Multiple granular cell tumours of the New born: A case report and Literature ReviewAbstractCongenital granular cell epulis affecting newborns is a rare benign tumor. It presents more in females, mostly in the maxillary region. Its presence is marked typically as pedunculated masses from the alveolar ridge. We report on a neonate, who, upon delivery, was observed to have multiple tumors projecting from the oral cavity. The treatment involves immediate planning of surgery so as not interfere with the newborns’ nutrition and respiration.Keywords: Congenital granular cell epulis, Granular cell lesion. Neumann tumor, granular cell myoblastomaIntroductionIn 1871, Dr. Franz Ernst Christian Neumann, a German pathologist was credited for the description of an uncommon and unusual neonatal lesion termed the congenital granular cell epulis (CGCE).  In Greek, Epulis means “swelling on the gingiva”1.  Alternative nomenclature used for this lesion may include any of the following: Neumann tumor, granular cell myoblastoma, gingival granular cell tumor (GCT), granular cell fibroblastoma, Abrikosov tumor, granular cell lesion, and congenital epulis. However, the World Health Organization recommends the distinctive term “congenital granular cell epulis”1,2.  Approximately 250 cases of this benign lesion have been documented to date3, with a female to male ratio of 10:14.Often, CGCE is present in the neonate’s oral cavity as a soft lesion primarily in the alveolar ridge.  It is a benign tumor with multiple lesions comprising nearly 10% of cases3.  Though its histogenesis is unknown and debatable, it has been suggested that CGCE initiation emanates from undifferentiated mesenchymal, epithelial, nerve-related cells, fibroblasts, pericytes, smooth muscle, or it could be neuroectodermal in origin5.  Previous occasional cases of minor midface hypoplasia, an absent or a hypoplastic tooth have been reported.  However, no cases are known to be associated with dental abnormalities or congenital anomalies4.  Diagnosis is primarily clinical, making the differential diagnosis broad; hence, the importance of imaging cannot be overemphasized4. Tumor detection prenatally is possible via magnetic resonance imaging (MRI) or ultrasound (US) since CGCE manifestation occurs during the third trimester of pregnancy3.  It is visible as a clear hypoechoic bulging oral mass accompanied by branched vascularization, with rapid growth during the third trimester of pregnancy and immediately ceasing at birth2. We present a case of CGCE noted immediately after birth.Case PresentationOne hour after a female neonate weighing 3400gm had been delivered through a caesarian section, an Oral Maxillofacial surgeon was sought to evaluate multiple pink colored pedunculated swellings projecting from the patient’s oral cavity (Fig.1). Based on the general pediatric assessment, it was noted that they were impending breast feeding and breathing challenges. Remarkably, there was lip incompetence, dryness and crusting. Intravenous support had been instituted for nutrition and hydration. Intraoral inspection revealed two large pedunculated masses {2.5cm largest diameter on the anterior maxillary alveolar mucosa and three smaller ones on the mandibular alveolar ridge (5-8 mm in diameter)}. The mucosa was well vascularized and pink in color. A differential diagnosis of a granular cell epulis was made.An MRI of the head and neck was requested to rule out the presence of feeder vessels close to the larger masses. The radiology scan reported two pedunculated masses iso dense on T1W1 and mixed signal intensity on T2W1 with post contrast enhancement were seen that appeared to arise from the alveolar aspect of the palate without erosion or cleft of the palate. The left mass was reported to be round and measured 13mm in diameter and the right measured 26mmx10mmx10mm{anteroposterior (AP)X transverse(TV)X craniocaudal(CC) }. The mass abutted the tongue with inferior and with slight posterior displacement. The airway was otherwise intact. All other structures including the neck and visualized vasculature were unremarkable. The radiological diagnosis was in keeping with the clinical differential diagnosis of an epulis (Fig. 2). Theatre was scheduled immediately due to the challenges in feeding. General anesthesia was administered via nasotracheal intubation, the masses were meticulously excised and the specimen submitted for histopathology and immunohistochemistry (IHC)(Fig 3). She was able to breast feed a couple of hours later and post operative recovery was uneventful. She was discharged on the third post operative day.The IHC report showed tumours cells were positive for Vimentin, neuron-specific enolase (NSE), 8% positivity K167 for and negative for Desmin, Smooth Muscle Actin(SMA), (cytokeratin)CK, CD34, CD68, Inhibin, S100, Calretinin. The histopathology report showed sections of a nodular tumor composed of sheets and nests of thin fibrous stroma. The tumour cells were rounded to polygonal cells with distinct cellular borders. There was abundant eosinophilic, granular cytoplasm, and smaller vesicular nuclei with no mitosis and necrosis. These features are consistent with those of CGCE (Fig.4.)DISCUSSIONThe occurrence of multifocal lesions within black neonates is found to be rare7.  The last documented case in Kenya to our knowledge was reported in 19948.  Owing to this rare occurrence, we report the third Kenyan case of a black female neonate who was postnatally diagnosed with CGCE3. The hallmarks of a CGCE tumor are as follows: it is soft, smooth surfaced, well-circumscribed, it can also be pedunculated/sessile, multilobed, pink/red colored ranging from a few millimeters with cases up to 9 centimeters in diameter.  It is predominantly found more in the maxillary than the mandibular alveolus.  Clinically, the lesion firmly attaches like a polyploid nodule to the labial or palatal gingiva.  It can be erythematous or ulcerated, with the bone and teeth not involved1,2,3,4,8.  