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There is no effective clinical prediction model to predict the prognosis of gastric signet ring cell carcinoma (GSRC) patients treated with radiotherapy. This study retrospectively analyzed the clinical data of 20-80-year-old patients diagnosed with GSRC between 2004 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Using Cox regression analyses revealed independent prognostic factors, and a nomogram was constructed. The C-index, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the nomogram were greater than those of the TNM staging system for predicting OS, indicating that the nomogram predicted prognosis with greater accuracy. The area under the curve (AUC) values were 0.725, 0.753 and 0.745 for the training group; 0.725, 0.763 and 0.752 for the internal validation group; and 0.795, 0.764 and 0.765 for the external validation group, respectively. Calibration plots demonstrated high agreement between the nomogram's prediction and the actual observations. The risk stratification system was able to accurately stratify patients who underwent radiotherapy for GSRC into high- and low-risk subgroups, with significant differences in prognosis. The Kaplan‒Meier survival analysis according to different treatments indicated that surgery combined with chemoradiotherapy is a more effective treatment strategy for improving OS in for GSRC patients. The nomogram is sufficiently accurate to predict the prognostic factors of GSRC receiving radiotherapy, allowing for clinicians to predict the 1-, 3-, and 5-year OS., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Sometimes non-neoplastic changes of the gastric mucosa mimic diffuse-type gastric carcinoma, specifically signet-ring cell adenocarcinoma. In fact, gastric epithelial cells undergoing signet-ring cell change have a cellular morphology that is almost identical to signet-ring cell adenocarcinoma, often leading to misdiagnosis. Accurate recognition of signet-ring cell change is essential to avoid overdiagnosis and overtreatment of signet-ring cell adenocarcinoma. Research on this topic is limited and clinicians lack formal diagnostic tools when signet-ring cells are detected in biopsy specimens. The aims of this study are 3-fold. Firstly, to increase the awareness of both clinicians and pathologists of this rare but highly significant entity. Secondly, to report 4 additional examples of signet-ring cell change and analyze them alongside signet-ring cell adenocarcinoma to compare their morphological and phenotypic features and their evolution over time. Finally, to highlight the potential utility of endoscopic resection to confirm the diagnosis. Cells in signet-ring cell change strongly express E-cadherin, show a wild-type p53 expression, and have a low Ki67 index. In contrast, cells in signet-ring cell adenocarcinoma strongly express p53, have high proliferation rates, and show either no or weak E-cadherin staining. Genetic analysis may be useful in identifying patients at risk of hereditary early diffuse gastric adenocarcinoma, which can mimic signet-ring cell change., 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.

Signet ring cell carcinoma (SRCC) is defined as carcinoma composed of epithelial cells with intracytoplasmic mucin that causes peripheral displacement of the nucleus, creating a crescent-shaped morphology. It can arise in many organs; however, pure primary SRCC of the breast is very rare. The WHO classification of tumours placed SRCC of the breast under mucin-producing carcinomas; however, nowadays, it is no longer regarded as a histological variant of invasive carcinoma. To date, only few cases have been reported in the literature. This report presents a woman in her 70s with primary pure SRCC of the breast. The patient underwent right lumpectomy with sentinel lymph node dissection and was proposed adjuvant chemotherapy followed by radiotherapy and hormonal treatment. She had no disease relapse until today. The histological features and treatment approach of this rare entity are debated in light of relevant literature., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective This study investigated the prevalence of gastric epithelial tumor in Helicobacter pylori-uninfected subjects who underwent esophagogastroduodenoscopy (EGD) as part of an annual checkup. Methods A total of 20,540 EGD examinations of H. pylori-uninfected individuals (12,917 men, 7,623 women; mean age 51.5±9.2 years old) were performed between April 2016 and March 2023. The prevalence of gastric epithelial tumor discovery and the size and location of each lesion type were analyzed. Results According to 20,540 examinations, 61 gastric epithelial tumors were endoscopically and histologically diagnosed in 58 of the subjects, with a prevalence rate of 0.28%. These tumors included signet-ring carcinoma (n=10, 0.05%), gastric adenocarcinoma of fundic-gland type (n=10, 0.05%), intestinal-type well-differentiated adenocarcinoma (n=2, 0.01%), and raspberry-type gastric foveolar tumors (n=36, 0.18%). One subject had two intestinal-type well-differentiated adenocarcinomas, and two each had two raspberry-type gastric foveolar tumors. The mean sizes of the signet-ring carcinomas, gastric adenocarcinoma of fundic-gland type, intestinal-type well-differentiated adenocarcinomas, and raspberry-type gastric foveolar tumors were 6.4, 4.7, 5.0, and 3.4 mm, respectively. Each lesion was located at a specific site in the stomach characteristic of its type. Conclusion In the present H. pylori-uninfected subjects, the prevalence of gastric epithelial tumors found on an EGD examination was 0.28%. Endoscopic examination should be performed in H. pylori-uninfected individuals to detect such tumors in characteristic locations.

