Superficial Flat-type Early-stage Gastric Signet Ring Cell Carcinoma in the Atrophic Background Mucosa: Two Case Reports

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. Two female cases of early-stage gastric signet ring cell carcinoma with atrophic background mucosa occurring in the middle and lower part of the stomach were found in our endoscopy center. The diagnosis was confirmed by upper gastrointestinal white light endoscopy combined with narrow-band imaging and endoscopic biopsy, both lesions less than 2.0cm in diameter were surgically removed and identified as intramucosal adenocarcinoma. Through these two cases, we aim to illustrate the difficulty of early detection of gastric signet ring cell carcinoma with mucosal atrophy. 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.

Establishment of gastric signet ring cell carcinoma organoid for the therapeutic drug testing

Signet ring cell carcinoma (SRCC) has specific oncogenesis and phenotypic and treatment resistance heterogeneity. Systemic therapies are often ineffective, and predictive biomarkers to guide treatment are urgently needed. Tumor organoids have recently emerged as an ideal model for drug testing and screening. Here, we report gastric organoids established from tumor tissues comprising four SRCCs and eight non-SRCCs. Tumor organoids demonstrated different growth characteristics and morphologies. Changes in the original tumor genome were maintained during long-term culture from whole-exome sequencing (WES) analysis. Immunohistochemistry and H&E staining showed that the tissue characteristics of the primary tumor could be recapitulated. In addition, organoid lines successfully formed tumors in immunodeficient mice and maintained tumorigenic character. Different responses to 5-fluorouracil, oxaliplatin, docetaxel and irinotecan treatment were observed in SRCC and non-SRCC organoids. These results demonstrate that gastric organoid drug models, including SRCC, were highly similar to the original tumors in phenotypic and genotypic profiling and could be as living biomarkers for drug response testing.

Quantifying the cell morphology and predicting biological behavior of signet ring cell carcinoma using deep learning

Signet ring cell carcinoma (SRCC) is a malignant tumor of the digestive system. This tumor has long been considered to be poorly differentiated and highly invasive because it has a higher rate of metastasis than well-differentiated adenocarcinoma. But some studies in recent years have shown that the prognosis of some SRCC is more favorable than other poorly differentiated adenocarcinomas, which suggests that SRCC has different degrees of biological behavior. Therefore, we need to find a histological stratification that can predict the biological behavior of SRCC. Some studies indicate that the morphological status of cells can be linked to the invasiveness potential of cells, however, the traditional histopathological examination can not objectively define and evaluate them. Recent improvements in biomedical image analysis using deep learning (DL) based neural networks could be exploited to identify and analyze SRCC. In this study, we used DL to identify each cancer cell of SRCC in whole slide images (WSIs) and quantify their morphological characteristics and atypia. Our results show that the biological behavior of SRCC can be predicted by quantifying the morphology of cancer cells by DL. This technique could be used to predict the biological behavior and may change the stratified treatment of SRCC.

A Case of Primary Signet-Ring Cell Cervical Carcinoma Treated with Chemoradiation, Brachytherapy, and Adjuvant Hysterectomy

Primary signet-ring cell carcinoma of the uterine cervix is a rare subtype of cervical mucinous adenocarcinoma. Approximately 20 cases of primary signet-ring cell carcinoma of the cervix have been reported. Pathologic examination shows that adenocarcinomas with mucin accumulation in intracytoplasmic vacuoles displacing the nucleus indicate signet-ring cell carcinoma. A thorough metastatic workup is needed both for staging and to rule out gastrointestinal tract origin. Due to the rarity of the disease, both the true incidence and optimal management are unknown. Herein, the authors present a case of stage 1B3 primary signet-ring cell cervical carcinoma treated with combined chemotherapy and radiation (including external beam radiation and brachytherapy), followed by resection for residual disease. This case is consistent with limited reports where all surviving patients received surgery as well as 1 surviving patient with bulky disease required with chemoradiation and adjuvant hysterectomy.

Metastatic Breast Signet-Ring Cell Carcinoma from a Colonic Primary: Review of a Rare Case Report

Introduction: Colonic signet-ring cell carcinoma is a distinctive rare subtype of adenocarcinoma with a predilection for early metastasis. Among the rare extramammary metastatic adenocarcinomas to the breast, colonic signet-ring cell carcinomas constitute a small percentage. The distinction of a primary from a secondary breast signet ring cell carcinoma is indispensable since it may result in different therapeutic approaches. Here we presented a rare case of metastatic breast signet-ring cell carcinoma from a rectal origin and review its distinctive histopathologic features. Case Presentation: A 37-year-old woman presented with a breast mass 3 months after undergoing low anterior resection surgery to remove a rectal mass, diagnosed as signet ring cell carcinoma. Histopathologic examination of the core needle breast mass biopsy revealed tumor cells with signet-ring cell cytomorphology. The performed immunohistochemistry confirmed carcinoma of colonic origin. Conclusions: Colorectal signet-ring cell carcinoma is a rare and aggressive tumor. Its metastatic spread is most seen in the intra-abdominal area, with seldom reported cases of breast metastasis. Histologically, it can mimic a primary breast carcinoma, especially if no prior history of colonic origin exists. Accurate diagnosis is important since these 2 entities carry different therapeutic management. Proper immunophenotyping, obtaining a thorough clinical history and imaging studies facilitate a correct diagnosis.

CDH1 germline variants are enriched in patients with colorectal cancer, gastric cancer, and breast cancer

Background and aims CDH1 germline variants have been linked to heritability in diffuse gastric (DGC) and lobular breast cancer (LBC). Studies have not yet assessed whether CDH1 is a cancer-susceptibility gene in other cancers. Herein, we mapped the landscape of pathogenic and likely pathogenic (P/LP) germline variants in CDH1 across various cancers and ethnicities. Methods We evaluated CDH1 germline P/LP variants in 212,944 patients at one CLIA-certified laboratory (Invitae) and described their frequency in 7 cancer types. We screened for CDH1 variant enrichment in each cancer relative to a cancer-free population from The Genome Aggregation Database version 3 (gnomADv3). Results CDH1 P/LP variants were identified in 141 patients, most commonly in patients with DGC (27/408, 6.6%) followed by colorectal signet-ring cell cancer (CSRCC; 3/79, 3.8%), gastric cancer (56/2756, 2%), and LBC (22/6809, 0.3%). CDH1 P/LP variants were enriched in specific ethnic populations with breast cancer, gastric cancer, CRC, LBC, DGC, and CSRCC compared to matched ethnicities from gnomADv3. Conclusion We report for the first time the prevalence of P/LP CDH1 variants across several cancers and show significant enrichment in CDH1 P/LP variants for patients with CSRCC, DGC, and LBC across various ethnicities. Future prospective studies are warranted to validate these findings.