Diagnosis can be based using clinical parameters; however, histopathological and histochemical criteria are equally fundamental in the determination of tumor diagnosis and management. The histological presentation was not of an atypical nature. The following IHC markers: S-100, laminin, CD34, CD68, Nerve growth factor receptor (NGFR)/ p75, inhibin-alpha, chromogranin, desmin, keratins, SMA, CD31, and GLUT-1 are absent during testing and those that test positive are Vimentin and NSE. As for our patient, the IHC tests showed the tumor to be negative for Desmin, SMA, CK, CD34, CD68, Inhibin, S100, Calretinin, while positive for Vimentin and NSE, identical to the trend reported 9.10. Conrad et al The proliferation index of the tumour disclosed was 8% showing Ki-67 positivity which is similar to the range documented in some studies, that is, from 11.1- 16.7% and 15.1-33.3% respectively11,12,13.The features outlined were typical of the tumor’s description in the literature. The presence of multiple tumors, compounded by their size/s, may have lead to the interference in the newborn’s respiration and nutrition. Hence the need for urgent surgical intervention.  The multidisciplinary team involved a gynecologist, neonatologist, maxillofacial surgeon and anesthesiologist. The recommended treatment of choice is surgical excision, which usually has excellent prognosis6.  Cases of recurrences have not been documented even when incomplete margins are excised, any malignant variation, or any futuristic disruption in teeth, nor gingiva4.  There has been no association of CGCE with any syndromes or genetic defects; therefore, patients have no risk factors for other deformities or passing it on as an inherited gene2.  After the meticulous excision we have had a follow up for a year and the patient has no signs recurrence (Fig. 5.)ConclusionNeonates born with CGCE need swift action due to the immediate respiratory and nutritional demands of the patient especially if the tumors are multifocal and large in size. Although a rare and benign lesion, the surgeon must be familiar with the differential diagnosis to proceed with ease and diligence. The treatment plan for CGCE should embrace a multidisciplinary approach including counseling the parents/caregivers, reassuring them of treatment outcomes and life normalcy for the newborn as the review process continues to life normalcy.Conflict of Interest: we have the authors declare no conflict of interest in refence to this case report.Funding: NoneConsent Form : A written and signed consent form from the patient guardian has been obtained uploaded.Author Contribution: Fawzia Butt : Role Conceptualization and Data curation: Shamim Butt Role : Writing of the Original Draft; Mark Chindia Role Review and EditingReferencesAresdahl, A., Lindell, B., Dukic, M., & Thor, A. (2015). Congenital granular cell epulis—A case report. Oral and Maxillofacial Surgery Cases, 1(1), 8–11. https://doi.org/10.1016/j.omsc.2015.04.001Conrad, R., & Perez, M. C. N. (2014). Congenital granular cell epulis. Archives of Pathology & Laboratory Medicine, 138(1), 128–131. https://doi.org/10.5858/arpa.2012-0306-RSTorresani, E., Girolami, I., Marletta, S., Eccher, A., & Ghimenton, C. (2021). Congenital granular cell epulis of newborn: Importance of prenatal diagnosis. Pathologica, 113(4), 280–284. https://doi.org/10.32074/1591-951X-135Xavier, A. M., Janardhanan, M., Veeraraghavan, R., & Varma, B. R. (2022). Congenital granular cell epulis: A rare paediatric tumour of newborn. BMJ Case Reports, 15(1), e244326. https://doi.org/10.1136/bcr-2021-244326Liang, Y., Yang, Y.-S., & Zhang, Y. (2014). Multiple congenital granular cell epulis in a female newborn: A case report. Journal of Medical Case Reports, 8, 413. https://doi.org/10.1186/1752-1947-8-413Feller, L., Wood, N. H., Singh, A. S., Raubenheimer, E. J., Meyerov, R., & Lemmer, J. (2008). Multiple congenital oral granular cell tumours in a newborn black female: A case report. Cases Journal, 1(1), 13. https://doi.org/10.1186/1757-1626-1-13Chindia, M. L., & Awange, D. O. (1994). Congenital epulis of the newborn: A report of two cases. British Dental Journal, 176(11), 426–428. https://doi.org/10.1038/sj.bdj.4808472Navas-Aparicio, M. del C., Acuña-Navas, A., & Colombari, D. G. (2024). Congenital granular cell tumor of the newborn. A case report and literature review. Odovtos - International Journal of Dental Sciences, 135–141. https://doi.org/10.15517/ijds.2022.51475Vered M, Dobriyan A, Buchner A. Congenital granular cell epu lis presents an immunohistochemical profile that distinguishes it from the granular cell tumor of the adult. Virchows Arch. 2009;454:303–10.Souto GR, Caldeira PC, Johann AC. Evaluation of GLUT-1 in the granular cell tumor and congenital granular cell epulis. J Oral Pathol Med. 2013;42:450–3.Cheung JM, Putra J. Congenital Granular Cell Epulis: Classic Presentation and Its Differential Diagnosis. Head Neck Pathol. 2020 Mar;14(1):208-211. doi: 10.1007/s12105-019-01025-1. Epub 2019 Mar 19. PMID: 30888637; PMCID: PMC7021869.Kato H, Nomura J, Matsumura Y, et al. A case of congenital granular cell epulis in the maxillary anterior ridge: a study of cell proliferation using immunohistochemical staining. J Maxillofac Oral Surg. 2013;12:333–7.Zhang B, Tan X, Zhang K, et al. A study of cell proliferation using immunohistological staining: a case report of congenital granular cell epulis. Int J Pediatr Otorhinolaryngol. 2016;88:58–62.Legends to figuresFig. 1A & 1B: Preoperative photo highlighting the exuberant pedunculate intra -oral maxillary massesFig. 2A: MRI showing two pedunculated masses which are iso dense on T1W1 and mixed signal intensity on T2W1 with post contrast enhancement seen that appear to arise from the alveolar aspect of the palate without erosion or cleft of the palateFig.3: Intra operative photo of the five excised massesFig.4: Hematoxylin and Eosin stain tissue (MagnificationX40) showing sections of a nodular tumor composed of sheets and nests of thin fibrous stroma. The tumour cells are rounded to polygonal cells with distinct cellular borders. There is abundant eosinophilic, granular cytoplasm, and smaller vesicular nuclei showing hardly any mitosis nor necrosis.Fig.5. Post operative photo after a 6 month period

