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The incidence of anal squamous cell carcinoma (SCC) has increased, and treatment has shifted from surgery to chemoradiotherapy (CRT), with salvage abdominoperineal resection being reserved for persistent/recurrent cases. This study evaluates the utility of different tumor regression scoring systems in predicting survival in anal SCC patients, using pathologists' observations and digital pathology. Data of cases managed surgically from 2005 to 2019 were collected. Residual tumor was assessed by multiple methods (gross tumor size, largest focus of tumor on hematoxylin and eosin (H&E) slide, average of residual tumor in all submitted H&E slides, Japanese Esophageal Society, Chirieac, Schneider, Hermann, and College of American Pathologists scoring system). Three expert pathologists individually estimated ("eyeballed") the residual tumor percentage based on residual tumor/tumor bed (single representative H&E slide). The QuPath software was used to measure tumor volume on the same slide. The American Joint Committee on Cancer eighth staging and outcome data were retrieved from electronic medical records. The study involved 48 participants, predominantly female (56%), with a median age of 57 years. Most were Caucasian. Human papillomavirus-positive was present in 77% of those assessed (17/22). Initial treatment included CRT, followed by abdominoperineal resection (79%) or pelvic exenteration (21%). Complications (13%), persistent disease (33%), and recurrence (54%) led to surgical interventions. Fifty-one percent had moderately differentiated SCC, whereas 42% were poorly differentiated. Lymphovascular invasion (44%), perineural invasion (38%), and lymph node metastasis (13%) were present. Distant metastasis was rare (2%). Median overall survival was 3.2 years. Positive margins (hazard ratio, 4.12; 95% CI, 1.83-9.28) and larger tumor size (hazard ratio, 1.02; 95% CI, 1.01-1.03) were associated with an increased hazard of death. Most residual tumor measurement methods were not significantly associated with overall survival. Interobserver agreement (based on "eyeballing") was moderate (kappa, 0.4). Computational pathology-based residual tumor percentage was the only method significantly associated with outcome, with each 10% increase in the residual tumor percentage corresponding to a 1.23-fold higher hazard death (95% CI, 1.03; 1.46; P = .024). This study highlights computational pathology's important role in predicting outcomes in anal SCC treated with CRT and surgery. Specifically, the computational assessment of the residual tumor percentage proves to be a strong predictor of overall survival, outperforming other established tumor regression scoring systems methods., (Copyright © 2025. Published by Elsevier Inc.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective. Whipple disease, caused by Tropheryma whipplei , is a rare infectious condition primarily presenting with malabsorptive diarrhea. Small bowel biopsies typically reveal foamy macrophages containing periodic acid-Schiff-positive/diastase (PAS/D) resistant T. whipplei bacilli, and PAS(D) staining is occasionally requested by clinicians in duodenal biopsies, which are often histologically unremarkable. The yield of PAS(D) staining in such biopsies has never been reported to our knowledge. Methods. The anatomic pathology database was searched for all specimens of duodenal biopsies stained with PAS(D) from 1993 to 2021. Specimens were categorized by the following histomorphologic features: unremarkable, nonspecific changes, or expansion of the lamina propria by aggregates of foamy histiocytes. Follow-up information was collected, including microbiologic confirmatory testing. Results. There was a total of 193 specimens of duodenal biopsies stained with PAS(D). Biopsies lacking foamy histiocytes on H&E ( n  = 158) were never PAS-positive. Thirteen biopsies contained PAS-positive histiocytes; 9 out of the 13 PAS-positive specimens were subsequently confirmed to be T. whipplei . Of the 193 specimens, 124 specimens had a clinical request for PAS(D) staining. Only 3 of the 124 (2.4%) specimens showed foamy histiocytes containing PAS-positive granules, all of which were confirmed positive for T. whipplei . Conclusion. PAS(D) staining is unnecessary to exclude Whipple disease in duodenal biopsies without foamy macrophage aggregates, regardless of clinical suspicion. Clinical suspicion-driven biopsies often yield negative results for Whipple disease., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Lymph node metastasis (LNM) is the most significant parameter affecting overall survival in patients