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Tian Q, Xu Y, Men F, Guo N, Wang P. An early-stage primary signet ring cell carcinoma of the colon. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:511-513. [PMID: 37929980 DOI: 10.17235/reed.2023.10016/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2023]
Abstract
Primary signet ring cell carcinoma of the colorectum is rarely detected at an early stage,here,we present a case with early stage primary signet ring cell carcinoma of the colon, and the patient was treated at an early stage, and the prognosis was well. We also provide endoscopic and histological characteristics of early stage SRCC.
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Affiliation(s)
- Qifei Tian
- Gastroenterology, Dongying People's Hospital, China
| | - Yuan Xu
- Gastroenterology, Dongying People's Hospital, China
| | - Fangli Men
- Gastroenterology, Dongying People's Hospital, China
| | - Ni Guo
- Gastroenterology, Dongying People's Hospital, China
| | - Ping Wang
- Gastroenterology, Dongying People's Hospital, China
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Nuytens F, Drubay V, Eveno C, Renaud F, Piessen G. Systematic review of risk factors, prognosis, and management of colorectal signet-ring cell carcinoma. World J Gastrointest Oncol 2024; 16:2141-2158. [PMID: 38764832 PMCID: PMC11099453 DOI: 10.4251/wjgo.v16.i5.2141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 01/27/2024] [Accepted: 03/19/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC. AIM To provide an updated overview of risk factors, prognosis, and management of CSRCC. METHODS A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: 'Signet ring cell carcinoma' and 'colorectal'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature. RESULTS In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients. CONCLUSION CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.
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Affiliation(s)
- Frederiek Nuytens
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, AZ Groeninge, Kortrijk 8500, Belgium
| | - Vincent Drubay
- Cambrai Hospital Center and Sainte Marie, Group of Hospitals of The Catholic Institute of Lille, Cambrai 59400, France
| | - Clarisse Eveno
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
| | - Florence Renaud
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
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Tanaka Y, Chino O, Kajiwara H, Hanashi T, Nakamura T, Makuuchi H. A rare case of esophageal metastasis from signet-ring cell carcinoma of the cecum. Surg Case Rep 2023; 9:186. [PMID: 37872388 PMCID: PMC10593686 DOI: 10.1186/s40792-023-01768-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 10/17/2023] [Indexed: 10/25/2023] Open
Abstract
BACKGROUND Metastatic esophageal cancer is rare. Its common primary lesions include lung cancer and breast cancer. Metastatic esophageal cancer originating from colorectal cancer is rarer. CASE PRESENTATION A 79-year-old woman visited our hospital because of lower abdominal discomfort. She was endoscopically diagnosed with type 0-IIa + IIc cancer of the cecum, and biopsy of the lesion showed signet-ring cell carcinoma. With a preoperative clinical staging of cStage I (cT2, cN0, cM0), the patient underwent laparoscopic ileocecal resection with D3 lymphadenectomy. Histopathological examination of the resected specimens revealed signet-ring cell carcinoma [type 4, pT4a, pN3 (No. 203), M0, pRM1, stage IIIc, R1]. Despite radial margin positivity, the patient refused resection of the residual tumor and received oral tegafur and uracil. KRAS mutation test showed KRAS wild-type colon cancer, but she refused anti-epidermal growth factor receptor therapy. One year after surgery, her blood carcinoembryonic antigen concentration elevated. Colonoscopy showed anastomotic recurrence and biopsy of the lesion showed signet-ring cell carcinoma. Upper gastrointestinal endoscopy showed multiple longitudinal submucosal tumors with erosions on their surfaces in the esophagus. Tumor biopsy revealed signet-ring cell carcinoma. Immunohistochemistry showed that the histological type of the esophageal tumors was the same as that of the primary colon cancer. Based on these findings, the esophageal tumors were diagnosed with metastasis from signet-ring cell carcinoma of the cecum. The oral chemotherapy was replaced with FOLFOX plus bevacizumab. However, the patient's condition required treatment discontinuation, and she died of cancer progression 1 year and 5 months after surgery. CONCLUSIONS To our knowledge, this is the first case report on metastatic esophageal cancer from signet-ring cell carcinoma of the cecum. Esophagoscopy showed multiple longitudinal submucosal tumors, which is similar to an endoscopic finding of intramural metastasis from primary esophageal cancer. We consider that the multiple longitudinal submucosal tumors are a notable feature of our case. When metastatic esophageal cancer is suspected, clinicians, endoscopists, and pathologists should consider signet-ring cell carcinoma of the colon as one of potential primary lesions. This consideration could lead the specialists to appropriate examinations and treatments, thereby improving clinical outcomes in patients with the metastasis.
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Affiliation(s)
- Yoichi Tanaka
- Department of Surgery, Tokai University Tokyo Hospital, 1-2-5 Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan.
| | - Osamu Chino
- Department of Surgery, Tokai University Tokyo Hospital, 1-2-5 Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan
| | - Hiroshi Kajiwara
- Department of Pathology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
| | - Tomoko Hanashi
- Department of Surgery, Tokai University Tokyo Hospital, 1-2-5 Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan
| | - Tomoki Nakamura
- Department of Surgery, Tokai University Tokyo Hospital, 1-2-5 Yoyogi, Shibuya-ku, Tokyo, 151-0053, Japan
| | - Hiroyasu Makuuchi
- Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan
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Han Y, Yang W, Ma Q, Cai Z, Yang Y, Gou J, Yuan T, Zhang M, Zhang B. Case Report: Systemic treatment for breast and vulvar metastases from resected rectal signet ring cell carcinoma. Front Oncol 2023; 13:1213888. [PMID: 37483522 PMCID: PMC10359816 DOI: 10.3389/fonc.2023.1213888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Accepted: 06/22/2023] [Indexed: 07/25/2023] Open
Abstract
BACKGROUND Breast and vulvar metastases from rectal signet ring cell carcinoma (SRCC) represent a rare and obscure clinical entity associated with poor survival. Managing patients with metastatic rectal SRCC is extremely challenging due to the absence of high-quality evidence. CASE PRESENTATION A 26-year-old woman presented with progressively worsening anal pain, constipation, and hematochezia for approximately two years. Following the diagnosis of locally advanced rectal cancer (cT3N0-1M0), she received neoadjuvant chemotherapy with modified FOLFOX6 regimen and underwent laparoscopic abdominoperineal resection. Metastases to the breast and vulva developed during postoperative chemotherapy. Genetic testing revealed RAS/BRAF wild-type and microsatellite instability (MSI)-low status. Though sequential administration of irinotecan plus tegafur and tegafur plus raltitrexed-based chemotherapy in combination with bevacizumab, the disease progressed rapidly. Sadly, the patient passed away 15 months after initial diagnosis due to rapidly progressive disease. CONCLUSION Rectal SRCC is associated with younger on-set, aggressive behaviors, and worse survival outcomes. Due to poor cohesiveness, SRCC tends to develop metastases. A patient's medical history and immunohistochemical staining (such as CK20, CK7, and CDX-2) can aid in identifying the tumor origin of breast and vulvar metastases. Mutations and signaling pathways predominant in the tumorigenesis of SRCC remains unveiled. There is poor effect of conventional chemotherapies, targeted and immunotherapies for colorectal adenocarcinoma on SRCC, so novel therapies are needed to treat this patient population.
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Affiliation(s)
- Yihui Han
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Wenming Yang
- Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Qin Ma
- Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of General Surgery, West China Shangjin Hospital, Sichuan University, Chengdu, China
| | - Zhaolun Cai
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yun Yang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of General Surgery, West China Shangjin Hospital, Sichuan University, Chengdu, China
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Junhe Gou
- Department of Pathology, West China Shangjin Hospital, Sichuan University, Chengdu, China
| | - Tao Yuan
- Department of Anesthesiology, West China Shangjin Hospital, Sichuan University, Chengdu, China
| | - Mingming Zhang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Department of General Surgery, West China Shangjin Hospital, Sichuan University, Chengdu, China
- Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Zhang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
- Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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Allart M, Leroy F, Kim S, Sefrioui D, Nayeri M, Zaanan A, Rousseau B, Ben Abdelghani M, de la Fouchardière C, Cacheux W, Legros R, Louafi S, Tougeron D, Bouché O, Fares N, Roquin G, Bignon AL, Maillet M, Pozet A, Hautefeuille V. Metastatic colorectal carcinoma with signet-ring cells: Clinical, histological and molecular description from an Association des Gastro-Entérologues Oncologues (AGEO) French multicenter retrospective cohort. Dig Liver Dis 2022; 54:391-399. [PMID: 34384712 DOI: 10.1016/j.dld.2021.06.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 06/21/2021] [Accepted: 06/27/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Metastatic signet-ring cell colorectal carcinoma is rare. We analyzed its clinicopathological and molecular features, prognostic factors and chemosensitivity. METHODS Retrospective study from 2003 to 2017 in 31 French centers, divided into three groups: curative care (G1), chemotherapy alone (G2), and best supportive care (G3). RESULTS Tumors were most frequently in the proximal colon (46%), T4 (71%), and poorly differentiated (86%). The predominant metastatic site was peritoneum (69%). Microsatellite instability and BRAF mutation were found in 19% and 9% (mainly right-sided) of patients and RAS mutations in 23%. Median overall survival (mOS) of the patients (n = 204) was 10.1 months (95%CI: 7.9;12.8), 45.1 for G1 (n = 38), 10.9 for G2 (n = 112), and 1.8 months for G3 (n = 54). No difference in mOS was found when comparing tumor locations, percentage of signet-ring cell contingent and microsatellite status. In G1, relapse-free survival was 14 months (95%CI: 6.5-20.9). In G2, median progression-free survival (PFS) was 4.7 months (95%CI: 3.6;5.9]) with first-line treatment. Median PFS was higher with biological agents than without (5.0 vs 3.9 months, p = 0.016). CONCLUSIONS mSRCC has a poor prognosis with specific location and molecular alterations resulting in low chemosensitivity. Routine microsatellite analysis should be performed because of frequent MSI-high tumors in this population.
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Affiliation(s)
- Marion Allart
- Department of Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France
| | - Florence Leroy
- Department of Cancer Medicine, Gustave Roussy Institute, Villejuif, France
| | - Stephano Kim
- Department of Medical Oncology, Jean Minjoz University Hospital, Besançon, France
| | - David Sefrioui
- Department of Hepato-Gastroenterology, Rouen University Hospital, Rouen, France
| | - Mihane Nayeri
- Department of Digestive and Oncological Surgery, Lille University, Claude Huriez University Hospital, Lille, France
| | - Aziz Zaanan
- Department of Gastroenterology and Digestive Oncology, European Georges Pompidou Hospital, APHP, Univ. Paris, Paris, France
| | - Benoit Rousseau
- Department of Medical Oncology, Henri Mondor University Hospital - Créteil, Memorial Sloan Kettering Cancer Center, New York, United States of America
| | | | | | - Wulfran Cacheux
- Department of Medical Oncology, Private Hospital Pays de Savoie, Annemasse, France
| | - Romain Legros
- Department of Gastroenterology, Limoges University Hospital, Limoges, France
| | - Samy Louafi
- Department of Medical Oncology, Oncology Federation of Essonne - Corbeil-Essonnes, France
| | - David Tougeron
- Department of Gastroenterology, Poitiers University Hospital, Poitiers, France
| | - Olivier Bouché
- Department of Gastroenterology and Digestive Oncology, Reims University Hospital, Reims, France
| | - Nadim Fares
- Department of Hepato-Gastroenterology, Toulouse University Hospital, Toulouse, France
| | - Guillaume Roquin
- Department of Gastroenterology and Digestive Oncology, Angers University Hospital, Angers, France
| | - Anne Laure Bignon
- Department of Hepato-Gastroenterology and Nutrition, Caen University Hospital, Caen, France
| | - Marianne Maillet
- Department of Gastroenterology, Saint Louis Hospital, APHP, Paris, France
| | - Astrid Pozet
- Methodology and Quality of Life in Oncology Unit, INSERM UMR 1098, Besançon University Hospital, Besançon, France
| | - Vincent Hautefeuille
- Department of Gastroenterology and Digestive Oncology, Amiens University Hospital, Amiens, France.
