Intramural gastric masses arise in the wall of the stomach (generally within the submucosa or muscularis propria), often with intact overlying mucosa. These tumors are typically mesenchymal in origin and have overlapping radiologic appearances. A combination of features such as location, attenuation, enhancement, and growth pattern may suggest one diagnosis over another. Gastrointestinal stromal tumors (GISTs) account for the majority of intramural tumors and can vary widely in appearance, from small intraluminal lesions to exophytic masses that protrude into the peritoneal cavity, commonly with areas of hemorrhage or necrosis. A well-circumscribed mass measuring -70 to -120 HU is a lipoma. Leiomyomas usually manifest as low-attenuation masses at the gastric cardia. Homogeneous attenuation is a noteworthy characteristic of schwannomas, particularly for larger lesions that might otherwise be mistaken for GISTs. A hypervascular mass in the antrum is a common manifestation of glomus tumors. Hemangiomas are also hypervascular but often manifest in childhood. Inflammatory fibroid polyps usually arise as a polypoid mass in the antrum. Inflammatory myofibroblastic tumors are infiltrative neoplasms with a propensity for local recurrence. Plexiform fibromyxomas are rare, usually antral tumors. Carcinoid tumors are epithelial in origin, but often submucosal in location, and therefore should be distinguished from other intramural lesions. Multiple carcinoid tumors are associated with hypergastrinemia, either in the setting of chronic atrophic gastritis or Zollinger-Ellison syndrome. Sporadic solitary carcinoid tumors not associated with hypergastrinemia have a higher rate of metastasis. Histopathologic analysis, including immunohistochemistry, is usually required for diagnosis of intramural masses.

Context.-The prognosis of appendiceal goblet cell carcinoid tumors (GCTs) is believed to be intermediate between appendiceal adenocarcinomas and conventional carcinoid tumors. However, GCTs can have mixed morphologic patterns, with variable amount of adenocarcinoma.Objective.-To evaluate the behavior of GCTs and related entities with variable components of adenocarcinoma.Design.-We classified 74 cases of appendiceal tumors into 3 groups: group 1, GCTs or GCTs with less than 25% adenocarcinoma; group 2, GCTs with 25% to 50% adenocarcinoma; group 3, GCTs with more than 50% adenocarcinoma; and a comparison group of 68 adenocarcinomas without a GCT component (group 4). Welldifferentiated mucinous adenocarcinomas were excluded. Clinicopathologic features and follow-up were obtained from computerized medical records and the US Social Security Death Index.Results.-Of the 142 tumors studied, 23 tumors (16%)were classified as group 1; 27 (19%) as group 2; 24 (17%) as group 3; and 68 (48%) as group 4. Staging and survival differed significantly among these groups. Among 140 patients (99%) with available staging data, stages II, III, and IV were present in 87%, 4%, and 4% of patients in group 1 patients; 67%, 7%, and 22% of patients in group 2; 29%, 4%, and 67% of patients in group 3; and 19%, 6%, and 75% of patients in group 4, respectively (P ¼ .01). Mean (SD) overall survival was 83.8 (34.6), 60.6 (30.3), 45.6 (39.7), and 33.6 (27.6) months for groups 1, 2, 3, and 4, respectively (P ¼ .01). By multivariate analysis, only stage and tumor category were independent predictors of overall survival. Conclusion.-Our data highlight the importance of subclassifying the proportion of adenocarcinoma in appendiceal tumors with GCT morphology because that finding reflects disease stage and affects survival.

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Purpose The molecular basis of the adenoma to carcinoma transition has been deduced using comparative analysis of genetic alterations observed through the sequential steps of intestinal carcinogenesis. However, comprehensive genomic analyses of adenomas and at-risk mucosa are still lacking. Therefore, our aim was to characterize the genomic landscape of colonic at-risk mucosa and adenomas. Experimental Design We analyzed the mutation profile and copy number changes of 25 adenomas and adjacent mucosa from 12 familial adenomatous polyposis patients using whole-exome sequencing and validated allelic imbalances in 37 adenomas using SNP arrays. We assessed for evidence of clonality and performed estimations on the proportions of driver and passenger mutations using a systems biology approach. Results Adenomas had lower mutational rates than did colorectal cancers and showed recurrent alterations in known cancer-driver genes (APC, KRAS, FBXW7, TCF7L2) and allelic imbalances in chromosomes 5, 7 and 13. Moreover, 80% of adenomas had somatic alterations in WNT pathway genes. Adenomas displayed evidence of multiclonality similar to stage I carcinomas. Strong correlations between mutational rate and patient age were observed in at-risk mucosa and adenomas. Our data indicate that at least 23% of somatic mutations are present in at-risk mucosa prior to adenoma initiation. Conclusions The genomic profiles of at-risk mucosa and adenomas illustrate the evolution from normal tissue to carcinoma via greater resolution of molecular changes at the inflection point of premalignant lesions. Furthermore, substantial genomic variation exists in at-risk mucosa before adenoma formation, and deregulation of the WNT pathway is required to foster carcinogenesis.