with oral cavity squamous cell carcinomas (OCSCC). Elective neck dissection (END) is the standard of care in the early management of OCSCC with a depth of invasion (DOI) greater than 2-4 mm. However, most patients show no LNM in the final pathologic report, indicating overtreatment. Thus, more detailed indicators are needed to predict LNM in patients with OCSCC. In this study, we critically evaluate the existing literature about the risk of different histological parameters in estimating LNM., Methods: A systematic review was conducted using PRISMA guidelines. PubMed, Web of Science, Cochrane, and Scopus were searched from inception to December 2023 to collect all relevant studies. Eligibility screening of records was performed, and data extraction from the selected studies was carried out independently. Inclusion in our systematic review necessitated the following prerequisites: Involvement of patients diagnosed with OCSCC, and examination of histological parameters related to lymph node metastasis in these studies. Exclusion criteria included animal studies, non-English articles, non-availability of full text, and unpublished data., Results: We included 217 studies in our systematic review, of which 142 were eligible for the meta-analysis. DOI exceeding 4 mm exhibited higher risk for LNM [Risk ratio (RR) 2.18 (1.91-2.48), p<0.00001], as did perineural invasion (PNI) [RR 2.04 (1.77-2.34), p<0.00001], poorly differentiated tumors [RR 1.97 (1.61-2.42), p<0.00001], lymphovascular invasion (LVI) [RR 2.43 (2.12-2.78), p<0.00001], groups and single pattern of invasion [RR 2.47 (2.11-2.89), p<0.00001], high tumor budding [RR 2.65 (1.99-3.52), p<0.00001], tumor size over 4 cm [RR 1.76 (1.43-2.18), p<0.00001], tumor thickness beyond 4 mm [RR 2.72 (1.91-3.87), p<0.00001], involved or close margin [RR 1.73 (1.29-2.33), p = 0.0003], and T3 and T4 disease [RR 1.98 (1.62-2.41), p <0.00001]., Conclusion: Our results confirm the potential usefulness of many histopathological features in predicting LNM and highlight the promising results of others. Many of these parameters are not routinely incorporated into pathologic reports. Future studies must focus on applying these parameters to examine their validity in predicting the need for elective neck treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alqutub, Alqutub, Bakhshwin, Mofti, Alqutub, Alkhamesi, Nujoom, Rammal, Merdad and Marzouki.)

Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Myxofibrosarcomas (MFS) present as slowly enlarging superficial masses in elderly patients. Even though these tumors fail to exhibit a distinct immunophenotype, diagnosis is straightforward when they present in subcutaneous tissue. Intramuscular MFS, however, are more challenging to diagnose as the differential also includes dedifferentiated liposarcoma with myxoid features. The vast majority of dedifferentiated liposarcomas show MDM2 amplification, whereas limited data exists as to the MDM2 status of MFS. We sought to explore the rate of MDM2 amplification in cases of classic MFS. Our archives were searched for MFS; only subcutaneous well-sampled resections were included. FISH for MDM2 amplification was performed on each tumor. A cohort of myxoid dedifferentiated liposarcoma resections was studied for comparison. Twenty-two MFS arose in patients aged 44 to 85 years. All tumors contained an infiltrative population of atypical cells embedded in a myxoid stroma with curvilinear blood vessels. MDM2 amplification by FISH was identified in 3 (of 22; 14%) tumors. Available follow up on 17 patients (range 1-96 months; median 13 months) revealed 6 patients with local recurrence and 1 with distant metastasis. Of 3 patients with MDM2- amplified MFS, 1 experienced recurrence and died of unrelated causes, while the second was alive without disease 12 months after diagnosis. Even though the rate of MDM2 amplification by FISH in MFS appears to be low, a subset of cases may show this genetic alteration, which pathologists should be aware of to avoid misclassification as myxoid dedifferentiated liposarcomas. Further studies are necessary to determine if amplification status adds prognostic value., Competing Interests: Author's NoteNooshin K. Dashti is currently affiliated to the Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH and Geisel School of Medicine at Dartmouth College, Hanover, NH, USA. Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethical ApprovalThis study was performed in accordance with current ethical guidelines of the Declaration of Helsinki and the requirements of the Institutional Review Board of Mayo Clinic, Rochester, MD, USA (Approval number IRB18-006968).