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6
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Suthar M, Baheti AD, Ankathi SK, Choudhari A, Haria PD, Engineer R, Ostwal V, Ramadwar MS, Desouza A, Saklani A. MRI features of signet ring rectal cancer. Abdom Radiol (NY) 2021; 46:5536-5549. [PMID: 34427742 DOI: 10.1007/s00261-021-03250-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/10/2021] [Accepted: 08/11/2021] [Indexed: 12/28/2022]
Abstract
PURPOSE Signet Ring Rectal Cancer (SRRC) of rectum is rare high-grade subtype with poor prognosis and characteristic histopathology. We evaluated its imaging appearance and correlated its outcomes. MATERIALS AND METHODS We conducted a retrospective review of the rectal MRIs of 97 patients with rectal SRRC, evaluating tumor morphology, T2 signal, length, location, pattern of tumor growth, nodal status and location, EMVI (extramural vascular invasion), site of metastases, and response to chemotherapy. The tumor signal on T2W images was categorized into intermediate, T2 hyperintense, and fluid/mucin bright. Imaging findings were correlated with risk of metastatic/ recurrent disease, disease-free survival, and overall survival. RESULTS The median age of patients of SRRC in our study was 35 years and more frequently found in male patients. The common imaging features of SRRC were T2-hyperintense signal (63%), infiltrative growth pattern (76%), positive MR CRM (Circumferential Resection Margin on MRI) (84%), presence of EMVI (51%), and advanced T and N stage (97% and 84%, respectively). Peritoneum and nodes were the most common sites of metastases. Raised serum CEA (Carcino-embryonic Antigen) levels, positive MR CRM status, extramesorectal adenopathy, and advanced N stage had statistically significant predictive value for recurrence or metastases. Elevated serum CEA levels (p = 0.019) and intermediate T2 signal (p = 0.012) demonstrated significant independent association with poor overall survival, while advanced N stage (p = 0.033) demonstrated significant independent association with worse disease-free survival in multivariate analysis. CONCLUSION SRRC affected young patients and demonstrated T2-hyperintense signal and subepithelial spread in an infiltrative pattern. Elevated CEA levels and T2-intermediate signal intensity are independent predictors for worse overall survival and advanced nodal stage is independent prognostic factor of poor disease-free survival. MRI rectum can pinpoint the pathology given the distinct MRI morphology and age of presentation.
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Affiliation(s)
- Meena Suthar
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
| | - Akshay D Baheti
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India.
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India.
| | - Suman K Ankathi
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
| | - Amit Choudhari
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
| | - Purvi D Haria
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
| | - Reena Engineer
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India
| | - Vikas Ostwal
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of Medical Oncology, Tata Memorial Centre, Mumbai, India
| | - Mukta S Ramadwar
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of Pathology, Tata Memorial Centre, Mumbai, India
| | - Ashwin Desouza
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of GI Surgical Oncology, Tata Memorial Centre, Mumbai, India
| | - Avanish Saklani
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of GI Surgical Oncology, Tata Memorial Centre, Mumbai, India
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7
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Franko J, Le VH, Tee MC, Lin M, Sedinkin J, Raman S, Frankova D. Signet ring cell carcinoma of the gastrointestinal tract: National trends on treatment effects and prognostic outcomes. Cancer Treat Res Commun 2021; 29:100475. [PMID: 34655861 DOI: 10.1016/j.ctarc.2021.100475] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Signet ring cell carcinoma (SRCC) is a distinct malignancy occurring across the tubular gastrointestinal tract (tGIT). We comprehensively examined the outcomes of patients diagnosed with SRCC across tGIT. METHODS SRCC and not-otherwise-specified adenocarcinoma (NOS) patients reported to the National Cancer Database from 2004 to 2015 were included. Baseline characteristics, outcomes and site-specific adjusted hazard ratios (aHR) derived from Cox models of SRCC patients were compared to those of NOS patients. Overall survival (OS) was primary endpoint. RESULTS A total of 41,686 SRCC (4.6%) and 871,373 NOS patients (95.4%) were included. SRCC patients were younger (63.1 ± 14.7 vs. 67.0 ± 13.4 y, p < 0.001) and more likely to present with Stage IV disease than NOS patients (42.5% vs. 24.5%, p < 0.001). Stomach (n = 24,433) and colon (n = 9,914) contributed highest frequency of SRCC. SRCC histology was associated with shorter OS (aHR = 1.377, p < 0.001) in multivariate model. There was an interaction between SRCC and chemotherapy effects on risk of death (interaction aHR = 1.072, pinteraction< 0.001) and between SRCC histology and disease site, suggesting that the effect of SRCC on OS is site-dependent, with a higher increased risk of death in patients with rectal SRCC (aHR = 2.378, pinteraction< 0.001). CONCLUSION Significant negative prognostic effect associated with SRCC is site-dependent across the GIT. Surgical and or systemic therapy was associated with improved OS among SRCC patients, but remained lower than NOS patients. Further understanding of gastrointestinal SRCC molecular profile is needed to better inform future treatment strategies.
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Affiliation(s)
- Jan Franko
- MercyOne Medical Center, Des Moines, IA, USA.
| | - Viet H Le
- MercyOne Medical Center, Des Moines, IA, USA
| | - May C Tee
- MercyOne Medical Center, Des Moines, IA, USA
| | - Mayin Lin
- MercyOne Medical Center, Des Moines, IA, USA
| | | | | | - Daniela Frankova
- MercyOne Medical Center, Des Moines, IA, USA; Des Moines University, Des Moines, IA, USA
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Tajiri K, Sudo T, Ishi K, Kawahara A, Nagasu S, Shimomura S, Yuge K, Katagiri M, Yomoda T, Fujiyoshi K, Kenichi K, Ohchi T, Yoshida T, Mizobe T, Fujita F, Akiba J, Akagi Y. Investigation of clinicopathological characters and gene expression features in colorectal signet-ring cell carcinoma utilizing CMS classification. Mol Clin Oncol 2021; 14:98. [PMID: 33767867 PMCID: PMC7976453 DOI: 10.3892/mco.2021.2260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 02/04/2021] [Indexed: 11/26/2022] Open
Abstract
Signet ring cell carcinoma (SRCC) is a rare pathological type of colorectal cancer, of which the clinicopathological features and genetic background have not yet been fully investigated. Previous research has focused on the optimization of colorectal cancer treatment utilizing consensus molecular subtyping (CMS). However, it is not known what type of CMS would be designated to SRCC treatment. In the current study, of 1,350 patients diagnosed with colorectal cancer who underwent surgery, 14 were diagnosed with SRCC. The case-control cohort that fit the clinical background of the SRCC case was constructed. Statistical comparison between the SRCC group and the case-control cohort was performed among clinicopathological variables. SRCC and well to moderately adenocarcinoma case mRNA were submitted to microarray analysis and CMS analysis. Compared with the case-control cohort, the SRCC group was located more in the right-sided colon, the lymphatic invasion was more severe and the peritoneal dissemination was more frequent. The cancer-specific survival and the progression-free survival were significantly worse in the SRCC group compared with the case-control cohort. Microarray and CMS analysis identified that one SRCC case was significantly well assigned in the CMS 4 group and the other case was assigned in the CMS 1 group. Gene set analysis revealed the upregulation of EMT related genes and the downregulation of fatty acid, glycolysis, differentiation, MYC, HNF4A, DNA repair genes. In conclusion, the clinical characteristics of SRCC are severe but there is a possibility of the presence of different phenotypes according to CMS analysis.
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Affiliation(s)
- Kensuke Tajiri
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan.,Research Center for Innovative Cancer Therapy, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Tomoya Sudo
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan.,Research Center for Innovative Cancer Therapy, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Kazuo Ishi
- Biostatistics Center, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Akihiko Kawahara
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Sachiko Nagasu
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan.,Research Center for Innovative Cancer Therapy, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Susumu Shimomura
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Kotaro Yuge
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Mitsuhiro Katagiri
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan.,Research Center for Innovative Cancer Therapy, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Takato Yomoda
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Kenji Fujiyoshi
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Koshi Kenichi
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Takafumi Ohchi
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Takefumi Yoshida
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Tomoaki Mizobe
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Fumihiko Fujita
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Jun Akiba
- Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | - Yoshito Akagi
- Department of Surgery, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan.,Research Center for Innovative Cancer Therapy, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
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9
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Jiang H, Shao D, Zhao P, Wu Y. The Predictive and Guidance Value of Signet Ring Cell Histology for Stage II/III Colon Cancer Response to Chemotherapy. Front Oncol 2021; 11:631995. [PMID: 33708632 PMCID: PMC7940524 DOI: 10.3389/fonc.2021.631995] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 01/05/2021] [Indexed: 11/22/2022] Open
Abstract
PURPOSE To evaluate the predictive and guidance value of signet-ring cell carcinoma for chemotherapy response in stage II/III colon cancer. METHODS Eligible patients were recruited from the Surveillance, Epidemiology and End Results (SEER) database. The differences between adenocarcinoma (AD) and SRCC groups in the incidence of patients' demographic and clinical characteristics were analyzed by Pearson's chi-squared (×2) test. Survival was analyzed using the Kaplan-Meier method, and the differences were determined by the log-rank test. Some Cox regression models were built to assess hazard ratios (HRs) of different variables with 95% confidence intervals (95% CIs). RESULTS In stage II AD, it was found that the receipt of chemotherapy had significantly 12.6% decreased risk of cancer-specific mortality (HR = 0.874, 95% CI = 0.825-0.927, P < 0.001). In stage II SRCC, however, the receipt of chemotherapy had significantly 70.00% increased risk of cancer-specific mortality (HR = 1.700, 95% CI = 1.032-2.801, P = 0.037). In stage III AD, it was found that the receipt of chemotherapy had significantly 45.3% decreased risk of cancer-specific mortality (HR = 0.547, 95% CI = 0.530-0.564, P < 0.001). In stage III SRCC, the receipt of chemotherapy had significantly 24.6% decreased risk of cancer-specific mortality (HR = 0.754, 95% CI = 0.632-0.900, P = 0.002). CONCLUSIONS The cancer-specific survival (CSS) difference between AD and SRCC was not statistically significant in stage II colon cancer. We provided the first compelling evidence that chemotherapy should not be treated in stage II SRCC, while stage III SRCC should be treated with chemotherapy.
