Glutathione system to characterize the biological aggressiveness of the gastric cancer.

e15512 Background: The aim was a comparative study of glutathione system of tumor and its peritumoral tissues at gastric signet ring cell carcinoma (SRCC) and gastric adenocarcinoma (AC) to identify pathogenetic features of malignancy. Methods: Content of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST) were determined in the samples of tumor and peritumoral tissues, obtained during the surgery in 21 primary patients: 13 patients with SRCC, 8 patients with AC (G2-G3) without preoperative therapy. Tissue of intact stomach was studied in 12 randomly bereaved. Results: In the AC tumor tissue the GSH level was decreased by 43% and the activity of GPx and the GST was increased by 121.7% and 44.3% (p < 0.05–p < 0.001) compared with intact stomach. In peritumoral tissue both the level of GSH and GPX activity were less than in the tumor tissue at 40-45% (p < 0.05–p < 0.01). In SRCC both the GSH level and the activity of GPx and GST were increased in tumor tissue by 78%, 93.6% and 49.5% (p < 0.05–p < 0.001) compared with the intact stomach. In peritumoral tissue the GSH level was lower than in the tumor tissue by 60.2% (p < 0.01), the enzymes activity was unchanged remaining higher than in the intact stomach. The GSH level both in tumor and in peritumoral tissues was 2-3 folds higher in gastric SRCC than in AC. No significant differences in the activity of glutathione-dependent enzymes in tumors of different histotype were revealed. Conclusions: The results show the differences in the functioning of the glutathione system, depending on the histological type of gastric tumors. It is possible that greater activity of glutathione-dependent system in tissue of SRCC is needed to maintain its increased proliferative activity and determines the features of the biological behavior of this tumor histotype.

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Primary Signet Ring Cell/Histiocytoid Carcinoma of the Eyelid: Somatic Mutations in CDH1 and Other Clinically Actionable Mutations Imply Early Use of Targeted Agents

Current Oncology ◽

10.3390/curroncol28010090 ◽

2021 ◽

Vol 28 (1) ◽

pp. 918-927

Author(s):

Lei-Chi Wang ◽

Tai-Chi Lin ◽

Yi-Chen Yeh ◽

Hsiang-Ling Ho ◽

Chieh-Chih Tsai ◽

...

Keyword(s):

Next Generation Sequencing ◽

Cell Carcinoma ◽

Tumor Tissue ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Next Generation ◽

Signet Ring ◽

Ring Cell ◽

Generation Sequencing ◽

E Cadherin

Primary signet ring cell/histiocytoid carcinoma of the eyelid is a rare ocular malignancy and its diagnosis is often delayed. This neoplasm presents as an insidious, diffusely infiltrative mass in the periocular area that later infiltrates the orbit. An exenteration is usually indicated; however, nearly one-third of patients develop local recurrence or metastasis. Morphologically, it resembles signet ring cell carcinoma of the stomach and breast, raising the possibility of mutations in CDH1, the gene encoding E-cadherin. To determine whether primary signet ring cell/histiocytoid carcinoma harbors the CDH1 mutation or other actionable mutations, we analyzed the tumor tissue via next-generation sequencing. We identified only one case of primary signet ring cell carcinoma of the eyelid with adequate DNA quality for sequencing from the pathological archive during the period 2000 to 2020. A comprehensive evaluation including histopathology, immunohistochemistry, and next-generation sequencing assay was performed on tumor tissue. Immunohistochemically, the tumor exhibited E-cadherin membranous staining with the aberrant cytoplasmic staining of β-catenin. Using next-generation sequencing, we demonstrated the mutation in the CDH1 gene. In addition, other clinically actionable mutations including ERBB2 and PIK3CA were also detected. The alterations in other actionable genes indicate a need for larger studies to evaluate the pathogenesis and potential therapies for primary signet ring cell/histiocytoid carcinoma of the eyelid.

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Signet ring cell carcinoma of rectum metastasizing to synchronous renal cell carcinoma: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-02749-x ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Blagica Krsteska ◽

Rubens Jovanovic ◽

Aleksandar Eftimov ◽

Boro Ilievski ◽

Dragan Hadzi-Mancev ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Cancer Metastasis ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Biological Behavior ◽

Synchronous Tumors ◽

Signet Ring ◽

Ring Cell

Abstract Background Rectal signet ring cell carcinoma is a rare type of colorectal adenocarcinoma characterized by an aggressive biological behavior and poor prognosis. The co-occurrence of colorectal carcinoma and renal cell carcinoma (RCC) has found in many hundreds of patients, many of whom also have additional malignancies. Cancer to cancer metastasis is rare and an uncommon phenomenon in malignancy, especially at the time of initial diagnosis, suggesting a genetic susceptibility. Case presentation We present the case of a 66-year-old Macedonian man with synchronous rectal signet ring cell carcinoma and RCC with tumor to tumor metastasis feature. He underwent a left nephrectomy and anterior rectal resection after complaining of constipation for 3–4 months and the appearance of synchronous tumors on the imaging studies. Morphology and immunohistochemical analysis of specimens from the RCC revealed signet ring cells identical to the rectal signet ring cell carcinoma. The next-generation sequencing study revealed mutations in TP53 and ERBB2, and microsatellite stable signet ring cell carcinoma was determined by deoxyribonucleic acid (DNA) sequencing. Conclusions Cancer to cancer metastasis, although rare, needs to be considered in synchronous tumors. RCC, when diagnosed in multiple synchronous tumors, should be examined carefully. The paucity of reported cases indicates the need for advanced research in imaging methods for metastasis and new therapeutic approaches.

