Intestinal metaplasia of gallbladder diagnosed after laparoscopic cholecystectomy in patient with Dubin-Johnson syndrome; Does hyperbilirubinemia protect against gallbladder cancer development?
Abstract
This manuscript describes the incidental diagnosis of Dubin–Johnson Syndrome (DJS), a rare autosomal recessive disorder characterized by impaired hepatic bilirubin excretion and the hallmark appearance of a grossly black liver, in a 34-year-old female who underwent laparoscopic cholecystectomy for symptomatic cholelithiasis. The patient presented with right upper quadrant abdominal pain and mild hyperbilirubinemia. Intraoperatively, the liver was noted to have a strikingly dark pigmentation, prompting a biopsy. Histopathological analysis confirmed the diagnosis of DJS. Additionally, examination of the resected gallbladder revealed focal intestinal metaplasia—an established premalignant lesion associated with an increased risk of gallbladder carcinoma. This report underscores the rare coexistence of DJS and gallstone disease and confirms that the presence of DJS does not complicate laparoscopic cholecystectomy or predispose to postoperative cholestasis. To our knowledge, this is the first documented case of intestinal metaplasia of the gallbladder in a patient with DJS. These findings highlight the importance of routine histopathological evaluation of cholecystectomy specimens, even in cases where DJS is discovered incidentally, to facilitate early detection of potential premalignant changes.
Keywords
Dubin Johnson Syndrome Intestinal Metaplasia Gallbladder Cancer Laparoscopic Cholecystectomy Bilirubin cytoprotection.
Ethical Statement
Informed consent is available in the patient's file.
Supporting Institution
None
Thanks
The authors declare no conflicts of interest related to this manuscript. Thank you for considering this manuscript for possible publication.
References
- 1. Kim JH, Kang MW, Kim S, Han JW, Jang JW, Choi JY, et al. Genotype-Phenotype Association in ABCC2 Exon 18 Missense Mutation Leading to Dubin-Johnson Syndrome: A Case Report. Int J Mol Sci. 2022;23(24):16168.
- 2. Rastogi A, Krishnani N, Pandey R. Dubin-Johnson syndrome--a clinicopathologic study of twenty cases. Indian J Pathol Microbiol. 2006;49(4):500-504.
- 3. Sticova E, Elleder M, Hulkova H, Luksan O, Sauer M, Wunschova-Moudra I, et al. Dubin-Johnson syndrome coinciding with colon cancer and atherosclerosis. World J Gastroenterol. 2013;19(6):946-950.
- 4. Siddiqui AH, Alsabe MR, Tehseen Z, Hatamleh MI, Taslim S, Abdelrahman A, et al. Dubin-Johnson Syndrome: A Case Report. Cureus. 2023;15(3):e36115. 5. Renault M, Nowicki M. Persistent cholestasis following cholecystectomy: A case of Dubin–Johnson syndrome. J Pediatr. 2010;157(3):167.
- 6. Wang B, Yang S, Hu X, Zhang Y. Laparoscopic cholecystectomy for cholecystolithiasis with Dubin-Johnson syndrome. JGH Open. 2019;3(6):532-533.
- 7. Kumar H, Kini H, Tiwari A. Histological evaluation of 400 cholecystectomy specimens. J Pathol Nep [Internet]. 2015;5(10):834-840.
- 8. Poget M, Salvatori Chappuis V, Carbó Descamps F, Saadi A. Gallbladder mucocele caused by intestinal metaplasia in lithiatic cholecystitis: A case report and literature review of a rare association. Int J Surg Case Rep. 2024;116:109405.
- 9. Tashiro K, Yamauchi M, Takao Y, Ogoshi E, Yamazaki Y, Aoki T. A case of Gallbladder cancer with Dubin-Johnson Syndrome. Nihon Rinsho Geka Gakkai Zasshi. 2000;61(10):2453-2457.