Understanding how organisms respond to multiple environmental stressors is essential for predicting ecosystem impacts in the face of increasing anthropogenic pressures. However, few studies have explicitly examined how genotypes of the same species respond to combined stressors, with the specific objective of disentangling variation both within and across geographic locations. In this study, we examined the individual and combined effects of copper contamination and elevated salinity on multiple genotypes of Daphnia magna from U.S. and French populations. Our findings revealed that copper exposure consistently increased mortality across all genotypes, with U.S. genotypes displaying greater sensitivity than French counterparts. Salinity stress primarily reduced fecundity, and again, U.S. genotypes exhibited lower resilience. Under combined copper and salinity stress, however, U.S. genotypes showed survival benefits, suggesting potential cross-tolerance mechanisms between these stressors. Moreover, there was substantial variation in the response to both stressors within both locations. This genotype-specific variation underscores the necessity of considering genetic factors and genotype-specific sensitivity/tolerance into ecosystem management and conservation strategies, particularly under multiple-stressor scenarios. Further exploration of the genetic pathways and adaptation potential driving these responses will enhance our ability to support biodiversity and ecosystem resilience amid global environmental change.

The double-blind placebo-controlled oral food challenge (DBPCFC) has been the “gold standard” for diagnosing IgE-mediated food allergy for the past 50 years. Despite tremendous strides in our understanding of basic mechanisms and clinical features of food allergy, we remain dependent on refinements of old technologies, i.e. skin tests and serum IgE measurements, to complement clinical history in making an accurate diagnosis of food allergies. However, recent technical advances in two effector cell assays, i.e. the basophil and mast cell activations tests, may soon bring these diagnostic biomarkers to the clinic. In addition, new advances in antibody assays, T-cell assays, transcriptomics, and metabolomics in conjunction with machine learning and artificial intelligence may soon enable us to diagnose food allergy and accurately monitor immunotherapeutic outcomes without the need for an oral food challenge.

A document by Genyuan Yang. Click on the document to view its contents.

IntroductionPerivascular epithelioid cell tumor (PEComa) is a rare mesenchymal-derived tumor composed of perivascular epithelioid cells (PECs) with a distinctive morphology and immunophenotype, first proposed by Bonetti [1], which is a family of tumors encompassing a variety of subtypes including angiomyolipomatous smooth muscle lipomas (AMLs), lymphatic smooth muscle myelomatosis (LAMs), clear cell ”sugar” tumors (CCST), clear cell myeloma (CCMMT), and non-specific types of PEComa (PEComa-NOS), among others[2]; their common features are that morphologically the tumor cells are epithelioid or spindle shaped, with abundant, translucent, or eosinophilic cytoplasm, and conspicuous nucleoli, often radially arranged around blood vessels, and in immunohistochemistry, melanocyte and smooth muscle markers, including HMB-45, Melan-A, SMA, desmin, are usually expressed, and some of them may express Cathepsin K[3].Common sites of PEComa include the uterus, skin, and liver, and so on. PEComa originating in the bone is extremely rare, with only a few cases or small-sample studies reported in the literature, and its diagnosis and treatment relies on comprehensive multidisciplinary evaluation. In this paper, we report a case of an elderly patient with PEComa originating in the femur with postoperative supplemental radiation therapy，aiming to provide a reference for the clinical diagnosis and treatment of PEComa in rare sites.