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Quantifying the Cell Morphology and Predicting Biological Behavior of Signet Ring Cell Carcinoma using Deep Learning

10.21203/rs.3.rs-660589/v1 ◽

2021 ◽

Author(s):

Qian Da ◽

Shijie Deng ◽

Jiahui Li ◽

Hongmei Yi ◽

Xiaodi Huang ◽

...

Keyword(s):

Deep Learning ◽

Cell Carcinoma ◽

Histopathological Examination ◽

Morphological Characteristics ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Biological Behavior ◽

Signet Ring ◽

Poorly Differentiated ◽

Ring Cell

Abstract 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.

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Prognosis and Biological Behavior of Gastric Signet-Ring Cell Carcinoma Better or Worse: A Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.603070 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shuai Zhao ◽

Ling Lv ◽

Kai Zheng ◽

Yu Tian ◽

Jian-Chun Zheng ◽

...

Keyword(s):

Cell Carcinoma ◽

Early Stage ◽

Meta Analysis ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Biological Behavior ◽

Advanced Stage ◽

Female Ratio ◽

Signet Ring ◽

Ring Cell

BackgroundThe clinical pathology of gastric signet-ring cell carcinoma (SRC) is still unclear. This meta-analysis was performed to evaluate the difference in biological behavior and prognosis between SRC and non-signet ring cell carcinoma (NSRC).MethodsA total of 58 eligible studies were analyzed using RevMan and other auxiliary software. Biological behaviors were compared based on odds ratio (OR) and mean difference (MD). Hazards ratio (HR) was calculated for prognosis based on Kaplan–Meier curves.ResultsTotally, 28,946 SRC patients were compared with 81,917 NSRC patients. Compared with NSRC patients, lower male: female ratio (OR = 0.53, P < 0.01), younger age (MD = −4.89, P < 0.01), more middle location (OR = 1.64, P < 0.01), more depressed type at early stage (OR = 1.31, P < 0.05), higher incidence of Borrmann type IV (OR = 1.96, P < 0.01), less lymph node metastasis at early stage (OR = 0.78, P < 0.05), better prognosis at early stage (HR = 0.59, P < 0.01), and worse prognosis at advanced stage (HR = 1.19, P < 0.01) were associated with SRC patients.ConclusionThe prognosis of SRC at early stage is better than other types of gastric cancer, while that of SRC at advanced stage is relatively poorer.

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Primary signet ring cell carcinoma of the breast: A rare entity with unique biological behavior—A clinical study based on pure signet ring cell carcinoma cohort

Pathology - Research and Practice ◽

10.1016/j.prp.2020.152948 ◽

2020 ◽

Vol 216 (6) ◽

pp. 152948

Author(s):

Tong Wang ◽

Beibei Shen ◽

Liang Wang ◽

Fangfang Liu

Keyword(s):

Clinical Study ◽

Cell Carcinoma ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Biological Behavior ◽

Rare Entity ◽

Carcinoma Of The Breast ◽

Signet Ring ◽

Ring Cell

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

Scientific Reports ◽

10.1038/s41598-021-03984-4 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Qian Da ◽

Shijie Deng ◽

Jiahui Li ◽

Hongmei Yi ◽

Xiaodi Huang ◽

...

Keyword(s):

Deep Learning ◽

Cell Carcinoma ◽

Histopathological Examination ◽

Morphological Characteristics ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Biological Behavior ◽

Signet Ring ◽

Poorly Differentiated ◽

Ring Cell

AbstractSignet 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.

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Signet Ring Carcinoma of the Appendix Presenting as Crohn’s Disease in a Young Male

Case Reports in Gastroenterology ◽

10.1159/000489298 ◽

2018 ◽

Vol 12 (2) ◽

pp. 277-285 ◽

Cited By ~ 2

Author(s):

Jonatan Vukovic ◽

Pavle Vrebalov Cindro ◽

Snjezana Tomic ◽

Ante Tonkic

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Cell Carcinoma ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Biological Behavior ◽

Special Importance ◽

Ileocecal Region ◽

Signet Ring ◽

Ring Cell

Primary signet ring cell carcinoma is a rare event in surgery. It looks like acute appendicitis and it is difficult to diagnose it on clinical grounds alone. The diagnosis is always confirmed by histopathology of a surgically removed appendix. A young man, 22 years old, presented with vomiting, diarrhea, and cramps in his abdomen without abdominal tenderness (mild abdominal discomfort in the right lower abdominal quadrant without signs of peritoneal irritation) during the previous month. The first endoscopic results showed only changes of mucosa that could be attributed to endoscopic and clinical representation of Crohn’s disease. A few days after the initiation of the therapy with aminosalicylates and corticosteroids, the patient went into ileus and was transferred to the Department of Surgery, where he underwent an emergency right-sided hemicolectomy with resection of the transversal colon and forming of an ileostoma. The first pathohistological diagnosis was pseudomembranous colitis. Because the patient’s condition was deteriorating, a revision of the pathohistological diagnosis was done. After careful revision and extensive sampling, a signet ring cell carcinoma arising in the appendix with infiltration of the ileocecal region was found. Immunohistochemically, tumor cells were positive for CDX-2 CK7, CK20, CK19, and carcinoembryonic antigen and negative for chromogranin A. Sixteen isolated lymph nodes were negative. Although the patient had a disease that was localized to the appendix and ileocecal region with no apparent distal metastasis, his clinical condition was worsening rapidly and he died after 2 months. This case shows the aggressive biological behavior of the appendix signet ring cell carcinoma. Scrupulous histopathological examination of the appendix is an obligatory procedure. Elimination of the signet ring cell carcinoma from other carcinoma subtypes is of special importance as it has an exceptionally poor prognosis and is generally diagnosed in its advanced stages.

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