Integrated Genomic DNA/RNA Profiling vs Fluorescence in Situ Hybridization in the Detection of MYC and BCL2 (and BCL6) Rearrangements in Large B-Cell Lymphomas: Updates Amid the New WHO Classification of Lymphoid Neoplasms.

OBJECTIVES: Large B-cell lymphomas (LBCLs) are a heterogeneous group of lymphoid neoplasms whose molecular and cytogenetic profile has predictive and prognostic implications. The concept of double-hit lymphomas (DHLs) was recently updated in the fifth edition of the World Health Organization classification, with the exclusion of MYC and BCL6 rearranged tumors from the group. Now, DHLs are referred to as diffuse large B-cell lymphoma/high-grade B-cell lymphoma with MYC and BCL2 rearrangements. Fluorescence in situ hybridization (FISH) is the current gold standard for detecting rearrangements in LBCLs, but comprehensive genomic profiling (CGP) has recently been suggested to be at least as accurate as FISH in classifying these neoplasms and providing additional genetic information. METHODS: We analyzed a cohort of 131 patients in whom FISH and CGP studies were performed as part of our normal clinical workflow and compared the effectiveness of FISH and CGP in detecting these clinically relevant rearrangements. RESULTS: Our findings are in agreement with our previously published study, which analyzed a cohort of 69 patients, supporting our hypothesis that the best approach to maximize detection of DHLs while limiting waste seems to be a combination of CGP and MYC break-apart FISH testing, the latter to capture the presence of non-IGH::MYC events. CONCLUSIONS: Our study supports the combined use of FISH and GCP rather than either method alone to better detect MYC and BCL2 (and BCL6) gene rearrangements.

The Paris System "atypical urothelial cells" category: can the current criteria be improved?

INTRODUCTION: The Paris System (TPS) for reporting urine cytology was developed for standardization of diagnosis focusing on the detection of high-grade urothelial carcinoma (HGUC). Probably the most challenging task for TPS is to provide criteria for the atypical urothelial cell (AUC) category. The TPS criteria for AUC include increased nuclear/cytoplasmic (N/C) ratio (>0.5) and 1 of the 3 minor criteria including nuclear hyperchromasia (NH), coarse chromatin (CC) and irregular nuclear membrane (INM). We evaluated TPS-AUC diagnostic value and investigated whether other morphologic parameters can improve its criteria. MATERIALS AND METHODS: Urine samples with diagnoses of AUC collected during a 6-month period were re-reviewed. Data captured included N/C ratio >0.5, NH, CC, INM, and 2 additional criteria including enlarged nuclear size (ENS) and the presence of nucleolus (N). ENS was considered when the nucleus was 2 times larger than the urothelial cell or 3 times larger than lymphocyte. RESULTS: By applying the TPS-AUC criteria, the rate of atypia diagnosis reduced in comparison to Pre-TPS (9% versus 13%, P = 0.02). Among the AUC minor criteria, NH was the best criterion with the highest interobserver agreement (IOA) and correlation with HGUC (k = 0.342, r = 0.61, P < 0.001) and strong PPV (93.6%). ENS had the highest PPV (95.8%) and, after NH, had the highest IOA and correlation with HGUC (k = 0.29, r = 0.52, P < 0.001). CONCLUSION: TPS improves the diagnostic value of urine cytology, particularly in cases with atypia. ENS is a strong criterion for increasing the diagnostic value of AUC and potentially can improve TPS performance as a minor criterion.

Advances in the Molecular Taxonomy of Breast Cancer.

Breast cancers are heterogeneous with variable morphologic features, biologic behavior and response to therapy. Traditional histopathologic features such as size, grade, and lymph node status may be used to provide a general estimate of outcome, stratifying patients into broad prognostic groups with prescribed guidelines for therapy. With this approach however, up to 85% of breast cancer patients are overtreated, and at the other end of the spectrum, 20% of patients succumb to their disease despite receiving maximum therapy. The current routine testing for the Estrogen receptor (ER) and HER2 growth factor receptor (HER2) represents the earliest attempts to provide a targeted approach to breast cancer therapy, based on molecular drivers of the disease. The pioneering works by Perou and Sorlie et al using global gene expression profiling introduced a molecular taxonomy of breast cancer with associated prognostic implications. The Luminal, HER2-enriched, and Basal-like intrinsic subtypes are generally characterized by the presence or absence of ER and HER2. They have been further analyzed and refined using integration of genomic and transcriptomic data made possible by advancements in high throughput molecular techniques and bioinformatics. Indeed, an increased understanding of the genomic landscape of these subtypes, and the molecular basis of breast cancer growth regulation, holds the promise of a more personalized patient selection for specific targeted therapies and improved outcomes.

Adult Renal Neoplasms: Cytology, Immunohistochemistry, and Cytogenetic Characteristics.

Tissue sampling of renal masses is traditionally performed using percutaneous sonographic or CT guidance core biopsy (CB) with or without touch preparation cytology and/or fine-needle aspiration cytology (FNAC). The combined used of CB and FNAC is expanding in clinical practice, especially in small renal masses and plays a pivotal role in therapeutic decision making. Grouping the renal neoplasms in differential diagnostic groups helps in choosing specific immunohistochemical markers and reaching an accurate diagnosis.