Mixed clear cell/endometrioid and clear cell/serous carcinoma of the uterus are clinicopathologically similar to pure clear cell carcinoma: An NRG Oncology/Gynecologic Oncology Group (GOG-210) study of 311 women.

Objectives: Clear cell carcinoma is a high-risk subtype of endometrial cancer. Some patients have a mixture of clear cell carcinoma with other histologic types (endometrioid or serous) or cannot be neatly assigned to one of these types. Protocol GOG-8032 within GOG-210 was designed to determine whether these tumors differ from pure clear cell carcinoma in stage at diagnosis, initial pattern of spread, or patient survival.

Endometrial Stromal Sarcomas With BCOR Internal Tandem Duplication and Variant BCOR/BCORL1 Rearrangements Resemble High-grade Endometrial Stromal Sarcomas With Recurrent CDK4 Pathway Alterations and MDM2 Amplifications.

The distinction between low-grade and high-grade endometrial stromal sarcomas (LGESS, HGESS) is increasingly defined by genetics. Recently, variant genomic alterations involving BCOR or BCORL1 have been reported in endometrial stromal sarcoma (ESS), although it remains unclear whether these justify a diagnosis of LGESS or HGESS. In this study, we describe clinicopathologic and molecular features of ESS with such alterations to help clarify their classification in the spectrum of ESS.

The presence of an endometrioid component does not alter the clinicopathologic profile or survival of patients with uterine serous cancer: A gynecologic oncology group (GOG/NRG) study of 934 women.

Objective: While most cases of endometrial cancer can readily be classified as pure endometrioid, pure serous, or another type, others show an apparent mixture of serous and endometrioid components, or indeterminate serous versus endometrioid features. Since serous histology carries a worse prognosis than endometrioid, Gynecologic Oncology Group protocol GOG-8032 was established to examine whether the presence of a non-serous component is a favorable feature in an otherwise serous cancer.

Methods: 934 women with serous cancer were prospectively identified among a larger group enrolled in GOG-0210.

FGFR2 mutations are associated with poor outcomes in endometrioid endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study.

Purpose: Activating FGFR2 mutations have been identified in ~10% of endometrioid endometrial cancers (ECs). We have previously reported that mutations in FGFR2 are associated with shorter disease free survival (DFS) in stage I/II EC patients. Here we sought to validate the prognostic importance of FGFR2 mutations in a large, multi-institutional patient cohort.

Performance of residents using digital images versus glass slides on certification examination in anatomical pathology: a mixed methods pilot study.

Background: It is anticipated that many licensing examination centres for pathology will begin fully digitizing the certification examinations. The objective of our study was to test the feasibility of a fully digital examination and to assess the needs, concerns and expectations of pathology residents in moving from a glass slide-based examination to a fully digital examination.

Methods: We conducted a mixed methods study that compared, after randomization, the performance of senior residents (postgraduate years 4 and 5) in 7 accredited anatomical pathology training programs across Canada on a pathology examination using either glass slides or digital whole-slide scanned images of the slides.

Pattern classification of endocervical adenocarcinoma: reproducibility and review of criteria.

Previously, our international team proposed a three-tiered pattern classification (Pattern Classification) system for endocervical adenocarcinoma of the usual type that correlates with nodal disease and recurrence. Pattern Classification-A tumors have well-demarcated glands lacking destructive stromal invasion or lymphovascular invasion, Pattern Classification-B tumors show localized, limited destructive invasion arising from A-type glands, and Pattern Classification-C tumors have diffuse destructive stromal invasion, significant (filling a 4 × field) confluence, or solid architecture. Twenty-four cases of Pattern Classification-A, 22 Pattern Classification-B, and 38 Pattern Classification-C from the tumor set used in the original description were chosen using the reference diagnosis originally established.

Pattern-based classification of invasive endocervical adenocarcinoma, depth of invasion measurement and distinction from adenocarcinoma in situ: interobserver variation among gynecologic pathologists.

A pattern-based classification for invasive endocervical adenocarcinoma has been proposed as predictive of the risk of nodal metastases. We aimed to determine the reproducibility of such classification in the context of common diagnostic challenges: distinction between in situ and invasive adenocarcinoma and depth of invasion measurement. Nine gynecologic pathologists independently reviewed 96 cases of endocervical adenocarcinoma (two slides per case).

