Mutant POLQ and POLZ/REV3L DNA polymerases may contribute to the favorable survival of patients with tumors with POLE mutations outside the exonuclease domain.

Background: Mutations in the exonuclease domain of POLE, a DNA polymerase associated with DNA replication and repair, lead to cancers with ultra-high mutation rates. Most studies focus on intestinal and uterine cancers with POLE mutations. These cancers exhibit a significant immune cell infiltrate and favorable prognosis.

Guidelines to Aid in the Distinction of Endometrial and Endocervical Carcinomas, and the Distinction of Independent Primary Carcinomas of the Endometrium and Adnexa From Metastatic Spread Between These and Other Sites.

In most cases of suspected endometrial neoplasia tumor origin can be correctly assigned according to a combination of clinical, radiologic, and pathologic features, even when the latter are based upon the examination of relatively small biopsy samples. However there are well-recognized exceptions to this rule which continue to create diagnostic difficulty, and sometimes difficulties persist even after the detailed examination of resection specimens. Among the most common problems encountered in practice are the distinction of primary endometrial and primary endocervical adenocarcinomas, and the determination of tumor origin when there is synchronous, multifocal involvement of gynecologic tract sites, for example the endometrium and the ovary.

Redefining the Positive Margin in Pancreatic Cancer: Impact on Patterns of Failure, Long-Term Survival and Adjuvant Therapy.

Purpose: There is debate regarding the definition and clinical significance of margin clearance in pancreatic ductal adenocarcinoma (PDA). A comprehensive archival analysis of surgical resection margins was performed to determine the effect on locoregional recurrence and survival, and the impact of adjuvant therapy in PDA.

Methods: We identified 105 patients with resected PDA.

Role of Lymphovascular Invasion in Pattern C Invasive Endocervical Adenocarcinoma.

Lymphovascular invasion (LVI) has been reported as an independent predictor of patient outcome in cervical carcinoma. However, not all studies support independent significance, especially in multivariable analyses. A risk stratification system recently introduced for endocervical adenocarcinoma was reported to better predict risk of lymph node (LN) metastasis.

Comparison of endoscopic ultrasound guided fine needle aspiration and PET/CT in preoperative diagnosis of pancreatic adenocarcinoma.

Background: Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the procedure of choice to investigate and sample pancreatic masses for the preoperative diagnosis of pancreatic ductal adenocarcinoma (PDAC). The role of fluoro-deoxyglucose positron emission tomography/computed tomography (PET/CT) in PDAC is debated. This study evaluates the role of EUS-FNA as compared to PET/CT in the preoperative evaluation of PDAC.

Interobserver Reproducibility Among Gynecologic Pathologists in Diagnosing Heterologous Osteosarcomatous Component in Gynecologic Tract Carcinosarcomas.

Distinguishing hyalinized stroma from osteoid production by a heterologous osteosarcomatous component can be challenging in gynecologic tract carcinosarcomas. As heterologous components in a carcinosarcoma may have prognostic and therapeutic implications, it is important that these are recognized. This study examines interobserver reproducibility among gynecologic pathologists in the diagnosis of osteosarcomatous components, and its correlation with expression of the novel antibody SATB2 (marker of osteoblastic differentiation) in these osteosarcomatous foci.

Adipose Triglyceride Lipase (ATGL) Expression Is Associated with Adiposity and Tumor Stromal Proliferation in Patients with Pancreatic Ductal Adenocarcinoma.

Background: Obesity is an established risk factor for the development of pancreatic ductal adenocarcinoma (PDAC). However, the pathophysiology of how increased adiposity increases the risk for PDAC has not been fully elucidated. Adipose triglyceride lipase (ATGL) is a lipase that catabolizes triglyceride hydrolysis and has been implicated in the development of breast cancer.

Factors Predicting Pelvic Lymph Node Metastasis, Relapse, and Disease Outcome in Pattern C Endocervical Adenocarcinomas.

A pattern-based classification system has recently been proposed for invasive endocervical adenocarcinoma (EAC), which is predictive of the risk for lymph node metastases (LNM). The main utility of the system lies in separating cases with very low risk for LNM (pattern A) from those with higher risk (pattern B and C). Different growth patterns (GPs) are found in pattern C cases.

