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Esophageal neuroendocrine tumors are rare and often found incidentally on endoscopy. We present a unique case of an esophageal neuroendocrine tumor found in the setting of dysplasia associated with Barrett’s esophagus. The tumor was removed endoscopically. This case highlights the incidence, prognosis, and management of esophageal neuroendocrine tumors.

Cutaneous signet-ring cell squamous cell carcinoma (SRCSCC) is a rare variant, most commonly occurring in the head and neck. We report a case of a 66-year-old transgender woman with an ulcerated growing facial mass measuring 5.6 × 4.0 × 2.0 cm. Histological analysis showed features consistent with SRCSCC. Immunohistochemical analysis showed positive staining for high-molecular-weight cytokeratin, estrogen receptor (1-2+ in 10%), E-cadherin (mostly positive with partial loss), and p40 and negative staining for Ber EP-4, cytokeratin 7, low-molecular-weight cytokeratin, mucicarmine, Alcian blue PAS, HER2, and MUC4. The tumor had invaded the perineurium, lymphovascular spaces, and subcutaneum. Additionally, microsatellite instability testing was negative. This case adds to the limited knowledge of this poorly characterized entity.

Synovial sarcoma is a rare malignant mesenchymal neoplasm that often occurs in the extremities. Less than 70 cases of primary synovial sarcoma occurring in the digestive system have been reported. We present a case of a 48-year-old woman with a spindle cell tumor in the rectum that stained positive for AE1/3 (focal), vimentin, CD99, BCL2, EMA (focal), and MiB-1 (15%). Ultimately, the lesion was diagnosed as a primary rectal monophasic synovial sarcoma and confirmed by molecular testing for SYT/SSX1 gene fusion. Analysis of previous publications indicated that patients of advanced age or a large tumor size (≥5 cm) have a higher risk of progressing rapidly to death after diagnosis of synovial sarcoma in the digestive system.

BACKGROUND Uterus transplantation (UTx) enables pregnancy in infertile women. This study describes the histopathological changes of ischemia reperfusion injury and mostly acute T cell-mediated rejection (TCMR) in UTx and proposes modification toward a working formulation grading system with associated treatments. METHODS Protocol and indication biopsies from 11 living and 2 deceased donor UTx recipients were analyzed. Serving as a control were 49 age-matched nontransplanted uteri. All posttransplant histopathological specimens were evaluated in a blinded fashion by 3 pathologists. Response to treatment was assessed by follow-up biopsies. Serial serum donor-specific antibody (DSA) responses were also recorded. RESULTS Changes attributed to ischemia reperfusion resolved within 2 weeks of UTx in most of the patients. For TCMR grading, perivascular inflammation, focal capillary disruption, and interstitial hemorrhage were added to interface inflammation, intercellular edema, stromal inflammation, and epithelial apoptotic bodies. Of the 173 protocol biopsies, 98 were classified as negative for TCMR; 34, indeterminate-borderline; 35, mild; 3, moderate; and 3, severe, 1 of which occurred in a DSA-positive recipient and also showed microvascular injury. Corticosteroids successfully treated all moderate to severe TCMR episodes. Mild TCMR was treated by increasing existing baseline immunosuppression. Indeterminate-borderline episodes were not treated. Neither ischemia reperfusion injury nor TCMR with DSA adversely affected embryo transfer. CONCLUSION Relying on a modified histopathological grading system, we developed a treatment strategy resulting in resolution of TCMR and successful pregnancies.

Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) is a malignant small round cell sarcoma commonly occurring among children, adolescents, and adults. We report a rare case of ES/pPNET arising from the lung in a 49-year-old woman. She was found to have a mass in the right lung on a screening imaging study for her BRCA2 mutation. A lobectomy was performed and the mass had histological, immunohistochemical, and molecular features of ES/pPNET. Few cases of primary pulmonary Ewing sarcoma have been reported.

The cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is an uncommon variant of papillary thyroid carcinoma. CMV-PTC can be associated with familial adenomatous polyposis (FAP), an autosomal-dominant polyposis syndrome caused by a mutation in the APC gene that leads to a disruption of the Wnt/beta-catenin pathway. Understanding the relation between CMV-PTC and FAP is a diagnostic tool for both pathologists and clinicians, because FAP has several implications for patients and their families.

Dermatofibromas (DF) are common, benign, skin tumors, usually easily differentiated from dermatofibrosarcoma protuberans (DFSP) by the presence of a relative low cellularity, lesser degree of infiltration of subcutaneous tissue, and immunohistochemical pattern (eg, FXIIIa in DF and CD34 in DFSP). Atypical fibrohistiocytic lesions (AFL) have features intermediate to DF and DFSP (trunk location, storiform pattern, infiltration of the subcutaneous tissue, and focal expression of both CD34 and Factor XIIIa). It is unclear if mitotic counts/degree of proliferation is helpful to distinguish DF from DFSP. To study the mitotic rate and proliferation index in DF, AFL/DFSP, anti-ki67, and anti-PHH3 were performed on 10 cases of DF (including 4 cellular DF), 10 standard DFSP, and 2 AFL. The proliferation index and mitotic figures were counted per square millimeter in a "hotspot" (in a fashion similar to mitotic counts in melanoma). All cases of DF showed much higher Ki67 proliferation index (P = 0.0001) along with increased mitotic figures both on H&E and with anti-PHH3 (P = 0.0001) when compared to AFL/DFSP. Our data indicate that DF has a higher proliferation index and mitotic counts when compared to superficial/peripheral portion of AFL and DFSP. This finding may be helpful in the differential diagnosis among these fibrohistiocytic lesions.

Myxoid lesions of the kidney are rare. We present a case of a 74-year-old man who presented with an 8.5 × 8.0 × 6.0 cm left kidney mass that was grossly confined to the kidney and had a gelatinous cut surface. Histology of the tumor showed bland spindle cells in a myxoid stroma with interspersed thin-walled vessels. The tumor was negative for smooth muscle actin, desmin, CD34 (highlighted vessels), S100, and HMB-45 by immunohistochemistry. There was focal, nonspecific staining of MDM2 and CDK4. The lesion appeared more vascular than would be expected for a classic myxoma and, therefore, fluorescence in situ hybridization was performed for the 12q13 (DDIT3 or CHOP) rearrangement to rule out myxoid liposarcoma and the result was negative for a rearrangement. This case highlights the difficulty of delineating a primary myxoma of the kidney from a well-differentiated myxoid liposarcoma.

Neuroendocrine tumors are rarely found in the esophagus. We present a case of a 71 year old female with a history of Barrett's esophagus with high grade dysplasia that on screening endoscopy was found to have a squamous patch proximal to the gastroesophageal junction and underwent an endoscopic mucosal resection. Within the resection, there was a small tumor with a monomorphic population with speckled nuclear chromatin located within the lamina propria extending into the muscularis mucosae. The tumor measured 1 mm in greatest dimension and the overlying epithelium showed no evidence of the presence of Barrett's esophagus. Immunohistochemical staining of the tumor was consistent with carcinoid tumor: positive for chromogranin, synaptophysin, and pan-cytokeratin. The Ki-67 index was

Intraductal papillary neoplasm of the bile duct is characterized by intraductal papillary growth with fibrovascular cores that can grow anywhere along the biliary tree. Most cases have high-grade intraepithelial neoplasia or an associated invasive carcinoma. These tumors can spread superficially along the biliary tree and be multifocal, and preoperative biopsy cannot always reflect the maximum degree of atypia. Frozen section to assess the distal common bile duct margin is crucial to avoid the risk of recurrence. Theoretically, resection of the entire biliary tree by liver transplantation and pancreaticoduodenectomy is regarded as the only curative treatment.