We present the case of a 67-year-old woman referred to our outpatient clinic presenting dyspepsia. Gastroscopy was performed, showing antral gastritis. Random biopsies were taken, being positive for poorly differentiated Lauren's diffuse gastric adenocarcinoma. Narrow-band imaging gastroscopy was performed, combining random and targeted biopsies, with negative results. The study was completed with echoendoscopy and thoraco-abdominal-pelvic CT scan, showing no relevant pathological findings. Control endoscopic was performed after 12 months, showing no macroscopic lesions. Random biopsies were repeated, being positive for diffuse gastric adenocarcinoma. Gastroscopy with conventional chromoendoscopy was performed, showing a completely flat area of approximately 2cm of diameter in the body-antrum junction, in the greater curvature; it was well delimited and no indigo carmine staining was observed (Figure 1). Electronic magnification was performed, showing disruption of the crypt pattern and aberrant neovessels (Figures 2 and 3). Targeted biopsies were taken, being positive for poorly differentiated gastric adenocarcinoma. The case was discussed in a multidisciplinary session and subtotal gastrectomy was performed. Magnification endoscopy offers a better performance diagnosing early gastric cancer than white light endoscopy. [1] It allows the identification of patterns that can predict malignancy, such as distortion of the mucosal glandular pattern or aberrant proliferation of neovessels. [2] Once the diagnosis has been established, assessing the depth of invasion has great clinical relevance, as it guides therapeutic decisions. Works such as that of Zhou et al. [3] underline the usefulness of linear echoendoscopy in this process.

We describe two cases of pseudo-signet ring cells in gastric biopsies of otherwise asymptomatic adult patients. One male patient was diagnosed during follow-up of a previous intestinal type gastric adenocarcinoma and underwent surgery before recognition of this non-malignant entity. He suffered from a secondary anastomotic stenosis requiring dilatation. A second male patient was spared from surgery thanks to timely recognition by the pathologist and is still declared cancer-free until today. This extremely rare nonmalignant mimicker of cancerous signet ring cells, as seen in diffuse type gastric cancer can potentially mislead the clinician. The absence of any endoscopic abnormality should prompt a revision by an experienced pathologist, digestive oncologist and surgeon to avoid unnecessary interventions and morbidity., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Abstract: Appendicitis is the most common cause of the acute abdomen and usually occurs because of the fecalith in adults and lymphoid hyperplasia in childhood. Gastric cancer metastasis to the appendix is a rare condition that might be present with symptoms of acute appendicitis. The English literature describes only thirteen cases of gastric carcinoma metastasizing to the appendix and presenting as acute appendicitis. In this report, we describe the first case of metastatic signet ring cell carcinoma of appendix presenting with clinical features of acute appendicitis., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Abstract: Primary signet ring cell carcinoma (SRCC) of the breast is a rare and aggressive type of breast cancer characterized by increased intracellular mucin production. It has a high risk of metastasis and poor prognosis compared to other breast cancer types. We report a 56-year-old woman with primary SRCC of the breast who first presented with retraction on her left breast. Radiological examination revealed a mass that causes the retraction. The patient underwent left modified radical mastectomy, and pathology results showed a 70% signet ring cell pattern. Chemotherapy consists of an adriamycin-cyclophosphamide regimen administered. in this case, we aim to review the literature on this topic and inform the physicians., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

Introduction : Signet-ring cells are typically associated with mucin-secreting epithelium; thus, they are most commonly found in the gastrointestinal tract, but not exclusively. Primary signet-ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical Case : In June of 2023, a 54-year-old Caucasian male presented with a complaint of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups, including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma stage IV. Unfortunately, due to the advanced stage of the disease, PE, and third-degree thrombocytopenia, the patient was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion : Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results, which may contribute to its late diagnosis. Inconsistent immunohistochemical findings and an unpredictable response to hormonal treatment together pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusions : This study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease, which may positively influence the prognosis.

Background: Gastric signet ring cell carcinoma (GSRCC) is a rare and highly malignant disease with a poor prognosis. To assess the overall survival (OS) and cancer-specific survival (CSS) of patients with GSRCC, prognostic nomograms were developed and validated using common clinical factors., Methods: This retrospective cohort study included patients diagnosed with GSRCC between 2011 and 2018 from the National Cancer Center (n = 1453) and SEER databases (n = 2745). Prognostic nomograms were established by identifying independent prognostic factors using univariate and multivariate Cox regression analyses. The calibration curve and C-index were used to assess the predictions. The clinical usefulness of the survival prediction model was further evaluated using the DCA and ROC curves. The models were internally validated in the training cohort and externally validated in the validation cohort. Two web servers were created to make the nomogram easier to use., Results: Patients with GSRCC were divided into training ( n  = 2938) and validation ( n  = 1260) cohorts. The nomograms incorporated six predictors: age, race, tumor site, tumor size, N stage, T stage, and AJCC stage. Excellent agreement was observed between the internal and exterior calibration plots for the GSRCC survival estimates. The C-index and area under the ROC curve were roughly greater than 0.7. Both nomograms had adequate clinical efficacy, as demonstrated by the DCA plots. Furthermore, we developed a dynamic web application utilizing the constructed nomograms available at https://jiangyujuan.shinyapps.io/OS-nomogram/ and https://jiangyujuan.shinyapps.io/DynNomapp-DFS/., Conclusion: We developed web-based dynamic nomograms utilizing six independent prognostic variables that assist physicians in estimating the OS and CSS of patients with GSRCC., 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 Jiang, Hu, Shao, Li, Lu, Liang and Tian.)

Competing Interests: Declaration of interests We declare no competing interests.

