A novel web-based dynamic prognostic nomogram for gastric signet ring cell carcinoma: a multicenter population-based study.

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.

Invasive lobular carcinoma metastasis to pancreas mimicking pancreatic signet ring cell carcinoma: A case report and systematic review of the literature.

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.

Gastrointestinal signet ring cell malignancy: current advancement and future prospects.

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.

Primary signet ring cell carcinoma of prostate: A rare case report and review of literature.

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.

Pseudoachalasia as the first manifestation of signet-ring cell duodenal carcinoma.

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.

Signet-ring cell sinus histiocytosis: report of the clinicopathologic characteristics of 4 cases with emphasis on the differential diagnosis of signet-ring cell lesions.

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.

A rare cause of intestinal obstruction in children: signet-ring cell adenocarcinoma of the colon.

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.

The clinicopathological and immunohistochemical features of breast carcinomas with signet-ring-cell differentiation.

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.

A rare case of signet ring cell carcinoma with diffuse cutaneous systemic sclerosis: A case report.

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.

Metastasis of primary signet ring cell carcinoma of prostate to bone marrow: A rare occurrence with review of literature.

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.

Gastric Flat Elevated Undifferentiated Signet-ring Cell Mucosal Cancer Lesion Detected in a Case without Helicobacter pylori Infection.

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.

Signet ring cell-like diffuse large B-cell lymphoma involving the breast: a case report.

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.

Cancer surveillance as an alternative to prophylactic total gastrectomy in hereditary diffuse gastric cancer: a prospective cohort study.

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.

Superficial Flat-Type Early-Stage Gastric Signet Ring Cell Carcinoma in the Atrophic Background Mucosa: Two Case Reports.

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.

Endoscopic and clinicopathologic features of early gastric signet ring cell carcinoma ≤20 mm: a retrospective observational study.

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.