Immunotactoid deposition is a rare fibrillary deposition disease that is primarily seen in the kidney and is associated with paraproteinemia. Here, we report a case of hepatic immunotactoid deposition in a 67-year-old male with a history of smoldering myeloma and chronic kidney disease who underwent liver transplantation for metabolic dysfunction-related cirrhosis. Immunotactoid deposition was first identified in the explanted liver and recurred in the allograft within only 7 weeks following transplantation, presenting as ascites with normal liver function tests. The patient's posttransplant course was complicated by proteinuria and renal failure requiring dialysis. Histologic examination of both native and allograft livers demonstrated pink amorphous material occupying sinusoidal spaces that were Congo-red negative and immunoglobulin M Kappa-restricted. Electron microscopy revealed characteristic deposits of electron-dense bundles of hollow microtubules with a 40 nm diameter within the sinusoids and space of Disse, consistent with immunotactoids. Therapy of the patient's underlying plasma-cell dyscrasia utilizing a daratumumab-based regimen showed decreased serum paraproteins, resolution of ascites, and improved kidney function, no longer requiring dialysis, without inducing rejection. The patient continues to respond to treatment 10 months posttransplant., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose, as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Spindle cell mesenchymal neoplasms are a diverse and often challenging diagnostic group. While morphological impression is sufficient for some diagnoses, increasingly immunohistochemical and even molecular data is required to render an accurate diagnosis, which can lead to the characterization of new entities. We describe five cases of novel mesenchymal neoplasms with rearrangements in the NCOA2 and NCOA3 genes partnered with either CTCF or CRTC1. Three tumors occurred in the head and neck (palate, auditory canal), while the other two were in visceral organs (lung, urinary bladder). All cases occurred in adults (range 33-86) with a median age of 42 and fairly even sex distribution = (male-to-female = 3:2). Morphologically, they had similar features consisting of monotonous, bland spindle to ovoid cells with fascicular and reticular arrangements in a myxohyaline to collagenous stroma. However, immunophenotypically they had essentially a null phenotype, with only two tumors staining partially for CD34 and smooth muscle actin. Targeted RNA sequencing detected in-frame CTCF::NCOA2 (one case), CRTC1::NCOA2 (two cases), and CTCF::NCOA3 (two cases) fusions. Treatment was surgical resection in all cases. Local recurrence and/or distant metastases were not observed in any case (median follow-up, 7.5 months; range, 2-19 months). Given their morphologic, immunohistochemical, and molecular similarities, we believe that these cases may represent an emerging family of low-grade NCOA2/3-rearranged fibroblastic spindle cell neoplasms., (© 2023 The Authors. Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

Background: Desmoplastic fibroblastoma (collagenous fibroma) is a rare soft tissue tumor that usually arises in the subcutis or skeletal muscle. Cases superficial to fascia are unusual and can cause diagnostic difficulty. We present 11 cases of superficial desmoplastic fibroblastoma involving a wide anatomic distribution., Methods: Archives were searched using the term "desmoplastic fibroblastoma" over a 10-year period (2012-2022). Cases superficial to fascia were retrieved, and available clinicopathologic features were recorded. Only cases involving the dermis were included., Results: Eleven cases were identified, all of which were received in consultation. Tumors involved the head and neck (2), lower extremity (2), back (2), foot (1), shoulder (1), axilla (1), hand (1), and breast (1). Each consisted of a hypocellular proliferation of bland stellate to spindled fibroblasts set in a collagenous to focally myxoid stroma. The immunohistochemical stains available for review demonstrated SMA positivity (4/7) and negative immunoreactivity for CD34 (0/6), EMA (0/3), desmin (0/3), and S100 (0/7)., Conclusions: Desmoplastic fibroblastoma may present superficially in the dermis to subcutis, posing a potential source of diagnostic difficulty. Recognition of the characteristic histopathologic features of desmoplastic fibroblastoma with judicial use of immunohistochemical stains should allow for accurate diagnosis., (© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Cholangiocarcinoma is the second most common primary liver malignant neoplasm. It usually affects older individuals