New pattern-based personalized risk stratification system for endocervical adenocarcinoma with important clinical implications and surgical outcome.

We present a recently introduced three tier pattern-based histopathologic system to stratify endocervical adenocarcinoma (EAC) that better correlates with lymph node (LN) metastases than FIGO staging alone, and has the advantage of safely predicting node-negative disease in a large proportion of EAC patients. The system consists of stratifying EAC into one of three patterns: pattern A tumors characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture and lacking destructive stromal invasion or lymphovascular invasion (LVI), pattern B tumors demonstrating localized destructive invasion (small clusters or individual tumor cells within desmoplastic stroma often arising from pattern A glands), and pattern C tumors with diffusely infiltrative glands and associated desmoplastic response. Three hundred and fifty-two cases were included; mean follow-up 52.

Malignant Melanoma of Vulva and Vagina: A Histomorphological Review and Mutation Analysis--A Single-Center Study.

Objectives: The aim of this work was to determine molecular characteristics and specifically, the frequency of BRAF, C-KIT, and NRAS mutations in vulvar and vaginal melanomas.

Methods: A retrospective review of all cases of vulvar and vaginal melanoma between 2002 and 2013 was performed. We reviewed the clinical and histological characteristics of all cases and performed genotyping studies on cases that had tissue available for the study, using next-generation sequencing.

Invasive endocervical adenocarcinoma: a new pattern-based classification system with important clinical significance.

A new 3-tier pattern-based system to classify endocervical adenocarcinoma was recently presented. In short, pattern A tumors were characterized by well-demarcated glands frequently forming clusters or groups with relative lobular architecture. Pattern B tumors demonstrated localized destructive invasion defined as desmoplastic stroma surrounding glands with irregular and/or ill-defined borders or incomplete glands and associated tumor cells (individual or small clusters) within the stroma.

Invasive endocervical adenocarcinoma: proposal for a new pattern-based classification system with significant clinical implications: a multi-institutional study.

The management of endocervical adenocarcinoma is largely based on tumor size and depth of invasion (DOI); however, DOI is difficult to measure accurately. The surgical treatment includes resection of regional lymph nodes, even though most lymph nodes are negative and lymphadenectomies can cause significant morbidity. We have investigated alternative parameters to better identify patients at risk of node metastases.

Endometrial sarcomas: an immunohistochemical and JAZF1 re-arrangement study in low-grade and undifferentiated tumors.

The current World Health Organization classification divides endometrial sarcomas into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma. Recent studies suggest undifferentiated endometrial sarcoma is a heterogeneous group and a subgroup with uniform nuclei is more akin to low-grade endometrial stromal sarcoma in terms of morphologic, immunohistochemical and genetic features. We classified endometrial sarcomas treated at our institution from 1998 to 2011 into low-grade endometrial stromal sarcoma and undifferentiated endometrial sarcoma, the latter being further categorized into a group with either uniform or pleomorphic nuclei.

Reclassification of serous ovarian carcinoma by a 2-tier system: a Gynecologic Oncology Group Study.

Background: A study was undertaken to use the 2-tier system to reclassify the grade of serous ovarian tumors previously classified using the International Federation of Gynecology and Obstetrics (FIGO) 3-tier system and determine the progression-free survival (PFS) and overall survival (OS) of patients treated on Gynecologic Oncology Group (GOG) Protocol 158.

Methods: The authors retrospectively reviewed demographic, pathologic, and survival data of 290 patients with stage III serous ovarian carcinoma treated with surgery and chemotherapy on GOG Protocol 158, a cooperative multicenter group trial. A blinded pathology review was performed by a panel of 6 gynecologic pathologists to verify histology and regrade tumors using the 2-tier system.

Best predictors of grayscale ultrasound combined with color Doppler in the diagnosis of retained products of conception.

Objectives: To determine the best predictors of the presence of retained products of conception (RPOC) on grayscale and color Doppler transvaginal sonographic examination.

Methods: This was a retrospective study of 91 consecutive patients who underwent transvaginal sonography (TVS) with color Doppler to evaluate for the presence of RPOC. The images of TVS studies were reviewed by two radiologists in consensus blinded to the final outcome.