Septal reduction therapy remains a cornerstone in the management of drug-refractory obstructive hypertrophic cardiomyopathy (HOCM), with surgical myectomy and alcohol septal ablation (ASA) as established modalities. However, both approaches are limited by procedural morbidity, particularly injury to the cardiac conduction system. This editorial examines a preclinical investigation by Xu et al., which evaluates a novel retractable needle-tipped radiofrequency (RF) ablation catheter designed to deliver intramyocardial energy with the aim of preserving the subendocardium. Using a healthy canine model, this technique generated significantly deeper and broader lesions compared to conventional surface RF ablation, with associated reductions in septal motion and no observed compromise in conduction parameters or global cardiac function. While constrained by the use of healthy dogs rather than a true HOCM model and a small sample size, the findings point to the potential of this approach as a minimally invasive, conduction-sparing alternative for septal reduction, while leaving many remaining questions. This commentary contextualizes the study within the evolving field of structural electrophysiology and highlights the imperative for further translational and clinical evaluation of novel ablation technologies.

Title PageComment on ” Ototoxicity in Pediatric Hematopoietic Stem Cell Transplantation with High-Dose Carboplatin: Identifying Modifiable Risk Factors through the Inclusion of Younger Patients” Authors:Rachana Mehta, MSc 1 1 Clinical Microbiology, RDC, Manav Rachna International Institute of Research and Studies, Faridabad, Haryana 121004, India. Email: rachanamehta0909@gmail.comRanjana Sah, MD 2,32 Department of Paediatrics, Dr. D. Y. Patil Medical College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Pune – 411018, Maharashtra, India.3 Department of Public Health Dentistry, Dr. D. Y. Patil Dental College Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed-to-be-University), Pimpri, Pune – 411018, Maharashtra, India. Email: ranjanasah384@gmail.com*Corresponding Author: Rachana Mehta, MScClinical Microbiology, RDC, Manav Rachna International Institute of Research and Studies, Faridabad, Haryana 121004, India Email:  rachana.mehta0909@gmail.comKey words: Ototoxicity, Pediatric HSCT, Carboplatin, Furosemide, Modifiable Risk FactorsWord count: 415Reference count: 4Tables and figure count: 0Statements and Declarations:Declaration of Funding:  No funding was received for this study.Declaration of Financial Interests:  The authors declare no financial interests relevant to this study.Declaration of Non-Financial Interests:  The authors declare no non-financial interests relevant to this study.Ethical Approval:  Not required.Clinical Trial Registration Details/Number:  Not applicable, as this study does not report a clinical trial.Research Registry Number:  Not applicable.Human Ethics and Consent to Participate Declarations:  Not applicable as no patient data were collected or analyzed in this commentary.Generative AI Use Statement:  Generative AI tools, including Paperpal and ChatGPT-4o, were utilized solely for language refinement, grammar enhancement, and stylistic refinement. These tools had no role in the conceptualization, data analysis, interpretation of results, or substantive content development of this manuscript. All intellectual contributions, data analysis, and scientific interpretations remain the sole work of the authors. The final content was critically reviewed and edited to ensure accuracy and originality. The authors take full responsibility for the accuracy, originality, and integrity of the work presented.Data Availability Statement:  Not applicable as no data was generated or analyzed in this study.CRediT Author Statement:Rachana Mehta:  Conceptualization, Methodology, Writing—Original Draft, Writing—Review & Editing.Ranjana Sah: Validation, Supervision, Project Administration, Writing—Original Draft, Writing—Review & Editing.Manuscript