Metastasis to the gastrointestinal tract is a rare instance in the natural history of breast cancer, usually in association with lobular histology and widespread dissemination of disease. We report the case of a 74-year-old woman with a history of invasive lobular carcinoma presenting with a pancreatic metastasis mimicking a primary pancreatic adenocarcinoma; we also present a systematic review of the relevant literature. The presentation of pancreatic metastasis in the setting of breast cancer is unspecific, and histology is of paramount importance for a correct diagnosis; surgical metastasectomy could be of some benefit in the correct clinical setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Protruded signet-ring cell carcinoma (SRCC) is extremely rare. We herein report a rare case of flat elevated gastric SRCC in a patient without Helicobacter pylori infection. Esophagogastroduodenoscopy of a woman in her 50s revealed a flat, whitish lesion in the gastric body with elevation. Histological results of an endoscopically biopsied specimen led to a diagnosis of SRCC. Resection using endoscopic submucosal dissection was performed, and histology results revealed that the tumor was localized in the lamina propria. The size was 10×6 mm, and a protrusion had been formed by SRCC enlargement without destruction of the surface epithelium structure.

Globally, gastrointestinal cancer is the most widespread neoplastic disease and the primary contributor to cancer-associated fatalities. Gastrointestinal signet ring cell carcinoma (SRCC) exhibits unique distinguishing features in several aspects when compared to adenocarcinomas (ACs). The scarcity of signet ring cell carcinoma has resulted in a heightened significance of related clinical and molecular investigations. However, a comprehensive and systematic review of the clinical, molecular, therapeutic, and research aspects of this disease is currently absent. This review provides an overview of the latest developments in our understanding of the clinical and molecular features of gastrointestinal signet ring cell carcinoma (SRCC). Additionally, we have compiled a list of potential therapeutic targets or biomarkers, as well as an examination of the current treatment options and the possible mechanisms of formation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Systemic sclerosis, an autoimmune disease characterized by fibrosis and vasculopathy of the skin and other multiple organs has been associated with an increased risk of malignancy. We present the case of a 74-year-old woman who had diffused cutaneous systemic sclerosis and uterine cervical cancer. The patient was initially diagnosed with stage IIB squamous cell carcinoma and concurrent chemoradiotherapy was planned. However, cisplatin could not be administered due to acute renal failure, so the patient was treated solely with radiotherapy. However, complications of systemic sclerosis progressed rapidly, and the patient died 63 days later from pulmonary edema. An autopsy later revealed that uterine cervix had primary signet ring cell carcinoma. We suspected that this patient had a combination of signet ring cell carcinoma and squamous cell carcinoma, with squamous cell carcinoma disappearing after radiotherapy. This case highlighted the importance of systemic management for cancers associated with systemic sclerosis., (© 2023 Japan Society of Obstetrics and Gynecology.)

Signet-ring cell sinus histiocytosis (SRCSH) represents a distinctly rare reactive phenomenon predominantly affecting axillary and pelvic lymph nodes (LNs) of individuals with breast or prostatic adenocarcinoma. Reports of SRCSH in the literature are sparse with only 12 previous examples, thus underscoring the rarity of this process. Here, we report 4 additional SRCSH cases affecting 2 women and 2 men (M/F = 1:1; age range: 50-71 years; mean age = 61 years). In the 2 men, pelvic LNs were excised during radical cystoprostatectomy for genitourinary cancer, whereas in one woman, SRCSH was incidentally discovered in axillary LNs during mastectomy for breast adenocarcinoma. The other female patient presented with a history of aortic valve replacement and enlarged supraclavicular LNs. Microscopically, all involved LNs exhibited marked distention with filling of the subcapsular and medullary sinuses by sheets of signet-ring histiocytes containing a singular large, cytoplasmic vacuole and a crescentic nucleus. Overt cytologic atypia, pleomorphism, and mitoses were absent. Erythrophagocytosis and occasional fibrosis were appreciated. None of the LNs with SRCSH showed evidence of metastatic tumor. Immunohistochemically, signet-ring sinus histiocytes were invariably positive for CD68 and CD163 but were negative for pancytokeratins. The histopathologic characteristics of SRCSH, albeit bland, in conjunction with the patient's medical history, may be misinterpreted as metastatic adenocarcinoma with signet-ring cell configuration. Immunohistochemical confirmation of the histiocytic lineage of the lesional cells in SRCSH usually suffices for rendering an accurate diagnosis. The underlying pathogenetic mechanism and possible biologic significance of SRCSH remain currently unknown., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Primary signet ring cell carcinoma (PSRCC) of the prostate is an extremely rare variant of prostatic adenocarcinoma. A PubMed search of the English language literature from January 2000 to June 2020 using the keywords "signet ring cell carcinoma" and "prostate," identified 20 cases of PSRCC of the prostate. On the basis of the combined data from this study and the literature review, 21 such patients were evaluated for clinical characteristics, histologic diagnoses, special and immunohistochemical staining, and treatment. The mean age at the diagnosis was 68.47 years (range 50-85 years). The prostate-specific antigen (PSA) levels varied from 0.19 to 6658 ng/mL, with a mean of 509.15 ng/mL. Most (50%) presented with Stage 3 cancer. The most common Gleason grade group was 5 (Gleason score 9 to 10), seen in 61.5%. The extent of signet ring cell involvement of the specimen when reported was documented as more than 20% of the tumor-containing signet ring cells, with a range of 25%-90%. For pathologic diagnosis, the most common special stains performed were periodic acid-Schiff and Alcian blue, and among the immunohistochemical stains, the most common were PSA, CK20, and prostate-specific acid phosphatase. A detailed clinicoradiological and pathological workup is essential to rule out primary from other common sites, in view of its grave prognosis and lack of an established treatment protocol.