Gastric cancer is the second leading cause of cancer related death in the world. In United States, gastric polyps are found in approximately 6% of upper endoscopy. The incidence of gastric polyps increased with widespread use of esophagogastroduodenoscopy and more liberal use of proton pump inhibitors. They are usually asymptomatic, but infrequently cause symptoms of bleeding, pain and gastric outlet obstruction. It is important to distinguish premalignant conditions and mimickers of malignancy. Helicobacter pylori eradication therapy leads to regression of hyperplastic polyps but it is not clear for adenoma. Endoscopy plays key role not only in diagnosis but also in surveillance. With narrow band imaging and chromo endoscopy, we are much better today in detecting and discerning these. Also, with endoscopic mucosal resection and endoscopic submucosal dissection, we can manage these better. In this review article we will discuss the various diagnostic tools and therapeutic options for hyperplastic polyp, fundic gland polyp, gastrointestinal stromal tumor, adenoma, neuroendocrine tumor, linitis plastica, and intestinal metaplasia.

Classification of breast cancers into different molecular subtypes using immunohistochemistry as a surrogate tool to DNA microarray technology has been identified. Aim of this study was to find the precise prevalence of molecular subtypes of invasive breast carcinoma using immunohistochemistry and to correlate it with histological and clinical prognostic factors.A descriptive study design wherein 56 breast carcinoma cases diagnosed between May 2012 and Apr 2014 were reviewed and molecular subtyped using relevant immunohistochemical markers. Age, histological type, tumor size, tumor grade, lymphovascular emboli (LVE), nodal status and basal marker expressions were analyzed for all cases. Correlations between molecular subtypes and clinico-pathological characteristics were evaluated statistically.In our study group, average age of patients was 50.5 years and most of patients were diagnosed in stage II (54%). Luminal A subtype was most prevalent 34%, followed by Basal like/Triple negative subtype 25%. Luminal B and Her2/neu subtypes had same prevalence i.e. 18% each and Breast Tissue like/Unclassified subtype/Penta Negative subtype was 5%. All cases demonstrated positivity for the luminal cytokeratins 8/18. Histological grade and ER negative status showed strong correlations with basal markers.On the basis of hormone receptor, Her2 neu, EGFR and CK 5/6 expressions, breast carcinoma cases were classified into five distinct molecular subtypes which show significant differences in regards to morphological features, prognostic markers and there by predicting possible clinical outcome.

Background Addition of nimotuzumab to weekly cisplatin and radiation improves outcomes in head and neck cancer. HPV-negative oropharyngeal cancer has unsatisfactory treatment outcomes and is a candidate for escalation of treatment. Hence we wanted to determine whether the addition of nimotuzumab to cisplatin-radiation can improve outcomes in these subsets of poor-risk tumors. Methods This was a subgroup analysis of a phase 3 randomized study. In this study locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin (30 mg/m2 IV )- radiation (66-70 Gy) {CRT arm} or nimotuzumab (200 mg weekly) -weekly cisplatin (30 mg/m2)-radiation (66-70 Gy) {NCRT arm}. The data for HPV-negative oropharyngeal cancer was extracted from the database of this study for the current analysis. HPV testing was done with p16 IHC staining and reported according to the CAP criteria. The outcomes assessed were progression-free survival (PFS), disease-free survival (DFS), locoregional control (LRC), and overall survival (OS). Interaction test was performed between the study arms and HPV status prior to doing any HPV-specific analysis for each of the studied outcomes. Kaplan Meier estimates for 2-year OS with 95% CI is provided. The hazard ratio was calculated using Cox regression analysis. Results We had 187-HPV negative oropharyngeal cancers, 91-CRT arm and 96 in NCRT arm. The interaction test was significant for PFS (p = 0.000), locoregional control (p = 0.007) and overall survival (p = 0.002) but not for DFS (p = 0.072). The 2-year PFS was 31.5% (95%CI 21.5-42) in CRT arm versus 57.2% (95%CI 45.8-67.1) in NCRT arm (HR -0.54;95%CI 0.36-0.79, p = 0.002). While the 2-year LRC was 41.4 % (95%CI 29.8-52.6) in CRT arm versus in 60.4% (95%CI 48.7-70.2) in NCRT arm (HR -0.61;95%CI 0.4-0.94, p = 0.024). The addition of nimotuzumab also led to an improvement in OS from 39.0% (95%CI 28.4-49.6) to 57.6% (95%CI 46.3-67.4) (HR-0.63, 95%CI 0.43-0.92, p = 0.018). Conclusions The addition of nimotuzumab to weekly cisplatin-radiation improves outcomes inclusive of OS in HPV-negative oropharyngeal cancers. Clinical trial identification CTRI/2014/09/004980. Legal entity responsible for the study The authors. Funding Biocon Ltd, TRAC. Disclosure K. Prabhash: Research grant / Funding (institution): Dr. Reddy’s Laboratories Inc; Research grant / Funding (institution): Fresenius Kabi India Pvt Ltd; Research grant / Funding (institution): Alkem Laboratories; Research grant / Funding (institution): Natco Pharma Ltd; Research grant / Funding (institution): BDR Pharmaceutics Intl Pvt Ltd; Research grant / Funding (institution): Roche Holding AG. V. Noronha: Research grant / Funding (institution): Dr. Reddy’s Laboratories Inc; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Sanofi Aventis. All other authors have declared no conflicts of interest.