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Affiliation(s)
- Huici Jiang
- Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Shanghai, China
| | - Dongxuan Shao
- Department of Obstetrics and Gynecology, Shanghai Eighth People’s Hospital, Shanghai, China
| | - Peiyu Zhao
- Department of Obstetrics and Gynecology, Suzhou Municipal Hospital, Suzhou, China
| | - Yupeng Wu
- Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Shanghai, China
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10
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Raghavan S, Singh DK, Rohila J, DeSouza A, Engineer R, Ramaswamy A, Ostwal V, Saklani A. Outcomes of Definitive Treatment of Signet Ring Cell Carcinoma of the Rectum: Is Minimal Invasive Surgery Detrimental in Signet Ring Rectal Cancers? Indian J Surg Oncol 2020; 11:597-603. [PMID: 33299278 PMCID: PMC7714872 DOI: 10.1007/s13193-020-01142-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 06/17/2020] [Indexed: 01/18/2023] Open
Abstract
The outcome of surgery for signet ring adenocarcinoma of rectum is suboptimal with high predilection for locoregional and peritoneal metastases. Lack of intercellular adhesion due to focal loss of epithelial cell adhesion molecule (EpCAM) may account for this. In such patients, whether minimal invasive surgery carries a high risk of dissemination by pneumoperitoneum and tumor implantation remains uncertain. The aim of this study was to compare the outcomes of patients undergoing minimally invasive surgery (MIS) versus open surgery in patients with signet ring cell adenocarcinoma of rectum. A retrospective study was conducted at a tertiary care center over 3 years on 39 patients undergoing open surgery and 40 patients undergoing MIS diagnosed with signet ring cell carcinoma (SRCC) identified from our surgical database. Patient characteristics in terms of demographics, clinicoradiological staging, neoadjuvant therapy, and type of surgery with morbidity were compared in the two groups. Data on patients undergoing adjuvant therapy and 3 years disease-free survival (DFS) and overall survival (OS) were analyzed. Recurrence patterns in both groups were separately identified as locoregional, peritoneal, or systemic. The number of patients undergoing surgery in the two arms was 40 (MIS) and 39 (open). In the MIS arm, mean DFS was 29 months whereas in the open arm, it was 25.8 months. The mean OS was 33.65 months for the MIS arm and that for the open arm was 36.34 months. This retrospective study reveals no significant difference in outcomes of surgery for signet ring cell rectal cancers with either MIS or open approach.
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Affiliation(s)
- S. Raghavan
- Colorectal Disease Management Group, Department Of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Deepak Kumar Singh
- Colorectal Disease Management Group, Department Of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - J. Rohila
- Colorectal Disease Management Group, Department Of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - A. DeSouza
- Colorectal Disease Management Group, Department Of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - R. Engineer
- Colorectal Disease Management Group, Department Of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - A. Ramaswamy
- Colorectal Disease Management Group, Department Of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - V. Ostwal
- Colorectal Disease Management Group, Department Of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - A. Saklani
- Colorectal Disease Management Group, Department Of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
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11
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Undiagnosed Case of Signet Ring Cell Colorectal Carcinoma: A Case Report and Review of the Literature. Clin Colorectal Cancer 2020; 19:e83-e86. [PMID: 32586730 DOI: 10.1016/j.clcc.2020.04.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 04/13/2020] [Accepted: 04/23/2020] [Indexed: 11/20/2022]
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12
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Rare Signet Ring Cell Adenocarcinoma of the Colon Metastasis to the Orbit. Case Rep Ophthalmol Med 2020; 2020:2940579. [PMID: 32158576 PMCID: PMC7061104 DOI: 10.1155/2020/2940579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Revised: 01/03/2020] [Accepted: 02/08/2020] [Indexed: 12/03/2022] Open
Abstract
Metastases arising from primary tumors of the gastrointestinal tract are not commonly encountered in the orbit. Colorectal carcinomas are subcategorized based on morphological and genetic characteristics with these distinctions bearing therapeutic and prognostic significance. The behavior of these subcategories, including their propensity for orbital metastasis, differs, and clinicians treating these tumors must be aware of their metastatic profiles. This report describes a 51-year-old female with right upper lid swelling and ptosis ultimately found, what we believe to be, the first reported case of signet ring cell colon carcinoma metastasizing to the levator muscle and superior orbit. This case serves as a reminder to all clinicians to consider orbital metastasis even in malignancies not typically found in this location.
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13
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Signet ring cell colorectal cancer: genomic insights into a rare subpopulation of colorectal adenocarcinoma. Br J Cancer 2019; 121:505-510. [PMID: 31406299 PMCID: PMC6738104 DOI: 10.1038/s41416-019-0548-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 07/16/2019] [Accepted: 07/24/2019] [Indexed: 12/14/2022] Open
Abstract
Background Signet ring cell carcinoma (SRCC) is a rare subtype of colorectal cancer (CRC). The aim of this study was to characterise the genomic alterations and outcomes of SRCC. Methods Medical records of metastatic CRC (mCRC) patients whose tumours were evaluated by NGS analysis were reviewed. SC-mCRC were classified into two groups: SRCC (>50% signet ring cells) and adenocarcinoma (AC) with SC component (≤50% signet ring cells). Results Six hundred and sixty-five mCRC patients were included. Of the 93 mCRC cases with SC features, 63 had slides for review. Of those 63 cases, 35 were confirmed SRCC, and 28 were AC with SC component. Compared with AC group, KRAS and PIK3CA mutations (mts) were found in only 11% (OR: 0.13) and 3% (OR: 0.15) of SRCC cases, respectively. In contrast to the 44% rate of APC mts in AC group, only 3% of SRCC patients had APC mts (OR = 0.04). Conclusions SRCC has distinct molecular features, including low rates of KRAS, PIK3CA and APC mts. Further study to identify activation pathways and potential therapeutic targets are needed.
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14
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Kim H, Kim BH, Lee D, Shin E. Genomic alterations in signet ring and mucinous patterned colorectal carcinoma. Pathol Res Pract 2019; 215:152566. [PMID: 31400926 DOI: 10.1016/j.prp.2019.152566] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 07/10/2019] [Accepted: 07/26/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The genetic alterations (GAs) in two specific histological subtypes of colorectal cancer (CRC), signet ring cell colorectal carcinoma (SRC) and mucinous colorectal carcinoma (MC), are not well known. In the present study, we employed next-generation sequencing to perform genetic profiling of SRC and MC, and compared the spectrum of GAs with the alterations found in conventional type colorectal cancer (CON). MATERIALS AND METHODS We selected 46 CRCs comprising 17 SRCs and mucinous carcinoma with signet ring cell component (SRCCs), 17 MCs, and 12 CONs with microsatellite stability or microsatellite instability-low. Deep sequencing was performed using a targeted cancer panel composed of 171 cancer-related genes. SMAD4 protein expression was evaluated by immunohistochemical staining. RESULTS We detected 108 mutations in 18 different genes. Overall, 2.34 GAs were detected per tumor (range, 0-14). The overall frequency of GA and alteration in targetable genes was less prevalent in SRC/SRCC compared to the frequency of alteration in MC/CON (p = 0.040 and p < 0.001, respectively). The GA profile of SRC/SRCC included TP53 (8/17, 47.1%), SMAD4 (5/17, 29.4%), KRAS (4/17.23.5%), APC (4/17.23.5%), PIK3CA, ATM, BRAF, and PIK3R1 (1/17, 5.9%, each). KRAS mutation was significantly less prevalent in SRC/SRCC compared to the number of KRAS mutations in MC (12/17, 70.6%) and CON (9/12, 75.0%) (p = 0.015 and 0.01, respectively). Compared to the 152 non-hypermutated CONs from TCGA database, SMAD4 alteration was predominant in SRC/SRCC (p = 0.045) with aberrant loss of SMAD4 expression (13/17, 76.5%) compared to the SMAD4 alterations in CON (5/15, 33.3%) (p = 0.031). Accordingly, KRAS (12/17, 70.6%), APC (6/17, 35.3%), SMAD4, TP53 (4/17, 23.5%, each), PIK3CA (3/17, 17.6%), AKT1, ATM, BRAF, EGFR, and EZH2 (1/17, 5.9%, each) were altered in MC. APC and TP53 mutations were less frequent in MC compared to those in TCGA-CON (p < 0.001 and 0.003, respectively) whereas KRAS mutation was prevalent (p = 0.041). CONCLUSION Alterations of known cancer associated genes and targetable genes in SRC/SRCC are infrequent. The profile of GAs in SRC/SRCC and MC differs from the GA profile of CON. Specifically, SMAD4 mutation and loss of SMAD4 expression is frequently found in SRC/SRCC. The genetic profiles revealed in the present study may aid in developing precision medicine for CRC treatment based on histological subtype.
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Affiliation(s)
- Hyunchul Kim
- Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Gyeonggi, South Korea
| | - Bo-Hyung Kim
- Department of Clinical Pharmacology and Therapeutics, Kyung Hee University College of Medicine and Hospital, Seoul, South Korea
| | - Donghwan Lee
- Department of Statistics, Ewha Womans University, Seoul, South Korea
| | - Eun Shin
- Department of Pathology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Gyeonggi, South Korea; Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, South Korea.
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15
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Morales-Cruz M, Salgado-Nesme N, Trolle-Silva AM, Rodríguez-Quintero JH. Signet ring cell carcinoma of the rectum: atypical metastatic presentation. BMJ Case Rep 2019; 12:12/4/e229135. [PMID: 31040144 DOI: 10.1136/bcr-2018-229135] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Colorectal cancer is the third most common cancer in the world and the fourth most common cause of death related to cancer. Signet ring cell carcinoma represents an uncommon histological type for rectal cancer with less than 1% of all rectal neoplasms. It usually behaves aggressively and has an inferior prognosis. We present the case of a young man diagnosed with signet ring cell rectal carcinoma. He underwent neoadjuvant therapy with partial response, had surgery with curative intent and showed local recurrence after only 3 months. Disease progression happened only weeks after recurrence with metastasis to vertebrae, extraocular muscles, bone marrow and skin. He is currently receiving palliative chemotherapy.
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Affiliation(s)
- Mariana Morales-Cruz
- Department of Colorectal Surgery, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico
| | - Noel Salgado-Nesme
- Department of Colorectal Surgery, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico
| | - Alicia Maybi Trolle-Silva
- Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Tlalpan, Mexico City, Mexico
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16
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Primary Signet Ring Cell Carcinoma of Rectum Diagnosed by Boring Biopsy in Combination with Endoscopic Mucosal Resection. Case Rep Med 2018; 2018:5860815. [PMID: 29560010 PMCID: PMC5818929 DOI: 10.1155/2018/5860815] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Revised: 11/16/2017] [Accepted: 11/26/2017] [Indexed: 12/13/2022] Open
Abstract
A 46-year-old man with severe back pain visited our hospital. Magnetic resonance imaging revealed extensive bone metastasis and rectal wall thickness. Colonoscopy revealed circumferential stenosis with edematous mucosa, suggesting colon cancer. However, histological findings of biopsy specimens revealed inflammatory cells but no malignant cells. The patient underwent endoscopic ultrasound, which demonstrated edematous wall thickness without destruction of the normal layer structure. After unsuccessful detection of neoplastic cells by boring biopsies, we performed endoscopic mucosal resection followed by boring biopsies that finally revealed signet ring cell carcinoma. Herein, we present a case and provide a review of the literature.
