Mixed pancreatic ductal adenocarcinoma and well-differentiated neuroendocrine tumor: A case report.

Background: Pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare malignancies affecting the pancreas. The World Health Organization defines MiNENs as neoplasms composed of morphologically recognizable neuroendocrine and non-neuroendocrine components, each constituting 30% or more of the tumor volume. Adenocarcinoma-neuroendocrine carcinoma is the most frequent MiNEN combination.

Encephalitis associated with a monoclonal protein band present in blood, urine and cerebrospinal fluid.

Introduction: Monoclonal protein bands are present mainly in blood and secondary in urine representing specific antibody produced in excess by abnormal lymphocytes or plasma cells.We describe a case of a patient with acute encephalitis associated with an unexpected finding of a monoclonal protein band present in blood, urine and in cerebrospinal fluid (CSF).

Case Presentation: This 50-year-old woman with no significant past medical history, with the exception of unintentional weight loss exceeding 5 kg over the last 3 months, presented to the emergency department with seizures and altered mental status, after 3 days of vomiting and headaches.

A Rare Case of Multifocal Asynchronous Benign Granular Cell Tumors with Subclonal Mutation Identified in One Tumor by Next-Generation Sequencing.

Granular cell tumor (GCT) is a benign neuroectodermal tumor typically in the dermis or subcutis, although deep soft tissues and organs are occasionally involved. Multifocal GCTs are estimated to occur as many as 10% of patients. A 40-year-old female presented with multiple GCTs asynchronously involving various body sites including gastrointestinal, gynecologic, breast, urinary, and soft tissue systems.

Implementation of Laboratory Review of Test Builds Within the Electronic Health Record Reduces Errors.

Context.—: As electronic health records (EHRs) become more ubiquitous, physicians have come to expect that laboratory data from a variety of sources will be incorporated into the EHR in a structured format. The Clinical Laboratory Improvement Amendments have standards for data transmission traditionally met by pathologist review of their own hospital laboratory information system transmissions.

Optimization of the Order Menu in the Electronic Health Record Facilitates Test Patterns Consistent With Recommendations in the Choosing Wisely Initiative.

Objectives: Thyroid and rheumatologic autoimmune testing are areas where evidence-based guidance from specialty organizations and Choosing Wisely support utilizing screening tests for autoimmune and thyroid disorders prior to more specialized testing. Adjustment of the orderable options in the electronic health record (EHR) can influence ordering patterns without requiring manual review or additional effort by the clinician.

Methods: The menu was adjusted to reflect recommendations from Choosing Wisely to favor screening tests that automatically reflex to specialized testing on primary care providers' preference lists.

Classification of the four main types of lung cancer using a microRNA-based diagnostic assay.

For patients with primary lung cancer, accurate determination of the tumor type significantly influences treatment decisions. However, techniques and methods for lung cancer typing lack standardization. In particular, owing to limited tumor sample amounts and the poor quality of some samples, the classification of primary lung cancers using small preoperative biopsy specimens presents a diagnostic challenge using current tools.

A second-generation microRNA-based assay for diagnosing tumor tissue origin.

Background: Cancers of unknown primary origin (CUP) constitute 3%-5% (50,000 to 70,000 cases) of all newly diagnosed cancers per year in the United States. Including cancers of uncertain primary origin, the total number increases to 12%-15% (180,000 to 220,000 cases) of all newly diagnosed cancers per year in the United States. Cancers of unknown/uncertain primary origins present major diagnostic and clinical challenges because the tumor tissue of origin is crucial for selecting optimal treatment.

Aspirin and low-dose nitric oxide-donating aspirin increase life span in a Lynch syndrome mouse model.

Nonsteroidal anti-inflammatory drugs (NSAID) appear to be effective cancer chemopreventives. Previous cellular studies showed that aspirin (acetylsalicylic acid: ASA) and nitric oxide-donating ASA (NO-ASA) suppressed microsatellite instability (MSI) in mismatch repair (MMR)-deficient cells linked to the common cancer predisposition syndrome hereditary nonpolyposis colorectal cancer or Lynch syndrome (LS/HNPCC), at doses 300- to 3,000-fold less than ASA. Using a mouse model that develops MMR-deficient intestinal tumors that appear pathologically identical to LS/HNPCC, we show that ASA (400 mg/kg) and low-dose NO-ASA (72 mg/kg) increased life span by 18% to 21%.

Accurate classification of metastatic brain tumors using a novel microRNA-based test.

Background: Identification of the tissue of origin of a brain metastatic tumor is vital to its management. Carcinoma of unknown primary (CUP) is common in oncology, representing 3%-5% of all invasive malignancies. We aimed to validate a recently developed microRNA-based quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) test for identifying the tumor tissue of origin, first in a consecutive cohort of metastatic tumors of known origin and then in a cohort of CUP cases resected from the central nervous system (CNS).

Activating mutation (V617F) in the tyrosine kinase JAK2 is absent in locally-confined or castration-resistant prostate cancer.