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.

Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy.

Background: Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT).

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.

Update on pathology, staging and molecular pathology of endometrial (uterine corpus) adenocarcinoma.

Endometrial carcinoma is comprised of two major groups: type I that is hormonally driven with a good prognosis and type II that is hormone independent with a poor prognosis. The two most common subtypes are endometrioid adenocarcinoma, the prototypic type I cancer, and uterine serous carcinoma, the prototypic type II cancer, each with their own distinct precursor lesion. The histologic type, as codified by the WHO Tumor Classification system, grade, and stage are used to guide treatment.

Vascular invasion in uterine sarcomas and its significance. A multi-institutional study.

Although metastases and high-mortality are frequent in high-grade endometrial sarcomas (HGSs), these findings are less commonly seen in low-grade endometrial stromal sarcomas (LGESSs), even in cases with lymphovascular invasion (LVI). We hypothesized that the "bulging plugs" of tumor characteristic of LVI in LGESS are fundamentally different from LVI seen in HGS. We reviewed 70 uterine sarcomas: 42 HGSs (high-grade endometrial stromal sarcomas, undifferentiated uterine sarcoma, and leiomyosarcoma) and 28 LGESSs.

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.

A small organ takes center stage: selected topics in fallopian tube pathology.

In this paper we consider a number of non-neoplastic and neoplastic lesions of the fallopian tube. Emphasis has been placed on diagnostically difficult entities, some of which result in misdiagnosis and consequent alteration of treatment, including "pseudocarcinomas" that represent a florid epithelial response to acute and/or chronic salpingitis. Endometriosis-related lesions may cause infertility, or undergo malignant transformation to a Mullerian carcinoma, most frequently endometrioid and clear cell types.

Mechanism of hepatotoxicity due to black cohosh (Cimicifuga racemosa): histological, immunohistochemical and electron microscopy analysis of two liver biopsies with clinical correlation.

Background: Consumption of herbal supplements in the developed world remains high. Cimicifuga racemosa (C. racemosa) extract, or black cohosh, is widely used as a hormone replacing and an anti-inflammatory agent, and has been shown to cause idiosyncratic hepatitis.

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.

Desmoplastic stromal response as defined by positive α-smooth muscle actin staining is predictive of invasion in adenocarcinoma of the uterine cervix.

The objective of this research was to examine the immunohistochemical profiles of adenocarcinoma in situ (AIS) and early invasive adenocarcinoma (AC) to identify biomarkers that enhance the accurate diagnosis of early invasive glandular lesions of the cervix. The University of California, Irvine, and Long Beach Memorial tumor registries were used to identify 20 women with AIS or early AC treated between 1990 and 2008. An immunohistochemical study was performed, and the primary endpoint measured was the correlation between biomarker expression and invasive disease as diagnosed on hematoxylin and eosin examination.

DNA mismatch repair deficiency in endometrial carcinoma.

Microsatellite instability (MSI) is the hallmark of a molecular pathway to carcinogenesis due to sporadic or inherited abnormalities of DNA mismatch repair genes. Inherited mutations are seen in hereditary nonpolyposis colorectal cancer syndrome. Endometrial carcinoma shows as high an incidence of MSI as does colorectal carcinoma.

Margin distance and other clinico-pathologic prognostic factors in vulvar carcinoma: a multivariate analysis.

Objectives: To determine the importance of margin status and other prognostic factors associated with the recurrence and survival of patients with squamous cell vulvar carcinoma.

Methods: Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression. All slides were re-reviewed by two gynecologic pathologists.

p16-Positive small cell neuroendocrine carcinoma of the endometrium.

We report herein a small cell neuroendocrine carcinoma of the endometrium that extended to the cervix and showed strong immunohistochemical staining for p16. The p16 staining raised the possibility of a human papillomavirus (HPV)-related tumor, because in the cervix, a positive p16 immunohistochemical stain is presumptive evidence of HPV. However, the current case was HPV negative.