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17
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Yun SO, Cho YB, Lee WY, Kim HC, Yun SH, Park YA, Huh JW. Clinical Significance of Signet-Ring-Cell Colorectal Cancer as a Prognostic Factor. Ann Coloproctol 2017; 33:232-238. [PMID: 29354606 PMCID: PMC5768478 DOI: 10.3393/ac.2017.33.6.232] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 09/29/2017] [Indexed: 12/22/2022] Open
Abstract
Purpose The aim of this study is to evaluate the prognosis for patients with a signet-ring-cell carcinoma (SRCC) who undergo curative surgery by comparing them to patients with an adenocarcinoma (ADC), excluding a mucinous ADC. Methods Between September 1994 and December 2013, 14,110 patients with colorectal cancer underwent surgery and among them, 12,631 patients were enrolled in this study. 71 patients with a SRCC and 12,570 patients with a ADC were identified. We analyzed the disease-free survival and the overall survival rates before and after a 1:2 propensity score matching and evaluated those rates after stage stratification. Results The median follow-up durations were 48.5 months for the SRC group and 48.6 months for the ADC group. The disease-free survival rates and the overall survival rates were significantly lower in the SRC group before and after propensity score matching (P < 0.001). After stratification by stage, no differences were observed between the SRC and the ADC groups for the disease-free survival (DFS) and the overall survival (OS) rates for patients with cancer in its early stages (P = 0.913 and P = 0.380 for the DFS and the OS, respectively, in stages 0 and I, and P = 0.223 and P = 0.991 for the DFS and the OS, respectively, in stage II), but those rates were significantly lower in the SRC group for cancer in its later stages (P < 0.001, respectively in stages III and IV). Conclusion For cancer in advanced stages, patients with a resectable colorectal SRCC had a poorer prognosis after propensity score matching than those with an ADC did. Therefore, more intensive surveillance and closer observation should be offered to such patients.
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Affiliation(s)
- Sang-Oh Yun
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong Beom Cho
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Woo Yong Lee
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hee Cheol Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seong Hyeon Yun
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Ah Park
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jung Wook Huh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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18
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Alvi MA, Loughrey MB, Dunne P, McQuaid S, Turkington R, Fuchs MA, McGready C, Bingham V, Pang B, Moore W, Maxwell P, Lawler M, James JA, Murray GI, Wilson RH, Salto-Tellez M. Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies. Br J Cancer 2017; 117:203-209. [PMID: 28595259 PMCID: PMC5520517 DOI: 10.1038/bjc.2017.168] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Revised: 05/06/2017] [Accepted: 05/15/2017] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Signet ring cell colorectal cancer (SRCCa) has a bleak prognosis. Employing molecular pathology techniques we investigated the potential of precision medicine in this disease. METHODS Using test (n=26) and validation (n=18) cohorts, analysis of mutations, DNA methylation and transcriptome was carried out. Microsatellite instability (MSI) status was established and immunohistochemistry (IHC) was used to test for adaptive immunity (CD3) and the immune checkpoint PDL1. RESULTS DNA methylation data split the cohorts into hypermethylated (n=18, 41%) and hypomethylated groups (n=26, 59%). The hypermethylated group predominant in the proximal colon was enriched for CpG island methylator phenotype (CIMP), BRAF V600E mutation and MSI (P<0.001). These cases also had a high CD3+ immune infiltrate (P<0.001) and expressed PDL1 (P=0.03 in intra-tumoural lymphoid cells). The hypomethylated group predominant in the distal colon did not show any characteristic molecular features. We also detected a common targetable KIT mutation (c.1621A>C) across both groups. No statistically significant difference in outcome was observed between the two groups. CONCLUSIONS Our data show that SRCCa phenotype comprises two distinct genotypes. The MSI+/CIMP+/BRAF V600E+/CD3+/PDL1+ hypermethylated genotype is an ideal candidate for immune checkpoint inhibitor therapy. In addition, one fourth of SRCCa cases can potentially be targeted by KIT inhibitors.
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Affiliation(s)
- Muhammad A Alvi
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
| | - Maurice B Loughrey
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
- Department of Histopathology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK
| | - Philip Dunne
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
| | - Stephen McQuaid
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
| | - Richard Turkington
- Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK
| | - Marc-Aurel Fuchs
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
| | - Claire McGready
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
| | - Victoria Bingham
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
| | - Brendan Pang
- Department of Pathology, National University Hospital, National University Health System, Singapore, Singapore
| | - Wendy Moore
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
| | - Perry Maxwell
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
| | - Mark Lawler
- Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK
| | - Jacqueline A James
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
| | - Graeme I Murray
- Department of Pathology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK
| | - Richard H Wilson
- Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast, UK
| | - Manuel Salto-Tellez
- Northern Ireland Molecular Pathology Laboratory, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7AE, UK
- Department of Histopathology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK
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19
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Liang Z, Yan D, Li G, Cheng H. Clinical Analysis of Primary Colorectal Signet-Ring Cell Carcinoma. Clin Colorectal Cancer 2017; 17:e39-e44. [PMID: 28789931 DOI: 10.1016/j.clcc.2017.06.010] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Revised: 04/18/2017] [Accepted: 06/29/2017] [Indexed: 11/28/2022]
Abstract
The objective of the study was to investigate the clinicopathological features of primary colorectal signet-ring cell carcinoma. We retrospectively analyzed the clinical and survival data of 37 patients with primary colorectal signet-ring cell carcinoma. The mean survival time of patients in stage II, III, and IV were estimated using Student t test and the cumulative survival rates were estimated according to the method of Kaplan-Meier. The significance of the differences in survival rates were calculated using the log rank test. The incidence of primary colorectal signet-ring cell carcinoma was 1.40%, the median age of 37 patients was 50 years, the male to female ratio was 1.47:1, and 21 patients (56.8%) received a radical resection. Most patients 33 (89.2%) had an advanced tumor stage at the time of diagnosis (17 patients 45.9% stage III and 16 patients 43.2% stage IV), 34 (94.5%) patients showed a tumor depth of >T3, lymph node involvement occurred in 26 patients (70.3%), patients had a high incidence of peritoneal metastasis (16 patients 43.2% at presentation, 30 patients 81.1% at presentation and recurrence) and a low incidence of liver metastases (1 patients 2.7% at presentation, 5 patients 13.5% at presentation and recurrence). The 5-year survival rate after the initial surgery was 10.8%, the mean survival time of 37 patients was 27.1 ± 3.3 months, the mean survival time of patients in stage II, III, and IV were 47.0 ± 12.8 months, 37.1 ± 3.9 months, and 10.5 ± 1.4 months, respectively (P < .000). Colorectal signet-ring cell carcinoma is a rare neoplasm with a predominance in men. Its characteristic features were the advanced stage at the time of diagnosis, a high incidence of peritoneal metastases, a low incidence of liver metastasis, and a poor prognosis.
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Affiliation(s)
- ZhengZi Liang
- Division of Colorectal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - DengGuo Yan
- Division of Colorectal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
| | - GuoSheng Li
- Division of Colorectal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
| | - HaiYu Cheng
- Division of Colorectal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
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20
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Li H, Huang K, Wang H, Wang L, Yang M, Wang L, Lin R, Liu H, Gao J, Shuai X, Liu X, Tao K, Wang G, Wang Z. Immature enteric ganglion cells were observed in a 13-year-old colon signet ring cell carcinoma patient: A case report and literature review. Medicine (Baltimore) 2017; 96:e7036. [PMID: 28640080 PMCID: PMC5484188 DOI: 10.1097/md.0000000000007036] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
RATIONALE All the enteric ganglion cells are fully mature by 2 to 5 years of age in human. No one had reported the presentation of immature enteric ganglion cells in elder ones. Colorectal carcinoma is also rare in the adolescent population. The coincidence of these 2 rare events in a 13-year-old boy has never been reported elsewhere, which may suggest some linkage between them. PATIENT CONCERN A 13-year-old boy presented with progressive abdominal pain and melena for 3 months. Computed tomography (CT) scan and endoscopic ultrasonography showed significant abnormality in the transverse colon characteristic of marked mural thickening. The biopsy results indicated signet ring cell carcinoma. DIAGNOSES A 13-year-old male patient with advanced colon signet ring cell carcinoma. In addition, immature but not mature ganglion cells could be observed in almost all of the slices of the resected nontumorous area of the specimen. INTERVENTIONS The transverse colon tumor was resected and the subsequent histopathological examination confirmed the diagnosis of primary colon signet ring cell carcinoma. Then the patient received adjuvant chemotherapy and biological target therapies subsequently. OUTCOMES After 6 cycles of adjuvant chemotherapy and biological target therapies, metastasis was however detected within a year. LESSONS In this case, a 13-year-old male patient with advanced colon signet ring cell carcinoma were presented. Unexpectedly, immature ganglion cells could be observed in almost all of the slices of the resected nontumorous area of the specimen. It is critical to raise medical awareness and improve the diagnosis and treatment of the signet ring cell carcinoma. This malignancy and the immature ganglion cells may be associated, possibly caused by some unidentified genetic defects. Genome sequencing, histopathological examination, and long-term follow-up of young patients with related diseases, would help further reveal the potential relationship between tumorigenesis and ganglion cells' immaturity, contributing to understanding the molecular mechanisms.
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Affiliation(s)
- Huili Li
- Department of Gastrointestinal Surgery
| | - Kun Huang
- Institution of Cardiology, Union Hospital
| | - Hui Wang
- Department of Medical Genetics, School of Basic Medicine and the Collaborative Innovation Center for Brain Science
| | - Lin Wang
- Center for Tissue Engineering and Regenerative Medicine
- Department of Clinical Laboratory
| | | | | | | | - Hongli Liu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jinbo Gao
- Department of Gastrointestinal Surgery
| | | | | | | | | | - Zheng Wang
- Department of Gastrointestinal Surgery
- Center for Tissue Engineering and Regenerative Medicine
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21
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Ling CR, Wang R, Wang MJ, Ping J, Zhuang W. Prognosis and value of preoperative radiotherapy in locally advanced rectal signet-ring cell carcinoma. Sci Rep 2017; 7:45334. [PMID: 28345614 PMCID: PMC5366911 DOI: 10.1038/srep45334] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Accepted: 02/21/2017] [Indexed: 02/06/2023] Open
Abstract
As well known, signet-ring cell carcinoma (SRCC) is a rare histological subtype of colorectal adenocarcinoma, which has been associated with poor prognosis and resistant to non-surgery therapy compared with common adenocarcinoma. In this study, we assessed the effect of preoperative radiotherapy (PRT) for locally advanced rectal SRCC in a large patient group from the Surveillance, Epidemiology, and End Results program (SEER, 1988–2011) database. SRCC was found in 0.9% (n = 622) rectal cancer (RC) patients in our study. In the PRT setting, SRCC had significantly worse cancer-specific survival than mucinous adenocarcinoma and nonmucinous adenocarcinoma patients (log-rank, P < 0.001). In terms of SRCC, stage III RC patients benefited from PRT (log-rank, P < 0.001) while stage II did not (P = 0.095). The multivariate Cox proportional hazard model showed that PRT was an independent benefit factor in stage III rectal SRCC patients (HR, 0.611; 95% CI, 0.407–0.919; P = 0.018). In conclusion, SRCC was an independent predictor of poor prognosis in stage III RC patients, but not in stage II. In the PRT setting of locally advanced RC, SRCC patients had significantly worse prognosis. PRT was an independent prognostic factor associated with improved survival in stage III rectal SRCC.