IntroductionAcute myeloid leukemia (AML), according to the WHO classification of hematolymphoid malignancies is mainly divided into two separate groups: AML with defining genetic abnormalities and AML defined by differentiation1-2. The former is genetically diverse consisting of multiple molecular aberrations in the form of fusion genes resulting from chromosomal translocations such as RUNX1::RUNX1T1, PML::RARalpha, CBFB::MYH11, RUNX1::MECOM and/or gene mutations such as FLT3-ITD/TKD, NPM1 and CEBPα, which could occur either in combination with chromosomal abnormality or in cytogenetically normal AML (CN-AML)3-6. These genetic abnormalities help categorize AML patients into favorable, intermediate or poor risk stratification. AML patients with CEBPα mutation (also called CEBPα-mutated AML) belong to the favorable risk group and is a provisional entity in the WHO classification, with the recommendation that all CN-AML be tested for CEBPα mutation7. CEBPα gene mutation testing is part of NGS-based myeloid tumor panel, currently a routine practice in the diagnostic work-up of AML patients.CEBPα (CCAAT enhancer-binding protein alpha, OMIM#116897) gene maps to chromosome 19q13.1, is intronless and the deduced 357-amino acid protein consists of an N-terminal transcription activation domain 1/2 (TAD1/2) and a C-terminal basic leucine zipper (bZIP) domain that recognizes the CCAAT motif in the promoters of target genes8. Two main types of mutations in the CEBPα gene have been reported in AML9. One, nonsense mutations (frameshift) in the TAD1/2 of the N-terminus leading to a dominant negative CEBPα protein, and two, ‘in-frame indels’ in the bZIP of the C-terminus leading to the disruption of dimerization and diminished DNA-binding function of CEBPα protein. Mice with Cebpα-mutation lack granulocytes whereas conditional expression of C/EBPα triggers neutrophilic differentiation indicating an important role of CEBPα mutations in the pathogenesis of AML10.Here, we report a case of AML with two distinct likely pathogenic CEBPα mutations but associated with aggressive disease behavior and poor clinical response. This case contributes to the evolving understanding of CEBPα-mutated AML and highlights the potential need for revised prognostic classification and tailored treatment approaches.

Aim: Risankizumab is a high-cost biologic treatment for chronic plaque psoriasis, an immune-mediated inflammatory disease presenting with painful red scaly skin lesions. It is unclear whether inter-individual heterogeneity in treatment response might be better addressed with personalised rather than fixed dosing. We sought to develop a pharmacokinetic/pharmacodynamic (PK/PD) model to characterise the relationship between risankizumab exposure and treatment response. Methods: A sequential population PK/PD model was developed using real-world data ( UK Biomarkers of Systemic Treatment Outcomes in Psoriasis study) comprising serial PK and Psoriasis Area and Severity Index (PASI) measures. Models were built using R (V4.3.1) with nlmixr2 package (V2.0.9). One and two-compartment PK models were tested. A maximal effect turnover model was used to describe PASI, with drug effect on lesion development rate ( Kin). Results: The dataset (82 serum risankizumab concentrations; 101 PASI observations) comprised 50 patients with psoriasis (median weight 79.3 kg; age 47 years). PK data were described by a one-compartment model with first-order absorption/elimination. Absorption rate (K a) was fixed from the literature (0.229). Estimated plasma clearance was 0.34 L/day, and volume of distribution 12.9 L. Baseline PASI at model initiation, drug potency (EC 50), and lesion recovery rate (K out) were estimated at 23.4, 0.11 mg/L and 0.05 day − 1, respectively. Conclusions: Pharmacokinetic parameters were similar to risankizumab clinical trials. K out estimates aligned with other psoriasis turnover models, highlighting the capture of disease dynamics that may be applied across drugs. This model may inform personalised dosing based on individual patient characteristics, drug exposure and response, to optimise treatment outcomes.

caRCINOMA middle ear WITH EXTENSIVE CUTANEOUS SPREAD - A rare CASE presentation

Hydatid Cyst in a Post-Tuberculosis Patient: A Persistent Pulmonary Puzzle- A Case ReportAuthors :Abdul Rehman Shahid1, Amina Asad2, Janmejay Kumar Singh3, Malik Muhammad Kabir4, Kainat Husain5, Fazeela Bibi6, Muhammad Hassan7, Bilal Aslam8, Said Hamid Sadat9

Here we review the use of Saccharomyces cerevisiae as a powerful model organism for studying cellular processes implicated in neurodegenerative disorders, including stress responses, proteostasis impairment, and vesicle trafficking defects. Over the last two decades, baker’s yeast models have been developed for complex diseases such as Parkinson’s, Alzheimer’s, Huntington’s, and Amyotrophic Lateral Sclerosis (ALS). Yeast cells expressing human proteins like amyloid-β, α-synuclein, huntingtin, and TDP-43 have become crucial tools for high-throughput drug screening aimed at counteracting disease progression. These yeast models have unveiled key components involved in the metabolism and toxicity of these proteins, enabling the identification of interacting partners and novel factors within each pathway. Importantly, these pathways were subsequently shown to be conserved in mammalian models. Furthermore, drug candidates identified using yeast models have provided significant leads for drug discovery, highlighting their potential for developing treatments for these neurodegenerative diseases.

Many parasites change the behavior of their host. Parasitoid wasps, for example, frequently engage in body guard manipulation to induce behaviors in their hosts that enhance parasite survival after pupation. Parasitoids of aphids have repeatedly been found to alter host location on the plant, thereby influencing location where their host mummifies, i.e. their pupation site. Potential benefits of this behavior for the parasite, however, remain under debate. Combining experiments in the laboratory and the field, we tested whether the parasitoid Aphelinus chaonia induces behavioral changes in its aphid host to influence its mummification location and whether these reduce hyperparasitism, an important source of mortality to the developing parasitoid. Aphelinus chaonia clearly caused aphids to move either off the plant or into the leaf axil prior to mummification and host death. However, movement to the leaf axil did not result in any reduction of hyperparasitism. Nevertheless, in the field, mummies situated on the stem were less likely to survive than those elsewhere on the plant, including in the leaf axil. We discuss our findings in the light of potential host manipulation.

