A Rare Presentation of Recurrent Malignant Peripheral Nerve Sheath Tumor with Glandular Differentiation-A Case Report.

Malignant peripheral nerve sheath tumors (MPNST) are rare heterogeneous group of soft tissue neoplasms. In most cases, they originate within the pre-existing neurofibromatosis. The emergence of glandular structures in MPNST is curious and enigmatic. We report a case of recurrent MPNST with glandular differentiation arising in the background of neurofibroma in a 20-year-old lady. By immunohistochemistry, MPNST showed focal positive staining for S100 and negative staining for SOX10 while adjacent neurofibroma showed diffuse positivity for S100 and SOX10. The glandular tumor cells showed positive staining for CDX2, Cam5.2, CK19, and CK7 (focal), while negative for SOX10 and S100. MPNST with glandular differentiation is quite rare which may pose a diagnostic challenge. The glandular differentiation in MPNST should be excluded from the metastasis from second primary with the aid of clinical and radiological correlation.

Malignant Gastrointestinal Neuroectodermal Tumor of Small Intestine Showing DOG1 Expression: A Case Report and Review of Literature.

Malignant gastrointestinal neuroectodermal tumor (GNET), also referred to as clear cell sarcoma-like tumor of the GI tract is a rare mesenchymal tumor of the gastrointestinal tract. It has to be distinguished from various mimickers including gastrointestinal stromal tumor (GIST) due to its aggressive course and different natural history and therapeutic approach. Here we report a case of GNET arising in the small intestine with aberrant DOG1 expression posing a diagnostic challenge. In this context, the combination of clinical, histomorphological, immunohistochemical, and molecular features helped to establish a proper diagnosis.

Langerhans Cell Hyperplasia Mimicking Langerhans Cell Histiocytosis: A Rare Complication of COVID-19 Vaccination.

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the abnormal proliferation of Langerhans cells, a type of immune cell that is normally present in the skin and various other tissues. LCH can affect people of any age but is most commonly diagnosed in children. We report a case of a patient with LCH who developed ipsilateral axillary lymphadenopathology post-COVID-19 vaccination. Lymph node biopsy showed diffuse Langerhans cell hyperplasia which mimicked LCH. Clinically and radiologically, it looked to be a reactive lymph node. The patient was kept on follow up only and after 1 year of follow up the size of lymph nodes regressed confirming to be reactive in nature rather than neoplastic. To the best of our knowledge, this is the second case of Langerhans cell hyperplasia post-COVID-19 vaccination being reported in the literature.

Signet ring cell carcinoma of the rectal stump in a known ulcerative colitis patient.

Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer worldwide and is the second most common cause of cancer-related deaths. However, the Omani population shares the major burden as the most prevalent carcinoma. The disease is comparatively higher in males than females. Patients with pre-existing risk factors, including inflammatory bowel disease, are at increased risk of developing neoplasia. Among the various histopathological subtypes of adenocarcinoma in the rectum, signet ring cell carcinoma is the rarest and accounts for approximately 1% of the cases. Given the aggressive nature of this tumor, advanced presentation, stage, and poor prognosis, regular endoscopic surveillance is essential. Hereby, we report a rare case of signet ring cell carcinoma arising in the rectal stump in an already diagnosed and operated patient of Ulcerative colitis.

Signet ring cell carcinoma of the rectal stump in a known ulcerative colitis patient

ABSTRACT Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer worldwide and is the second most common cause of cancer-related deaths. However, the Omani population shares the major burden as the most prevalent carcinoma. The disease is comparatively higher in males than females. Patients with pre-existing risk factors, including inflammatory bowel disease, are at increased risk of developing neoplasia. Among the various histopathological subtypes of adenocarcinoma in the rectum, signet ring cell carcinoma is the rarest and accounts for approximately 1% of the cases. Given the aggressive nature of this tumor, advanced presentation, stage, and poor prognosis, regular endoscopic surveillance is essential. Hereby, we report a rare case of signet ring cell carcinoma arising in the rectal stump in an already diagnosed and operated patient of Ulcerative colitis.

Gum Arabic Supplementation Suppresses Colonic Fibrosis After Acute Colitis by Reducing Transforming Growth Factor ß1 Expression.