BACKGROUND The current study was conducted to determine whether quantified pathologic response assessed as a percentage of residual tumor cells is predictive of recurrence-free survival (RFS) in patients with rectal cancer. METHODS The authors studied 251 patients with rectal adenocarcinoma who were treated with neoadjuvant chemoradiation and radical resection. Quantified pathologic response was defined as an estimated percentage of residual cancer cells in relation to the tumor bed: complete, no residual cancer cells; near-complete, ≤ 5% residual cancer cells; major, > 5%, and

BACKGROUND To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM). METHODS One hundred seventy-one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response—defined as the proportion of tumor cells remaining (complete, 0%; major

Background/Purpose The median survival for patients with metastatic colorectal cancer (mCRC) has progressively increased over the past decades. Since the introduction of 5-fluorouracil (5-FU)-based chemotherapy, followed by hepatic resection of metastases, and more recently the adoption of newer chemotherapeutic regimens associated with targeted therapy, the gains are getting more substantial. Despite the recognition of the potential for long-term survival after surgical resection of metastatic disease, long-term survival data to determine the potential curative role of chemotherapy alone is lacking. Methods We performed a retrospective review of 2751 patients who presented with mCRC at The MD Anderson Cancer Center from 1990 through 2003. Patients alive at 5 years who achieved complete response with chemotherapy and were not submitted to any surgical or interventional procedures directed to the metastatic sites were included in the analysis. Results The 5-year overall survival rate for all patients with mCRC during this period was 10.8%. Among these long-term survivors, 2.2% achieved a sustained complete response after chemotherapy (all 6 with fluoropyrimidines and 2 with irinotecan) as the only treatment modality and were without evidence of disease until the last follow-up visit (median of 10.3 years). This number corresponds to 0.24% (6 of 2541) of all patients with mCRC included in this review. Conclusion Cure with chemotherapy alone is possible for a very small number of patients with metastatic colorectal cancer. Improved therapies are increasing complete response rates, but the impact of modern chemotherapy on durable complete responses will require additional follow up.

