Somatic deletions of the polyA tract in the 3' untranslated region of epidermal growth factor receptor are common in microsatellite instability-high endometrial and colorectal carcinomas.

CONTEXT: Epidermal growth factor receptor (EGFR) is overexpressed in up to 80% of colorectal and endometrial carcinomas. Deletions of the polyA tract in the 3' untranslated region (3' UTR) have been reported in microsatellite instability-high (MSI-H) colonic carcinomas, but their impacts on EGFR expression and downstream pathways are unclear. This phenomenon has not been reported in other MSI-H tumors. OBJECTIVE: To assess the 3' UTR polyA tract of EGFR in both endometrial and colorectal carcinomas and the mutational status of EGFR downstream pathways. DESIGN: Ninety-eight colorectal carcinomas and 47 endometrial carcinomas were included. EGFR 3' UTR polyA status was detected by capillary electrophoresis and Sanger sequencing. EGFR gene expression, EGFR copy numbers, and KRAS and BRAF mutation status were analyzed accordingly. RESULTS: The 3' UTR polyA tract was deleted in 18 of 23 (78%) MSI-H versus 0 of 24 microsatellite-stable endometrial carcinomas (P < .001). Similar observations were seen in colorectal carcinomas, in which 29 of 36 (81%) MSI-H, 1 of 62 (1.6%) microsatellite instability-low, and none of the microsatellite-stable tumors harbored the deletion (P < .001). A moderate increase in EGFR mRNA level was observed in endometrial carcinomas with 3' UTR polyA deletions versus those with wild-type polyA tract. Amplification of the EGFR gene was not observed. Deletions in polyA tract do not seem to affect the frequency of KRAS and BRAF mutations. CONCLUSIONS: Deletions of EGFR 3' UTR polyA are frequent in endometrial and colorectal carcinomas, are confined almost exclusively to MSI-H tumors, and do not affect KRAS and BRAF mutations.

CTNNB1 genotyping and APC screening in pediatric desmoid tumors: a proposed algorithm.

Desmoid fibromatosis is a rare, locally aggressive fibroblastic/myofibroblastic tumor that occasionally involves children. We examined a series of pediatric desmoids for CTNNB1 mutations, seen in sporadic tumors, and APC germline mutations, associated with familial adenomatous polyposis (FAP). Forty-four desmoids in pediatric patients were identified in the pathology files of 2 large referral centers (1995-2009). Clinical charts were reviewed for history of FAP. Germline APC gene mutations were determined on blood samples from patients presenting with FAP. Immunohistochemistry for beta-catenin was performed. CTNNB1 genotyping was done by Sanger sequencing on formalin-fixed paraffin-embedded tissue. CTNNB1 mutations were observed in 29 of 44 (66%) desmoids, with 3 mutations identified: T41A (64%), S45F (29%), and S45P (7%). Germline APC mutations were present in 7 (16%) desmoid patients. Eight (18%) patients had desmoids that were wild type for CTNNB1 and had no known clinical signs or family history suspicious for FAP at the time of testing or with extended follow up (n  =  6). Beta-catenin nuclear labeling was observed in 38 of 41 (92%) tested cases, 34 (89%) of which showed mutations in either CTNNB1 (n  =  29) or APC (n  =  5). Nuclear localization of beta-catenin was seen in the majority of pediatric desmoids and was most often associated with somatic mutations in CTNNB1. However, a significant proportion of pediatric patients harbored germline mutations in APC. Given the implications, genetic counseling is recommended for children diagnosed with desmoid tumors lacking CTNNB1 mutations because this population is enriched for FAP patients.

Analysis of pathology department Web sites and practical recommendations.

CONTEXT: There are numerous customers for pathology departmental Web sites, including pathology department staff, clinical staff, residency applicants, job seekers, and other individuals outside the department seeking department information. Despite the increasing importance of departmental Web sites as a means of distributing information, no analysis has been done to date of the content and usage of pathology department Web sites. OBJECTIVE: In this study, we analyzed pathology department Web sites to examine the elements present on each site and to evaluate the use of search technology on these sites. Further, we examined the usage patterns of our own departmental Internet and internet Web sites to better understand the users of pathology Web sites. DESIGN: We reviewed selected departmental pathology Web sites and analyzed their content and functionality. Our institution's departmental pathology Web sites were modified to enable detailed information to be stored regarding users and usage patterns, and that information was analyzed. RESULTS: We demonstrate considerable heterogeneity in departmental Web sites with many sites lacking basic content and search features. In addition, we demonstrate that increasing the traffic of a department's informational Web sites may result in reduced phone inquiries to the laboratory. We propose recommendations for pathology department Web sites to maximize promotion of a department's mission. CONCLUSIONS: A departmental pathology Web site is an essential communication tool for all pathology departments, and attention to the users and content of the site can have operational impact.

The complications of scar formation associated with intrathecal pump placement.

A 40-year-old man had an intrathecal morphine-baclofen pump inserted for the treatment of severe dystonia affecting all limbs and severe low back pain. The etiology of his dystonic symptoms, despite thorough investigations, was uncertain. At age 45, the patient fell resulting in a cervical spinal cord injury. He underwent C2 through C5 instrumentation and fusion for cervical spine stabilization. Subsequently, an intrathecal morphine-baclofen pump was implanted to control pain and decrease spasticity. The patient ultimately died at age 48 from complications of pneumonia, and an autopsy was performed. Gross pathologic examination revealed that the intrathecal catheter entered the posterior aspect of the lumbar thecal sac, but coursed superiorly in the anterior intradural space. The catheter tip exited the thecal sac in the upper thoracic spine and became embedded in a fibrotic scar. Displacement of the catheter tip of the intrathecal morphine-baclofen pump and subsequent formation of scar tissue resulted in decreased drug delivery, contributing to diminished pain control and functional status. Catheter displacement and epidural scar formation must be considered as a potential cause of ineffective pain control and decreased functional status in patients with intrathecal morphine-baclofen pumps.