Intraepithelial T cells and tumor-associated macrophages in ovarian cancer patients.

The aims of this study were to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) in patients with familial ovarian cancer. Clinical and pathological information were retrieved from the Gilda Radner Familial Ovarian Cancer Registry (GRFOCR) in Buffalo, NY. Immunohistochemistry was performed on paraffin-embedded tissue specimens of GRFOCR participants using specific antibodies for CD3+, CD8+, CD25+, FOXP3+, CD68+, and CD163+. The correlation between the frequencies of TILs and TAMs and clinic-pathologic parameters were determined. Overall survival was determined using univariate and multivariate Cox proportional hazards models. High tumor grade correlated with higher frequencies of CD3+ (p = 0.019), CD68+ (p = 0.025), CD163+ (p = 0.018), and T(reg) (CD25+ FOXP3+) (p = 0.024) cells. Higher stage correlated with higher frequencies of CD163+ cells (p = 0.012). There were correlations between the frequencies of CD68+ and CD3+ (p = 0.029), between T(reg) and each of CD3+ (p = 0.002), CD8+ (p = 0.018), and CD68+ (p = 0.028) cells. In univariate analysis, age and T(reg) significantly predicted patient survival. In multivariate survival analysis, T(reg) frequency was the only significant predictor of prognosis in patients with familial ovarian cancer [HR = 0.92; 95% CI 0.87 - 0.98; p = 0.012]. We concluded that interaction between TILs and TAMs in familial EOC also exists, and tumors with high T(reg) frequencies have a more favorable outcome. Thus, therapeutic strategies to modulate tumor T(reg) infiltration could be beneficial for patients with familial ovarian cancer.

Fibrin-associated large B-cell lymphoma: part of the spectrum of cardiac lymphomas.

Cardiac lymphomas are rare, and the spectrum of pathologic features is not well defined. We encountered an unusual case of cardiac lymphoma residing within a presumed thrombus. To place such cases in context, we reviewed all cardiac lymphomas presenting to a large US cardiovascular medicine referral center during a 30-year period. A total of 14 cardiac lymphomas were identified, and these included 6 primary cardiac lymphomas (PCLs) and 8 lymphomas secondarily involving cardiac structures. Upon review, 3 of the PCLs were confirmed to be diffuse large B-cell lymphoma, not otherwise specified, involving the myocardium. The other 3 cases of PCL lacked myocardial invasion and showed lymphoma cells embedded in fibrin thrombus. Acute inflammation was not evident. These lymphomas presented in immunocompetent male individuals and involved either a prolapsed myxomatous mitral valve, a pseudomyxoma from the left atrium, or a thrombus arising in a synthetic aortic root graft. All 3 consisted of large atypical lymphocytes expressing a nongerminal center B-cell immunophenotype. Two cases were positive for Epstein-Barr virus (latency type III), but none demonstrated human herpes virus-8 latent nuclear antigen. No systemic disease was found at presentation or during follow-up. In our experience, fibrin-associated large B-cell lymphoma arising in the heart represents a substantial proportion of PCL. These lymphomas appear to represent an underrecognized variant of diffuse large B-cell lymphoma with favorable outcome. Further study is needed to understand their natural history.

From morphologic to molecular: established and emerging molecular diagnostics for breast carcinoma.

Diagnostics in the field of breast carcinoma are constantly evolving. The recent wave of molecular methodologies, both microscope and non-microscope based, have opened new ways to gain insight into this disease process and have moved clinical diagnostics closer to a 'personalized medicine' approach. In this review we highlight some of the advancements that laboratory medicine technology is making toward guiding the diagnosis, prognosis, and therapy selection for patients affected by breast carcinoma. The content of the article is largely structured by methodology, with a distinct emphasis on both microscope based and non-microscope based diagnostic formats. Where possible, we have attempted to emphasize the potential benefits as well as limitations to each of these technologies. Successful molecular diagnostics, applied in concert within the morphologic context of a patient's tumor, are what will lay the foundation for personalized therapy and allow a more sophisticated approach to clinical trial stratification. The future of breast cancer diagnostics looks challenging, but it is also a field of great opportunity. Never before have there been such a plethora of new tools available for disease investigation or candidate therapy selection.