Proactive Management of Gestational Hypertension in a Patient with Uterine Fibroids: A Case Report of a Successful Outcome

A document by Rajesh Kabra. Click on the document to view its contents.

AbstractBackground: Colorectal cancer is the third most common cancer worldwide, and as such is a significant global health concern. Distant metastases of colorectal cancer to the lung, liver and bone are well documented, while gastrointestinal tract (GIT) metastases are very rare. Herein, we report a case of gastric metastasis from sigmoid colon cancer.Case summary: A 78-year-old male was diagnosed with both gastric and colorectal cancer, which occurred synchronously. The presence of two primary cancers was diagnosed, and radical subtotal gastrectomy and anterior resection were performed simultaneously. The postoperative pathology report showed a moderately differentiated adenocarcinoma in the sigmoid colon and stomach. Immunohistochemical (IHC) analysis revealed that the resected gastric specimens showed tumor cells that were positive for both cytokeratin 20 (CK20) and caudal-type homeobox gene 2 (CDX2), and negative for CK7. This confirmed that the gastric lesion was a metastasis from colorectal cancer.Conclusion: Clinicians should be aware of the potential presence of metastatic gastric cancer, whether synchronous or metachronous, in other solid organ malignancies.Key word: Sigmoid neoplasm; Neoplasm metastasis; Stomach neoplasm; Synchronous; Case reportCore tip: We report a case of gastric metastasis from sigmoid colon cancer. A 78-year-old male was diagnosed gastric cancer and colorectal cancer that occurred synchronously. We performed radical subtotal gastrectomy and anterior resection simultaneously. The postoperative pathology report showed a moderately differentiated adenocarcinoma in the sigmoid colon and stomach. IHC analysis revealed that resected gastric specimens showed tumor cells stained positive for CK20 and CDX2, and negative for CK7. The IHC analysis confirmed that the gastric lesion was metastasis from colorectal cancer. Clinicians should be aware of the potential presence of metastatic gastric cancer in other malignancies of solid organs.INTRODUCTIONColorectal cancer is the third most common cancer worldwide and the second leading cause of cancer-related mortality in the world.[1] Approximately 20% of patients with colorectal cancer already have metastases at the time of initial diagnosis with the liver (50%) and lung (10-15%) being the most commonly involved sites of metastasis from colorectal cancer. Primary cancers from other organs rarely metastasis to the stomach. The rarity of stomach metastasis from colorectal cancer is further supported by a large-scale autopsy study, which reported a range of 0.7-5.4% for gastric metastases across various cancers, indicating that colorectal contributes only minimally within this range.[2] Here, we report a notable case of synchronous metastasis to the stomach in a sigmoid colon cancer patient.CASE PRESENTATIONChief complaints and history of present illness: A 78-year-old male underwent upper and lower endoscopy as part of a routine health examination.History of past illness: The patients had an Alzheimer’s diseaseLaboratory examinations: The carcinoembryonic antigen (CEA) level was 0.87 ng/mlImaging examinations: The esophagogastroduodenoscopy (EGD) revealed a 3x2cm ulcerofungating mass in the lesser curvature side of the mid antrum of the stomach (Figure 1A), and a colonoscopy showed a 4x2cm ulcerofungating mass in the distal sigmoid colon, located 16cm from the anal verge (Figure 1B). The pathological examination of the endoscopic biopsy specimens obtained from the stomach and sigmoid colon indicated well-differentiated adenocarcinoma, which showed similar histologic characteristics with each other. The abdominal computed tomography (CT) scan revealed a tumor involving the antrum to pylorus with peri-gastric infiltration (Figure 2A) and a 5.5 cm sized mass at the distal sigmoid colon (Figure 2B). On positron emission tomography/CT (PET/CT) imaging, only the gastric and colon mass were observed. The diagnosis of double primary cancer was made, and radical subtotal gastrectomy and anterior resection were performed simultaneously.FINAL DIAGNOSISThe postoperative pathology report revealed a moderately differentiated adenocarcinoma in the sigmoid colon (Figure 3A) and stomach (Figure 3B). The Immunohistochemical (IHC) analysis of the gastric lesion showed positive staining for CK20 (Figure 4A) and CDX2 (Figure 4B), and negative staining for CK7 (Figure 4C). These results suggest that the cancer of the sigmoid colon had metastasized to the stomach. The patient recovered uneventfully and was discharged 10 days after surgery without complications. The patient had combined targeted agents with standard cytotoxic chemotherapy.TREATMENTThe initial diagnosis of double primary cancer was made, and radical subtotal gastrectomy and anterior resection were performed simultaneously. The postoperative pathology showed gastric metastasis of sigmoid colon cancer, the patient had combined targeted agents with standard cytotoxic chemotherapy.OUTCOME AND FOLLOW-UPA five-year