- 10. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y et al. Hyperbilirubinemia, Augmentation of Endothelial Function, and Decrease in Oxidative Stress in Gilbert Syndrome. Circulation. 2012;126(5):598-603.
- 11. Inoguchi T, Nohara Y, Nojiri C, Nakashima N. Association of serum bilirubin levels with risk of cancer development and total death. Sci Rep. 2021;11(1):13224.
- 12. Shin JW, Kim N, Minh NT, Chapagain DD, Jee SH. Serum bilirubin subgroups and cancer risk: Insights with a focus on lung cancer. Cancer Epidemiol. 2025;94:102727.
- 13. Ihira H, Nakano S, Yamaji T, Katagiri R, Sawada N, Inoue M, et al. Plasma albumin, bilirubin, and uric acid and the subsequent risk of cancer: a case-cohort study in the Japan Public Health Center-based Prospective Study. Am J Epidemiol. 2024;193:1460–1469.
- 14. Yoon HS, Shu XO, Shidal C, Wu J, Blot WJ, Zheng W et al. Associations of Pre-Diagnostic Serum Levels of Total Bilirubin and Albumin with Lung Cancer Risk: Results from the Southern Community Cohort Study. Front Oncol. 2022;12:895479.
- 15. Yi F, Tao S, Wu H. Bilirubin metabolism in relation to cancer. Front Oncol. 2025;15:1570288.
Dubin-Johnson sendromlu bir olguda laparoskopik kolesistektomi sonrası saptanan safra kesesi inestinal metaplazisi: Hiperbilirubineminin safra kesesi kanseri gelişimine karşı koruyucu etkisi olabilir mi?
Abstract
Bu yazıda, semptomatik kolelitiazis nedeniyle laparoskopik kolesistektomi uygulanan 34 yaşındaki bir kadında, nadir görülen ve otozomal resesif kalıtım gösteren Dubin–Johnson Sendromu’nun (DJS) rastlantısal tanısı anlatılmaktadır. DJS, hepatik bilirubin atılımında bozulma ve karakteristik olarak belirgin siyah renkli karaciğer görünümü ile tanımlanan bir hastalıktır. Hasta, sağ üst kadranda karın ağrısı ve hafif hiperbilirubinemi ile başvurmuştur. Operasyon sırasında karaciğerin belirgin koyu pigmentasyonu fark edilmiş ve bu durum biyopsi yapılmasına neden olmuştur. Histopatolojik inceleme sonucunda DJS tanısı doğrulanmıştır. Ek olarak, çıkarılan safra kesesinin incelenmesinde odak intestinal metaplazi saptanmıştır; bu lezyon, safra kesesi karsinomu gelişme riski ile ilişkilendirilen bilinen premalign bir değişikliktir. Bu olgu, DJS ile safra taşı hastalığının nadir birlikteliğini vurgulamakta ve DJS varlığının laparoskopik kolesistektomiye engel oluşturmadığını ya da postoperatif kolestaza yatkınlık yaratmadığını ortaya koymaktadır. Bildiğimiz kadarıyla, DJS tanısı almış bir hastada safra kesesi intestinal metaplazisinin rapor edildiği ilk olgudur. Bu bulgular, DJS tanısı rastlantısal olarak konmuş olsa bile, olası premalign değişikliklerin erken saptanabilmesi açısından kolesistektomi materyallerinin rutin histopatolojik değerlendirilmesinin önemini ortaya koymaktadır.
Keywords
Dubin-Johnson sendromu İntestinal metaplazisi Safra kesesi kanseri Laparoskopik kolesistektomi Bilirübin sitoproteksiyonu
Ethical Statement
Hastanın onamı dosyasında mevcuttur.
Supporting Institution
YOK
Thanks
Yazarlar, bu makale ile ilgili herhangi bir çıkar çatışması bulunmadığını beyan etmektedir. Bu çalışmayı olası yayın için değerlendirdiğiniz için teşekkür ederiz.