These findings challenge the canonical model, based on the observations made in carcinomas, that emphasizes a dependency of immune activation on the acquisition of high levels of mutations and neoantigens, thus opening the door to the implementation of immune checkpoint inhibitors and vaccines for cancer prevention in LS.

Solid pseudo-papillary tumors are rare pancreatic tumors, which occur in females and are typically indolent neoplasms. However, atypical, aggressive variants can occur with locally advanced disease or metastases. They have characteristic imaging features, which vary according to size. This article provides a current update on the molecular biology, histopathology, clinico-radiological features, and management of these tumors.

We investigated the effect of delay before nerve repair on neuropathic pain after injury to the brachial plexus. We studied 148 patients, 85 prospectively and 63 retrospectively. The mean number of avulsed spinal nerves was 3.2 (1 to 5). Pain was measured by a linear visual analogue scale and by the peripheral nerve injury scale. Early repair was more effective than delayed repair in the relief from pain and there was a strong correlation between functional recovery and relief from pain.

Background. Appendiceal adenocarcinomas (AAs) are rare and this has limited their molecular understanding. The purpose of our study was to characterize the molecular profile of AA and explore the role of targeted therapy against cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR). Patients and Methods. Weperformedaretrospectivereviewof 607 patients with AA at a single institution. A total of 149 patients underwent molecular testing for at least one of the following: activating mutations in KRAS, BRAF, cKIT, EGFR, or PI3K; protein expression of c-KIT or COX-2; or microsatellite instability (MSI) status by immunohistochemistry. Kaplan-Meier product limit method and log-rank test were used to estimate overall survival (OS)andtodetermineassociationsamongOS,COX-2expression, KRAS mutations, and other characteristics. Results. Age, grade, stage, signet ring cells, mucinous histology, and completeness of cytoreduction score correlated with survival outcomes. COX-2 expression, KRAS, PI3K, and BRAF mutations were seen in 61%, 55%, 17%, and 4% of patients, respectively. High MSI was seen in 6% of patients. KRAS mutation was strongly associated with well differentiated or moderately differentiated AA (p Ͻ .01). COX-2 expression (p ϭ .33) and the presence of KRAS mutation (p ϭ .91) had no impact on OS. The use of celecoxib in patients whose tumors expressed COX-2 (p ϭ .84) and the use of cetuximab or panitumumab in patients with KRAS wild-type tumors (p ϭ .83) also had no impact on OS. Conclusion.In this cohort, we demonstrated that COX-2 expression and KRAS mutations were frequently seen in AA, although neither exhibited any prognostic significance. MSI was infrequent in AA. Targeted therapy against COX-2 and EGFR appeared to provide no clinical benefit. Well and moderately differentiated AA were molecularly distinct from poorly differentiated AA. The Oncologist 2013;18:1270 -1277 Implications for Practice: Appendiceal adenocarcinomas (AAs) are rare, and current understanding of their molecular biology is poor. Surgical resection is the mainstay of therapy. Limited data exists to guide medical management, and the role of targeted therapy in AAs has not been studied. This study endeavors to define molecular alterations in AAs. Activating KRAS mutations represent the most common alteration, occurring in 55% cases. Interestingly, well and moderately differentiated tumors demonstrate similar high rates of KRAS mutation, contrary to the low rates seen in poorly differentiated tumors. These data link clinical behavior with molecular biology and suggest that moderately differentiated tumors resemble well-differentiated tumors and should be treated similarly. Further prospective trials are needed to evaluate the efficacy of targeted therapies such as antiepidermal growth factor receptor therapy in AAs, prior to their implementation in clinical practice. Constructing a molecular sketch of AAs is a necessary first step toward recognizing molecular pathways involved in their carcinogenesis and advancing the ro...