Molecular and pathological basis of HPV-negative cervical adenocarcinoma seen in a global study.

International surveys find HPV-negativity in up to 30% of cervical adenocarcinomas. We investigated the pathological diagnosis by expert consensus with immunohistochemistry and the presence of somatic mutations in recognised tumour genes in HPV-positive and negative cervical adenocarcinomas (CADC). A sample was selected of 45 paraffin-embedded cervical blocks diagnosed locally as usual cervical adenocarcinoma from a global study.

p16 Positive Histologically Bland Squamous Metaplasia of the Cervix: What does It Signify?

With increasing use of p16 immunohistochemistry (IHC) in diagnosis of premalignant lesions of cervix, we occasionally encounter p16 positivity in squamous metaplasia that lacks morphologic characteristics of "atypical squamous metaplasia" or of squamous intraepithelial lesion (SIL). Our study aims to investigate if transcriptionally active human papilloma virus (HPV) can be identified in such foci and if they have any relationship with squamo-columnar junction (SCJ) cells. Twenty-two cases of cervical specimens with at least a focus of p16 positive bland squamous metaplasia, were selected.

Gastric-type Adenocarcinoma of the Cervix: Tumor With Wide Range of Histologic Appearances.

Gastric-type endocervical adenocarcinoma (GAS) is a recently described diagnostic entity originally characterized as a tumor with (1) voluminous cytoplasm that is (2) clear or pale eosinophilic, and (3) cells showing distinct cell borders. Since the initial tumor description there has been accumulating experience that the neoplasm, in addition to classic features, may show a wide spectrum of morphologic appearances. This paper describes and illustrates cases of GAS with focal or diffuse findings that include: densely eosinophilic cytoplasm, foamy cytoplasm, goblet cells, glands with elongated, stratified nuclei, glands with small cuboidal cells, glands with flattened cells, papillary growth, single cell infiltration and infiltration with microcystic elongated and fragmented pattern.

The Variable Characteristics of Human Papillomavirus in Squamous Cell Carcinoma and Adenocarcinoma of Cervix in China.

Objective: A hospital-based multicenter, retrospective study was conducted to compare the distribution of human papillomavirus (HPV) in squamous cell carcinoma (SCC) and cervical adenocarcinoma (CADC) in China.

Methods: Paraffin-embedded tissue blocks diagnosed as SCC and CADC across China were collected, as well as the total number of diagnosed invasive cervical cancer of the 9 selected centers. DNA enzyme immunoassay, reverse hybridization, and multiplex type-specific polymerase chain reaction were used for HPV genotyping.

Fluorescence microscopy of H&E stained cervical biopsies to assist the diagnosis and grading of CIN.

Background: Prevention of cervical cancer is based upon the accurate diagnosis and grading of cervical lesions identified during screening. The pathological classification of cervical intraepithelial neoplasia (CIN) is problematic, as it relies on subjective criteria and is known to have high interobserver variability and low reproducibility. These limitations can result in either over or under treatment of patients.

Presence or Absence of Significant HPVE4 Expression in High-grade Anal Intraepithelial Neoplasia With p16/Ki-67 Positivity Indicates Distinct Patterns of Neoplasia: A Study Combining Immunohistochemistry and Laser Capture Microdissection PCR.

Progression of anal intraepithelial neoplasia (AIN) involves transition from productive to transforming human papillomavirus (HPV) infection. Grading aims to distinguish productive low-grade AIN from high-grade anal intraepithelial neoplasia (HGAIN) with risk of cancer. We describe immunohistochemical patterns in AIN adding a novel marker for initiation of the productive phase of the HPV life cycle (panHPVE4) to those for cell cycle activity (Ki-67) and transforming activity of HPVE7 gene (p16).

Despite Diagnostic Morphology, Many Mixed Endometrial Carcinomas Show Unexpected Immunohistochemical Staining Patterns.

Historically, endometrial carcinomas have been classified primarily according to their histology. However, the use of immunohistochemistry has become commonplace in their evaluation, particularly in diagnostically challenging cases. Our objective was to evaluate mixed endometrial carcinomas using a well-established panel of biomarkers to assess the consistency and utility of these stains in clinical diagnosis.

Utility of Stathmin-1 as a Novel Marker in Evaluating Anal Intraepithelial Neoplasia (AIN).

The aim of this study is to determine whether immunohistochemistry for Stathmin-1 enhances diagnostic accuracy of anal dysplasia. The study included 40 biopsies with diagnosis of benign anal transitional zone (n=10), low-grade anal intraepithelial neoplasia (AIN) (AIN1, n=10), and high-grade AIN (AIN2, n=10, AIN3, n=10). The cases were selected to represent classic features.

Novel Fumarate Hydratase Mutation in Siblings With Early Onset Uterine Leiomyomas and Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome.

Hereditary leiomyomatosis renal cell cancer syndrome is an autosomal dominant disorder characterized by uterine and cutaneous leiomyomas and increased predisposition to renal cell carcinoma, papillary type II. The syndrome is caused by heterozygous mutations to the fumarate hydratase (FH) gene located on chromosome 1. Affected females generally present with early onset, atypical uterine leiomyomas and cutaneous findings, however, delays in diagnosis are very common in patients with isolated uterine findings.

Cervical Adenocarcinoma: Diagnosis of Human Papillomavirus-Positive and Human Papillomavirus-Negative Tumors.

Context: - Cervical adenocarcinomas span a diverse group of tumors with several distinct histologic tumor types, which include endocervical, endometrioid, intestinal, villoglandular, gastric, signet ring, serous, clear cell, and mesonephric. Diagnosis of cervical adenocarcinoma, especially early diagnosis, poses a significant challenge.

