|Year : 2016 | Volume
| Issue : 1 | Page : 210-213
Signet-ring gastric carcinoma, at Bahrain
Amal Almahroos1, Khalid A Al-Sindi2, Mandeep Bedi3, Maitham Alsadadi4, Mohamed A Alhamar5, Mulazim Hussain Bukhari6
1 SHO, University Medical Center, King Abdulla Medical City, Kingdom of Bahrain
2 Prof of Pathology, King Hamad University Hospital, Bahrain
3 Pathologist, Kolkata Police Hospitals, Kolkata, India
4 Consultant gastroenterologist, University Medical Center, King Abdulla Medical City, Kingdom of Bahrain
5 Senior House officer, Histopathology, King Hamad University Hospital, Building 2345, Road 2835, Block 228, Busaiteen, Kingdom of Bahrain
6 Prof of Pathology, Punjab Medical University, Faisal Abad, Pakistan
|Date of Web Publication||5-Jul-2017|
Mulazim Hussain Bukhari
Prof of Pathology, Punjab Medical University, Faisal Abad
Source of Support: None, Conflict of Interest: None
Signet ringcarcinoma (SRC), a variant of gastric adenocarcinoma, is known to have a poor prognosis, especially when arising in the young population. In this report, two cases of gastric SRC carcinomas with different outcomes are described. The first case is a 49 years old Bahraini lady who presented with abdominal pain and was found to have a gastric ulcerover the lesser curvature on endoscopy and her biopsy showed features ofa poorly differentiated signet ring adenocarcinoma. This patient was managed by a timelysubtotal gastrectomy with adjuvant chemoradiotherapy. The second caseis ofa 34 years old Bahraini male whom presented withmild dyspepsia and in whomSRCwas an incidental finding on initial endoscopic biopsy that was later confirmed by targeted biopsy.This patientwas advised total gastrectomybut died due to delay in appropriate and timely interventions primarily due to his multiple consultations regarding the same matter.
Keywords: Signet ring cell carcinoma, prognosis, Urgent treatment
|How to cite this article:|
Almahroos A, Al-Sindi KA, Bedi M, Alsadadi M, Alhamar MA, Bukhari MH. Signet-ring gastric carcinoma, at Bahrain. Acta Med Int 2016;3:210-3
| Background|| |
Gastric carcinoma (GC) is the 15th most common cancer in the USA and the 3rd most common cause of cancer-related death worldwide. The majority of GC patients present for medical attention inan advanced disease stagewhich makes cure for GC a real challenge. The incidence.The incidence of GC though found to be less than 2% in persons below the age of 35,was found to be more aggressive than in the other age groups.
SRC is one of the sub types of adenocarcinoma that produce mucus, and owing to its characteristic infiltrative pattern and the associated high peritoneal carcinomatosis rate has shown to be a key independent anticipator of poor prognosis., Nonetheless, lesions that are diagnosed at an early stage demonstrated a favorable prognosis.
This case report presents the course of two cases of SRC gastric carcinoma,both of which were diagnosed at an early stage, with their respective different outcome.
| Case Presentation|| |
A 49 years old Bahraini ladypresented with a history of abdominal painsince one yearalong with a change in bowel habits. Gastroscopy and colonoscopy were done in August 2014. Gastroscopy showed fundal gastric ulcerover the lesser curvature that had well defined margins with central depression. Microscopic examination of gastric biopsies revealed erosive gastritis. Gastric body mucosa showed features of moderately severe, chronic active (erosive)gastritis with prominent surface polymorph induced inflammation and pits abscesses. No apparent glandular atrophy wasseen. However abnormal acidic mucin production was noted on special (Alcian blue/PAS) stain, signifying an abnormal shift to the incomplete metaplasia. Pylori infection was noted on special (Warthin-Starry) stain. No equivocal evidence ofdysplasia or neoplasia was found. Colonoscopy was negative. The patient received the standard triple therapy for Pyloriinfection (14 days of Amoxicillin, Clarithromycin and a proton pump inhibitor) followed by one month of proton pump inhibitor. Gastroscopy repeatedone month after triple therapy showed persistence of gastric ulcer over the same [Figure 1]. It was biopsied again. Microscopic examination confirmed eradication ofH. Pyloribut showed features of differentiated signet ring adenocarcinoma [Figure 2].The tumor was characterized by ill defined sheets and cords of mildly pleomorphic but large cells with both eosinophilic and clear bubbly cytoplasm with signet ring differentiation and foci of apparent intracellular (PAS/Alcian blue positive) mixed mucin production. No tumor cell necrosis was seen. Tumor cells were found within the lamina propia and the attached superficial part of the submucosa. Both computed tomography (CT) scansand positron emission tomography negative and the patient was referred for laparoscopic evaluation followed by subtotal gastrectomy on 16 October 2014. Postoperative pathology reveled a 3 x 2.5 cm ulcer on the lesser curvature showing poorly differentiated (grade 3) tubular adenocarcinoma. Lesion was invading lamina propria into muscularis propria. Five out of 22 examined perigastric lymphnodes were involved. Pathologic staging pT1a pN2 (Stage II), M0. Treatment was continued with concurrent chemotherapy and radiotherapy (CCRT)- (Capecitabine 1000 mg PO BD for 5 days per week with 5 weeks of radiation). Post treatment imaging showed no recurrence of the disease.