in their seventh decade of life with no gender predilection. Recently, a distinct subtype of cholangiocarcinoma has emerged with 2 proposed names: "cholangioblastic" and "solid tubulocystic." This variant predominantly occurs in younger women who lack the common risk factors for patients diagnosed with cholangiocarcinomas, such as older age and chronic liver disease or cirrhosis. We describe 3 new patients with a cholangioblastic variant of intrahepatic cholangiocarcinoma. At the time of diagnosis, the patients were aged 19-, 46-, and 28-year-old; 2 females and 1 male (the 46-year-old). None of our patients had a history of chronic liver disease or known predisposing factors for liver tumors. Tumor size ranged from 2.3 to 23 cm in greatest dimension. Histological examination of these tumors demonstrated reproducible morphology characterized by trabecular, nested, and multicystic patterns with micro and macro follicles filled with eosinophilic material. The immunohistochemical profile showed that the tumor cells were positive for keratin 7, inhibin, synaptophysin, and albumin in situ hybridization, while negative for HepPar1, arginase, and INSM1. All tumors lacked conventional intrahepatic cholangiocarcinoma/adenocarcinoma morphology. We also review the literature and emphasize that neuroendocrine tumors should be recognized as a major diagnostic pitfall of this variant., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Microcystic/reticular schwannoma (MRS) is a benign variant of schwannoma with a predilection for the gastrointestinal tract and skin. To date, genetic characterization of this tumor is limited. Prompted by the identification of TFE3::NONO fusion and ALK overexpression in an index case of MRS, a cohort of tumors was collected from institutional and consultation archives of two institutions. Next-generation sequencing (NGS), TFE3 fluorescence in situ hybridization (FISH), and TFE3 and ALK immunohistochemistry were performed, while clinicopathologic variables were documented. Eighteen MRS cases were identified (35 to 85 years) arising in the skin (n=8), gastrointestinal tract (n=5), adrenal gland (n=3), abdominal wall (n=1), and unknown site (n=1). Tumors showed a circumscribed to multinodular to plexiform low-power architecture with variable amounts of microcystic/reticular and solid schwannian components. Mitotic figures were scarce (0-1/10 HPFs), and atypia was absent. S100 protein and/or SOX10 immunoreactivity was noted in the microcystic/reticular and schwannian areas of all cases. NGS performed on two cutaneous tumors yielded NONO exon 12 fusion with TFE3 exon 4, and these lesions also showed HMB45 and ALK expression. Two additional cases showed ALK expression (1 weak), while a third was positive for TFE3, but these cases failed to show ALK or TFE3 rearrangement by FISH/NGS. There were no morphologic variables that correlated with the presence of NONO::TFE3. We identified a subset of microcystic/reticular schwannomas with NONO::TFE3 fusions and ALK co-expression, adding to the cohort of mesenchymal neoplasms that show ALK overexpression without rearrangement of the ALK gene., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Systemic mastocytosis is a rare myeloproliferative disorder characterized by abnormal accumulation of mast cells in a variety of organs. When affecting the gastrointestinal tracts, it may manifest with steatorrhea, malabsorption, hepatomegaly, splenomegaly, portal hypertension, and ascites, among others. To our knowledge, only one case of systemic mastocytosis has been reported affecting the appendix. We present another case of a 47-year-old woman who was admitted for right-sided acute abdominal pain and found to have systemic mastocytosis in her appendectomy specimen as the first and only manifestation of her disease., (© 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Neuroendocrine carcinomas are extremely rare in the esophagus as they represent less than 0.04% of all neuroendocrine tumors. To date, only 14 cases of poorly differentiated, high-grade esophageal NEC have been described in the literature. The majority of these patients presented with typical dysphagia symptoms. Due to its rarity, no standardized guidelines have been proposed to treat esophageal neuroendocrine carcinoma, although general recommendations suggest surgery with adjuvant chemoradiotherapy as the treatment of choice., Case Presentation: A 67-year-old previously healthy White male presented with a year-long intermittent nonspecific retrosternal discomfort, with the absence of any other symptoms. Esophagogastroduodenoscopy revealed an ulcerative mass in his lower esophagus, with concern of malignancy. Endoscopic ultrasound-guided biopsy revealed poorly differentiated neuroendocrine carcinoma of the esophagus with metastasis to a diaphragmatic lymph node. He was treated with neoadjuvant chemoradiation followed by surgery, and he has been in remission for over 5 years., Conclusion: Here, we review the literature and report a unique case of a patient with a vague presentation of esophageal neuroendocrine carcinoma as he enters his sixth year of survival following neoadjuvant chemoradiotherapy., (© 2023. The Author(s).)

