Although grading has been demonstrated to be an important prognostic factor in ovarian serous carcinoma, there is no system universally used to perform this task. A few years ago, we proposed a two-tier system for grading ovarian serous carcinoma that is based primarily on the assessment of nuclear atypia (uniformity vs. pleomorphism) in the worst area of the tumor. Tumor grade in this two-tier system is correlated with survival. After being used by numerous pathologists and trainees at The University of Texas M.D. Anderson Cancer Center (MDACC) for 15 years, we have observed that this system is user-friendly and reproducible. We undertook this study to evaluate the interobserver and intraobserver variability among a group of 7 gynecologic pathologists and 2 general surgical pathologists using this grading system. A total of 80 cases of ovarian serous carcinoma, 40 low-grade and 40 high-grade, were circulated twice among these pathologists. Slides with examples of low-grade and high-grade serous carcinoma were sent with the unknowns. A website was used to provide diagnostic criteria, images of examples of ovarian low-grade and high-grade carcinoma, and a log form to facilitate data entry. Statistical analysis demonstrated an overall kappa statistic among the different observers of 0.909. The intergrader kappa's ranged from 0.717 to 1.000 in the first round of the review and from 0.701 to 1.000 in the second round. Eight of the participants had an intragrader kappa ranging from 0.775 to 1.000 (excellent agreement), whereas a single participant had an intragrader kappa of 0.725 (good agreement). This study demonstrates that the two-tier grading system (the MDACC grading system) for ovarian serous carcinoma on the basis of the assessment of nuclear atypia is easy to learn and is highly reproducible. These findings would support its universal use, which would be beneficial for the standardization of clinical trials and protocols, thus facilitating the understanding of this disease and investigation into the treatment of patients affected by these tumors.
A National Cancer Institute (NCI) "Thyroid Fine-Needle Aspiration (FNA) State of the Science Conference" recently proposed standardized nomenclature and "risks of malignancies" associated with various diagnostic categories. We evaluated the evidence levels of the data used by NCI to predict malignancy risks and whether those estimates had clinical validity in our patient population.Eight hundred seventy-nine patients underwent thyroid FNA during 2006. FNA diagnoses were translated into NCI diagnostic categories, and 2-year follow-up retrospective information was obtained. Four percentages of malignancies were calculated for each diagnostic category using follow-up information from FNA, thyroidectomy, both, and all patients as denominators. 95% confidence intervals (CI) were estimated for all proportions, and results were analyzed with chi-square statistics. "Relative risk" calculations were performed using the percentage of malignancies in the entire population under study as a denominator.Most of the studies cited by the NCI provided incomplete and variable level III evidence based mainly on surgical follow-up. Among our patients, the percentages of malignancies calculated with follow-up data from all patients as the denominator were similar to the "risk estimates" proposed by the NCI, but estimates based on surgical follow-up overestimated the probability of thyroid malignancy for patients with FNA diagnosis of "benign" and "follicular lesions of undetermined significance" (FLUS). Relative risk and 95% CI calculations suggested that the NCI classification could be simplified into three categories: "benign," "FLUS + neoplasm," and "suspicious + malignant."
Initial investigations reported GATA3 to be a sensitive and relatively specific marker for mammary and urothelial carcinomas. Recently, GATA3 expression has been described in several other epithelial tumors. However, there has been only limited investigation of GATA3 expression in cutaneous epithelial tumors. The objective of this study was to examine the immunohistochemical expression of GATA3 in a wide variety of cutaneous epithelial neoplasms. GATA3 expression was evaluated in 99 benign and 63 malignant cutaneous epithelial tumors. GATA3 was consistently and usually strongly expressed in clear cell acanthoma, trichofolliculoma, trichoepithelioma, trichilemmoma, sebaceous adenoma, sebaceoma, apocrine hidrocystoma, apocrine tubular papillary adenoma, hidradenoma papilliferum, and syringocystadenoma papilliferum. Hidradenomas exhibited variable positive staining. Most poromas, syringomas, chondroid syringomas, cylindromas, and spiradenomas were negative or only focally and weakly positive. Focal staining was present in all pilomatrixomas. Thirteen of 14 basal cell carcinomas, 21 of 24 squamous carcinomas, and all 6 sebaceous carcinomas exhibited positive staining. The 1 apocrine carcinoma, both mucinous carcinomas, and 2 of 3 microcystic adnexal carcinomas also exhibited positive staining, whereas the 1 eccrine porocarcinoma and the 1 adenoid cystic carcinoma were negative. One of 11 Merkel cell carcinomas exhibited focal weak staining. Our findings demonstrate that GATA3 is expressed in a wide variety of benign and malignant cutaneous epithelial neoplasms. In addition to carcinomas of breast and urothelial origin and other more recently described GATA3-positive tumors, the differential diagnosis of a metastatic tumor of unknown primary origin that expresses GATA3 should also include a carcinoma of cutaneous epithelial origin.
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