Background: Signet-ring cell adenocarcinoma of the colon is well-recognized in adult patients who are extremely rare and not well-documented in children. Our study aims to raise awareness about this rare disease and its long-term outcomes., Methods: We retrospectively evaluated patients with signet-ring cell colon adenocarcinoma., Results: Six patients, three boys and three girls, with a mean age of 14.83 (range, 13-17 years), presented with signs of intesti-nal obstruction and were diagnosed with signet-ring cell colon adenocarcinoma. All patients had air-fluid levels on abdominal X-ray. Abdominal ultrasonography of all patients revealed subileus. Abdominal computed tomography was performed in five patients, and pre-operative colonoscopy was conducted in two patients before the emergency intervention. All of the patients underwent emergent exploratory laparotomy with the preliminary diagnosis of acute abdomen. In two patients, debulking surgery followed by a stoma was performed. The remaining four patients were treated with anastomosis following intestinal resection. All girls had metastases on the ovary. One of the patients died due to the burden of multiple metastases in the early period, and three died in the sixth post-operative year. We have been following the remaining two patients since then., Conclusion: Although signet-ring cell carcinomas (SRCCs) are rare, they should be considered in the differential diagnosis of acute abdomen and intestinal obstruction in pediatric patients. Despite early diagnosis and treatment, SRCC has a poor prognosis in the pediatric population.

Background: This study investigated the clinicopathological features, immunophenotypic characteristics and differential diagnosis of primary breast carcinomas with signet ring cell differentiation, as well as differences in the traits of signet ring-like cell mucin., Methods: A total of five cases of primary breast cancer diagnosed with signet ring cell differentiation and treated at The First People's Hospital of Jingmen from January 2016 to December 2021 were collected. HE, immunohistochemical staining, and AB-PAS staining were used for the analysis., Results: Although we strictly selected all the primary breast cancer cases with signet ring cell differentiation, there were differences in the arrangement of the cells and the grading of nuclei. Our immunohistochemical results showed that the ER was consistently strongly positive, and the PR expression was not consistent, while all the cases of HER2 were negative. CK7 was negative in one case, and CK20 and CK5/6 were not expressed in all the cases. The mucin MUC1 was positive and showed two patterns. MUC2 was strongly positive in all the cases. All the cases were negative for CDX2, SATB2, PAX8, TTF-1, and Napsin A, while the positive expression of COX2, Villin, and WT-1 was not constant. One case expressed neuroendocrine markers. The expression level of Ki67 was between 10 and 30%. AB (pH 2.5)-PAS staining revealed that the intracellular mucus contained more cells with neutral mucus, while the extracellular mucus was mainly acidic., Conclusion: We found that histological morphology, cell morphology, and nuclear grading differentiate among different cases. The immunohistochemical characteristics of primary breast cancers diagnosed with signet ring cell differentiation are helpful for identification. The differences in the expression patterns of mucins may be related to unfavorable clinicopathological factors, but their usefulness as a prognostic marker remains to be further understood. The heterogeneity of cell mucus, the differentiation of tumor cells, and the phenotypic changes of tumors also need further study., (© 2023. The Author(s).)