Recently, the use of immunotherapy has increased substantially for the treatment of several malignancies. It is associated with several gastrointestinal adverse events; however, severe complications such as intestinal perforation are rare. We present a 75-year-old man with metastatic melanoma, presented with profuse diarrhea and abdominal pain, after ipilimumab and nivolumab administration. Shortly after, he developed fulminant colitis and intestinal perforation and was found to have concurrent Rosai-Dorfman disease of pericolonic lymph nodes. With the increasing use of immunotherapy, reporting of serious adverse events and their mimics is essential. In addition, further studies are required to investigate whether an association exists between Rosai-Dorfman disease and immunotherapy., (© 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Examination of pancreatic ductal adenocarcinoma after NAT with the intent of diagnosis and outcome prediction remains a challenging task. The lack of a uniform approach to macroscopically assess these cases along with variations in sampling adds to the complexity. Several TRG systems have been proposed to correlate with an overall survival. In clinical practice, most of these TRG schemes have shown low level of interobserver agreement arguing for a need of larger studies and more innovative ways to assess outcome in this population., Competing Interests: Disclaimer Dr A. Bakhshwin has nothing to disclose. Dr D.S. Allende has participated as Advisory Board member for Incyte., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: A pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (COVID 19) incidence data are largely available online. Until August 17, COVID 19 has hit more than 22 million individuals all over the globe. So, it is urged to get clear information about the prevalence of the virus. Therefore, one can manipulate easily a suitable mathematical model to fit these published data., Methods: We propose a mathematical model that considers the total population, in 25 countries, either infected by COVID 19 or confined (safe) during the period from November 17, 2019, to August 17, 2020. The model considers the total population as a complex number; the imaginary part is the number of infected individuals and the real part is the number of confined individuals. This classification combined with mathematical treatments leads to a transmission dynamics of the virus to be as wave-like motion. The virus can hit any country either by one wave or by successive waves (up to 11 waves)., Findings: We find net discrimination between the 25 countries investigated in this report. The immediate response to the first attack is a substantial parameter to determine whether the epidemic attack will be in one wave or it can be in successive waves. For example, the best case was such as individuals in China hit by one wave while the individuals in the USA were attacked by nine waves; it is the worst case all over the globe. In addition, the model differentiates between the daily reproduction numbers (R d0 ) and the median reproduction number (R 0 ). We have found that R d0 decreases exponentially with time from high values down to zero at the wave maximum point; and R 0 varies from a country to another. For example, the virus hit individuals in Germany in R 0  = 1.39 (96% CI 1.01-3.87) and in the USA R 0  = 3.81 (91% CI 1.71-5.15). We have found that twice the virus has hit both the USA and Iran. The great protestation of black matter lives in the USA and the great assemblage of the new Iranian year, on March 21, 2020, have been the cause of the second epidemic attack in both countries., Interpretation: Our results show that COVID 19 transmission depends on the prompt reaction against the first viral-wave. The reaction depends on both the social behaviour of individuals and on the swift system-decision by the governmental decision-maker(s). The Chinese strictly follow the decision-maker and therefore the virus hit by only one wave; while in the USA, the system-decision was different and the American-responses were different, therefore ten waves followed the first wave., (© 2021. The Author(s).)

