Role of Megakaryocytes in Breast Cancer Metastasis to Bone.

Little is known about how megakaryocytes may affect metastasis beyond serving as a source of platelets. In this study, we explored the functional implications of megakaryocyte accumulation in the femurs of mice after injection of metastatic or non-metastatic breast cancer cells in 4T1.2 BALB/cJ and MDA-MB-231 nude mouse models. At bone metastatic sites, but not primary growth sites, tumor growth was associated with increased megakaryopoiesis in both model systems. In the orthotopic BALB/cJ model, extramedullary hematopoiesis occurred in the spleen, resulting in a four-fold increase in megakaryocytes. In support of the hypothesis that reducing megakaryocytes may reduce metastasis, we found that thrombopoietin-deficient mice exhibited a 90% relative decrease in megakaryocytes, yet they developed more aggressive metastasis than wild-type hosts. In human clinical specimens, we observed an increase in megakaryocytes in the bone marrow of 6/8 patients with metastatic breast cancer compared with age- and gender-matched controls. Taken together, our results suggested that an increase in megakaryocytes occurring in response to metastatic cells entering the bone marrow confers some measure of protection against metastasis, challenging present views on the role of megakaryocytes in this setting. Cancer Res; 77(8); 1942-54. ©2017 AACR.

Increasing diagnostic accuracy to grade dysplasia in Barrett's esophagus using an immunohistochemical panel for CDX2, p120ctn, c-Myc and Jagged1.

BACKGROUND: Patients with non-dysplastic Barrett's esophagus (ND-BE) and low-grade dysplasia (LGD) are typically monitored by periodic endoscopic surveillance, while those with high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) are usually treated by more aggressive interventions like endoscopic mucosal resection, ablation or surgery. Therefore, the accurate grading of dysplasia in Barrett's esophagus (BE) is essential for proper patient care. However, there is significant interobserver and intraobserver variability in the histologic grading of BE dysplasia. The objective of this study was to create an immunohistochemical (IHC) panel that facilitates the grading of BE dysplasia and can be used as an adjunct to histology in challenging cases. METHODS: 100 BE biopsies were re-graded for dysplasia independently by 3 subspecialized gastrointestinal pathologists. IHC staining for CDX2, p120ctn, c-Myc and Jagged1 proteins was then performed and assessed by two separate methods of semi-quantitative scoring. Scores were integrated using a principal component analysis (PCA) and receiver operating characteristic (ROC) curve. RESULTS: Principal component analysis demonstrated the ability of this panel of proteins to segregate ND-BE/LGD and HGD/EAC, as the expression of the four proteins is significantly altered between the two subsets. Analysis of the receiver operating characteristic curve showed that this panel has the potential to aid in the grading of dysplasia in these two subcategories with both high sensitivity and specificity. While not able to discriminate between ND-BE and LGD, this panel of four proteins may be used as an adjunct to help discriminate subsets of ND-BE/LGD from HGD/EAC. CONCLUSIONS: We propose that the maximum utility of this IHC panel of CDX2, p120ctn, c-Myc, and Jagged1 proteins would be to distinguish between LGD and HGD in histologically challenging cases, given the aggressive interventions still used for HGD in many institutions, and hence may aid in the optimal patient management. The results of this initial study are promising, though further validation is needed before this panel can be used clinically, including future randomized prospective studies with larger patient cohorts from diverse locations.

Spectrum of Gastric Histopathologies in Severely Obese American Patients Undergoing Sleeve Gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a commonly performed weight loss procedure, but the pathologic findings in sleeve specimens have not been investigated in a US population. METHODS: We performed a retrospective review of histopathologic findings in LSG specimens from 310 consecutive bariatric patients at the Hershey Medical Center between June 2008 and August 2014. RESULTS: Patients were 19 to 75 years old (mean 45 years) with a female-to-male ratio of 3:1. The histopathologic findings included the following: no pathological alteration in 214 patients (69.0 %), chronic inactive gastritis in 41 (13.2 %), fundic gland polyp in 17 (5.5 %), proton pump inhibitor therapy effect in 12 (3.9 %), Helicobacter pylori (H. pylori)-associated chronic active gastritis in 10 (3.2 %), chronic active gastritis (H. pylori negative) in 5 (1.6 %), chronic gastritis with intestinal metaplasia in 4 (1.0 %), gastrointestinal stromal tumor (GIST) in 3 (1.0 %), and hyperplastic polyp, granulomatous inflammation, xanthogranulomatous inflammation, and mucosal ulceration in 1 patient each (0.3 %). Prior endoscopy was performed in 8 patients (2.6 %) for unrelated causes, and the results did not change the surgical management. Nine patients (2.9 %) had a concurrent liver biopsy for visual evidence of significant hepatic fibrosis. CONCLUSION: Although most cases showed no pathologic alteration, a minority had significant findings, with the incidence of GISTs higher than that reported in other series. Despite negative preoperative H. pylori testing, 3.2 % were still histologically positive, raising questions about the accuracy of preoperative methods used for H. pylori testing and treatment. Preoperative endoscopy may not be needed in sleeve patients.

Mimics of duplication cysts: intraperitoneal nodules in a 14-year-old boy.

Hemangiomas are the most common primary hepatic tumors, but there are few reports of their occurrence elsewhere in the abdomen. The concurrent existence of multiple fibrous nodules of the omentum, mesentery, and porta hepatis, along with a gastric hemangioma, in a child raises the question of syndromic association. Our search of the English literature revealed only rare mentions of hemangiomas involving the stomach and mesentery or omentum. These lesions have attracted clinical attention by symptoms of obstruction, gastrointestinal bleeding, intussusception, infection, perforation, or vague abdominal pain. Although some tumors exist unnoticed for many decades and are identified only incidentally, others present emergently and require immediate surgical attention. We report the case of a 14-year-old boy who presented with symptoms similar to those for appendicitis or duplication cyst, who was found to have a torsed gastric hemangioma and multiple benign fibrous nodules in the abdomen. The presence of multiple vascular or fibrous lesions is associated with genetic syndromes that can have lifelong and reproductive repercussions; so it is imperative that these tumors be recognized by diagnosticians.

Dedifferentiated epithelial-myoepithelial carcinoma: analysis of a rare entity based on a case report and literature review.

Dedifferentiated epithelial-myoepithelial carcinoma (DEMC) is very rare salivary gland neoplasm with only anecdotal reports. We present an analysis of DEMC, based on a case and review of literature. Our patient, an 85-year-old woman, presented with a submandibular mass of 5 years duration that was increasing in size over a 5-week period. Histologically, there were areas of typical epithelial-myoepithelial carcinoma, with dedifferentiation of both components, manifesting morphologically as salivary duct carcinoma and areas of myoepithelial carcinoma. A review of literature revealed 21 previously reported cases of DEMC. DEMC occurs at an average age of 72 years, most often in the parotid gland (72%) followed by submandibular gland (17%). Dedifferentiation more often involves the epithelial component (13/15 cases) than the myoepithelial component (5/15 cases). Although typical epithelial-myoepithelial carcinomas are fairly indolent (average disease-free survival of 11.34 years), dedifferentiation confers a poor prognosis (survival reported from 1 to 72 months).