References
- 1. Kim JH, Kang MW, Kim S, Han JW, Jang JW, Choi JY, et al. Genotype-Phenotype Association in ABCC2 Exon 18 Missense Mutation Leading to Dubin-Johnson Syndrome: A Case Report. Int J Mol Sci. 2022;23(24):16168.
- 2. Rastogi A, Krishnani N, Pandey R. Dubin-Johnson syndrome--a clinicopathologic study of twenty cases. Indian J Pathol Microbiol. 2006;49(4):500-504.
- 3. Sticova E, Elleder M, Hulkova H, Luksan O, Sauer M, Wunschova-Moudra I, et al. Dubin-Johnson syndrome coinciding with colon cancer and atherosclerosis. World J Gastroenterol. 2013;19(6):946-950.
- 4. Siddiqui AH, Alsabe MR, Tehseen Z, Hatamleh MI, Taslim S, Abdelrahman A, et al. Dubin-Johnson Syndrome: A Case Report. Cureus. 2023;15(3):e36115. 5. Renault M, Nowicki M. Persistent cholestasis following cholecystectomy: A case of Dubin–Johnson syndrome. J Pediatr. 2010;157(3):167.
- 6. Wang B, Yang S, Hu X, Zhang Y. Laparoscopic cholecystectomy for cholecystolithiasis with Dubin-Johnson syndrome. JGH Open. 2019;3(6):532-533.
- 7. Kumar H, Kini H, Tiwari A. Histological evaluation of 400 cholecystectomy specimens. J Pathol Nep [Internet]. 2015;5(10):834-840.
- 8. Poget M, Salvatori Chappuis V, Carbó Descamps F, Saadi A. Gallbladder mucocele caused by intestinal metaplasia in lithiatic cholecystitis: A case report and literature review of a rare association. Int J Surg Case Rep. 2024;116:109405.
- 9. Tashiro K, Yamauchi M, Takao Y, Ogoshi E, Yamazaki Y, Aoki T. A case of Gallbladder cancer with Dubin-Johnson Syndrome. Nihon Rinsho Geka Gakkai Zasshi. 2000;61(10):2453-2457.
- 10. Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y et al. Hyperbilirubinemia, Augmentation of Endothelial Function, and Decrease in Oxidative Stress in Gilbert Syndrome. Circulation. 2012;126(5):598-603.
- 11. Inoguchi T, Nohara Y, Nojiri C, Nakashima N. Association of serum bilirubin levels with risk of cancer development and total death. Sci Rep. 2021;11(1):13224.
- 12. Shin JW, Kim N, Minh NT, Chapagain DD, Jee SH. Serum bilirubin subgroups and cancer risk: Insights with a focus on lung cancer. Cancer Epidemiol. 2025;94:102727.
- 13. Ihira H, Nakano S, Yamaji T, Katagiri R, Sawada N, Inoue M, et al. Plasma albumin, bilirubin, and uric acid and the subsequent risk of cancer: a case-cohort study in the Japan Public Health Center-based Prospective Study. Am J Epidemiol. 2024;193:1460–1469.
- 14. Yoon HS, Shu XO, Shidal C, Wu J, Blot WJ, Zheng W et al. Associations of Pre-Diagnostic Serum Levels of Total Bilirubin and Albumin with Lung Cancer Risk: Results from the Southern Community Cohort Study. Front Oncol. 2022;12:895479.
- 15. Yi F, Tao S, Wu H. Bilirubin metabolism in relation to cancer. Front Oncol. 2025;15:1570288.
Details
| Primary Language | English |
|---|---|
| Subjects | General Surgery |
| Journal Section | Letter to Editor |
| Authors | |
| Submission Date | September 8, 2025 |
| Acceptance Date | October 2, 2025 |
| Publication Date | April 1, 2026 |
| DOI | https://doi.org/10.4717/jsa.1780311 |
| IZ | https://izlik.org/JA96YB29HD |
| Published in Issue | Year 2026 Volume: 19 |
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