follow-up was conducted on the patient; this case was then closed due to the absence of evidence of metastasis.DISCUSSIONThe determination of the true incidence of metastasis to the stomach is challenging due to its low prevalence. Several studies have reported an incidence of 0.2-0.8% [3-6] and autopsy studies have reported higher incidences of 1.7-5.4% [4,7-9]. Studies based on autopsy results conducted on individuals with certain neoplasms are a reliable source of actual incidence data.Gastric metastasis from colorectal cancer is rarely documented in the literature [3,4,8,10] and only one case has been reported, found during a routine health check-up with no symptoms. Patients diagnosed with gastric metastasis may present with various symptoms. Green et al. documented that among the ten cases identified through surgical biopsy, notable clinical symptoms and physical examination outcomes encompassed diffuse abdominal pain, nausea and vomiting, anorexia, guaiac-positive stools, and gastrointestinal bleeding.[4]Previous studies have demonstrated that endoscopic patterns, including multiple nodules, bull’s eye pattern, exophytic mass lesions, ulcers, and multiple tumors, are prevalent and characteristic. These findings are often accompanied by doughnut-shaped ridged lesions and volcanic ulcers. These endoscopic patterns have been shown to be useful in the diagnosis of gastric metastases.[11] However, some cases of gastric metastasis are difficult to distinguish from primary gastric cancer.[10,12] Hirano K et al. reported that more than half were solitary metastases. Despite the heterogeneity of the morphologies observed, approximately half of the cases exhibited a resemblance to early gastric cancer.[13] In the present study, EGD revealed an ulcerofungating mass with mucosal invasion, which was diagnosed as typical primary gastric cancer rather than metastatic gastric cancer.In the field of cancer research, a significant body of literature has emerged on the use of immunohistochemical testing for the identification of carcinomas of unknown primary origin. A seminal study by Bayrak R et al. reported the expression of CK7 in upper GIT tumors, whereas CK20 was found to be predominantly expressed in lower GIT tumors.[14] Building on this, Park SY et al. undertook a comprehensive evaluation of multiple immunohistochemical markers for each tumor with the aim of determining the combination of the 10 markers that most effectively predicted primary sites.[15] The most predictive multi-marker phenotypes, as determined by a combination of specificity and positive predictive value, were CDX2+/CK7-/CK20+ for colorectal primary tumors and CDX2+/CK7+/CK20- for upper GI tumors. The patient in question had a CK7-/CK20+ pattern and positive staining for CDX2.In the management of metastatic colorectal cancer, curative surgery is widely accepted as the preferred method for the removal of resectable metastases in the lung or liver. However, for metastases in extremely rare sites, such as the stomach, a consensus on the optimal approach has yet to be established.[16] Nushijima et al. reported a case.[17] A 52-year-old woman was diagnosed with transverse colon cancer, underwent left hemicolectomy and received adjuvant XELOX therapy for 6 months. One year and 3 months after left hemicolectomy, EGD revealed a submucosal tumor in the stomach and histology showed metastatic gastric cancer from transverse colon cancer. Radical distal gastrectomy was performed, but peritoneal dissemination and para-aortic lymph node recurrence were noted 7 months after the second surgery. The prognosis is generally poor because gastric involvement typically indicates an advanced stage of disease and is often associated with metastases to other sites. In our case, metastatic lesion in the stomach were diagnosed simultaneously with the diagnosis of colorectal cancer. Radical resection was performed on both sites with a favorable prognosis. Therefore, it is imperative to perform EGD in patients diagnosed with colorectal cancer.CONCLUSIONTumor metastases to distant anatomical structures can disrupt normal function and significantly increase disease morbidity and mortality. Consequently, metastases from a known primary cancer have a critical impact on staging, prognosis, and treatment strategies. In addition, cancers that initially present with distant metastases often require extensive evaluation to identify the primary site and guide optimal treatment. In conclusion, clinicians should be aware of the potential presence of metastatic gastric cancer, whether synchronous or metachronous, in other solid organ malignancies. Appropriate systemic treatment, including chemotherapy or hormonal therapy for the primary tumor, is the most desirable treatment for metastatic tumors in the stomach; however, surgical resection of metastatic gastric tumors may be recommended to improve the patient’s quality of life if there is a risk of complications such as bleeding or tumor perforation.REFERENCES1 Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2024; 74 : 229-263 [PMID: 38572751 DOI: 10.3322/caac.21834]2 Disibio G, French SW. Metastatic patterns of cancers: results from a large autopsy study. Arch Pathol Lab Med 2008; 132 : 931-939 [PMID: 18517275 DOI: 10.5858/2008-132-931-MPOCRF]3 Davis GH, Zollinger RW. Metastatic melanoma of the stomach. Am J Surg 1960; 99 : 94-96 [PMID: 13814449 DOI: 10.1016/0002-9610(60)90258-0]4 Green LK. 