|Figure 1: Lesser curvature fundal gastric ulcer with well-defined margins and central depression|
Click here to view
|Figure 2: Adenocarcinoma, Signet Ring Type: III-defined sheet of pleomorphic, poorly differentiated adenocarcinoma with apparent large cells containing eosinophilic and clear cytoplasm and signet ring differentiation (arrow). [H & E stain, MPF]|
Click here to view
A 34 years old Bahraini gentleman with a short history of dyspepsiaunderwent gastroscopy, which showed mild antral gastritis. Endoscopic biopsies obtained were suggestive of gastric adenocarcinoma. Due to the unexpected findings gastroscopy was repeated by a different operator. After careful examination a small antral superficial ulcer was foundand biopsied. Results confirmed the presenceof SRC gastric adenocarcinoma. The patient was advised for total gastrectomy. PET scan was negative. Considering the mild presentation, diagnosis came as a surprise to the patient. Consequently, the patient kept obtaining several opinions. Investigations done at different hospitals were conclusive of the same diagnosis. But unfortunately by the time the patient agreed to undergo surgical resection, peritoneal metastatic depositshad takenplace and due to unnecessary delay of 17 months between diagnosis and appropriate intervention, it lead to death of the patient.
| Discussion|| |
Signet ring cell adenocarcinoma, a form of gastric adenocarcinoma, as declared by the majority of researchers has high invasive propensity with poor prognosis. Having said that, the nature of SRC carcinoma remains controversial. Some researchers, like Hyung WJ et al, stated that SRC has better survival rate and lower rate of lymph node metastasis when compared to non-SRC carcinoma. Moreover, recent studies demonstrated that SRC carcinomas portend no worse prognosis compared to other forms of gastric carcinoma when adjusted for stage.,
Upon studying SRC lesions, it was found that those diagnosed at an early stage had a favorable prognosis, while those diagnosed at a later stage had much worse prognosis., It was also observed that early lesions, restricted to the mucosal lining, had higher cure rates than within those with regional lymph node or distant metastasis. The above findings suggest the urgent application of treatment early in the course of the disease leading to better outcomes. This can also be appreciated on reviewing the outcomes of the cases presented above. As the first case (in which the disease was limited up to perigastric lymph nodes) responded well to treatment, while the second one (which developed peritoneal metastasis) ended with mortality as a result of the delay in treatment.
Diagnosis tend to be remarkably delayed among younger patients due to the low level of suspicion though they have high prevalence of the lesion thus posing diagnostic challenges.As early diagnosis appears to play a crucial role in the management of SRC carcinoma, researchers have worked hard to improve the early diagnosis. One of the endoscopic signs that was found to be specific for the diagnosis of early SRC carcinoma is the “stretch sign” that is the”elongation of the architecture of the submucosa”. This along with other signs can aid in the endoscopic diagnosis of early gastric cancer, knowing that early gastric cancer produces subtle mucosal changes in contrast to advancer cancer.
One of the rare, however interesting, laboratory abnormalities that is found to be associated with gastric adenocarcinoma is thrombocytopenia., It is believed that this phenomenon is mediated by immune mechanisms. However this phenomenon was not noted in either of the cases presented here.
Treatment plan highly depends on the stage of the disease, therefore accurate locoregional staging is required to decide upon treatment modalities needed for each patient. Endoscopic ultrasonographgy (EUS)is one of tools used for the diagnosis and staging of gastric cancer. Various studies reviewed the accuracy of EUS-guided T-staging, which was found to be between 60 - 90%. (14) On the other hand, N-staging accuracies were found to be slightly lower, 50-80%. However EUS influence on management is still controversial. The disease of the first case presented earlier was staged through the following: endoscopic biopsy, preoperative laparoscopic exploration, PET and CT scans, and postoperative pathology examination.
Among the various lines of management of gastric cancer, curative resection has shownto be the most efficacious. Curative resection generally includes lymphadenectomy.
Regarding resection techniques used, many studies compared subtotal versus total gastrectomy with no observable difference in the survival rate.,, Some suggest that subtotal gastrectomy is superior as it provides a better nutritional status and therefore better quality of life. The latter complies with a study conducted in 200 which suggested that early SRC carcinomas may be managed through less invasive surgery for a better quality of life.