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Affiliation(s)
- Chun-Run Ling
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Rui Wang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Mo-Jin Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jie Ping
- Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
| | - Wen Zhuang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
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Kermanshahi TR, Magge D, Choudry H, Ramalingam L, Zhu B, Pingpank J, Ahrendt S, Holtzman M, Zeh H, Bartlett D, Zureikat A, Pai RK. Mucinous and Signet Ring Cell Differentiation Affect Patterns of Metastasis in Colorectal Carcinoma and Influence Survival. Int J Surg Pathol 2016; 25:108-117. [DOI: 10.1177/1066896916664990] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Peritoneal metastasis in colorectal carcinoma is associated with a dismal prognosis; however, features that correlate with patterns of metastatic spread are not well characterized. We analyzed the clinicopathologic and molecular features of 166 patients with colorectal carcinomas stratified by metastases to the peritoneum or liver. Mucinous and signet ring cell differentiation were more frequently observed in colorectal carcinoma with peritoneal dissemination compared to colorectal carcinoma with liver metastasis (mucinous differentiation: 62% vs 23%, P < .001; signet ring cell differentiation: 21% vs 0%, P < .0001). The significant association of mucinous differentiation with peritoneal dissemination compared with liver metastasis was identified in patients with both synchronous and metachronous development of metastasis ( P < .01). In contrast, colorectal carcinomas with liver metastasis were more frequently low-grade (90% vs 72%, P = .005) and associated with dirty necrosis (81% vs 56%, P = .001) compared with colorectal carcinomas with peritoneal dissemination. No significant differences were identified between colorectal carcinoma with peritoneal metastasis versus liver metastasis with respect to KRAS mutations, BRAF mutation, or high levels of microsatellite instability. Patients with tumors involving the peritoneum had a significantly worse overall survival in comparison to patients with liver metastasis lacking peritoneal involvement ( P = .02). When including only those patients with peritoneal metastasis, the presence of any mucinous or signet ring cell differentiation was associated with a significantly worse overall survival ( P = .006). Our findings indicate that mucinous and signet ring cell differentiation may be histologic features that are associated with an increased risk of peritoneal dissemination and poor overall survival in patients with peritoneal metastasis.
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Affiliation(s)
| | - Deepa Magge
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Haroon Choudry
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | | | - Benjamin Zhu
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - James Pingpank
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Steven Ahrendt
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | | | - Herbert Zeh
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David Bartlett
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Amer Zureikat
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Reetesh K. Pai
- University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Wang R, Ma X, Li Y, He Y, Huang D, Cai S, Peng J. The Characteristics and Prognostic Effect of E-Cadherin Expression in Colorectal Signet Ring Cell Carcinoma. PLoS One 2016; 11:e0160527. [PMID: 27509205 PMCID: PMC4980044 DOI: 10.1371/journal.pone.0160527] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 07/19/2016] [Indexed: 12/20/2022] Open
Abstract
Purpose Signet ring cell carcinoma (SRCC) is rare. The aim of this study is to understand the clinicopathological features and identify the possible prognostic factors in colorectal SRCC. Methods Patients with SRCC who underwent primary lesion resection at Fudan University Shanghai Cancer Center from September 2008 to July 2014 were retrospectively analyzed. Patient’s gender, age, tumor location, depth of invasion, lymph node metastasis, synchronous distant metastasis, perineural invasion, lymphovascular invasion, and E-cadherin expression were studied with prognosis, and the correlation between E-cadherin expression and clinicopathological features were analyzed. All clinicopathological and molecular factors were put into multivariate analysis using Cox proportional hazards model for detecting independent prognostic factors. Results 59 patients accounting for 0.89% of total colorectal cancer patients met the criteria and were enrolled in the study. The median survival time is 28.9 months, and the 3-year survival rate is 62.7%. SRCC were seen more common in young male patients. Advanced stage was more common in SRCC, 58 (98.3%) patients had T3/T4 lesions, 52 (88.1%) patients had lymph node metastasis, and 14 (23.7%) patients had distant metastasis. Distant metastases were seen more common in peritoneal cavity. Distant metastasis (HR = 4.194, 95% CI: 1.297–13.567), lymphovascular invasion (HR = 2.888, 95% CI: 1.115–7.483), and E-cadherin expression (HR = 0.272, 95% CI: 0.096–0.768) were independent predictors for survival. Conclusions SRCC is a rare subtype of colorectal cancer with poor prognosis. Distant metastasis, lymphovascular invasion, and E-cadherin expression can predict prognosis of colorectal SRCCs independently. More precise therapy and more close surveillance are needed for these patients.
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Affiliation(s)
- Renjie Wang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, P. R. China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Xiaoji Ma
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, P. R. China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Yaqi Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, P. R. China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Yiping He
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
- Department of Endoscopy, Fudan University Shanghai Cancer Center, Shanghai, P. R. China
| | - Dan Huang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, P. R. China
| | - Sanjun Cai
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, P. R. China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
| | - Junjie Peng
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, P. R. China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P. R. China
- * E-mail:
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Kuczma P, Vidal Fortuny J, Essia S, de Lassus A, Morel P, Ris F. Odd localisation for a gastric cancer histology. Int J Surg Case Rep 2016; 27:51-54. [PMID: 27543724 PMCID: PMC4992006 DOI: 10.1016/j.ijscr.2016.07.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2016] [Revised: 07/20/2016] [Accepted: 07/23/2016] [Indexed: 12/11/2022] Open
Abstract
More than 96% of signet-ring cell carcinomas occur in the stomach. Primary SRC carcinoma of the colon and rectum is very rare. It spreads mainly to the lymph nodes and to the peritoneum and rarely to the liver. It presents at advanced stages and has a dismal prognosis. Upper endoscopy is the investigation of choice to exclude a primary gastric cancer. Introduction More than 96% of signet-ring cell carcinomas occur in the stomach and the rest in other organs, including the gallbladder, pancreas, urinary bladder and breast. Primary signet-ring cell carcinoma of the colon and rectum is very rare, accounting for 0.1%–2.4% of all colorectal cancers. Presentation of case We report a case of a 55-year old man who is operated for a caecal mass evocative of an appendicitis abscess. Intraoperatively, we discover a large, ulcerated ilio-caecal mass with several lymphadenopathies. The further workup reveals a primary signet-ring cell carcinoma of the colon with multiple lymph nodes and osteolytic bony metastases. Discussion Primary signet-ring cell carcinoma of the colon and rectum presents usually as an advanced stage disease with a dismal prognosis. It spreads mainly to the lymph nodes and to the peritoneum and very rarely to the liver. The mean age of patients diagnosed with primary signet-ring cell carcinoma is significantly younger than for ordinary adenocarcinoma. The upper endoscopy is the investigation of choice to exclude a primary gastric pathology. There are very few reports about this type of cancer and no reports about this type of cancer associated with osteolytic bony metastases. Conclusion The characteristics and pathophysiology of a primary signet-ring cell carcinoma of the colon and rectum are not well understood. Usually only palliative treatment is possible. The importance of an early diagnosis of this tumor is mandatory to have a curative approach.
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Affiliation(s)
- Paulina Kuczma
- Department of Visceral Surgery, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
| | - Jordi Vidal Fortuny
- Department of Visceral Surgery, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
| | - Saiji Essia
- Department of Pathology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
| | - Ariane de Lassus
- Department of Pathology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
| | - Philippe Morel
- Department of Visceral Surgery, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
| | - Frédéric Ris
- Department of Visceral Surgery, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland.
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Wei Q, Wang X, Gao J, Li J, Li J, Qi C, Li Y, Li Z, Shen L. Clinicopathologic and Molecular Features of Colorectal Adenocarcinoma with Signet-Ring Cell Component. PLoS One 2016; 11:e0156659. [PMID: 27300552 PMCID: PMC4907485 DOI: 10.1371/journal.pone.0156659] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Accepted: 05/17/2016] [Indexed: 12/12/2022] Open
Abstract
Background We performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component. Methods Between November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing. Results A slight male predominance was detected in these patients (59.0%). Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54) cases with KRAS mutations in 16.7% (9/54) cases and Nras mutations in 5.4%(3/54) cases. BRAF V600E mutation was detected in 3.7% (2/54) cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9%) cases were composed of ≥50% signet-ring cells; 22 (36.1%) cases were composed of <50% signet-ring cells. We compared clinical parameters, molecular and genetic alterations between the two groups and found no significant differences. Conclusions Colorectal adenocarcinoma with signet-ring cell component is characterized by advanced stage at diagnosis with remarkable family history of malignant tumor. It is likely a negative prognostic factor and tends to affect male patients with low rates of RAS /BRAF mutation. Colorectal patients with any component of signet-ring cells, regardless of the extent, shared similar clinicopathological characteristics, molecular alterations and genetic profiles.
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Affiliation(s)
- Qing Wei
- Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Xicheng Wang
- Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jing Gao
- Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jian Li
- Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Jie Li
- Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Changsong Qi
- Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Yanyan Li
- Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhongwu Li
- Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
- * E-mail: (LS); (ZL)
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
- * E-mail: (LS); (ZL)
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Bellan A, Cappellesso R, Lo Mele M, Peraro L, Balsamo L, Lanza C, Fassan M, Rugge M. Early signet ring cell carcinoma arising from colonic adenoma: the molecular profiling supports the adenoma-carcinoma sequence. Hum Pathol 2016; 50:183-6. [PMID: 26997454 DOI: 10.1016/j.humpath.2015.12.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 10/21/2015] [Accepted: 12/01/2015] [Indexed: 01/20/2023]
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27
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Outcomes of surgical treatment of primary signet ring cell carcinoma of the colon and rectum: 22 cases reviewed with literature. Int Surg 2016; 99:691-8. [PMID: 25437572 DOI: 10.9738/intsurg-d-14-00067.1] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Colorectal primary signet ring cell carcinoma (PSRCCR) is a rare entity with a dismal prognosis, mainly because of delayed diagnosis. The objective of this study was to investigate the clinicopathologic features and prognostic factors for PSRCCR. This is a retrospective study including the data of 22 patients with PSRCCR who underwent surgery. Patients were categorized by age, sex, tumor site, and stage. Fifteen patients were male. Median age was 40 years. Sites for metastases were lymph nodes (86.4%), peritoneum (40.9%), and liver (9.1%). Most of the patients (91%) had stage III or IV tumors. The rates of curative and palliative resections performed were equal. Mean overall survival and mean progression-free survival times were found to be 33.3 ± 7.1 months (95% confidence interval, 19.4-47.2 months) and 11.8 ± 3.5 months (95% confidence interval, 4.9-18.7 months), respectively. It was concluded that site of the tumor, presence of bowel obstruction, peritoneum and lung metastases, adjacent organ infiltration, TNM stage, and efficiency of surgery have significant effects on survival. All in all, these aggressive tumors are generally diagnosed at advanced stages. Depending on the situation, survival is shorter. A high degree of vigilance is required for these patients to avoid the negative impact of late diagnosis on survival.
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28
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Ohnita K, Isomoto H, Akashi T, Hashiguchi K, Matsushima K, Minami H, Akazawa Y, Yamaguchi N, Takeshima F, To K, Takeshita H, Yasui H, Abe K, Nakao K. Early stage signet ring cell carcinoma of the colon examined by magnifying endoscopy with narrow-band imaging: a case report. BMC Gastroenterol 2015. [PMID: 26205810 PMCID: PMC4512161 DOI: 10.1186/s12876-015-0317-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Background Signet ring cell carcinoma of the colon and rectum is rare, and most cases are detected at an advanced stage. We present a case of primary signet ring cell carcinoma detected at an early stage by magnifying endoscopy with narrow-band imaging (NBI) and crystal violet staining. Case presentation A 73-year-old man visited our hospital for screening colonoscopy. Six years previously, he had undergone endoscopic submucosal dissection (ESD) for early gastric cancer. The pathological diagnosis was a well-differentiated adenocarcinoma, invading into the mucosa without lymphovascular invasion. Colonoscopy revealed a flat elevated lesion with a slightly depressed area, 20 mm in diameter, in the cecum. Further, magnifying endoscopy with NBI revealed that the surface pattern was slightly irregular and microvessels had a regular diameter and distribution in the margin of the lesion, but in the central part of the lesion, irregularity in the tumor surface pattern and form as well as in the diameter and distribution of microvessels was noted. Additionally, due to mucus, avascular areas were also observed. Magnifying endoscopy combined with 0.05 % crystal violet staining showed IIIL and VI pit patterns in the margin of the lesion, and a VI pit pattern in the central part of the lesion; however, due to mucus exudate, this finding could not be established with certainty. The lesion was successfully removed en bloc using ESD without complications. The tumor was composed mainly of signet ring cell carcinoma, partially mixed with moderately differentiated (tub2) and well-differentiated (tub1) adenocarcinomas. The tumor cells infiltrated 250 μm into the submucosal layer and involved lymphatic vessels. Therefore, the patient underwent an additional laparoscopic ileocecal resection, and the resected specimen revealed no residual carcinoma or lymph node metastasis. Conclusion In this case report, we present a case of primary signet ring cell carcinoma detected at an early stage and identified by magnifying endoscopy with NBI and crystal violet staining.
