Type I and II endometrial cancers: have they different risk factors?

PurposeEndometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors.Patients and MethodsIndividual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors.ResultsParity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m(2) increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (P-heterogeneity < .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar.ConclusionThe results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed. (C) 2013 by American Society of Clinical Oncolog

Small cell carcinoma of the gynecologic tract : a multifaceted spectrum of lesions

Objective Small cell carcinoma (SmCC) of the female genital tract constitutes a diagnostic and clinical challenge given its rarity and the lack of standardized therapeutic approaches. Here we review the morphological, clinical and molecular features of gynecologic SmCCs and discuss potential areas for future research. Methods Data for this review article were identified by searches of PubMed, EMBASE and the Internet using the search terms "small cell carcinoma" or "neuroendocrine carcinoma" and "gynecologic", "uterine cervix", "cervix", "uterus", "endometrium", "ovary", "vagina", "fallopian tube" or "vulva", and research articles published in English between 1972 and February 2014 were included. Results SmCCs arising from different organs within the gynecologic tract share the same histopathologic characteristics, which closely resemble those of small cell lung carcinoma. The expression of at least one immunohistochemical neuroendocrine marker is a common finding. The uterine cervix is the most frequent site of SmCC in the female genital tract. HPV infection seems to play a role in the development of cervical SmCC but not in cancers of other gynecologic sites. FIGO stage is an established prognostic factor, in particular in SCCs of the cervix. Irrespective of the site, SmCCs of the gynecologic tract display an aggressive clinical behavior with few reported long-term survivors. The therapeutic management includes surgery, radiotherapy and chemotherapy. Conclusions Despite the potential differences in etiology and risk factors, SmCCs from different sites of the gynecologic tract have similar morphologic appearances and clinical behavior. Recent genomic analyses of small cell carcinoma of the lung have revealed potential driver genomic alterations. We posit that the comprehensive genomic characterization of gynecologic SmCCs may lead to the identification of markers that result in an improvement of diagnostic reproducibility of SmCCs of the gynecologic tract, and of molecular aberrations that may be exploited therapeutically in subgroups of the disease

Interobserver variability in the interpretation of tumor cell necrosis in uterine leiomyosarcoma

10.1097/PAS.0b013e3182851162American Journal of Surgical Pathology375650-658AJSP

Diagnostic Performance of Computed Tomography for Preoperative Staging of Patients with Non-endometrioid Carcinomas of the Uterine Corpus

Item does not contain fulltextPURPOSE: The aim of this study was to assess the diagnostic performance of computed tomography (CT) for initial staging of non-endometrioid carcinomas of the uterine corpus. MATERIALS AND METHODS: Waiving informed consent, the Institutional Review Board approved this Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study of 193 women with uterine papillary serous carcinomas, clear cell carcinomas, and carcinosarcomas, who underwent surgical staging between May 1998 and December 2011 and had preoperative CT within 6 weeks before surgery. Two radiologists (R1, R2) independently reviewed all CT images. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and area under the curve were calculated using operative notes and surgical pathology as the reference standard. RESULTS: The respective sensitivities and specificities achieved by R1/R2 were 0.79/0.64 and 0.87/0.75 for detecting deep myometrial invasion (MI) on CT; 0.56/0.63 and 0.93/0.79 for detecting cervical stromal invasion; 0.52/0.45 and 0.95/0.93 for detecting pelvic nodal metastases; and 0.45/0.30 and 0.98/0.98 for detecting para-aortic nodal metastases. Although CT had suboptimal sensitivity for the detection of omental disease, it had high PPV for omental seeding at surgical exploration (1.00 for R1 and 0.92 for R2). Inter-observer agreement ranged from moderate in the detection of deep MI (kappa = 0.42 +/- 0.06) to almost perfect in the detection of para-aortic nodal metastases (kappa = 0.88 +/- 0.08). CONCLUSION: In patients with uterine non-endometrioid carcinomas, CT is only moderately accurate for initial staging but may provide clinically valuable information by 'ruling-in' isolated para-aortic lymph node metastases and omental dissemination

Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Preoperative CT-based nomogram for predicting overall survival in women with non-endometrioid carcinomas of the uterine corpus

Item does not contain fulltextTo develop a preoperative CT-based nomogram for predicting overall survival (OS) in patients with non-endometrioid carcinomas of the uterine corpus.Waiving informed consent, the institutional review board approved this HIPAA-compliant, retrospective study of 193 women with histopathologically proven uterine papillary serous carcinomas (UPSC), uterine clear cell carcinomas (UCCC), and uterine carcinosarcomas (UCS) who underwent primary surgical resection between May 1998 and December 2011, and had a preoperative CT ≤ 6 weeks before surgery. All CT scans were reviewed for local or/and regional tumor extent, presence of pelvic or/and para-aortic adenopathy, and presence of distant metastases. Univariate survival analysis was performed using log-rank test and Cox regression. Variables shown significant by the univariate analysis were evaluated with the multivariable Cox regression analysis and the results were used to create a nomogram for predicting OS. The predictive accuracy of the nomogram was assessed with the concordance probability index (c-index) and a 3-year calibration plot.Mean patient age was 67.2 years (range 49.0-85.9); histologies included UPSC (n = 116), UCCC (n = 27), and UCS (n = 50). Median follow-up was 38.1 months (0.9-168.5 months). At multivariate analysis, patient age, ascites, and omental implants on CT were significant adverse predictors of OS and were used to build the nomogram. Concordance index for the nomogram was 0.640 ± 0.028.We developed a nomogram with a good concordance probability at predicting OS based on readily available pretreatment clinical and imaging characteristics. This preoperative nomogram has the potential to improve initial treatment planning and patient counseling

Molecular Classification of Grade 3 Endometrioid Endometrial Cancers Identifies Distinct Prognostic Subgroups

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Validation of an algorithm for the diagnosis of serous tubal intraepithelial carcinoma

It has been reported that the diagnosis of serous tubal intraepithelial carcinoma (STIC) is not optimally reproducible on the basis of only histologic assessment. Recently, we reported that the use of a diagnostic algorithm that combines histologic features and coordinate immunohistochemical expression of p53 and Ki-67 substantially improves reproducibility of the diagnosis. The goal of the current study was to validate this algorithm by testing a group of 6 gynecologic pathologists who had not participated in the development of the algorithm (3 faculty and 3 fellows) but who were trained in its use by referring to a website designed for the purpose. They then reviewed a set of microscopic slides, which contained 41 mucosal lesions of the fallopian tube. Overall consensus (Z4 of 6 pathologists) for the 4 categories of STIC, serous tubal intraepithelial lesion (our atypical intermediate category), p53 signature, and normal/ reactive was achieved in 76% of the lesions, with no consensus in 24%. Combining diagnoses into 2 categories (STIC versus non-STIC) resulted in an overall consensus of 93% and no consensus in 7%. The j value for STIC versus non-STIC among all 6 observers was also high at 0.67 and did not significantly differ, whether for faculty (j=0.66) or fellows (j=0.60). These findings confirm the reproducibility of this algorithm by a group of gynecologic pathologists who were trained on a website for that purpose. Accordingly, we recommend its use in research studies. Before applying it to routine clinical practice, the algorithm should be evaluated by general surgical pathologists in a community setting