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.

Prognostic Analysis of Primary Breast Signet Ring Cell Carcinoma and Mucinous Breast Adenocarcinoma: A SEER Population-Based Study

BackgroundPrimary breast signet ring cell carcinoma (SRCC) is a rare type of breast cancer with typical morphological characteristics, high aggressiveness, and poor prognosis. SRCC is different from mucinous breast adenocarcinoma (MBC). However, only a few studies have explored the clinicopathological features and prognosis of SRCC and MBC.MethodsData retrieved from the Surveillance, Epidemiology, and End-Results (SEER) database (2004–2015) were used to explore the prognostic effect of clinicopathological features and treatment modalities on survival outcomes of SRCC and MBC patients. Kaplan–Meier plot analysis, multivariate Cox proportional risk model, propensity score matching (PSM), and subgroup analysis were performed.ResultsA total of 167 patients with SRCC and 11,648 patients with MBC were included in the study. SRCC patients exhibited higher histological grade (p < 0.001), larger tumor volume (p < 0.001), higher rate of lymph node metastasis (p < 0.001), and higher frequency of distal metastasis (p < 0.001) compared with MBC patients. Cox proportional hazards regression analysis showed that SRCC patients had lower overall survival (OS) and breast cancer-specific survival (BCSS) compared with MBC patients. Subgroup survival analysis showed that the SRCC patients had lower OS and BCSS in subgroups including younger than 60 years old, white race, married, without chemotherapy, and received radiotherapy compared with the MBC patients in these subgroups. In addition, the SRCC patients had lower BCSS in subgroups including other races (including Asian or Pacific Islander and American Indian/Alaska Native), without surgery, and lymph node metastasis.ConclusionThe findings showed that primary breast SRCC patients have unique clinical characteristics and worse prognosis compared with MBC patients. Notably, different treatment methods resulted in different prognosis for SRCC and MBC types; therefore, SRCC patients should be distinguished from MBC patients to improve efficacy of treatment.