Ulcerative colitis is a chronic inflammation of the colonic mucosa. Gum Arabic (GA) has been reported to exert anti-inflammatory and antifibrotic activity. This study aimed to evaluate the effect of GA on disease activity in an experimental model of colitis. Dextran sodium sulfate (DSS) was used to induce colitis in C57BL/6 mice and the animals were then switched to normal drinking water to monitor recovery. Mice received 140 g/L GA before (pre-GA group) or after (post-GA group) induction of colitis. Disease activity and recovery were assessed by changes in body weight, disease activity index (DAI), and histological assessment. Gene expression of proinflammatory, anti-inflammatory, and fibrotic markers was measured in colonic tissues. Mice in the pre-GA group showed an increase in body weight, with no differences in DAI scores, during the recovery phase and had lower histological colitis scores than mice in the post-GA group, which showed higher DAI and histological scores during the recovery phase. During the recovery phase, mice in the pre-GA group showed increased expression of proinflammatory markers, while gene expression of the fibrotic markers, transforming growth factor ß1 (TGFß1) and procollagen I, was reduced. The reduced fibrotic marker expression was associated with reduced collagen staining and increased epithelial cell proliferation. Administration of GA had protective and alleviative effects on the severity of DSS-induced colitis, with a reduction in colonic fibrosis and TGFß1 expression. These data warrant further in vitro and in vivo investigations on the effect of GA on fibroblast activity.

Balancing risk in a patient with primary bone histiocytic sarcoma during pregnancy: Case report and review of the literature.

INTRODUCTION AND IMPORTANCE: Histiocytic sarcoma (HS) is a rare, aggressive malignant neoplasm of hematopoietic cell origin. Primary HS of the proximal humerus, without involvement of lymph nodes or bone marrow, or systemic features, is very rare. CASE PRESENTATION: We report a rare case of primary bony HS of the proximal humerus without bone marrow involvement in a healthy 33-year-old pregnant woman. She was successfully treated with surgical resection during pregnancy and radiotherapy post-delivery. CLINICAL DISCUSSION: This is the first report of a patient with primary bony HS during pregnancy. This highlights the fact that although HS is a neoplasm of hemolymphoid cell lineage, it frequently arises in non-lymphoid organs. CONCLUSION: This case emphasizes the importance of a multidisciplinary approach and the need for balancing treatment risk in a patient with primary bone HS during pregnancy.

Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFß Pathway.

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-/-) mice were treated with 3% dextran sodium sulphate (DSS), followed by a recovery period. SOCS2-/- mice showed higher disease activity during colitis with increased mRNA expression of the pro-inflammatory cytokines nitric oxide synthase 2 (NOS2) and interleukin 1 ß (IL1-ß). At recovery time point, SOCS2-/- showed better recovery with less fibrosis measured by levels of α-SMA and collagen deposition. Protein and mRNA expressions of transforming growth factor beta ß1 (TGF-ß1) receptors were significantly lower in SOCS2-/- mice compared to wild-type littermates. Using an in vivo bromodeoxyuridine (BrdU) proliferation assay, SOCS2-/- 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 TGFß-mothers against the decapentaplegic homolog (Smad) pathway.

Primary Gastric Yolk Sac Tumour.

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.

The ubiquitin ligase Cullin5SOCS2 regulates NDR1/STK38 stability and NF-κB transactivation.

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.

Soft Tissue Rosai-Dorfman Disease: Case report.

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.

Gleason's Grading of Prostatic Adenocarcinoma: Inter-Observer Variation Among Seven Pathologists at a Tertiary Care Center in Oman

Prostatic adenocarcinoma is the commonest solid malignancy seen in Omani elderly males 60-80 years of age. The Gleason grade is the most widely used grading system for prostatic carcinoma and is recommended by the World Health Organization. A peer review was carried out at the Pathology Department of Sultan Qaboos University Hospital (SQUH), Oman, to assess the quality of reporting at the center. The aim of this study was to determine inter-observer variation among 7 pathologists working at a tertiary care center in Oman. A total of 47 consecutive prostatic biopsies were interdependently reviewed by seven pathologists and the results obtained were compared with each other and the original diagnosis. This peer review indicated a fair inter-observer agreement (0.482) among 7 pathologists in the department, with fair to moderate agreement when the results were compared to the reported diagnosis, comparable to the published literature. Dual and sub-specialty reporting are being instituted to improve the performance in this vital aspect of pathology.

