Urothelial carcinoma involving the ureteral orifice: a clinicopathologic analysis of 93 cases.

Although tumors involving the bladder and ureter have been well described, there are only few studies in the pathology literature specifically analyzing tumors involving the ureteral orifice (UO). A search was performed for biopsy and resection specimens (transurethral resection, radical cystectomy/cystoprostatectomy, nephroureterectomy and bladder cuff resection) of urothelial carcinoma (UCa) involving the UO. Ninety-three cases were identified. Sixty-two (67%) patients were male. Mean patient age was 71 years (range, 43-91 years). Forty-two of 93 (45%) cases were invasive UCa (41 high-grade UCa; 1 low-grade UCa); 17/42 (40%) were invasive into muscularis propria. Tumor laterality was as follows: right side, 43 (46% of cases); left side, 41 (44%); bilateral, 4 (4.5%); and in 5 cases (5.5%), the laterality was not specified by the urologist. Seven cases of UCa with variant histology were also identified. Five patients had lymph node (LN) metastasis at the time of resection, and another 3 presented with LN or distant metastasis after resection (range, 4-38 months). Although this study focused primarily on the index tumor involving the UO (Group 1 cases are those with only UO involvement), in 70/93 (75%) cases (Group 2 cases), at least one other tumor was located at another site within the bladder. The fact that the majority of cases (75%) had tumors located at other sites of the bladder, emphasizes that careful examination of the UO needs to be performed by both urologists and pathologists when examining cases of UCa of the bladder.

MYC Immunohistochemistry Predicts MYC Rearrangements by FISH.

MYC is the proto-oncogene classically associated with Burkitt lymphoma (BL) located at chromosomal locus 8q24. Rearrangements of MYC are seen in nearly 100% of BL but have been reported in 3-16% of diffuse large B-cell lymphomas (DLBCLs). Rearrangements of MYC are tested for by flourescence in situ hybridization (FISH). In this study, we compared immunohistochemistry (IHC) using a monoclonal antibody directed against the human Myc protein to the current method, FISH. 31 cases were identified that had been tested for MYC rearrangements by FISH over 27 months with heterogeneity in the diagnoses: 5 BL; 10 DLBCL; 3 B-cell lymphoma unclassifiable between DLBCL and BL; 5 B-cell lymphoma not otherwise specified; 1 EBV-related B-cell lymphoma; 1 composite CLL/SLL-large cell lymphoma; and 6 designated as high-grade or aggressive B-cell lymphoma. Analysis by FISH was performed as part of the clinical workup, where a MYC rearrangement is defined as a split fusion signal in at least 5.7% of cells. Myc-IHC was interpreted as a qualitative positive (overexpressed) or negative (not overexpressed) result. 12 cases (39%) were positive for MYC rearrangements by FISH. Overall, 13 cases (42%) showed Myc overexpression by IHC, 11 of which harbored a MYC rearrangement by FISH. There were two false positives and one false negative. Thus, Myc-IHC predicted a MYC rearrangement by FISH with 92% sensitivity and 89% specificity. We can thus conclude that Myc-IHC should be a potentially useful screening tool for identifying lymphomas that may harbor a MYC rearrangement.

Heat-induced Epitope Retrieval for Immunohistochemistry at High Altitude: A Quality Assurance Study.

INTRODUCTION: Heat-induced epitope retrieval (HIER) of formalin-fixed paraffin-embedded tissues is now a standard practice in immunohistochemistry (IHC). In this study, we aimed to test the effect of altering HIER temperature on IHC staining quality at high altitude, the hypothesis being that lower HIER temperatures would result in improved staining patterns. MATERIALS AND METHODS: In a laboratory at high altitude (Aurora, CO), we used a platform with automated onboard epitope retrieval, and systematically tested 3 different HIER temperatures (100°C, 95°C, 90°C) with 4 IHC stains that are commonly used in routine practice: CD3, Ki67, CK20, and Melan A (n=10 for each antibody/epitope retrieval temperature combination). A scoring system was devised, the slides were scored in a blinded manner, and statistical analysis was performed. For comparison, the same study was performed in a laboratory near sea level (Atlanta, GA). RESULTS: At high altitude, lower HIER temperatures resulted in improved staining patterns, as quantified by stronger staining intensity and greater area of the slides stained. The scores obtained with HIER temperatures of 95°C and 90°C were higher than those obtained with HIER of 100°C, and the difference was found to be statistically significantly for some antibody/epitope retrieval temperature combinations (P<0.05). This effect was not seen in the laboratory near sea level. CONCLUSIONS: We show that alternate epitope retrieval recommendations are warranted for laboratories at high altitude. Furthermore, we suggest that manufactures should consider how their instruments will perform at high altitude as they further automate the process of IHC.