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Gastrointestinal metastases from extra-abdominal tumors. Endoscopy 1985; 17 : 99-101 [PMID: 4006875 DOI: 10.1055/s-2007-1018470]10 Hsu CC, Chen JJ, Changchien CS. Endoscopic features of metastatic tumors in the upper gastrointestinal tract. Endoscopy 1996; 28 : 249-253 [PMID: 8739742 DOI: 10.1055/s-2007-1005437]11 Namikawa T, Hanazaki K. Clinicopathological features and treatment outcomes of metastatic tumors in the stomach. Surg Today 2014; 44 : 1392-1399 [PMID: 23896636 DOI: 10.1007/s00595-013-0671-9]12 Jones GE, Strauss DC, Forshaw MJ, Deere H, Mahedeva U, Mason RC. Breast cancer metastasis to the stomach may mimic primary gastric cancer: report of two cases and review of literature. World J Surg Oncol 2007; 5 : 75 [PMID: 17620117 DOI: 10.1186/1477-7819-5-75]13 Hirano K, Nomura K, Ochiai Y, Hayasaka J, Suzuki Y, Mitsunaga Y, Odagiri H, Masui A, Kikuchi D, Hoteya S. Metastatic Gastric Tumors: Clinical and Endoscopic Features. Cureus 2024; 16 : e58678 [PMID: 38770512 DOI: 10.7759/cureus.58678]14 Bayrak R, Haltas H, Yenidunya S. The value of CDX2 and cytokeratins 7 and 20 expression in differentiating colorectal adenocarcinomas from extraintestinal gastrointestinal adenocarcinomas: cytokeratin 7-/20+ phenotype is more specific than CDX2 antibody.Diagn Pathol 2012; 7 : 9 [PMID: 22268990 DOI: 10.1186/1746-1596-7-9]15 Park SY, Kim BH, Kim JH, Lee S, Kang GH. Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma. Arch Pathol Lab Med 2007;131 : 1561-1567 [PMID: 17922593 DOI: 10.5858/2007-131-1561-POIMHD]16 Terashima S, Watanabe S, Kogure M, Tanaka M. Long-term survival after resection of a gastric metastasis from transverse colon cancer: a case report. Fukushima J Med Sci 2019; 65 : 37-42 [PMID: 31167978 DOI: 10.5387/fms.2018-24]17 Nushijima Y, Nakano K, Sugimoto K, Nakaguchi K, Kan K, Maruyama H, Doi S, Okamura S, Murata K. 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Objective Eclampsia is associated with short- and long-term neurological deficits. Identifying which women may be at risk is important. Magnetic resonance imaging shows an incidence of 30–40% of subclinical cerebral infarcts among women with eclampsia. A simple screening tool would be useful to identify at-risk women. The objective of this study was to develop a clinical prediction model to identify women at highest risk of developing cerebral infarcts in women who have experienced eclampsia. Design This was a prospective, cross-sectional study at Tygerberg Hospital, a tertiary referral center in Cape Town, South Africa. Forty-nine women with eclampsia were included. Women were prospectively assessed for symptoms and signs known to be associated with eclampsia and all women underwent brain magnetic resonance imaging. Main outcome measure was the presence of cerebral infarcts. All symptoms and signs were assessed for accuracy against the outcome. Variables significant at the 20% level were assessed in a stepwise selection for a final multivariate model. Results A total of 49 women with eclampsia were included in the analysis, of whom 33% (n=16) had cerebral infarcts. Variables included in the diagnostic model for cerebral infarcts were highest systolic blood pressure and impaired hearing. The model demonstrated an AUC of 0.72 (95% CI 0.56 to 0.88) with corresponding sensitivity of 60% (95% CI 36 to 80%) and specificity of 84% (95% CI 67 to 93%) for cerebral infarcts. Conclusions A simple clinical risk assessment has moderate accuracy for identification of cerebral infarcts in eclampsia. This risk assessment tool may be a useful triage tool to help decide which women require imaging and neurological follow up.

Opening access to the products of scientific research is widely considered a key step toward both fairness and better science worldwide. Since the 1990s, different forms of open access (OA) to journal articles have emerged to make scientific findings more broadly available. However, a major unresolved challenge remains: how to fund open access sustainably and equitably. Commercial publishers have rapidly adopted profit-driven “Gold” OA models, which require authors to pay high Article Processing Charges. Although this approach ensures free access to readers, it creates a significant barrier for authors, particularly from institutions with limited resources. Drawing on an analysis of over 100,000 articles in ecology-related disciplines (i.e., agricultural, biological, and environmental sciences), we show that the shift to pay-to-publish OA has already reduced participation by researchers from many middle-income countries. This model imposes a growing bias in scientific publishing, with clear consequences for the inclusiveness, fairness, and global representativeness of fields like ecology. If not addressed, such biases risk entrenching systemic inequities and weakening the quality and diversity of the scientific evidence base.