Tissue and Serum miRNA Profile in Locally Advanced Breast Cancer (LABC) in Response to Neo-Adjuvant Chemotherapy (NAC) Treatment.

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.

Follicular Dendritic Cell Sarcoma: Cytogenetics and pathological findings.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with a non-specific and insidious presentation further complicated by the difficult diagnostic and therapeutic assessment. It has a low to intermediate risk of recurrence and metastasis. Unlike other soft tissue sarcomas or histiocytic and dendritic cell neoplasms, cytogenetic studies are very limited in FDCS cases. Although no specific chromosomal marker has yet been established, complex aberrations and different ploidy types have been documented. We report the case of a 39-year-old woman with FDCS who presented to the Sultan Qaboos University Hospital in Muscat, Oman, in February 2013. Ultrastructural, immunophenotypical and histological findings are reported. In addition, karyotypic findings showed deletions of the chromosomes 1p, 3q, 6q, 7q, 8q and 11q. To the best of the authors' knowledge, these have not been reported previously in this tumour. Techniques such as spectral karyotyping may help to better characterise chromosomal abnormalities in this type of tumour.

Molecular Evidence of Helicobacter Pylori Infection in Prostate Tumors.

OBJECTIVES: To determine whether Helicobacter pylori (H. pylori) is detectable in both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Epidemiological studies have shown significant associations between infective chronic prostatitis and prostatic carcinoma. Many bacteria have been found in the prostate of patients with chronic prostatitis, BPH, and PCa. METHODS: One hundred consecutive patients with prostate diseases were enrolled in the study. Detection of H. pylori DNA in prostate tissue from patients with BPH and PCa was performed using both immunohistochemistry and PCR, and the results were confirmed by DNA sequencing. Odds ratios and the Fisher Exact test were used for the analysis of the associations between the variables. RESULTS: Among the patients, 78% had BPH and 19% had PCa. While immunohistochemistry showed no positive sample for H. pylori, PCR combined with sequencing detected H. pylori DNA in prostate tissue samples from 5 patients. However, statistical analysis of the data showed that BPH and PCa are not significantly associated with the presence of H. pylori DNA in prostate tissue (odds ratio = 0.94, 95% confidence interval = 0.09-23.34, one-tailed Chi-square value = 0.660, p > 0.05). The limitation of this study was the small number of PCa patients. CONCLUSIONS: This study provides, for the first time, molecular evidence of the presence of H. pylori DNA in prostatic tissue of patients with BPH and PCa. It paves the way for further comprehensive studies to examine the association of H. pylori infection with BPH and PCa.

Inter-observer agreement in reporting HER 2 Neu protein over expression by immunohistochemistry.

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.

Immunohistological insight into the correlation between neuropilin-1 and epithelial-mesenchymal transition markers in epithelial ovarian cancer.

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.

The p53 Mutation/Deletion Profile in a Small Cohort of the Omani Population with Diffuse Large B-Cell Lymphoma.

OBJECTIVES: Mutations/deletions affecting the TP53 gene are considered an independent marker predicting a poor prognosis for patients with diffuse large B-cell lymphoma (DLBCL). A cohort within a genetically isolated population was investigated for p53 mutation/deletion status. METHODS: Deoxyribonucleic acid (DNA) samples were extracted from 23 paraffin-embedded blocks obtained from DLBCL patients, and subjected to polymerase chain reaction (PCR) amplification and sequencing of exons 4-9 of the p53 gene. RESULTS: While 35% of patients analysed displayed allelic deletions (P <0.01), immunohistochemical analysis revealed a mutation rate of 69.5%. It is noteworthy that the rate of p53 mutations/deletions in this small cohort was found to be higher than that previously reported in the literature. Interestingly, patients with p53 mutations displayed a better overall survival when compared to those without. The survival of patients treated with rituximab-containing combination chemotherapy was significantly better than those who did not receive rituximab (P <0.05). Furthermore, a modelling analysis of the deleted form of p53 revealed a huge structural change affecting the DNA-binding domain. CONCLUSION: The TP53 mutation/deletion status plays a role in mechanism(s) ruling the pathogenesis of DLBCL and may be useful for stratifying patients into distinct prognostic subsets.

Cytokeratin-positive primitive neuroectodermal tumor of the prostate: case report and review of literature.

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.