Objectives: Gastric signet ring cell carcinoma is a rare and highly malignant adenocarcinoma, which is characterized by early metastasis, rapid progression and poor prognosis. Several studies have shown that early-stage gastric signet ring cell carcinoma may have equal or better prognosis than other types of gastric cancer. However, most of the early-stage lesions are difficult to detect by endoscopy. We aim to illustrate the difficulty of early detection of gastric signet ring cell carcinoma with mucosal atrophy., Methods: The endoscopic and pathological features of two female cases were analyzed by upper gastrointestinal white light endoscopy combined with narrow-band imaging and endoscopic biopsy., Results: Two female cases were diagnosed with early-stage gastric signet ring cell carcinoma with atrophic background mucosa occurring in the middle and lower part of the stomach. Both lesions less than 2.0 cm in diameter were surgically removed and identified as intramucosal adenocarcinoma., Conclusion: We can roughly identify the demarcation of the lesion by combining white light endoscopy and narrow-band imaging, and slightly irregular microsurface and microvascular pattern of the lesion were found via magnifying endoscopic observation, but the demarcation can hardly be accurately identified., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Loss of function variants in CDH1 are the most frequent cause of hereditary diffuse gastric cancer. Endoscopy is regarded as insufficient for early detection due to the infiltrative phenotype of diffuse-type cancers. Microscopic foci of invasive signet ring cells are pathognomonic of CDH1 and precede development of diffuse gastric cancer. We aimed to assess the safety and effectiveness of endoscopy for cancer interception in individuals with germline CDH1 variants, particularly in those who declined prophylactic total gastrectomy., Methods: In this prospective cohort study, we included asymptomatic patients aged 2 years or older with pathogenic or likely pathogenic germline CDH1 variants who underwent endoscopic screening and surveillance at the National Institutes of Health (Bethesda, MD, USA) as part of a natural history study of hereditary gastric cancers (NCT03030404). Endoscopy was done with non-targeted biopsies and one or more targeted biopsy and assessment of focal lesions. Endoscopy findings, pathological data, personal and family cancer history, and demographics were recorded. Procedural morbidity, gastric cancer detection by endoscopy and gastrectomy, and cancer-specific events were assessed. Screening was defined as the initial endoscopy and all subsequent endoscopies were considered surveillance; follow-up endoscopy was at 6 to 12 months. The primary aim was to determine effectiveness of endoscopic surveillance for detection of gastric signet ring cell carcinoma., Findings: Between Jan 25, 2017, and Dec 12, 2021, 270 patients (median age 46·6 years [IQR 36·5-59·8], 173 [64%] female participants, 97 [36%] male participants; 250 [93%] were non-Hispanic White, eight [3%] were multiracial, four [2%] were non-Hispanic Black, three [1%] were Hispanic, two [1%] were Asian, and one [<1%] was American Indian or Alaskan Native) with germline CDH1 variants were screened, in whom 467 endoscopies were done as of data cutoff (April 30, 2022). 213 (79%) of 270 patients had a family history of gastric cancer, and 176 (65%) reported a family history of breast cancer. Median follow-up was 31·1 months (IQR 17·1-42·1). 38 803 total gastric biopsy samples were obtained, of which 1163 (3%) were positive for invasive signet ring cell carcinoma. Signet ring cell carcinoma was detected in 76 (63%) of 120 patients who had two or more surveillance endoscopies, of whom 74 had occult cancer detected; the remaining two individuals developed focal ulcerations each corresponding to pT3N0 stage carcinoma. 98 (36%) of 270 patients proceeded to prophylactic total gastrectomy. Among patients who had a prophylactic total gastrectomy after an endoscopy with biopsy samples negative for cancer (42 [43%] of 98), multifocal stage IA gastric carcinoma was detected in 39 (93%). Two (1%) participants died during follow-up, one due to metastatic lobular breast cancer and the other due to underlying cerebrovascular disease, and no participants were diagnosed with advanced stage (III or IV) cancer during follow-up., Interpretation: In our cohort, endoscopic cancer surveillance was an acceptable alternative to surgery in individuals with CDH1 variants who declined total gastrectomy. The low rate of incident tumours (>T1a) suggests that surveillance might be a rational alternative to surgery in individuals with CDH1 variants., Funding: Intramural Research Program, National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We report a case of a 65-year-old male who presented with multiple enlarged intraabdominal lymph nodes with lytic lesions over pelvic and lumbar vertebrae. His serum prostate-specific antigen (PSA) was markedly raised. Bone marrow investigation revealed the presence of diffuse infiltration of single cells having hyperchromatic nuclei, moderate amount of eosinophilic cytoplasm, and eccentrically placed nuclei resembling signet ring cells. Hence, a diagnosis of metastatic signet cell carcinoma of prostate was made on bone marrow biopsy. This variant of prostatic carcinoma is very rare and accounts for only 2.5% of all prostatic adenoacarcinomas that make our case worth reporting. To emphasize the rare occurrence of this variant, we performed a Pubmed-based literature review of 25 years., Competing Interests: None

Background: Diffuse large B-cell lymphoma (DLBCL) with signet ring cell components is extremely rare. Here, we present a case of DLBCL with signet ring cell components involving the breast, which can be easily confused with invasive lobular carcinoma of the breast or metastatic signet ring cell carcinoma of gastrointestinal origin., Case Presentation: A 66-year-old woman presented with a painless mass in her left breast. Enhanced magnetic resonance imaging (MRI) of the breast revealed a 42 × 29 × 28 mm mass in the left breast. Histological examination revealed a diffuse or scattered arrangement of round cells mixed with signet ring-like cells. Immunohistochemically, the neoplastic cells were positive for PAX-5, CD79a, CD20, Bcl-6, and MUM-1 but and negative for cytokeratin, ER, PR, E-cadherin, and P120. The Ki-67 proliferation index was approximately 70%. Fluorescence in situ hybridisation (FISH) demonstrated non-rearrangement of Bcl-2, Bcl-6, and c-MYC genes. Immunohistochemistry and FISH examination confirmed the diagnosis of DLBCL. Subsequently, immunofluorescence showed both IgM and IgG deposits in the signet ring-like lymphocytes. After confirming the diagnosis, the patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy in a specialist hospital and achieved partial remission; however, she unfortunately died of secondary pneumocystis pneumonia infection 3 months later., Conclusion: Malignant lymphoma with signet ring cell morphology is quite uncommon, and this variant can be a diagnostic pitfall. We emphasise that pathologists should consider lymphoma in the differential diagnosis of malignant breast tumours., (© 2023. The Author(s).)