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Affiliation(s)
- Ken Ohnita
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Hajime Isomoto
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Taro Akashi
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Keiichi Hashiguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Kayoko Matsushima
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Hitomi Minami
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Yuko Akazawa
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Naoyuki Yamaguchi
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Fuminao Takeshima
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Kazuo To
- First Department of Surgery, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Hiroaki Takeshita
- First Department of Surgery, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Haruna Yasui
- Department of Pathology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Kuniko Abe
- Department of Pathology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, Japan.
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Yadav J, Yadav SK, Gaurav K, Ahmed A, Reddy KA, Prakash O. Primary signet ring cell carcinoma of rectum: a rare entity with unusual presentation. Int J Colorectal Dis 2015; 30:709-710. [PMID: 25319935 DOI: 10.1007/s00384-014-2034-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/09/2014] [Indexed: 02/04/2023]
Affiliation(s)
- Jitin Yadav
- Department of General Surgery, Rajendra Institute of Medical Sciences, Hostel No. 03, Room No. 50, Rims, Ranchi, Jharkhand, 834009, India
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Engineer R, Basu T, Chopra S, Arya S, Patil P, Mehta S, Ramadwar M, Deodhar K, Shrivastava SK. Factors influencing response to neoadjuvant chemoradiation and outcomes in rectal cancer patients: tertiary Indian cancer hospital experience. J Gastrointest Oncol 2015; 6:155-64. [PMID: 25830035 DOI: 10.3978/j.issn.2078-6891.2014.111] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Accepted: 11/30/2014] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND In the treatment of rectal cancers several randomized trials have demonstrated benefits of neoadjuvant chemoradiotherapy (NACRT) in downstaging as well as survival among these patients. We investigated the patient and tumor related variables dictating the outcomes in these patients. METHODS Biopsy proven treatment naive 182 rectal cancer patients underwent NACRT from June 2006 to December 2010. The entire patients received long course conventionally fractionated external beam radiotherapy with concurrent oral Capecitabine. At 6 weeks from completion of NACRT clinico-radiological assessment was carried out for surgical feasibility. All patients were given postoperative adjuvant chemotherapy either single agent or multi drug regimen depending upon biopsy report. RESULTS Among 182 patients, 131 (72%) underwent surgery and initial T stage and signet ring cell morphology were major determinant of operability. Among the 131 operated patients at median follow up of 36 months, 94 (72%) are alive and disease free. With a median follow up of 42 months the 5-year disease free survival (DFS) and overall survival (OS) was 60% and 77%. The majority of the failures were distal but with more advanced disease at presentation both local and distal failures were similar. While assessing survival by multivariate analysis patients having positive nodes post-surgery had a significantly poorer DFS (P=0.001), while signet ring cell morphology and pre-treatment carcino-embryonic antigen (CEA) levels strongly influenced OS (P=0.03). CONCLUSIONS The outcome of our patients were similar to World Literature and signet ring cell morphology, pre-treatment CEA level, and pathological nodal staging all were influential in determining survival. Besides this, the study also highlights the fact that tumours with signet ring cell morphology appearing in younger population with poor survival needs prospective evaluation for more intense CRT regimen and aggressive surgical resections.
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Affiliation(s)
- Reena Engineer
- 1 Department of Radiation Oncology, 2 Department of Radiology, 3 Department of Medical Oncology, 4 Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India
| | - Trinanjan Basu
- 1 Department of Radiation Oncology, 2 Department of Radiology, 3 Department of Medical Oncology, 4 Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India
| | - Supriya Chopra
- 1 Department of Radiation Oncology, 2 Department of Radiology, 3 Department of Medical Oncology, 4 Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India
| | - Supreeta Arya
- 1 Department of Radiation Oncology, 2 Department of Radiology, 3 Department of Medical Oncology, 4 Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India
| | - Prachi Patil
- 1 Department of Radiation Oncology, 2 Department of Radiology, 3 Department of Medical Oncology, 4 Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India
| | - Shaesta Mehta
- 1 Department of Radiation Oncology, 2 Department of Radiology, 3 Department of Medical Oncology, 4 Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India
| | - Mukta Ramadwar
- 1 Department of Radiation Oncology, 2 Department of Radiology, 3 Department of Medical Oncology, 4 Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India
| | - Kedar Deodhar
- 1 Department of Radiation Oncology, 2 Department of Radiology, 3 Department of Medical Oncology, 4 Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India
| | - Shyam Kishore Shrivastava
- 1 Department of Radiation Oncology, 2 Department of Radiology, 3 Department of Medical Oncology, 4 Department of Pathology, Tata Memorial Hospital, Mumbai 400012, India
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31
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[Primary signet-ring cell carcinoma of the terminal ileum]. GASTROENTEROLOGIA Y HEPATOLOGIA 2014; 38:472-3. [PMID: 25454596 DOI: 10.1016/j.gastrohep.2014.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Accepted: 10/02/2014] [Indexed: 11/20/2022]
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32
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van Oudheusden T, Braam H, Nienhuijs S, Wiezer M, van Ramshorst B, Luyer P, de Hingh I. Poor outcome after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis with signet ring cell histology. J Surg Oncol 2014; 111:237-42. [DOI: 10.1002/jso.23784] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Accepted: 08/13/2014] [Indexed: 12/27/2022]
Affiliation(s)
| | - H.J. Braam
- Department of Surgery; St. Antonius Hospital; Nieuwegein The Netherlands
| | - S.W. Nienhuijs
- Department of Surgery; Catharina Hospital; Eindhoven The Netherlands
| | - M.J. Wiezer
- Department of Surgery; St. Antonius Hospital; Nieuwegein The Netherlands
| | - B. van Ramshorst
- Department of Surgery; St. Antonius Hospital; Nieuwegein The Netherlands
| | - P. Luyer
- Department of Surgery; Catharina Hospital; Eindhoven The Netherlands
| | - I.H. de Hingh
- Department of Surgery; Catharina Hospital; Eindhoven The Netherlands
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Prabhu R, Kumar N, Krishna S, Shenoy R. Primary colonic signet ring cell carcinoma in a young patient. BMJ Case Rep 2014; 2014:bcr-2013-200587. [PMID: 24654235 DOI: 10.1136/bcr-2013-200587] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 28-year-old woman presented with colicky abdominal pain for 3 months. Pain was associated with episodes of vomiting, abdominal distension and constipation. She also had loss of weight for this duration. General physical examination was unremarkable and the abdomen was soft, with no palpable organomegaly. A CT of the abdomen showed small bowel and ascending colon dilation with multiple air fluid levels. There was also a short segment of circumferential bowel wall thickening and luminal narrowing in the hepatic flexure with sudden transition of bowel diameter. She underwent a right hemicolectomy after necessary preoperative investigations. Histopathology revealed signet ring cell carcinoma (SRCC). This case highlights the importance of detecting such a lesion in a young, otherwise fit woman. The challenge lies in early diagnosis and awareness of general practitioners about this aggressive form of colonic tumours.
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Affiliation(s)
- Raghunath Prabhu
- Department of Surgery, Kasturba Medical College, Manipal, Karnataka, India
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Thota R, Fang X, Subbiah S. Clinicopathological features and survival outcomes of primary signet ring cell and mucinous adenocarcinoma of colon: retrospective analysis of VACCR database. J Gastrointest Oncol 2014; 5:18-24. [PMID: 24490039 DOI: 10.3978/j.issn.2078-6891.2013.051] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2012] [Accepted: 09/27/2013] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Signet ring cell carcinoma (SRCC) accounts for less than 1% of all colon cancers. We examined the clinicopathological features and prognosis of signet ring cell and mucinous adenocarcinoma (MCC) of colon. METHODS A total of 206 patients diagnosed with SRCC from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. Age, race, histology, grade, lymph node status, stage and type of treatment received data were collected. RESULTS Out of 206 patients, 173 (84%) were white, 31 (15%) were black, and 2 patients were listed as unknown. Median age of diagnosis was 67 years as compared to 70 years for both mucinous cell (MCC) and non-mucinous adenocarcinoma (NMCC) of colon. Pathological T-stages were as follows: T1 =3%, T2 =5%, T3 =34%, T4 =26%, and unknown 32%. Of the total, 22.3% were located in cecum, 7.7% in appendix, 21.8% in ascending colon, 7.7% in hepatic flexure of colon, 11% in transverse colon, 2.9% in splenic flexure 4.4% in descending colon, and 15.5% in sigmoid colon. 46.5% were lymph node positive, 21% were lymph node negative, and 32.5% were unknown. SRCC were in general poorly differentiated tumors (57%), small proportion of patients included were well-differentiated tumors with focal signet ring cell pathology (10%) and in 33% grade was unknown. Among stage 3 patients, 34% patients received only surgery while 64% received surgery with adjuvant chemotherapy and 2% received chemotherapy alone. The stage specific 5-year survivals for SRCC, MCC and NMCC were--Stage I: 100%, 61%, and 41% respectively (P<0.0001); Stage II: 42%, 58% and 32% respectively (P<0.0001); Stage III: 19%, 41% and 47% respectively (P=0.0002); Stage IV: 1.5%, 7% and 31% respectively (P<0.0001). Median survival of SRCC compared to NMCC was 18.6 vs. 46 months (P<0.0001) and mucinous cell adenocarcinoma versus NMCC was 47.8 and 46 months (P=0.63) respectively. CONCLUSIONS SRCC of colon has poor survival rates compared to other histological subtypes. SRCC presents at an earlier age, has higher tumor grade and advanced stage at diagnosis when compared to mucinous and NMCC of colon. Due to rarity of this disease further prospective multi-institute studies are required for in-depth understanding of this disease.
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Singh K, Singh A, Bhutra S, Pachori G, Jangir MK. Metastatic Primary Signet Ring Cell Carcinoma of Rectum: A Case Report of 10-Year-old Male Child. J Clin Diagn Res 2014; 8:177-8. [PMID: 24701526 PMCID: PMC3972554 DOI: 10.7860/jcdr/2014/6988.4051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2013] [Accepted: 12/25/2013] [Indexed: 12/19/2022]
Abstract
Signet ring cell carcinomas of the colon and rectum are well documented in the adult population, but the incidence is very low in the paediatric population. Signet ring cell carcinoma has more malignant potential, mostly present as advanced stage and carries very poor prognosis. We are describing a 10-year-old male patient who presented with acute intestinal obstruction; radiology revealed large bowel obstruction and was diagnosed metastatic primary signet ring cell carcinoma of rectum on biopsy. We have discussed the diagnostic work-up and the management of this rare entity. Due to the high mortality that can be caused by a delay in making the correct diagnosis, signet ring cell carcinoma of colorectum represents a special diagnostic and surgical challenge.
