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Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppressor of cytokine signaling 2 (SOCS2) deletion on colitis and recovery. To induce colitis, wild type and SOCS2 knockout (SOCS2&minus, /&minus, ) mice were treated with 3% dextran sodium sulphate (DSS), followed by a recovery period. SOCS2&minus, mice showed higher disease activity during colitis with increased mRNA expression of the pro-inflammatory cytokines nitric oxide synthase 2 (NOS2) and interleukin 1 &beta, (IL1-&beta, ). At recovery time point, SOCS2&minus, showed better recovery with less fibrosis measured by levels of &alpha, SMA and collagen deposition. Protein and mRNA expressions of transforming growth factor beta &beta, 1 (TGF-&beta, 1) receptors were significantly lower in SOCS2&minus, mice compared to wild-type littermates. Using an in vivo bromodeoxyuridine (BrdU) proliferation assay, SOCS2&minus, mice showed higher intestinal epithelial proliferation compared to wild-type mice. Our results demonstrated that deletion of the SOCS2 protein results in higher growth hormone sensitivity associated with higher pro-inflammatory signaling, however, it resulted in less tissue damage with less fibrotic lesions and higher epithelial proliferation, which are markers of GH-protective effects in IBD. This suggests a pleiotropic effect of SOCS2 and multiple cellular targets. Further study is required to study role of SOCS2 in regulation of TGF&beta, mothers against the decapentaplegic homolog (Smad) pathway.

Primary gastric yolk tumours are extremely rare. We report a 52-year-old male who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2017 after having undergone a gastrectomy abroad due to a suspected poorly-differentiated adenocarcinoma. The patient subsequently returned to Oman to receive chemotherapy. However, while undergoing chemotherapy, an abdominal computed tomography scan revealed a lobulated mesenteric mass. Microscopic examination of the resected lesion confirmed a diagnosis of a yolk sac tumour. The mass was diffusely positive for α-fetoprotein (AFP) and a gastric carcinoma stain was negative. Gastrectomy slides from the patient’s previous surgery were examined retrospectively. The morphology was typical for a yolk sac tumour and was negative for epithelial markers. An AFP stain showed diffuse immunoreactivity. Thus, the patient was deemed to have had a primary gastric yolk sac tumour which had later metastasised to the mesocolon. Germ cell tumour protocols were initiated and the patient responded well to treatment.Keywords: Yolk Sac Tumor; Germ Cell Tumor; Gastrectomy; Metastasis; Diagnostic Errors; Case Report; Oman.

SOCS2 is a pleiotropic E3 ligase. Its deficiency is associated with gigantism and organismal lethality upon inflammatory challenge. However, mechanistic understanding of SOCS2 function is dismal due to our unawareness of its protein substrates. We performed a mass spectrometry based proteomic profiling upon SOCS2 depletion and yield quantitative data for ~4200 proteins. Through this screen we identify a novel target of SOCS2, the serine-threonine kinase NDR1. Over-expression of SOCS2 accelerates turnover, while its knockdown stabilizes, endogenous NDR1 protein. SOCS2 interacts with NDR1 and promotes its degradation through K48-linked ubiquitination. Functionally, over-expression of SOCS2 antagonizes NDR1-induced TNFα-stimulated NF-κB activity. Conversely, depletion of NDR1 rescues the effect of SOCS2-deficiency on TNFα-induced NF-κB transactivation. Using a SOCS2−/− mice model of colitis we show that SOCS2-deficiency is pro-inflammatory and negatively correlates with NDR1 and nuclear p65 levels. Lastly, we provide evidence to suggest that NDR1 acts as an oncogene in prostate cancer. To the best of our knowledge, this is the first report of an identified E3 ligase for NDR1. These results might explain how SOCS2-deficiency leads to hyper-activation of NF-κB and downstream pathological implications and posits that SOCS2 induced degradation of NDR1 may act as a switch in restricting TNFα-NF-κB pathway.

Rosai-Dorfman disease (RDD) is a rare benign proliferative histiocytic disorder characterised by massive lymphadenopathy. While extranodal involvement can occur in generalised RDD, isolated soft tissue RDD (STRDD) is extremely rare. We report a 17-year-old male patient who presented to the maxillofacial outpatient department of the Sultan Qaboos Hospital, Salalah, Oman, in 2015 with a painless cheek mass which had been slowly growing over the previous two months. Routine histopathological examinations and immunohistochemistry confirmed a diagnosis of STRDD. Currently, surgical excision is considered to be the most effective curative treatment for STRDD, as the outcomes of other treatment modalities are still unknown. Despite its rarity, STRDD should be considered in the differential diagnosis of histiocytic soft tissue lesions.

INTRODUCTION:MicroRNAs (miRNAs) are small non-coding RNA that plays a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes. METHODS:Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, and Spearman, Wilcoxon signed-ranks tests. P≤0.05 was considered statistically significant. RESULTS:We analyzed 72 tissue samples and 108 serum samples from 9 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. This is one of the early reports on miR-3200 in response to treatment in breast cancer, as serum levels of miR-3200 found to decline during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates at time of diagnosis. CONCLUSION:Variations in serum miRNA levels during NAC treatment may be therapeutically significant for predicting response and survival outcomes.