Introduction: Pseudoachalasia is a rare clinical condition, often caused by malignancy. Rarely, this entity can reveal the underlying neoplasia. To the best of our knowledge, we report the first case of pseudoachalasia revealing a metastatic signet-ring cell carcinoma of the non-ampullary duodenum., Case Report: A previously healthy 67-year-old patient presented with a 3-month history of rapidly progressive intermittent dysphagia with 20kg weight loss. An upper endoscopy showed multiple duodenal ulcerations on congestive mucosa. Duodenal biopsies revealed tumor proliferation formed by independent cells with atypical nuclei. In immunohistochemistry, tumor cells expressed pan-cytokeratin. Esophageal manometry revealed an aspect in favor of achalasia type II. The CT scan showed ascites and pleural effusion. Their punctures confirmed the presence of neoplastic cells. The diagnosis of metastatic signet-ring cell duodenal carcinoma revealed by pseudoachalasia was retained., Conclusion: In the presence of rapidly progressive symptoms with significant weight loss, especially in the elderly patients, malignancyassociated pseudoachalasia should be suspected.

Background: Hereditary diffuse gastric cancer, generally caused by germline pathogenic variants in CDH1, presents with early-onset signet ring cell carcinoma. Prophylactic total gastrectomy is the definitive treatment. Endoscopic surveillance can inform the timing of prophylactic total gastrectomy through detection of microscopic signet ring cell carcinoma foci. However, evidence is scarce about the optimal endoscopic sampling technique and characterisation of signet ring cell carcinoma foci in hereditary diffuse gastric cancer. We aimed to formally assess the diagnostic yield of different sampling strategies and to identify criteria for the characterisation of endoscopic lesions., Methods: For this prospective longitudinal cohort study, we included individuals aged 18 years or older at the Cambridge University Hospitals National Health Service (NHS) Foundation Trust who fulfilled testing criteria for hereditary diffuse gastric cancer between June 1, 2005, and July 31, 2021. The primary outcome was detection of intramucosal signet ring cell carcinoma foci. We assessed the detection rate and anatomical location of signet ring cell carcinoma in random biopsy samples taken according to a systematic protocol compared with biopsies targeted to endoscopic findings. Endoscopic lesions were examined with white-light and narrow band imaging with magnification to assess the likelihood of cancerous foci., Findings: 145 individuals were included, of whom 68 (47%) were male and 92 (63%) carried the CDH1 pathogenic variant. 58 (40%) patients were diagnosed with invasive signet ring cell carcinoma over a median follow-up time of 51 months (IQR 18-80). The first diagnosis of signet ring cell carcinoma was most commonly made from random biopsies (29 [50%] of 58 patients), rather than targeted biopsies (15 [26%] patients). The anatomical distribution of signet ring cell carcinoma foci detected by random biopsies more accurately reflected those identified in prophylactic total gastrectomy specimens than did targeted biopsies. Omitting random biopsies in our cohort would have led to an under-diagnosis rate of 42%. Using a novel panel of endoscopic criteria, gastric lesions containing signet ring cell carcinoma were predicted with a sensitivity of 67·3% and a specificity of 90·2%., Interpretation: Random biopsies enhance the early detection of signet ring cell carcinoma and are complementary to targeted biopsies in surveillance of hereditary diffuse gastric cancer. This sampling method should be the standard of care when performing all surveillance endoscopies for individuals with hereditary diffuse gastric cancer., Funding: UK Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Limited literature exists on the characteristics of early gastric signet ring cell carcinoma (GSRCC) within 20 mm. This study aimed to explore this type of cancer from several aspects, to provide guidance for early detection and intervention of GSRCC., Methods: We retrospectively collected data from 24 patients diagnosed with early GSRCC ≤20 mm in Beijing Friendship Hospital from 2016 to 2021. According to tumor size, those lesions were divided into three groups: diminutive group (1-5 mm, n  = 4), small group (6-10 mm, n  = 12) and intermediate group (11-20 mm, n  = 8). The clinicopathologic and endoscopic characteristics of GSRCC were compared among the three groups., Results: Treatment strategies for lesions differed according to the size ( p <.05). There were no significant differences among the three groups with regard to age, sex, Helicobacter pylori infection, tumor location and macroscopic type. Lesions were often flat type and more likely to present with discoloration, uneven color, ulceration and submucosal invasion with the increase of diameter. Almost all cases showed abnormal intervening part (IP) under magnifying endoscopy., Conclusions: The location of early signet ring cell carcinoma is not specific, and the diminutive lesions are often flat. Abnormal IP may be the early endoscopic feature of early GSRCC.