Objective: - To review the pathogenesis, diagnostic criteria, immunohistochemical markers, and differential diagnosis of various subtypes of human papillomavirus (HPV)-positive and HPV-negative cervical adenocarcinomas.

Detection of and invasive endocervical adenocarcinoma on ThinPrep Pap Test: Morphologic analysis of false negative cases.

Background: The goal of this study was to calculate the sensitivity and false negative (FN) rate of ThinPrep Pap Test (TPPT) and carefully analyze missed cases for educational purposes.

Materials And Methods: Patients with histologically proven adenocarcinoma (AIS) or invasive endocervical adenocarcinoma (EAC) over a 17-year-period (1998-2015) were identified. The TPPT immediately preceding the histological diagnosis of AIS/ECA was designated as index Pap (IP).

The variable clinicopathological categories and role of human papillomavirus in cervical adenocarcinoma: A hospital based nation-wide multi-center retrospective study across China.

We investigated HPV in adenocarcinoma presenting and managed as cervical adenocarcinoma (CADC) at seven major representative regional cancer centres across China. From 1,051 CADC cases diagnosed locally in 2005-2010, 881 had available paraffin embedded tissue. Initial review excluded 154 cases as other diagnoses or inappropriate specimens.

The metabolic/pH sensor soluble adenylyl cyclase is a tumor suppressor protein.

cAMP signaling pathways can both stimulate and inhibit the development of cancer; however, the sources of cAMP important for tumorigenesis remain poorly understood. Soluble adenylyl cyclase (sAC) is a non-canonical, evolutionarily conserved, nutrient- and pH-sensing source of cAMP. sAC has been implicated in the metastatic potential of certain cancers, and it is differentially localized in human cancers as compared to benign tissues.

Prostate-specific Membrane Antigen (PSMA) Expression in the Neovasculature of Gynecologic Malignancies: Implications for PSMA-targeted Therapy.

The goal of the study was to examine expression of prostate-specific membrane antigen (PSMA) in neovasculature of gynecologic cancers, as PSMA-targeted therapy has showed a promise in treatment of advanced carcinomas. The study included cervical carcinoma (n=28), vulvar carcinoma (n=20), endometrial carcinoma (n=23), primary ovarian carcinoma (n=21), metastatic ovarian carcinoma (n=25), and normal cervix (n=12) as negative control. All cases were immunostained using anti-CD31 antibody to delineate capillary endothelial cells.

HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

Background: We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation.

Methods: Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection.

The complex relationship between human papillomavirus and cervical adenocarcinoma.

Human Papillomavirus (HPV) is reported in 60-100% of cervical adenocarcinoma (CADC) globally. We investigated this relationship in a hospital-based survey in China. 718 CADC samples from nine Chinese regions were analysed.

Diagnostic imaging of cervical intraepithelial neoplasia based on hematoxylin and eosin fluorescence.

Background: Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues.

Methods: Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center.

High grade endometrial stromal sarcoma on thinprep.

High grade endometrial stromal sarcoma (HGESS) is an uncommon malignancy recently re-defined in the new WHO classification of endometrial stromal tumors. In this article, we discuss the differential diagnoses of metastatic HGESS in a fine needle aspiration (FNA) of a lymph node and compare the cytomorphology of HGESS in ThinPrep [(TP), Hologic Inc., Boxborough, MA] to conventional smears (CS).

Human papillomavirus prevalence and type-distribution in cervical glandular neoplasias: Results from a European multinational epidemiological study.

Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type-distribution in CGN vary, providing uncertain evidence to support prophylactic vaccination and HPV screening. This study [108288/108290] assessed HPV prevalence and type-distribution in women diagnosed with cervical adenocarcinoma in situ (AIS, N = 49), adenosquamous carcinoma (ASC, N = 104), and various adenocarcinoma subtypes (ADC, N = 461) from 17 European countries, using centralised pathology review and sensitive HPV testing.

Immunohistochemistry and in situ hybridization for the diagnosis and classification of squamous lesions of the anogenital region.

Distinguishing anogenital squamous intraepithelial lesions from benign conditions and mimics may be problematic. Immunohistochemistry for surrogate markers of HPV infection, such as Ki-67, p16, and ProEx™ C, may aid the diagnosis in equivocal cases. The main diagnostic pitfall in the diagnosis of LSIL is the occurrence of "pseudokoilocytes" in benign squamous mucosa, which may lead to overdiagnosis.

Diagnosis of HPV-negative, gastric-type adenocarcinoma of the endocervix.

Gastric-type adenocarcinoma of the cervix (GAS) is a novel, recently described subtype of endocervical adenocarcinoma. The clinical importance of accurate diagnosis of GAS stems from the observation that it confers worse prognosis than the usual-type endocervical adenocarcinoma. There are two unique characteristics of GAS: the tumor cells contain voluminous amounts of gastric-type mucins, and the tumor pathogenesis is not related to infection with high-risk human papillomavirus types.

Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide.

Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011.

HPV prevalence and genotypes in different histological subtypes of cervical adenocarcinoma, a worldwide analysis of 760 cases.

The goal of our study was to provide comprehensive data on the worldwide human papillomavirus (HPV) genotype distribution in patients with invasive cervical adenocarcinoma in correlation with histologic tumor subtypes, geographical location, patients' age, and duration of sample storage. Paraffin-embedded samples of 760 cervical adenocarcinoma cases were collected worldwide. A three-level pathology review of cases was performed to obtain consensus histologic diagnoses and 682 cases were determined to be eligible for further analysis.