Unusual DNA mismatch repair-deficient tumors in Lynch syndrome: a report of new cases and review of the literature.

Immunohistochemical detection of DNA mismatch repair proteins and polymerase chain reaction detection of microsatellite instability have enhanced the recognition of mismatch repair-deficient neoplasms in patients with Lynch syndrome and, consequently, led to the identification of tumors that have not been included in the currently known Lynch syndrome tumor spectrum. Here, we report 4 such unusual tumors. Three of the 4, a peritoneal mesothelioma, a pancreatic acinar cell carcinoma, and a pancreatic well-differentiated neuroendocrine tumor, represented tumor types that, to the best of our knowledge, have not been previously reported in Lynch syndrome.

Urothelial carcinoma involving the gynecologic tract: a morphologic and immunohistochemical study of 6 cases.

Spread of urothelial carcinoma (UC) to the female genital tract occurs in a small subset of women with UC. We studied 6 patients with involvement of various gynecologic (GYN) sites and detailed natural history and pathologic features. Four patients initially presented with bladder lesions, including 1 high-grade pTa tumor, 2 pT1 tumors, and 1 pT2 tumor; 1 patient presented with pT2 disease of the renal pelvis and 1 with GYN involvement in the form of vulvar Paget's disease.

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.

Giant cell tumor of uterus resembling osseous giant cell tumor: case report and review of literature.

Osteoclast-like giant cells (OLGCs) are multinucleated cells of histiocytic lineage and have been identified in a wide array of neoplasms. In the uterus, they have most frequently been reported in association with leiomyosarcomas. This article describes a case of an osteoclast-like giant cell-rich uterine tumor that was essentially indistinguishable at the morphologic and immunophenotypic levels, from typical giant cell tumor of bone.

The impact of race and comorbidity on survival in endometrial cancer.

Background: Poorer survival from endometrial cancer in blacks than in whites is well documented. The aims of this study were to determine whether diabetes, hypertension, or other conditions influence survival and whether accounting for these conditions reduces this racial disparity.

Methods: Using the SEER-Medicare database, we investigated the influence of diabetes, hypertension, and other comorbid conditions on survival in black and white women age ≥66 with endometrial cancer.

Key features of extrauterine pelvic serous tumours (fallopian tube, ovary, and peritoneum).

Key features of extrauterine pelvic serous tumours (fallopian tube, ovary, and peritoneum) Ovarian serous carcinoma (OSC) is the most common of the ovarian epithelial malignancies, and accounts for most of the mortality. Traditionally, ovarian cancer has been considered to be one disease; however, it is now apparent that it actually consists of many different entities. OSC can be further segregated into two processes: high-grade serous carcinoma (HGSC) and low-grade serous carcinoma.

Surgical cytoreduction in patients with metastatic uterine leiomyosarcoma at the time of initial diagnosis.

Objective: To determine whether cytoreduction is associated with improved outcome in patients newly diagnosed with metastatic uterine leiomyosarcoma (LMS).

Methods: We retrospectively identified all patients treated at our institution for high-grade uterine LMS with extrauterine disease at the time of initial diagnosis from 7/1/82 to 7/31/07. Pattern of disease spread was classified as intraperitoneal (IP) or extraperitoneal (EP).

Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma.

This study was undertaken with the hypothesis that certain common morphologic features of ovarian carcinomas are predictably associated with BRCA1 and BRCA2 deficiencies. We selected 43 high-grade serous carcinomas diagnosed at Memorial Sloan-Kettering Cancer Center that were studied as part of The Cancer Genome Atlas pilot project. In addition to 12 randomly selected nonfamilial BRCA-unassociated cases, all 31 Memorial Sloan-Kettering Cancer Center cases with BRCA1 or BRCA2 abnormality were included (n=43).

Strategies for distinguishing low-grade endometrioid and serous carcinomas of endometrium.

Distinction between endometrioid and serous carcinomas of the endometrium has important prognostic and therapeutic implications. Misdiagnosing a serous carcinoma as endometrioid can have significant consequences for the patient and pathologist. Although many cases are straightforward and easy to classify, there are occasional problematic cases.

Pathologic scoring of PTEN immunohistochemistry in endometrial carcinoma is highly reproducible.

Endometrial carcinomas show frequent PTEN-PI3K pathway abnormalities, and there are currently multiple trials focused on PI3K pathway inhibitors in patients with endometrial carcinoma. PTEN immunohistochemistry may help to select patients with potential for response to targeted therapy, making it important to develop and validate this stain in formalin-fixed, paraffin-embedded tissue. Immunohistochemistry for PTEN was performed and scored independently on 118 cases of endometrial carcinomas from 2 cancer centers using monoclonal DAKO 6H2.

Immunohistochemical expression of estrogen and progesterone receptors and outcomes in patients with newly diagnosed uterine leiomyosarcoma.

Objective: We assessed the IHC expression of ER and PR and their prognostic significance in uterine leiomyosarcoma (LMS).

Methods: We identified 43 "high-grade" uterine LMS cases from 7/82-7/07 for whom ER/PR IHC analysis was performed at initial diagnosis at our institution.

Results: Disease was confined to the uterine body in 20/43 (47%).

TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma--evidence supporting the clonal relationship of the two lesions.

Serous tubal intraepithelial carcinomas (STICs) have been proposed to be the most likely precursor of ovarian, tubal and 'primary peritoneal' (pelvic) high-grade serous carcinoma (HGSC). As somatic mutation of TP53 is the most common molecular genetic change of ovarian HGSC, occurring in more than 95% of cases, we undertook a mutational analysis of 29 pelvic HGSCs that had concurrent STICs to demonstrate the clonal relationship of STICs and HGSCs. In addition, we correlated the mutational data with p53 immunostaining to determine the role of p53 immunoreactivity as a surrogate for TP53 mutations in histological diagnosis.

Diagnosis of serous tubal intraepithelial carcinoma based on morphologic and immunohistochemical features: a reproducibility study.

There is compelling evidence that serous tubal intraepithelial carcinoma (STIC) is a precursor of high-grade serous ovarian carcinoma. Large-scale studies are now required to determine its biological significance and clinical implication. Before conducting these studies, a reproducible classification for STIC is needed, and that is the goal of this study.

"Low-grade leiomyosarcoma" and late-recurring smooth muscle tumors of the uterus: a heterogenous collection of frequently misdiagnosed tumors associated with an overall favorable prognosis relative to conventional uterine leiomyosarcomas.

In most instances, uterine smooth muscle tumors (USMTs) are readily diagnosed as either benign or malignant. Rare patients whose smooth muscle tumors fail to meet leiomyosarcoma (LMS) diagnostic criteria will experience recurrence, and occasional cases of LMS patients experience a protracted clinical disease course. The aim of this study was to investigate whether "low-grade uterine LMS" can be defined as a clinicopathological entity and to learn which histologic features of USMTs correlate with indolent prognosis.

Accuracy of frozen section diagnosis of ovarian borderline tumor.

Objective: The objective of this study was to determine the incidence of invasive cancer in ovarian masses diagnosed as borderline tumor (BT) at the time of frozen section.

Methods: We performed a retrospective review of all patients diagnosed with ovarian BT on frozen section (FS) at our institution between 2000 and 2010. Clinical and pathologic data were extracted.

Morphologic features of uterine leiomyomas associated with hereditary leiomyomatosis and renal cell carcinoma syndrome: a case report.

Patients with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome are prone to develop smooth muscle tumors of the uterus and skin and also renal carcinomas. The morphologic features of renal tumors that arise in the setting of HLRCC are well described, the hallmark feature being the presence of prominent eosinophilic nucleoli surrounded by a clear halo. Renal tumors associated with HLRCC are aggressive and often present late with high-stage disease.

A nomogram to predict postresection 5-year overall survival for patients with uterine leiomyosarcoma.

Background: The clinical course of patients with uterine leiomyosarcoma (LMS) is difficult to predict with the currently available categorical staging systems of the American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics (FIGO). The objective of the current study was to develop and validate a novel, clinically relevant, individualized prognostic model for patients with uterine LMS.

Methods: Patients with uterine LMS who presented at the authors' institution from 1982 to 2008 were analyzed.

Clinicopathologic significance of DNA mismatch repair protein defects and endometrial cancer in women 40years of age and younger.

Background: The hereditary basis of endometrial cancer is apparent in young women with endometrial cancer. The objective of this study was to examine risk factors and outcomes in patients 40 years of age and younger with endometrial cancer.

Methods: We performed a retrospective cohort study of patients aged 40 years or less who were diagnosed with endometrial carcinoma between 1/93 and 5/08.

Unusual endocervical adenocarcinomas: an immunohistochemical analysis with molecular detection of human papillomavirus.

Background: Endocervical adenocarcinomas of the usual type are etiologically related to infection with oncogenic human papillomaviruses (HPVs). These tumors are typically diffusely positive for p16 and carcinoembryonic antigen (CEA) immunostains. The goal of our study was to determine the HPV status and immunohistochemical profiles of unusual histologic subtypes of endocervical adenocarcinoma.

The revised 2009 FIGO staging system for endometrial cancer: should the 1988 FIGO stages IA and IB be altered?

Objectives: The revised 2009 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer included many changes over the 1988 system, particularly for stage I subgroups. We sought to describe the overall survival (OS) of women with stage I endometrial cancer and examine how the estimated stage-specific OS is altered in the 2009 system.

Methods: A prospectively maintained institutional endometrial database was analyzed.

Histopathologic prognostic factors in stage I leiomyosarcoma of the uterus: a detailed analysis of 27 cases.

Uterine leiomyosarcomas (Ut-LMSs) are aggressive tumors with an overall poor prognosis (15% to 25% 5-year survival rate). However, patients with stage I Ut-LMSs are reported to have a relatively better outcome when compared with the overall group with a 5-year survival rate ranging from 25% to 75%. The purpose of this study was to evaluate the histopathologic parameters that may impact outcome in stage I Ut-LMSs.

Nonserous Ovarian Epithelial Tumors.

This review covers the group of relatively uncommon nonserous ovarian epithelial tumors. The authors focus on the group's distinctiveness from the much more common serous tumors and show the similarities across entities. Diagnostic criteria that separate the different entities are currently being debated.