BACKGROUND: It is hypothesized that BRAF mutant cancers represent a discrete subset of metastatic colorectal cancer (CRC) defined by poorer survival. This study investigates whether BRAF mutant CRC is further defined by a distinct pattern of metastatic spread and explores the impact of BRAF mutation and microsatellite instability (MSI) on prognosis in metastatic CRC. METHODS: By using prospective clinical data and molecular analyses from 2 major centers (Royal Melbourne Hospital and The University of Texas MD Anderson Cancer Center), patients with known BRAF mutation status were analyzed for clinical characteristics, survival, and metastatic sites. RESULTS: The authors identified 524 metastatic CRC patients where BRAF mutation status was known; 57 (11%) were BRAF mutant tumors. BRAF mutant tumors were significantly associated with right-sided primary tumor, MSI, and poorer survival (median, 10.4 months vs 34.7 months, P < .001). A distinct pattern of metastatic spread was observed in BRAF mutant tumors, namely higher rates of peritoneal metastases (46% vs 24%, P = .001), distant lymph node metastases (53% vs 38%, P = .008), and lower rates of lung metastases (35% vs 49%, P = .049). In additional survival analyses, MSI tumors had significantly poorer survival compared with microsatellite stable tumors (22.1 months vs 11.1 months, P = .017), but this difference was not evident in the BRAF mutant population. CONCLUSIONS: The pattern of metastatic spread observed in this study further defines BRAF mutant CRC as a discrete disease subset. The authors demonstrated that, unlikely early stage disease, MSI is associated with poorer survival in metastatic CRC, although this is driven by its association with BRAF mutation. Cancer 2011;. © 2011 American Cancer Society.

Progress in the treatment of hepatic colorectal metastases (HCRM) demands pathologic indicators of therapy response. We observed that a majority of residual tumor cells are seen at the tumor-normal interface (TNI) in resected HCRM specimens and hypothesized that tumor thickness at the TNI correlates with radiologic and pathologic response and recurrence-free survival (RFS).This study included 103 patients with HCRM resected after preoperative chemotherapy with or without bevacizumab. Imaging response was assessed by response evaluation criteria in solid tumors (RECIST) and recently described CT morphology criteria by Chun et al. The pathologic response was categorized as complete (no tumor cells), major (50% residual tumor cells), or minor (or =50% residual tumor cells). The maximum thickness of uninterrupted layers of tumor cells was measured perpendicular to the TNI by 2 pathologists independently, followed by consensus review for discrepant cases. For specimens containing1 tumor, the average tumor thickness at the TNI was used.Sixty-five patients received oxaliplatin-based chemotherapy, 38 received irinotecan-based chemotherapy, and 75 received concurrent bevacizumab. A complete pathologic response was seen in 9 patients, a major response in 44, and a minor response in 50. Median tumor thickness at the TNI was 2.8 mm (interquartile range, 0.5 to 6 mm). Tumor thickness correlated better with radiologic response as determined by Chun et al (P0.0001) than by RECIST criteria (Spearman r=0.35, P0.001). Tumor thickness correlated with pathologic response (Spearman r=0.80, P0.0001). Greater thickness predicted shorter recurrence-free survival, and this correlation remained in multivariate analysis (P=0.015). Tumor thickness was smaller in patients treated with bevacizumab than in patients not given bevacizumab (P=0.03).Tumor thickness measured at the TNI is potentially a new prognostic factor for therapy response and survival outcome in patients with resected HCRM.

Purpose Neoadjuvant chemoradiotherapy for rectal cancer is associated with improved local control and may result in complete tumor response. Associations between tumor response and disease control following radical resection should be established before tumor response is used to evaluate treatment strategies. The purpose of this study was to assess and compare oncologic outcomes associated with the degree of pathologic response after chemoradiotherapy. Patients and Methods All patients with locally advanced (cT3-4 or cN+ by endorectal ultrasonography, computed tomography, or magnetic resonance imaging) rectal carcinoma diagnosed from 1993 to 2008 at our institution and treated with preoperative chemoradiotherapy and radical resection were identified, and their records were retrospectively reviewed. The median radiation dose was 50.4 Gy with concurrent chemotherapy. Recurrence-free survival (RFS), distant metastasis (DM), and local recurrence (LR) rates were compared among patients with complete (ypT0N0), intermediate (ypT1-2N0), or poor (ypT3-4 or N+) response by using Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression. Results In all, 725 patients were classified by tumor response: complete (131; 18.1%), intermediate (210; 29.0%), and poor (384; 53.0%). Age, sex, cN stage, and tumor location were not related to tumor response. Tumor response (complete v intermediate v poor) was associated with 5-year RFS (90.5% v 78.7% v 58.5%; P < .001), 5-year DM rates (7.0% v 10.1% v 26.5%; P < .001), and 5-year LR only rates (0% v 1.4% v 4.4%; P = .002). Conclusion Treatment response to neoadjuvant chemoradiotherapy among patients with locally advanced rectal cancer undergoing radical resection is an early surrogate marker and correlate to oncologic outcomes. These data provide guidance with response-stratified oncologic benchmarks for comparisons of novel treatment strategies.