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Affiliation(s)
- Kumkum Singh
- Professor and Head, Department of Surgery,Jawahar Lal Nehru Medical College, Ajmer Rajasthan, India
| | - Amit Singh
- Senior Resident, Department of Surgery,Jawahar Lal Nehru Medical College, Ajmer Rajasthan, India
| | - Shyam Bhutra
- Associate Professor, Department of Surgery,Jawahar Lal Nehru Medical College, Ajmer Rajasthan, India
| | - Geeta Pachori
- Professor and Head, Department of pathology,Jawahar Lal Nehru Medical College, Ajmer Rajasthan, India
| | - Mahesh Kumar Jangir
- Postgraduate Student, Department of Surgery,Jawahar Lal Nehru Medical College, Ajmer Rajasthan, India
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Synchronous appendiceal and intramucosal gastric signet ring cell carcinomas in an individual with CDH1-associated hereditary diffuse gastric carcinoma: a case report of a novel association and review of the literature. BMC Gastroenterol 2013; 13:114. [PMID: 23849133 PMCID: PMC3716915 DOI: 10.1186/1471-230x-13-114] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Accepted: 07/10/2013] [Indexed: 02/08/2023] Open
Abstract
Background Hereditary diffuse gastric carcinoma is an autosomal dominant cancer syndrome associated with mutations of the E-cadherin gene (CDH1). E-cadherin is normally involved in cell-cell adhesion, so it not surprising that individuals with this syndrome are predisposed to develop malignancies with dyshesive morphologies at a young age, such as diffuse (signet ring cell) gastric carcinoma and lobular breast carcinoma. Herein we describe the first reported case of primary appendiceal signet ring cell carcinoma arising in a CDH1-associated hereditary diffuse gastric carcinoma kindred with synchronous primary diffuse gastric carcinoma. Case presentation A 51- year old woman, with known CDH1 mutation carrier status and a prior history of lobular breast carcinoma underwent prophylactic total gastrectomy which revealed multifocal intramucosal signet ring cell carcinoma. An appendectomy was performed at the same time due to a prior episode of presumed appendicitis, with pathologic examination significant for a primary signet ring cell carcinoma of the appendix. Conclusion As appendiceal signet ring cell carcinoma is exceedingly rare, the occurrence of this neoplasm in this patient, with this particular morphology, provides credence for it being part of the hereditary diffuse gastric carcinoma spectrum of malignancies.
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Kim JH, Park SJ, Park MI, Moon W, Kim SE. Early-stage primary signet ring cell carcinoma of the colon. World J Gastroenterol 2013; 19:3895-3898. [PMID: 23840131 PMCID: PMC3699035 DOI: 10.3748/wjg.v19.i24.3895] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2012] [Revised: 04/15/2013] [Accepted: 05/18/2013] [Indexed: 02/06/2023] Open
Abstract
Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its prognosis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the colon. Colonoscopic examination revealed a IIa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen revealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant metastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node metastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.
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Marone J, Patel S, Page M, Cheriyath P. Signet cell carcinoma of the colon in a 17 year old child. J Surg Case Rep 2012; 2012:3. [PMID: 24960789 PMCID: PMC3649616 DOI: 10.1093/jscr/2012.9.3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Signet cell carcinomas of the colon are well documented in the adult population, but this cancer incidence is very low in the adolescent population. A 17 year old male child presented with one month of progressive abdominal pain. CT scan of the abdomen showed significant abnormality involving the ascending colon characterized as marked mural thickening. Biopsy results indicated signet ring cell carcinoma. Signet cell carcinoma is presumed to be caused by genetic mutations just like the other colorectal cancers. Treatment for signet cell carcinoma is the same as other colorectal cancer. Surgery is part of the standard management of patients with colon and rectal cancer stages I, II and III. Signet cell cancer has a poor survival with the median survival period of about 9 months. The incidence among adolescence is much lower than that of the adult population.
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Affiliation(s)
- J Marone
- Medical Director of Research, Harrisburg Hospital, Harrisburg, Pennsylvania, USA
| | - S Patel
- Medical Director of Research, Harrisburg Hospital, Harrisburg, Pennsylvania, USA
| | - M Page
- Medical Director of Research, Harrisburg Hospital, Harrisburg, Pennsylvania, USA
| | - P Cheriyath
- Medical Director of Research, Harrisburg Hospital, Harrisburg, Pennsylvania, USA
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Wilmanns C, Steinhauer S, Großmann J, Schmitt-Gräff A, Ruf G. Cooperate concept of metastasis: site-specific requirement of activated differentiation and dynamic deterioration. Cancer Metastasis Rev 2012; 31:269-76. [DOI: 10.1007/s10555-012-9350-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Tumwine LK, Kagimu M, Ocama P, Segamwenge I, Masiira-Mukasa N, Wamala D, Dworak O, Opio CK. Atypical presentation of colon adenocarcinoma: a case report. J Med Case Rep 2012; 6:58. [PMID: 22330123 PMCID: PMC3305541 DOI: 10.1186/1752-1947-6-58] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2011] [Accepted: 02/13/2012] [Indexed: 12/24/2022] Open
Abstract
Introduction Adenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old). However, more recently, it has been observed that younger patients (less than 40 years of age) are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda. Case presentation A 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon. Conclusions Colorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the diagnosis of colorectal malignancy in young African patients.
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Affiliation(s)
- Lynnette K Tumwine
- Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P,O,Box 7072, Kampala, Uganda.
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Seretis E, Konstantinidou A, Arnogiannakis N, Xinopoulos D, Voloudakis-Baltatzis IE. Mucinous colorectal adenocarcinoma with signet-ring cells: immunohistochemical and ultrastructural study. Ultrastruct Pathol 2011; 34:337-43. [PMID: 21070165 DOI: 10.3109/01913123.2010.500069] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
A primary mucinous colorectal adenocarcinoma tissue with signet-ring cells, as revealed after histological evaluation, was examined ultrastructurally. The authors also analyzed the immunohistochemical data of the tissue for serotonin, vasoactive intestinal polypeptide (VIP), bombesin, somatostatin, and glucagon, using the peroxidase anti-peroxidase (PAP) method and the immunogold labeling method for light and electron microscope, respectively. Electron microscopically mucinous adenocarcinoma was characterized by the formation of small lumen. Adenocarcinoma cells were full of mucous granules of varying electron density, providing a good environment for the tumor cells to grow. They also exhibited a significant loss of microvilli and intracytoplasmic junctions, which could allow the cells to disseminate. Signet-ring cells were located in the basal site of the ducts or in the lamina propria and appeared neoplastic, with mucin accumulation intracellularly and an eccentric crescent-shaped nucleus. The cytoplasmic organelles were decreased and at the periphery of the cell. The PAP method demonstrated that these cells were strongly positive for bombesin and also positive for vasointestinal polypeptide (VIP). The immunogold method detected bombesin immunoreactivity in the vacuoles as well as in other cytoplasmic membranes, whereas VIP was localized mainly in the plasma membrane. The location of signet-ring cells combined with the immunoreactivity for bombesin and VIP indicated that signet-ring cells were of neuroendocrine origin and probably dedifferentiated enterochromaffin-like endocrine cells. These findings have implications for understanding the biological behavior of these composite malignant tumors and could help in the knowledge of the origin of signet-ring cells.
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Affiliation(s)
- E Seretis
- Department of Electron Microscopy-Cell Biology, G. Papanicolaou Research Center of Oncology and Experimental Surgery, Agios Savvas Anticancer Hospital of Athens, Athens, Greece.
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Gopalan V, Smith RA, Ho YH, Lam AKY. Signet-ring cell carcinoma of colorectum--current perspectives and molecular biology. Int J Colorectal Dis 2011; 26:127-33. [PMID: 20686774 DOI: 10.1007/s00384-010-1037-z] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/26/2010] [Indexed: 02/08/2023]
Abstract
PURPOSE Colorectal signet-ring cell carcinoma (SRCC) is rare, and very little detailed information on the molecular biology of the disease is available. METHODS The literature on the clinical, pathological and, in particular, the molecular biology of this rare entity was critically reviewed. The reviewed articles take into account a total of 1,817 cases of SRCC, but only 143 cases have molecular data available. The characteristics of two patients with colorectal SRCC were also discussed. RESULTS Colorectal SRCC mostly occurs in younger patients, is larger and has different site predilection compared with conventional colorectal adenocarcinoma. It can occur as one of the synchronous cancers in the colorectum. The cancer is usually diagnosed at advanced stages because of the late manifestation of symptoms, and aggressive treatment strategy is required. Limited reports in the literature have shown that the variant of colorectal cancer demonstrated a different pattern of genetic alterations of common growth kinase-related oncogenes (K-ras, BRAF), tumour suppressor genes (p53, p16), gene methylation and cell adhesion-related genes related to the Wingless signalling pathway (E-cadherin and beta-catenin) from conventional colorectal adenocarcinoma. Colorectal SRCC also showed high expression of mucin-related genes and genes related to the gastrointestinal system. There was also a higher prevalence of microsatellite instability-high tumours and low Cox-2 expression in colorectal SRCC as opposed to conventional adenocarcinoma. CONCLUSIONS Colorectal SRCC has unique molecular pathological features. The unique molecular profiles in SRCC may provide molecular-based improvements to patient management in colorectal SRCC.
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Affiliation(s)
- Vinod Gopalan
- School of Medicine, Griffith Health Institute, Gold Coast, QLD, Australia
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Yao WW, Zhang H, Ding B, Fu T, Jia H, Pang L, Song L, Xu W, Song Q, Chen K, Pan Z. Rectal cancer: 3D dynamic contrast-enhanced MRI; correlation with microvascular density and clinicopathological features. Radiol Med 2011; 116:366-74. [PMID: 21298356 DOI: 10.1007/s11547-011-0628-2] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2010] [Accepted: 07/16/2010] [Indexed: 01/27/2023]
Abstract
PURPOSE The primary aim of this prospective study was to evaluate the relationship between three-dimensional dynamic contrast-enhanced magnetic resonance (3D-DCE-MR) imaging parameters and clinicopathological features of rectal cancer and assess their potential as new radiological prognostic predictors. MATERIALS AND METHODS Three-dimensional DCE-MR was performed on 26 cases of pathologically proved rectal adenocarcinoma 1 week prior to operation. Data were analysed to calculate transfer constant (Ktrans), leakage space (Ve) and rate constant (Kep) of both tumour and normal rectal wall. Microvessel density (MVD) was evaluated by immunohistochemical staining of surgical specimens. All findings were analysed prospectively and correlated with tumour/node/metastasis (TNM) staging, Dukes staging, histological grading, presence of lymph node metastasis, serosal involvement and MVD. RESULTS Mean Ktrans, Ve and Kep for tumours were as follows: Ktrans 7.123±3.850/min, Ve 14.2±3.0%, Kep 49.446±20.404/min, revealing the significant difference between the tumour and normal rectal wall (p=0.001). There was a significant difference for Ktrans not only between patients with and without lymphatic involvement (p=0.000), but also among Dukes staging (p=0.04) and pTNM staging (p=0.03). Kep showed moderate correlation with TNM stages (r=0.479, p=0.02). Ve and MVD revealed no significant correlation with the clinicopathological findings described above (p>0.05). CONCLUSION Owing to the moderate and strong relationship between Ktrans and clinicopathological elements, Ktrans might be the prognostic indicator of rectal cancer. Threedimensional DCE high-resolution MR imaging provides a competing opportunity to assess contrast kinetics.