Background: The antioxidant, hypoglycemic, and insulin-enhancing effects of ginger and cinnamon were previously confirmed in experimental and human studies, while the combined effect of ginger and cinnamon was not thoroughly investigated until now. Objectives: This study was designed to assess the antidiabetic effect of combined administration of ginger ( Zingiber officinale Roscoe) and cinnamon ( Cinnamomum cassia L.) in streptozotocin (STZ)-induced diabetic rats compared to metformin and to explain the mechanism behind this effect. Materials and methods: STZ was utilized to induce diabetes mellitus in male Sprague-Dawley rats. Assessments of fasting blood glucose level (BGL), the total antioxidant capacity (TAC), serum insulin, HOMA-IR, and HOMA-β cells were performed. Pancreatic gene expression of β-catenin and p53 was assessed using RT-PCR. Assessment of histopathological alterations of pancreatic islet cells was performed using routine and immunohistochemical techniques. Results: BGL significantly decreased ( p = 0.01), while serum insulin and TAC significantly increased ( p < 0.001) in both metformin- and ginger plus cinnamon-treated groups compared to the untreated diabetic group. HOMA-β cell index significantly increased ( p = 0.001) in ginger plus cinnamon, indicating their enhancing effect on insulin secretion in diabetic conditions. p53 gene expression was significantly upregulated ( p < 0.001), while β-catenin was insignificantly downregulated ( p = 0.32) in ginger plus cinnamon-treated groups. Insulin immunoexpression in β cells significantly increased ( p = 0.001, p = 0.004) in metformin- and ginger plus cinnamon-treated groups, respectively. Conclusions: The combined administration of ginger and cinnamon has a significant hypoglycemic and antioxidant effect in STZ-induced diabetes mostly through enhancing repair of islet cells mediated via upregulation of pancreatic p53 expression. Therefore, testing this effect in diabetic patients is recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ayuob, Al-Shathly, Bakhshwin, Al-Abbas, Shaer, Al Jaouni and Hamed.)

Undifferentiated carcinoma of the esophagus and gastroesophageal junction is a recently recognized entity in the fifth edition of the World Health Organization Classification of Digestive Tumors and is diagnostically challenging, particularly on small biopsies. SMARCA4 and SMARCA2 are chromatin remodeling genes with key roles in oncogenesis. We retrieved 14 cases of SMARCA4/SMARCA2-deficient undifferentiated carcinoma of the gastroesophageal junction and esophagus from the authors' institutions. The tumors showed similar histologic findings: the sheet-like proliferation of tumor cells characterized by discohesion, large nuclei, and prominent macronucleoli with many tumor cells exhibiting a rhabdoid appearance. In 8 cases, adjacent specialized intestinal metaplasia was noted and 3 cases exhibited adjacent high-grade dysplasia. Immunohistochemically, tumors variably expressed keratins and disclosed loss of expression of SMARCA4 in 12 and SMARCA2 in 7 cases. In 2 cases SMARCA2 alone was lost without SMARCA4 loss. A mutant p53 immunohistochemical pattern was seen in 4 of 4 cases, 3 of which showed diffuse, strong nuclear expression, and 1 case displayed a complete loss of nuclear expression of p53, including invasive carcinoma and associated dysplasia, when present. Limited clinical follow-up was available, but 3 patients died of disease within 0.6, 2, and 7 months of diagnosis. We present the first series of undifferentiated carcinoma of the esophagus and gastroesophageal junction with this characteristic morphology associated with loss of SMARCA4 and/or SMARCA2 expression. This tumor type likely arises from dedifferentiation of a lower grade carcinoma in some cases, and Barrett esophagus and appears to be associated with an aggressive clinical course., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Statins are among the first line of pharmacological treatment of lipid disorders and lowering serum cholesterol, but they have many side effects., Aim: The study aim was to evaluate the role of raisins in protecting the thyroid function and structure