Postural orthostatic tachycardia syndrome (POTS) is an autonomic disturbance which has become better understood in recent years. It is now thought to encompass a group of disorders that have similar clinical features, such as orthostatic intolerance, but individual distinguishing parameters—for example, blood pressure and pulse rate. The clinical picture, diagnosis, and management of POTS are discussed.

Sinus histiocytosis with massive lymphadenopathy (SHML) also called as Rosai Dorfman disease is a rare histiocytic proliferative disorder of unknown etiology. Histological features currently define it. Persistent painless lymphadenopathy due to expansion of sinuses infiltrated with benign histiocytes and plasma cells and emperipolesis are the characteristic features of SHML. Our study includes seven cases (5 nodal and 2 extranodal) of SHML over a 5-year period whose slides and blocks were reviewed. IHC was performed on the main lesion, from a panel of S100, CD68, LCA, CD20, CD3, CD30, CD43, bcl2, cytokeratin and epithelial membrane antigen. In our series we have work up available in 7 cases out of which a detailed follow-up is available in 5 patients. Out of these 5 patients, 4 have a stable disease, while one developed histiocytic sarcoma after a gap of four years.

Ectopic thyroid tissue may be encountered anywhere from the foramen caecum to the lower neck. It is rarely seen in the mediastinum. True malignant transformation in ectopic thyroid tissue is extremely rare. Such a malignancy is virtually always diagnosed after surgical excision of the lesion at pathological examination. We report on an extremely rare case of true mediastinal thyroid cancer in a 45-year-old woman. The clinicopathologic features and diagnosis of the lesion, with regard to its mediastinal location are discussed.

Background Local complications of pancreatic necrosis may occur after surgery, but when they occur spontaneously render surgical treatment more hazardous and impair prognosis. Methods A retrospective review was carried out of 83 patients who underwent surgery for pancreatic necrosis from 1988 to 1995, to determine the incidence, type, treatment and outcome of locoregional complications caused by pancreatic necrosis associated with acute pancreatitis. Results Seventeen patients (20 per cent) were identified to have intra-abdominal complications with pancreatic necrosis either before operation or at the time of surgery. The majority of patients had a delay in intervention (mean 46 days). At presentation ten of the 17 patients had one or more organ system failures. Fourteen patients had gastrointestinal tract involvement, two had involvement of the biliary tract and one patient had a splenic rupture. Six patients died. Conclusions In patients with pancreatic necrosis, development of locoregional complications is associated with a high mortality rate. The presence of gastrointestinal bleeding, peritonitis, jaundice or pneumoperitoneum in such patients suggests the presence of a complication of the necrotic process and should prompt early intervention. Early referral of patients with severe acute pancreatitis to specialized units may reduce the risk of locoregional complications.

3592 Background: It has been hypothesized that BRAF mutant cancers represent a distinct subset of colorectal cancer (CRC), with BRAFV600E mutant metastatic CRC patients appearing to have a signific...

A simple reverse phase liquid chromatographic method has been developed and subsequently validated for simultaneous determination of salbutamol sulphate and bromhexine hydrochloride. The separation was carried out using a mobile phase consisting of acetonitrile, methanol and phosphate buffer, pH 4 in the ratio 60:20:20 v/v. The column used was SS Wakosil-II C-18 with a flow rate of 1 ml/min and UV detection at 224 nm. The described method was linear over a concentration range of 10-110 µg/ml and 20-140 µg/ml for the assay of salbutamol sulphate and bromhexine hydrochloride, respectively. The mean recovery was found to be 95-105% for salbutamol sulphate and 96.2-102.1% for bromhexine hydrochloride when determined at five different levels.