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Affiliation(s)
- W W Yao
- Department of Radiology, Shanghai No. 6 People's Hospital affiliated to Shanghai Jiaotong University, 600 Yishan Road, Shanghai, 200233, China
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Wachtel MS, Haynes AL, Griswold JA. Signet Ring, High Grade, and Undifferentiated Colorectal Adenocarcinomas Differ. J Surg Res 2010; 163:250-6. [DOI: 10.1016/j.jss.2010.03.066] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2010] [Revised: 03/11/2010] [Accepted: 03/29/2010] [Indexed: 10/19/2022]
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Bertuzzo VR, Coccolini F, Pinna AD. Peritoneal seeding from appendiceal carcinoma: A case report and review of the literature. World J Gastrointest Surg 2010; 2:265-9. [PMID: 21160886 PMCID: PMC2999252 DOI: 10.4240/wjgs.v2.i8.265] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2010] [Revised: 03/22/2010] [Accepted: 03/29/2010] [Indexed: 02/07/2023] Open
Abstract
Non-carcinoid appendiceal malignancies are rare entities, representing less than 0.5% of all gastrointestinal malignancies. Because of their rarity and particular biological behavior, a substantial number of patients affected by these neoplasms do not receive appropriate surgical resection. In this report, we describe a rare case of primary signet-ring cell carcinoma of the appendix with peritoneal seeding which occurred in a 40-year old man admitted at the Emergency Surgery Department with the clinical suspicion of acute appendicitis. After a surgical debulking and right hemicolectomy, the patient had systemic chemotherapy according to FOLFOX protocol. After completion of the latter, the patient underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy. This report offers a brief review of the literature and suggests an algorithm for the management of non-carcinoid appendiceal tumors with peritoneal dissemination.
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Affiliation(s)
- Valentina R Bertuzzo
- Valentina R Bertuzzo, Federico Coccolini, Antonio D Pinna, Department of General, Emergency and Transplant Surgery, Sant'Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy
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Bratland A, Vetrhus T, Grøholt KK, Ree AH. Preoperative radiotherapy in rectal signet-ring cell carcinoma - magnetic resonance imaging and treatment outcome: Report of six cases. Acta Oncol 2010; 49:42-9. [PMID: 20100143 DOI: 10.3109/02841860903081897] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND Signet-ring cell carcinoma (SRCC) is an uncommon tumor entity in rectal cancer, often considered to be resistant to non-surgical therapy. In locally advanced primary or recurrent rectal cancer, diagnostic information from magnetic resonance imaging (MRI) is considered superior in planning the optimal treatment strategy, which usually includes preoperative radiotherapy. The recognition of MRI features that correlate with the radiation response might ultimately be used to select patients for tailored treatment and, in addition, avoid potentially toxic therapy in non-responding patients. MATERIAL AND METHODS In a cohort of 120 rectal cancer patients who had received preoperative radiotherapy (50 Gy in 2 Gy fractions), six patients were noted to have SRCC tumor differentiation. Initial diagnostic MRI examination included assessment of local T- and N-stage and tumor morphology. Histological tumor response was subsequently assessed in the resected specimens, and postoperative follow-up data was compiled until disease recurrence. RESULTS Following the preoperative radiotherapy, two distinctly different histological responses - complete response (ypT0N0) or no response - were observed. Extensive mesorectal lymph node metastasis (N2 disease) at the pretreatment MRI examination was unambiguously associated with lack of response and rapid development of disseminated disease. Importantly, patients with complete response have been observed for 23-52 months postoperatively without evidence of recurrent disease. DISCUSSION Our review may suggest that patients with locally advanced growth of rectal SRCC, despite poorer outcome when compared to patients with conventional-type rectal adenocarcinoma, when presenting limited lymph node disease should be offered preoperative radiotherapy in a tentatively curative setting.
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Affiliation(s)
- Ase Bratland
- Division of Cancer Medicine and Radiotherapy, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway
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Mizushima T, Nomura M, Fujii M, Akamatsu H, Mizuno H, Tominaga H, Hasegawa J, Nakajima K, Yasumasa K, Yoshikawa M, Nishida T. Primary colorectal signet-ring cell carcinoma: clinicopathological features and postoperative survival. Surg Today 2010; 40:234-8. [PMID: 20180076 DOI: 10.1007/s00595-009-4057-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2009] [Accepted: 06/11/2009] [Indexed: 01/12/2023]
Abstract
PURPOSE The objective of this study was to investigate the clinicopathological features and postoperative survival of primary colorectal signet-ring cell carcinoma. METHODS Nineteen patients with primary colorectal signet-ring cell carcinoma were identified from a database of 5884 surgical patients with colorectal cancers treated surgically at Osaka University Hospital and affiliated hospitals between 1993 and 2007. The clinicopathological data of those patients were compared with those of 5792 patients with non-signet-ring cell colorectal carcinoma (5417 with well or moderately differentiated adenocarcinoma and 375 with poorly differentiated adenocarcinoma or mucinous carcinoma). RESULTS All patients showed a tumor depth of over T3. Lymph node involvement occurred in 14 patients. Seven of 19 patients presented with distant metastasis at the time of diagnosis. The overall 5-year survival rate in primary signet-ring cell carcinoma was significantly lower at 24.1%, in comparison to 77.5% in well or moderately differentiated adenocarcinoma and 57.7% in poorly differentiated adenocarcinoma or mucinous carcinoma. Likewise, the postoperative survival in Stage III was also significantly worse. On the other hand, no significant difference was observed in Stage II or IV. CONCLUSION The most important feature of primary colorectal signet-ring cell carcinoma is the advanced stage at the time of diagnosis. In addition, the postoperative survival is worse than for other types of colorectal cancer.
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Affiliation(s)
- Tsunekazu Mizushima
- Department of Surgery, Rinku General Medical Center, Izumisano Municipal Hospital, Izumisano, Osaka, Japan
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Klarskov L, Bernstein I, Holck S. HNPCC-associated synchronous early-stage signet-ring cell carcinomas of colonic origin. A comparative morphological and immunohistochemical study of an intramucosal and a submucosal example. Virchows Arch 2008; 454:115-24. [PMID: 19002494 DOI: 10.1007/s00428-008-0691-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2008] [Revised: 10/11/2008] [Accepted: 10/14/2008] [Indexed: 12/19/2022]
Abstract
Signet-ring cell carcinoma (SRCC) developing in the colorectum (CR) is infrequently identified at an early stage (no deeper than submucosa). Most such examples involve the submucosa. Merely 13 cases of intramucosal CR SRCC are at hand. We recently had the opportunity to study a specimen with two synchronous early-stage SRCC, developed in a 65-year-old hereditary nonpolyposis colorectal cancer male patient with a known disease-causing mutation in MLH1. A right hemicolectomy specimen comprised a 15-mm intramucosal cecal lesion, featuring zones of conventional tubular adenoma and intraepithelial SRCC as well as tumor cells multifocally permeating the lamina propria and a 12-mm submucosally expanding SRCC of the ascending colon. The intramucosal and intraepithelial as well as stromal lesional cells displayed a normal membranous expression of beta-catenin and E-cadherin; submucosally infiltrating cells featured alterations in this complex with loss of membranous expression of both proteins and a shift with nuclear accumulation of beta-catenin, suggesting a disruption of the Wingless signaling pathway taking place at the transition from the intramucosal to the submucosal level.
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Affiliation(s)
- Louise Klarskov
- Department of Pathology, HNPCC-register, Hvidovre Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
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Abstract
Colorectal carcinoma (CRC), although primarily a disease of adulthood, accounts for 2% of malignancies in adolescents and has been reported in children as young as 9 months of age. Our knowledge of CRC in pediatrics is based on a handful of case series and case reports. Apart from one small clinical trial, there has been a lack of prospective clinical studies in this age group. Based on these published reports, most CRC in children is sporadic, but it can also arise in the setting of predisposing conditions, such as gastrointestinal polyposis syndromes, nonpolyposis familial cancer syndromes, and inflammatory bowel disease. Despite some similarities to adult disease, CRC in childhood may be intrinsically different biologically, because it differs from adult-onset CRC in several respects. Childhood CRC tends to be diagnosed at an advanced stage, is largely of mucinous histology, and (probably because of these features) tends to have a poorer outcome. As a result of its rarity in children and the lack of prospective pediatric studies, recommendations for therapy are primarily extrapolated from adult clinical trials. A review of pediatric case series in the English literature emphasizes the prognostic significance of stage of disease, as well as extent of surgical resection. As in adults, early detection is critical in an effort to capture the disease at less advanced stages. Complete surgical resection with aggressive lymph node dissection is essential for cure, and neoadjuvant chemotherapy may be used in an effort to render unresectable lesions resectable. Active agents in adults with CRC include fluorouracil, folinic acid (leucovorin), oxaliplatin, and irinotecan. Furthermore, newer targeted therapeutic agents, such as bevacizumab and cetuximab, have added additional efficacy to the standard chemotherapy backbone. Collaborative multi-institutional pediatric clinical trials are needed to evaluate the prognosis, optimal treatment response, and the basic biology of childhood onset CRC.
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Affiliation(s)
- Raya Saab
- Pediatric Hematology-Oncology, American University of Beirut, Beirut, Lebanon
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Pande R, Sunga A, Levea C, Wilding GE, Bshara W, Reid M, Fakih MG. Significance of signet-ring cells in patients with colorectal cancer. Dis Colon Rectum 2008; 51:50-5. [PMID: 18030531 DOI: 10.1007/s10350-007-9073-7] [Citation(s) in RCA: 83] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2007] [Revised: 05/27/2007] [Accepted: 06/13/2007] [Indexed: 02/08/2023]
Abstract
PURPOSE We performed a retrospective study to determine the pattern of metastases and overall outcome of patients with tumors exhibiting a component of signet-ring cells comprising < 50 percent of the tumor mass. METHODS Medical records of 753 patients with primary colorectal cancer were retrospectively studied. Patients who had tumors with < 50 percent signet-ring cells were classified as having a component of signet-ring cells. The outcome of patients with a component of signet-ring cells was compared to all patients with mucinous adenocarcinoma (defined as adenocarcinomas with > or = 50 percent mucin) to all patients with adenocarcinomas with a component of mucin (defined as adenocarcinomas with < 50 percent mucin) and to 100 randomly selected patients with adenocarcinomas lacking mucin or signet-ring cells. RESULTS Five percent of patients had a component of signet-ring cells, 3 percent had mucinous adenocarcinoma, 9 percent had a component of mucinous adenocarcinoma, and 83 percent had adenocarcinoma lacking mucinous or signet components. Patients with a component of signet-ring cells and mucinous adenocarcinomas metastasized predominantly to the peritoneum/ovaries (75 and 56 percent of metastatic cases, respectively) and rarely to liver/lungs. The pattern of metastases of patients with adenocarcinoma without mucinous or signet components predominantly involved the liver/lungs and rarely the peritoneum/ovaries (12.5 percent). The pattern of metastases for patients with a component of mucinous adenocarcinoma was intermediate between mucinous adenocarcinoma and adenocarcinoma without mucin or signet-ring component. No differences in survival in Stage IV patients were seen among the four subgroups. CONCLUSIONS Patients with a component of signet-ring cells cancers, similar to mucinous adenocarcinoma, have a predisposition to metastasize to the peritoneum/ovaries.
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Affiliation(s)
- Rashmi Pande
- University at Buffalo/Roswell Park Cancer Institute, Elm and Carlton, Buffalo, NY 14263, USA
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