The mechanism by which neuropilin-1 (NRP-1) induces malignancy in Epithelial Ovarian Cancer (EOC) is still unknown. This study is the first to demonstrate the relationship between NRP-1 expression and EMT markers vimentin, N-cadherin, E-cadherin and Slug. We used tissue microarrays containing the three main subtypes of EOC tumors: serous, mucinous cystadenocarcinoma and endometrioid adenocarcinoma and representative cases retrieved from our pathology archives. Immunohistochemistry was performed to detect the expression levels and location of NRP-1 and the aforementioned EMT proteins. NRP-1 was mainly expressed on cancer cells but not in normal ovarian surface epithelium (OSE). The Immunoreactive Scoring (IRS) values revealed that the expression of NRP-1, Slug and E-cadherin in the malignant subtypes of ovarian tissues was significantly higher (5.18 ± 0.64, 4.84 ± 0.7, 4.98 ± 0.68, respectively) than their expression in the normal and benign tissues (1.04 ± 0.29, 0.84 ± 0.68, 1.71 ± 0.66, respectively), with no significant differences among the studied subtypes. Vimentin was expressed in the cancer cell component of 43% of tumors and it was exclusively localized in the stroma of all mucinous tumors. The Spearman’s rho value indicated that NRP-1 is positively related to the EMT markers E-cadherin and Slug. This notion might indicate that NRP-1 is a partner in the EMT process in EOC tumors.

Thyroid cancer is the commonest endocrine malignancy and is the second most common cancer affecting young females in Oman. The diagnosis of Papillary Thyroid Carcinoma (PTC) is based primarily on histologic architecture and nuclear morphology in routine Haematoxilin and Eosin (HE) stained slides. Whenever in doubt, immunohistochemistry may be helpful. This retrospective study included 115 cases of PTC diagnosed at a tertiary care center in Oman over 10 years period, from 2001 to 2010. Slides and blocks of these cases were retrieved from the pathology laboratory. Ninety five (95) were females and 20 were males. Papillary Thyroid Carcinoma (PTC) was most commonly seen in the 20 - 50 years of age. The commonest morphologic variant seen in this population was classical papillary variant in 44/115 (38%) followed by papillary micro-carcinoma (n=30/115, 26%) and follicular variant of papillary carcinoma (n=18/115, 15.6%). Out of the 30 micro-carcinoma cases, 18 were diagnosed incidentally in thyroids operated for multi-nodular goiter. Immunohistochemical marker CK-19 was positive in 29/31, HBME-1 and HMW-CK in 15/15 cases; CEA was in one case where it was reported negative. Immunohistochemical stains were useful in cases with atypical /doubtful morphology.

Ewing′s sarcoma/primitive neuroectodermal tumor (ES/PNET) of the prostate is extremely rare. Here, we report a case of ES/PNET of prostate in a 24-year-old man presenting with dysuria and pelvic discomfort. Computed tomography scan revealed a heterogeneous mass involving the prostate without evidence of distant metastases. Histologically, the tumor was composed of small round blue cells strongly and diffusely positive for CD99 and epithelial markers. Fluorescence in situ hybridization confirmed rearrangement of the Ewing′s sarcoma region on chromosome 22.

Ovarian leiomyoma is a rare and incidentally detected neoplasm, clinically indistinguishable from subserous leiomyomas and ovarian fibromas, until histopathological confirmation. We present a case of leiomyoma arising primarily from the ovary in a 35 year old woman.

Introduction: HER 2 Neu protein overexpression and its detection by immunohistochemistry (IHC) has become quiet critical because of its relevance in regards to Herceptin treatment. This peer review was done at a tertiary care center, which aimed at determining the inter-observer variation among five pathologists and evaluating the degree of agreement between them. Aims: The aim of our study was to determine the reproducibility of HER 2 Neu system of reporting in breast cancer cases and determine inter-observer variability among five pathologists at a tertiary care center. To compare the results with similar studies done at other centers. Settings and Design: Retrospective descriptive study. Materials and Methods: Hematoxylin and Eosin (H and E) and IHC stained slides of 104 cases of carcinoma breast, on which HER 2 Neu status had been reported were reviewed. The time period for selection was from January 2010 to December 2011 (2 year period). Five pathologists reviewed the H and E and IHC slides independently and scored the results on a specially designed work sheet. Kappa values for inter-observer variation and Cornbach′s alpha for internal consistency were calculated. Statistical Analysis Used: SPSS 20.0 (IBM). not known. Results: Complete agreement was seen between all five pathologists in 70 cases (70/104) = 67%. Agreement between four pathologists was seen in 78 cases (78/104) = 75%. Agreement between three pathologists was seen in 92 cases (92/104) = 88%. The global value for kappa co efficient for agreement between two pathologists was 0.706 and Cornbach alpha for internal consistency of reporting in the department was 0.987. Conclusion/Key Messages: Our departmental peer review indicated that there is good inter-observer concordance (agreement between two pathologists) and there is strong overall internal consistency of reporting for HER 2 Neu reporting by IHC. Our results are comparable to International reported data of similar studies.