Rationale: Anterior mediastinal signet ring cell carcinoma (SRCC) is a rare tumor that has only been reported in two cases of thymic cancer. Positive immunohistochemistry (IHC) staining for caudal-type homeobox (CDX) 2, cytokeratin (CK) 20 and special AT-rich binding protein (SATB) 2 usually indicate gastrointestinal tumors but begin to appear in thymic cancers with enteric differentiation. Here, we describe a case of the anterior mediastinal SRCC with enteric differentiation who was correctly treated with surgery and chemo-radiation and was alive after four months., Patient Concerns: A 48-year-old female presented without chest and lung symptoms had an anterior mediastinal mass during a routine physical examination. Laboratory examinations showed an elevated level of serum carbohydrate antigen (CA)-125 at 73.63 U/mL. Chest computed tomography (CT) showed an irregular soft tissue density shadow with heterogeneous enhancement in the anterior mediastinum. The tumor had invaded the pericardium, the left septal nerve and the innominate and was completely removed after anterior mediastinal surgery. Postoperative pathological examinations revealed signet ring cell features and positive staining for CDX2, CK20, SATB2 and Ki-67 (Li: 70%). The samples were negative for cluster of differentiation (CD)-5, CK7, thyroid transcription factor (TTF) 1, NapsinA, CerbB-2, P53 and PD-L1 by IHC examinations. The suspected diagnosis was an anterior mediastinal SRCC that had originated in the digestive system., Diagnosis: The patient was diagnosed with anterior mediastinal SRCC., Interventions: The patient was treated with surgery and combined chemo-radiotherapy., Outcomes: The patient had no recurrence or metastasis after five months., Lessons: We describe a rare case of the anterior mediastinal SRCC of unknown origin. Our case, for the first time shows that surgery combined with chemo-radiotherapy is an effective treatment regimen for anterior mediastinal SRCC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Skin metastases from gastric cancer are rare and usually occur very late in the course of the disease. The most common metastatic sites liver, the peritoneal surfaces, and the non regional or distant lymph nodes., Case Report: In this case we report the short-term survival of a 67-year-old man complined of multiple nodular lesions in various part of his skin. Histology showed a metastatic signet ring cell adenocarsinoma. Esophagogastroduodenoscopy was performed and a crater- like ulcer, about 3 cm in diameter, was observed on the anterior part of the stomach corpus distal. A biopsy specimen was obtained, and histopathological findings were consistent with gastric signet-ring cell carcinoma. XELOX chemotherapy regimen was initiated for the patient., Conclusion: Skin metastasis of gastric adenocarcinoma is a rare condition with a poor prognosis. It may be the first manifestation of a clinically silent visceral cancer or may represent a recurrence of an internal malignancy., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

BACKGROUND Synchronous malignancies are primary cancers that are diagnosed in a single individual within a 2-month period. Synchronous malignancies are uncommon, involving only 2.4-8% of all cancer cases, with a very low number of cases of simultaneous gastric and pancreatic cancer. Although cases of synchronous malignancies do exist, synchronous pancreatic adenocarcinoma and signet ring cell (SRC) gastric adenocarcinoma have not been documented. CASE REPORT A 76-year-old woman with a previously diagnosed intraductal papillary mucinous neoplasm (IPMN) presented with left-sided abdominal pain. Initial workup, including computed tomography imaging and endoscopic ultrasound with biopsy, led to the diagnosis of pancreatic adenocarcinoma. Within 1 month of diagnosis, the patient underwent an extended Whipple procedure and was also found to have a primary SRC gastric adenocarcinoma on evaluation of the gastric tissue margins that were removed during the procedure. The patient was initiated on chemoradiation therapy with 5-fluorouracil. However, following a subsequent decline in performance status and multiple hospitalizations, she could not tolerate further cancer treatment and died soon afterwards. CONCLUSIONS Few cases of synchronous malignancies involving the stomach and pancreas have been reported. Because gastric cancer could easily be missed on screening endoscopy; physicians must have a high index of suspicion. In those patients with a prior history of cancer, biopsies should be performed to aid in early diagnosis. To our knowledge, only metachronous cases of SRC gastric and pancreatic adenocarcinoma have been documented. Therefore, this report represents the first case of synchronous SRC gastric adenocarcinoma and IPMN-associated pancreatic adenocarcinoma in the literature.

Background: Primary duodenal cancer (PDC) is rare, especially signet-ring cell carcinoma (SRCC) of the duodenal bulb, and it is commonly misdiagnosed as an ulceration. Here, we report a rare case of SRCC of the duodenal bulb presenting with gastrointestinal hemorrhage in an 82-year-old man., Case Presentation: An 82-year-old man was admitted for gastrointestinal hemorrhage. Physical examination revealed upper abdominal tenderness and pale appearance, but was otherwise unrevealing. Laboratory workup was significant for anemia. Imaging showed no abnormalities. Two endoscopic evaluations along with interventional embolization were attempted and, unfortunately, adequate hemostasis was not achieved, resulting in distal subtotal gastrectomy, including the duodenal bulb. SRCC of the duodenal bulb was diagnosed based on pathology after surgery. Post-operatively, the patient experienced persistent gastrointestinal bleeding. Family declined further intervention and the patient eventually died one month post-resection., Conclusions: SRCC in the duodenal bulb is difficult to diagnose. For those with high-risk factors, endoscopic examination and biopsy are recommended. For patients who can receive radical tumor resection, pancreaticoduodenectomy (PD) is considered a first-line option. Early diagnosis and resection have been shown to improve prognosis., (© 2022. The Author(s).)

Goblet cell adenocarcinoma and signet-ring cell adenocarcinoma are well-known diagnostic pitfalls of routine appendectomy specimens. Here we present a case of acute appendicitis with prominent neuronal (ganglion cell) hyperplasia and swelling which histologically mimics goblet cell adenocarcinoma and signet-ring cell adenocarcinoma. Attention to the cytologic features of the lesional cells (absence of atypia, mitotic activity) and their close association with nerves and classic ganglion cells, along with the use of a limited panel of immunostains, ensures proper classification of this rare but striking benign process.