Background: Transcription factor Stat5a/b is highly critical for the viability of human prostate cancer cells in vitro and for prostate tumor growth in vivo. Stat5 is constitutively active in clinical prostate cancers but not in the normal human prostate epithelium. Moreover, Stat5a/b activation in prostate cancer is associated with high histological grade of prostate cancer.

Histopathologic features and microsatellite instability of cancers of the papilla of vater and their precursor lesions.

The prevalence and development of microsatellite instability (MSI) and underlying mismatch repair (MMR) deficiency in the carcinogenesis of adenocarcinomas of the papilla of Vater and their precursor lesions are not well established. We analyzed 120 ampullary adenomas (31 pure adenomas and 89 carcinoma-associated adenomas) and 170 pure adenocarcinomas for MSI, immunohistochemical expression of MMR proteins and specific histopathologic features. The most common histologic subtype was intestinal (46.

The modifier of Min 2 (Mom2) locus: embryonic lethality of a mutation in the Atp5a1 gene suggests a novel mechanism of polyp suppression.

Inactivation of the APC gene is considered the initiating event in human colorectal cancer. Modifier genes that influence the penetrance of mutations in tumor-suppressor genes hold great potential for preventing the development of cancer. The mechanism by which modifier genes alter adenoma incidence can be readily studied in mice that inherit mutations in the Apc gene.

Prevalence of the mismatch-repair-deficient phenotype in colonic adenomas arising in HNPCC patients: results of a 5-year follow-up study.

In hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, more than 90% of the carcinomas show microsatellite instability (MSI) due to a loss of mismatch repair (MMR) function. Although adenomas are very common in HNPCC and demonstrate an accelerated adenoma-carcinoma sequence, data about the prevalence and development of MSI in these early neoplastic lesions are lacking. To determine whether MSI and loss of MMR-protein expression are already present in early stages of tumorigenesis and could therefore be used as a screening tool to identify HNPCC patients before they develop an invasive carcinoma, we analyzed 71 adenomas of 36 HNPCC patients during a 5-year follow-up study.

Microsatellite analysis of hereditary nonpolyposis colorectal cancer-associated colorectal adenomas by laser-assisted microdissection: correlation with mismatch repair protein expression provides new insights in early steps of tumorigenesis.

Although microsatellite instability (MSI) testing is a useful tool for molecular screening of hereditary nonpolyposis colorectal cancer (HNPCC) carcinomas, conflicting results have been obtained in colorectal adenomas. This might result from different techniques of tissue sampling and MSI analysis. Alternatively, some HNPCC-associated adenomas may follow a molecular route that differs from the MSI pathway.

MSI-testing in hereditary non-polyposis colorectal carcinoma (HNPCC).

Genomic instability at simple repeated sequences, termed microsatellite instability (MSI), plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC) more than 90% of cases show MSI, whereas only 10-15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC.

Microsatellite status and cell cycle associated markers in rectal cancer patients undergoing a combined regimen of 5-FU and CPT-11 chemotherapy and radiotherapy.

Background: Microsatellite instability (MSI) and expression of cell cycle-related markers may predict a favorable outcome in colorectal cancer patients. The aim of this study was to elucidate the molecular profiles of patients with rectal cancers treated with neoadjuvant chemotherapy (5-Fluorouracil and CPT-11), radiotherapy and surgery that correlate with response to therapy.

Patients And Methods: Fifty-seven patients with rectal cancer were treated with the same preoperative chemotherapy regimen, radiotherapy (45 to 54 Gy) followed by surgery.

Challenges and pitfalls in HNPCC screening by microsatellite analysis and immunohistochemistry.

Hereditary non-polyposis colorectal cancer (HNPCC) accounts for approximately 2 to 4% of the total colorectal cancer burden. For economic reasons a diagnostic "stepladder" is recommended. After evaluation of the family history, diagnostic microsatellite instability (MSI) analysis has found its place as a valuable screening tool for HNPCC.

Penetrance and expressivity of MSH6 germline mutations in seven kindreds not ascertained by family history.

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by inherited mutations in DNA mismatch-repair genes, most commonly MLH1 or MSH2. The role MSH6 plays in inherited cancer susceptibility is less well defined. The aim of this study was to investigate the penetrance and expressivity of MSH6 mutations in kindreds ascertained through endometrial cancer probands unselected for family history.

Increased risk for hereditary nonpolyposis colorectal cancer-associated synchronous and metachronous malignancies in patients with microsatellite instability-positive endometrial carcinoma lacking MLH1 promoter methylation.

Purpose: The aim of this study was to evaluate number and types of synchronous and metachronous malignancies in patients with endometrial carcinoma with and without microsatellite instability (MSI).

Experimental Design: From a series of 413 endometrial cancer patients, we identified 94 patients with MSI-positive (MSI+) cancers and grouped them by tumor MLH1 promoter methylation status. These 94 patients were matched by year of surgery to 94 patients with MSI-negative (MSI-) endometrial cancers from the same series.