Carmen M. Perrino

Mismatch repair protein expression in 1049 endometrial carcinomas, associations with body mass index, and other clinicopathologic variables

OBJECTIVE Links between obesity, with its attendant estrogen abnormalities, and the endometrial carcinoma (EC) DNA Mismatch Repair Protein (MMR) system have recently been proposed. We investigated relationships between body mass index (BMI) and clinicopathological correlates including MMR expression in a large single institution EC cohort. METHODS Clinical and pathological databases from 2007 to 2012 were used to identify consecutive hysterectomy specimens with EC. Univariate and multivariate analyses were used to explore relationships between BMI, age, stage, tumor type and immunohistochemical results for MLH1, PMS2, MSH2 and MSH6. RESULTS 1049 EC were identified. Overall, BMI was higher amongst women with normal MMR (p=0.002). However, when stratified by age and specific MMR, statistically significant differences localized exclusively to women <50years old with loss of MSH2 and/or MSH6 (p=0.003 and p=0.005 respectively). Higher BMI correlated with endometrioid FIGO 1 and 2 tumors (p<0.001) and with stage 1a (p<0.001). Conversely, MMR abnormalities did not show significant associations with stage (p=0.302) or histologic grade (p=0.097). CONCLUSIONS BMI showed statistically significant associations with MMR expression, tumor grade and stage amongst 1049 consecutive EC. Obesity correlates with lower grade and stage EC. A link between BMI and maintenance of the MMR system is not supported by our data because the only statistically significant association occurred in women <50years old with MSH2 and/or MSH6 abnormalities where Lynch syndrome related cases are expected to cluster.

Genetic alterations in renal cell carcinoma with rhabdoid differentiation

Renal cell carcinoma with rhabdoid differentiation (RCC-R) in adult patients is an aggressive variant of renal cancer with no known specific genetic alterations. The aim of this study was to characterize genome-wide genetic aberrations in RCC-R via utilization of high-density single-nucleotide polymorphism (SNP) arrays. We identified 20 cases of RCC-R, which displayed both clear cell renal cell carcinoma and rhabdoid histomorphologic components. DNA was extracted from formalin-fixed, paraffin-embedded tissue (from clear cell renal cell carcinoma and RCC-R areas from each case) and subjected to high-density SNP array assay. Genetic aberrations present in 10% of cases were considered significant. In areas with clear cell histomorphology, gains were most commonly observed in chromosomes 5q (66.7%, 10/15), 7 (46.7%, 7/15), and 8q (46.7%, 7/15); and losses were most commonly identified in chromosomes 14 (60%, 9/15), 8p (46.7%, 7/15), and 22 (46.7%, 7/15). In areas with rhabdoid differentiation, gains were most commonly observed in chromosome 7 (58.8%, 10/17); and losses were most commonly identified in chromosomes 9 (70.6%, 12/17), 14 (58.8%, 10/17), 4 (52.9%, 9/17), and 17p (52.9%, 9/17). Rhabdoid cells shared many chromosomal abnormalities and exhibited a greater number of copy number variations in comparison with coexisting clear cells. Loss of 11p was specific for rhabdoid differentiation, with loss found in 29.4% of rhabdoid components compared with 0% of clear cell areas. The greater number of overall genetic alterations in the rhabdoid cells and the shared genetic background between rhabdoid and clear cell areas suggest genetic evolution of the rhabdoid cells that correlates with histomorphologic progression.

Microphthalmia transcription factor immunohistochemistry for FNA biopsy of ocular malignant melanoma

Microphthalmia transcription factor (MiTF) is a sensitive and specific immunohistochemistry (IHC) marker for malignant melanoma (MM) in surgical resections, but its utility in cytology specimens has not been extensively studied.

Challenges in the pathological reporting of urothelial carcinoma involving prostatic transurethral resection specimens within a single institution

Aim: Primary bladder urothelial carcinoma (UC) may involve the prostate with differing management depending on whether tumour is in situ or invades the prostatic subepithelium or fibromuscular stroma. We aim to understand challenges in reporting UC within prostate transurethral resection (TUR). Methods: A retrospective review from 2007 to 2010 identified prostate TUR performed for primary bladder UC. Results: 25.1% of cystoprostatectomy patients (60/239) had a prior prostate TUR; 129 patients had a prostate TUR for UC and 50.4% (65/129) were given a neoplastic diagnosis. Prostatic fibromuscular stroma was present in 84.6% of cases, with a comparable rate among surgeons. Diagnostic concordance of UC versus a non-neoplastic diagnosis was 96.7%, with rare cases initially diagnosed as non-neoplastic having in situ UC on review. Of reports with invasive tumour, 19.4% did not specify extent of invasion (e.g., bladder muscularis propria, prostate fibromuscular stroma) and 13.9% had discordant extent of invasion on review. Terminology typically used for bladder (lamina propria/muscularis propria) was found in 23.1% of reports without explicit reference to the bladder or prostate. Conclusion: This study reveals difficulties in reporting UC within prostatic TUR specimens. We recommend documenting tumour extent and referencing the organ of origin if ambiguous anatomical terms are used.