Subtotal gastrostomywas chosen as the resection technique for the 1st case presented, and showed good results along with the following adjuvant chemoradiotherapy. It concluded that ESD is a safe and possible modality to treat undifferentiated early gastric cancer, however close follow-up is required due to the higher recurrence rates among patients managed with ESD than the ratesfor patients managed with surgery.,,,,,,,,,,
| Conclusion|| |
In conclusion, after comparing the clinical course and the consequent different outcomes of the two cases discussed above in this report, emphasis need to be made on the importance of the application of aggressive treatment as early as possible aiming for a better outcome. This can be made possible through the use of effective diagnostic tools and accurate staging methods followed by the selection of the appropriate treatment modalities.
| References|| |
Bulent Kaya1, Hasan Abuoglu, Cengiz Eris, Mehmet Kamil Yildiz, Orhan Bat, Mehmet Odabasi, Nuriye Esen Bulut, Alper Şahbaz, Aziz Şener, Azamet Çezik and Umit Topaloglu. Clinical Features of the Gastric Signet Ring Cell Carcinoma Including CA 19- 9, CEA and CRP Levels. Journal of Cancer Science & Therapy, J Cancer Sci Ther. 2015, 7(4).
Piessen G, Messager M, Leteurtre E, Jean-Pierre T, Mariette C. Signet Ring Cell Histology is an Independent Predictor of Poor Prognosis in Gastric Adenocarcinoma Regardless of Tumoral Clinical Presentation. Annals of Surgery, Ann Surg. December 2009: 250 (6): 878–87.
Bamboat ZM, Tang LH, Vinuela E, Kuk D, Gonen M, Shah MA, Brennan MF, Coit DG, Strong VE. Stage-Stratified Prognosis of Signet Ring Cell Histology in Patients Undergoing Curative Resection for Gastric Adenocarcinoma. Annals of Surgical Oncology, Ann Surg Oncol. January 2014. 21(5): 1678–85.
Hyung WJ, Noh SH, Lee JH, Huh JJ, Lah KH, Choi SH, Min JS. Early Gastric Carcinoma with Signet Ring Cell Histology. Cancer. Jan 2002: 94(1):78–83.
Taghavi S, Jayarajan SN, Davey A, Willis AI. Prognostic significance of signet ring gastric cancer. Journal of Clinical Oncology, J Clin Oncol. 2012: 30(28): 3493–3498.
El-Zimaity HM, Itani K, Graham DY. Early diagnosis of signet ring cell carcinoma of the stomach: role of the Genta stain. Journal of Clinical Pathology, J Clin Pathol. 1997: 50(10): 867–879.
Phalanusitthepha C, Grimes K L, Ikeda H, Sato H, Sato C, Hokierti C, Inoue H. Endoscopic features of early-stage signet-ring- cell carcinoma of the stomach. World Journal of Gastrointestinal Endoscopy, WJGE. 2015: 7(7): 741–746.
Tomoyuki Yada, Chizu Yokoi, Naomi Uemura. The Current State of Diagnosis and Treatment for Early Gastric Cancer. Diagnostic and Therapeutic Endoscopy. 2012: 2013: 9–10
M Mathew, A Joshi, A Kurien. Autoimmune thrombocytopenia associated with carcinoma of the stomach. The Internet Journal of Surgery. 2008: 21(2): 1–2.
Seong Hin Hong, Joon Hong Song, Seok Jung, Seon Hoo Kim, Jae Who Park. Idiopathis Thrombocytopenic Purpura - like Syndrome in a Patient with Gastric Adenocarcinoma. Journal of the Korean Cancer Association. 1995: 27(1): 138–144.
Steven E Zimmerman, Frederick P Smith, Terence M Phillips, Robert J Coffey, Philip S Schein. Gastric carcinoma and thrombotic thrombocytopenic purpura: association with plasma immune complex concentrations. British Medical Journal, Br Med J. 1982: 284(6327): 1432–4.
Ioannis S. Papanikolaou, aMaria Triantafyllou, aKonstantinos Triantafyllou, Thomas Röschb. EUS in the management of gastric cancer. Annals of Gasteroenterology. 2011: 24(1): 9–15.
De Manzoni G, Verlato G, Roviello F, Di Leo A, Marrelli D, Morgagni P, Pasini F, Saragoni L, Tomezzoli A. Italian Research Group for Gastric Cancer. Subtotal versus total gastrectomy for T3 adenocarcinoma of the antrum. Gastric Cancer. 2003: 6(4): 237–42.
Gouzi JL, Huguier M, Fagniez PL, Launois B, Flamant Y, Lacaine F, Paquet JC, Hay JM. Total versus subtotal gastrectomy for adenocarcinoma of the gastric antrum. A French prospective controlled study. Annals of Surgery. 1989: 209(2): 162–6.
Bozzetti F, Marubini E, Bonfanti G, Miceli R, Piano C, Gennari L. Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group. Annals of Surgery. 1999: 230(2): 170–8.
[Figure 1], [Figure 2]