From melanocyte to metastatic malignant melanoma.

Malignant melanoma is one of the most aggressive malignancies in human and is responsible for almost 60% of lethal skin tumors. Its incidence has been increasing in white population in the past two decades. There is a complex interaction of environmental (exogenous) and endogenous, including genetic, risk factors in developing malignant melanoma.

D2-40, a novel immunohistochemical marker in differentiating dermatofibroma from dermatofibrosarcoma protuberans.

The distinction between dermatofibroma, particularly cellular variant, and dermatofibrosarcoma protuberans in excisional biopsies is usually straightforward. However, a separation between the two may be sometimes challenging, especially in superficial biopsies. Although factor XIIIa and CD34 immunostains are useful in differentiating dermatofibroma and dermatofibrosarcoma protuberans in most instances, focal CD34 positivity may be seen in cellular fibrous histiocytoma.

Assessment of sentinel lymph node in cervical cancer: review of literature.

Sentinel lymph node biopsy is a novel method for the surgical management of patients with cervical cancer. Sentinel nodes have a higher chance of harbouring metastases than non-sentinel nodes. Assessment of sentinel nodes provides an opportunity to stage patients intraoperatively and avoid complete pelvic lymph node dissection and hence its morbidities.

Radical vaginal trachelectomy vs. radical hysterectomy for small early stage cervical cancer: a matched case-control study.

Objective: To determine the efficacy and outcome from radical vaginal trachelectomy (RVT) compared to a matched group of patients undergoing radical hysterectomy for small early stage cervical cancer.

Methods: All patient data were entered prospectively. Patients wishing preservation of fertility with cervical cancer, tumor <2 cm, and not meeting the definition of microinvasive cancer were offered RVT.

Adenomyosis involved by endometrial adenocarcinoma is a significant risk factor for deep myometrial invasion.

Adenomyosis is commonly seen in association with endometrial adenocarcinoma where it may or may not be involved by malignancy. This study of grade 1 endometrioid adenocarcinoma investigates whether patients with cancer-positive adenomyosis are at a different risk for deep myometrial invasion compared with those with cancer-negative adenomyosis. Ninety-three hysterectomy specimens with FIGO (International Federation of Gynecologists and Obstetricians) grade 1 endometrial endometrioid adenocarcinoma associated with adenomyosis were studied.

Sentinel lymph node in vulvar cancer.

Background: The aim of the study was to assess the feasibility, efficacy, and accuracy of the sentinel lymph node (SLN) procedure in vulvar cancer.

Methods: From April 2004 to September 2006, all patients with vulvar cancer, clinical stages I and II, underwent SLN detection, followed by a complete inguinofemoral lymphadenectomy. Demographic, surgical, and pathologic data on all patients were prospectively entered in a database.

Adenomyosis is associated with myometrial invasion by FIGO 1 endometrial adenocarcinoma.

Adenomyosis is commonly seen in hysterectomy specimens for endometrial adenocarcinoma where it could be involved with the tumor. When adenocarcinoma involves adenomyosis, the tumor may remain limited to the adenomyosis or proceeds to invade the adjacent myometrium. The purpose of this study was to investigate whether the risk of myometrial invasion by grade 1 endometrioid adenocarcinoma in cases with cancer-positive adenomyosis is different from that of cases where cancer occurs in the absence of adenomyosis.

Sentinel lymph nodes in early stage cervical cancer.

Objectives: Lymph node status is the most important prognostic factor in cervical cancer. Sentinel lymph node (SLN) procedures have been purported to reduce peri- and postoperative morbidity and operative time.

Methods: All patients with surgically managed clinical FIGO stage IA/B1 cervical cancer underwent SLN followed by pelvic lymphadenectomy with technetium+/-lymphazurin from April 2004 to April 2006.

Cyclooxygenase-2 (COX-2) immunostaining does not correlate with the degree of vulvar neoplasia.

Objective: The cyclooxygenase-2 (COX-2) enzyme is up-regulated in inflammatory and neoplastic conditions. In the last decade, its biological role has been investigated in various pre-invasive and invasive cancers with the hope that it can serve as a target for cancer prevention and treatment.

Methods: We evaluated the expression of COX-2 in vulvar biopsies to determine its relationship to the degree of dysplasia.