in a rat model of hypercholesterolemia, through biochemical and histopathological investigation., Materials and Methods: Thirty male rats were randomly divided into three groups ( n = 10 each) of albino rats included the control, high cholesterol diet (HCD)-fed for 13 weeks and HCD plus Raisins were included in this study. Blood levels of glucose, insulin, cholesterol, lipids, thyroid-stimulating hormone (TSH), T3, T4, oxidants/anti-oxidants were assessed. Thyroid gland was processed and examined histopathologically using light and electron microscopy., Results: Feeding HCD resulted in hypercholesterolemia in rats after 13 weeks as evidence by lipid profile. Ingestion of raisins along with HCD resulted in a significant ( P < 0.001) decrease in the levels of insulin, blood glucose, thyroxine (T4) and malondialdehyde (MDA), while the levels of TSH, T3 and total anti-oxidant capacity significantly ( P < 0.001) elevated. Raisins histologically alleviated the HCD-induced structural changes in the thyroid glands that included degenerated mitochondria and increased lipid droplets in the cytoplasm., Conclusions: Simultaneous administration of raisins along with HCD, administrated for a short time, could modulate the negative effect on thyroid gland structure and function., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Microscopy and Ultrastructure.)

Solitary fibrous tumour (SFT) is well-described in the urinary tract, but malignant examples are rare. We studied our experience with high grade malignant SFT of the prostate to address the degree of histological and immunophenotypical overlap with sarcomatoid carcinoma and prostatic stromal sarcoma. Four cases were identified from the surgical pathology consultation archives. All available H&E stained sections were reviewed. Immunostains for STAT6, CAM5.2, NKX3.1, PAX-8, GATA3, high molecular weight cytokeratin (34BE12), p40, and p63 were performed on available material. Each case was evaluated by three separate SFT prognostic risk models based on clinicopathological features, and for features of 'dedifferentiated SFT'. The patient's ages were 49, 55, 69, and 73 years. Three presented with symptoms of benign prostatic hyperplasia and one with haematuria. Tumour sizes were 5, 9, 13, and 13 cm. Mitotic rate ranged from 6 to 20 mitoses per 10 high power fields, and two cases showed abrupt transition from conventional SFT to areas with marked nuclear pleomorphism/anaplasia (i.e., 'de-differentiation'). Immunophenotypically, all four cases had strong and diffuse nuclear reactivity for STAT6. For other markers, three of three had both focal PR and GATA3 nuclear expression (up to 30% of cells). One case with 'dedifferentiated' features showed expression of multiple epithelial markers, including EMA (focal), high molecular weight cytokeratin (focal), p63, and p40. In summary, malignant SFT may rarely occur in the prostate and may closely mimic sarcomatoid carcinoma or prostatic stromal sarcoma, both histologically and immunophenotypically. Consideration of the diagnostic possibility of malignant SFT, recognition of unexpected GATA3 and PR expression, and utilisation of monoclonal STAT6 immunohistochemistry facilitate appropriate diagnosis at this unusual anatomical site., (Copyright © 2020 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Smooth muscle tumors represent the second most common mural mesenchymal neoplasm in the gastrointestinal tract, but established criteria for prognostic assessment of these tumors are lacking. A large cohort of surgically resected intramural gastrointestinal smooth muscle tumors from 31 institutions was analyzed to identify potential prognostic features. Pathologic features were assessed by expert gastrointestinal and/or soft tissue pathologists at each center. Immunohistochemical confirmation was required. A total of 407 cases from the esophagus (n = 97, 24%), stomach (n = 180, 44%), small bowel (n = 74, 18%), and colorectum (n = 56, 14%) were identified. Patients ranged in age from 19 to 92 years (mean 55 years), with a slight female predominance (57%). Mean tumor size was 5.4 cm, with the largest tumor measuring 29 cm. Disease progression