Background: Cutaneous metastases of gastric signet-ring cell gastric carcinoma are very rare. Our following case report highlights the need for careful clinical examination and skin biopsy of newly developing scar-like or erythematous skin lesions in patients with a known history of malignant disease in order to prevent diagnostic and therapeutic delay., Case Report: A 68-year-old male patient presented with two slightly painful, erythematous, facial skin lesions (chin and forehead) 2 years after gastrectomy for a signet-ring cell gastric carcinoma. The patient complained of intermittent neuropathic pain in the area of the mental nerve. A biopsy of both skin lesions demonstrated metastasis of signet-ring cell gastric carcinoma. Following discussion within the multidisciplinary tumor board, palliative surgical excision was recommended for this patient. Both skin lesions were resected and the large defect in the chin region was primarily closed by a cervical skin transposition flap., Conclusion: The presented case report of a patient with a known history of malignancy illustrates that newly developing erythematous skin lesions may be suspicious for cutaneous metastases. Palliative surgical interventions may play a role even in an advanced disease stage., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A case of signet ring cell lymphoma of presacral lymph node is reported. The patient was diagnosed as follicular lymphoma on the basis of clinical and laboratory features, including immunohistochemistry (IHC) and gene rearrangement studies. Light microscopy examination showed neoplastic atypical cells with signet ring cell morphology in core biopsy of lymph node that stained for B-cell markers by IHC. In addition, the neoplastic cells expressed CD20, CD10, BCL-2, and BCL-6, indicating follicular center origin. Fluorescence in situ hybridization study demonstrated BCL2 gene arrangement. Especially in the case of deep-seated intra-abdominal lymph nodes with atypical presentation, the differential diagnosis arises with nonhemopoietic tumors, and this needs to be distinguished by specific immunostaining and gene arrangement studies., Competing Interests: None

Metastases to the testis are uncommon. Signet-ring cell carcinomas from the gastrointestinal tract (GIT) can rarely disseminate to the testicles, mimicking primary testicular malignancies with signet-ring cells. We hereby describe a case of a 26-year-old male who presented with left testicular swelling, multiple lymphadenopathies, and normal serum tumor markers. Lymph node biopsy revealed clusters and singly lying signet-ring cells. Judicious use of immunohistochemistry confirmed the tumor to be GIT primary. Further investigations confirmed a gastric tumor extending to the duodenum. Although rare, metastatic tumors to the testis should be considered in differential diagnoses of testicular masses in a young patient, particularly when serum germ cell tumor markers are normal or mildly deranged., Competing Interests: None

Background: Persistent elevations in beta-human chorionic gonadotropin (β-hCG) can be an ominous sign of both trophoblastic and non-trophoblastic malignancies. The absence of a clearly identified etiology of β-hCG elevation warrants pursuit of further diagnostic testing to determine the source of ectopic β-hCG., Case Report: A virginal 26-year-old woman with past medical history significant for persistently elevated β-hCG presented to our Emergency Department with shortness of breath, pleuritic chest pain, nausea, and vomiting, and was found to have widely metastatic gastric signet ring cell adenocarcinoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although elevated serum β-hCG is a generally a marker of pregnancy, β-hCG elevation without clear etiology necessitates ruling out other insidious processes. Failure to maintain and pursue a broad differential in the context of unexplained elevations of β-hCG can result in catastrophic missed or delayed diagnosis., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Signet ring cell (SRC) histology is considered a poor prognostic factor in various cancers. However, primary SRC lung adenocarcinoma is rare and poorly understood., Methods: The National Cancer Database was queried to identify treatment-naïve patients who received lobectomy for primary SRC or non-SRC pT1-2N0 lung adenocarcinoma <4 cm within four months of diagnosis. SRC lung adenocarcinoma was defined by ICD-O-3 code 8490, while non-SRC lung adenocarcinoma was defined by ICD-O-3 codes 8140, 8141, 8143, 8147, 8255, 8260, 8310, 8481, 8560, and 8570-8574. The Kaplan-Meier curve and log-rank test was used to compare five-year OS between SRC versus non-SRC lung adenocarcinoma cohorts. The impact of SRC histology on risk of death was assessed using the Cox proportional hazards regression model., Results: 48,399 patients were included in this study: 62 with primary SRC lung adenocarcinoma and 48,337 with non-SRC lung adenocarcinoma. The mean age of the overall cohort was 67.0 ± 9.6 years. Five-year OS following lobectomy did not differ significantly between SRC lung adenocarcinoma and non-SRC lung adenocarcinoma cohorts (SRC 73.9% vs. non-SRC 69.3%, p  = 0.64). SRC histology did not significantly impact risk of death within five years after lobectomy (HR 0.89, p  = 0.66)., Conclusions: Following lobectomy for pT1-2N0 tumors <4 cm, patients with primary SRC lung adenocarcinoma do not experience worse five-year OS or increased risk of death within five years relative to those with non-SRC lung adenocarcinoma. Additional study, including exploration of emerging molecular profiling data, may serve to better define optimal treatment for this histopathologic group of lung adenocarcinomas.

Cancer related thrombotic microangiopathies usually cause a diagnostic dilemma for hematologists and clinicians. In this case report, we presented a fifty-nine-year-old man who was admitted to our hospital with microangiopathic hemolytic anemia and thrombocytopenia due to the carcinoma metastasis to the bone marrow. As a result of rapid evaluations, it was revealed that the histological subtype of the cancer was signet ring cell carcinoma, and despite all the interventions, the patient died at a very short time after the initial presentation. Regardless of all the innovations in the diagnosis and treatment of thrombotic microangiopathies, cancer-associated thrombotic microangiopathy is still fatal and deadly today., Competing Interests: None