgent need to investigate new prognostic markers for identification of high-risk patients. In this study, we investigated the possible role of molecular markers involved in cell cycle regulation (B1 and D3 cyclins, and p27) and cell protection (metallothionein, MT) in predicting tumor behavior and clinical outcome in gastric cancer patients. METHODS: Analysis of the above indicators was performed by immunohistochemistry on 73 gastric cancer patient samples and 25 normal gastric mucosa specimens. RESULTS: Normal gastric mucosa cells displayed low expressions of B1 and D3 cyclins and MT, and intense p27 staining. Conversely, gastric tumor cells showed higher cyclin D3 and MT, and lower p27 expressions. B1 cyclin expressions were not different between normal and tumor tissue. p27 and MT expressions were altered in almost all cancer samples, and were strongly correlated with tumor progression. Advanced extent of the primary tumor, nodal metastasis, low p27, and high MT expressions were the best combination of variables for prediction of poor clinical outcome. Each marker predicted outcome better than staging based on tumor-node (TNM) system. Survival and recurrence rates decreased as molecular alterations increased. Finally, molecular profile determination correctly predicted the prognosis in patients with same TNM stage. CONCLUSIONS: p27 and MT expressions strongly correlated with clinical outcome allowing to identify an unfavorable group of patients that may benefit from tailored treatments. The role of B1 and D3 cyclins in gastric cancer remains to be elucidated.