following surgery, defined as local recurrence, metastasis, or disease-related death, occurred in 56 patients (14%). Colorectal tumors were most likely to progress, followed by small bowel and gastric tumors. None of the esophageal tumors in this series progressed. Receiver operator characteristic analysis identified optimal cutoffs of 9.8 cm and 3 mitoses/5 mm 2 for discriminating between progressive and non-progressive tumors. Histologic features strongly associated with progression by univariate analysis included moderate-to-severe atypia, high cellularity, abnormal differentiation (defined as differentiation not closely resembling that of normal smooth muscle), tumor necrosis, mucosal ulceration, lamina propria involvement, and serosal involvement (P < 0.0001 for all features). Age, sex, and margin status were not significantly associated with progression (P = 0.23, 0.82, and 0.07, respectively). A risk assessment table was created based on tumor site, size, and mitotic count, and Kaplan-Meier plots of progression-free survival for each subgroup revealed progression-based tiers. Based on our findings, it appears that nonesophageal gastrointestinal smooth muscle tumors measuring >10 cm and/or showing ≥3 mitoses/5 mm 2 may behave aggressively, and therefore close clinical follow-up is recommended in these cases.

Objective: Using a mouse model of intrauterine inflammation, we have demonstrated that exposure to inflammation induces preterm birth and perinatal brain injury. Mesenchymal stem cells (MSCs) have been shown to exhibit immunomodulatory effects in many inflammatory conditions. We hypothesized that treatment with human adipose tissue-derived MSCs may decrease the rate of preterm birth and perinatal brain injury through changes in antiinflammatory and regulatory milieu., Study Design: A mouse model of intrauterine inflammation was used with the following groups: (1) control; (2) intrauterine inflammation (lipopolysaccharide); and (3) intrauterine lipopolysaccharide+intraperitoneal (MSCs). Preterm birth was investigated. Luminex multiplex enzyme-linked immunosorbent assays were performed for protein levels of cytokines in maternal and fetal compartments. Immunofluorescent staining was used to identify and localize MSCs and to examine microglial morphologic condition and neurotoxicity in perinatal brain. Behavioral testing was performed at postnatal day 5., Results: Pretreatment with MSCs significantly decreased the rate of preterm birth by 21% compared with the lipopolysaccharide group (P<.01). Pretreatment was associated with increased interleukin-10 in maternal serum, increased interleukin-4 in placenta, decreased interleukin-6 in fetal brain (P<.05), decreased microglial activation (P<.05), and decreased fetal neurotoxicity (P<.05). These findings were associated with improved neurobehavioral testing at postnatal day 5 (P<.05). Injected MSCs were localized to placenta., Conclusion: Maternally administered MSCs appear to modulate maternal and fetal immune response to intrauterine inflammation in the model and decrease preterm birth, perinatal brain injury, and motor deficits in offspring mice., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: Post-stereotactic radiation-induced neoplasms, although relatively rare, have raised the question of benefit regarding CyberKnife® treatments versus the risk of a secondary malignancy. The incidence of such neoplasms arising in the nervous system is thought to be low, given the paucity of case reports regarding such secondary lesions., Case Presentation: Here we describe a case of a 43-year-old Middle Eastern woman with primary clear cell renal cell carcinoma and a metastatic focus to the left brain parenchyma who presented with focal neurologic deficits. Following post-surgical stereotactic radiation in the region of the brain metastasis, the patient developed a secondary high-grade astrocytoma nearly 5 years after the initial treatment., Conclusion: Although the benefit of CyberKnife® radiotherapy treatments continues to outweigh the relatively low risk of a radiation-induced secondary malignancy, knowledge of such risks and a review of the literature are warranted.