Histopathological Study of Gallbladder Carcinoma and its Mimics with Role of Carcinoembryonic Antigen Immunomarker in Resolving Diagnostic Difficulties

Abstract

Background: Gallbladder carcinoma (GBC) sometimes presents with nonspecific signs, without forming a mass, mimicking benign gallbladder (GB) diseases. On the contrary, benign GB diseases may mimic GBC. Material and Methods: We retrospectively reviewed 107 cases over a period of 3 years (May 2012–April 2015), which included 41 review cases and 66 departmental cases. Carcinoembryonic antigen (CEA) immunomarker expression was done. Results: In 27 of the 41 review cases, the diagnoses were benign diseases of GB associated with mild-to-moderate dysplasia of mucosal glands; however, after review in our department, it was found that of these 27 cases, nine cases were actually well-differentiated adenocarcinoma of GB with diffuse CEA expression and were mis diagnosed as benign diseases of GB with dysplasia. In 32 out of 66 departmental cases, initial histopathological diagnoses were benign diseases of GB associated with dysplastic mucosal glands. After CEA staining, 11 out of these 32 cases turned out to be adenocarcinoma of the GB. Among the rest 34 (34/66) departmental primary GBC cases, no CEA expression was seen in six cases, focal expression was seen in 12 cases, and diffuse expression was seen in 16 cases. No diffuse CEA expression was seen in benign diseases of the GB with dysplasia. Conclusion: GBC sometimes may not be diagnosed radiologically and grossly as it often presents without any mass and specific signs, which lead to under diagnosis. Some benign cases may mimic GBC and maycomplicate histological diagnosis. CEA expression may aid as an additional diagnostic aid in resolving diagnostic dilemmas.

Keywords

Carcinoembryonic antigen - gallbladder carcinoma - misdiagnosis

Publication History

Article published online:
04 July 2021

• References

• 1 Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol 2003;4:167-76.
• 2 Diehl AK. Epidemiology of gallbladder cancer: A synthesis of recent data. J Natl Cancer Inst 1980;65:1209-14.
• 3 Dhir V, Mohandas KM. Epidemiology of digestive tract cancers in India IV. Gall bladder and pancreas. Indian J Gastroenterol 1999;18:24-8.
• 4 Kapoor VK, McMichael AJ. Gallbladder cancer: An 'Indian' disease. Natl Med J India 2003;16:209-13.
• 5 Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: Geographical distribution and risk factors. Int J Cancer 2006;118:1591-602.
• 6 Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO Classification of Tumours of the Digestive System. Vol. 4. Lyon: IARC Press; 2010. p. 266-74.
• 7 Roa I, Araya JC, Villaseca M, Roa J, de Aretxabala X, Ibacache G. Gallbladder cancer in a high risk area: Morphological features and spread patterns. Hepatogastroenterology 1999;46:1540-6.
• 8 Donohue JH, Nagorney DM, Grant CS, Tsushima K, Ilstrup DM, Adson MA. Carcinoma of the gallbladder. Does radical resection improve outcome? Arch Surg 1990;125:237-41.
• 9 Cubertafond P, Gainant A, Cucchiaro G. Surgical treatment of 724 carcinomas of the gallbladder. Results of the French Surgical Association Survey. Ann Surg 1994;219:275-80.
• 10 Canil CM, Tannock IF. Doctor's dilemma: Incorporating tumor markers into clinical decision-making. Semin Oncol 2002;29:286-93.
• 11 Brandt-Rauf PW, Pincus M, Adelson S. Cancer of the gallbladder: A review of forty-three cases. Hum Pathol 1982;13:48-53.
• 12 Strom BL, Iliopoulos D, Atkinson B, Herlyn M, West SL, Maislin G, et al. Pathophysiology of tumor progression in human gallbladder: Flow cytometry, CEA, and CA 19-9 levels in bile and serum in different stages of gallbladder disease. J Natl Cancer Inst 1989;81:1575-80.
• 13 Kimura W, Shimada H, Kuroda A, Morioka Y. Carcinoma of the gallbladder and extrahepatic bile duct in autopsy cases of the aged, with special reference to its relationship to gallstones. Am J Gastroenterol 1989;84:386-90.
• 14 Giang TH, Ngoc TT, Hassell LA. Carcinoma involving the gallbladder: A retrospective review of 23 cases-Pitfalls in diagnosis of gallbladder carcinoma. Diagn Pathol 2012;7:10.
• 15 Agrawal V, Goel A, Krishnani N, Pandey R, Agrawal S, Kapoor VK. p53, carcinoembryonic antigen and carbohydrate antigen 19.9 expression in gall bladder cancer, precursor epithelial lesions and xanthogranulomatous cholecystitis. J Postgrad Med 2010;56:262-6.
• 16 Roa I, Araya JC, Wistuba I, De Aretxabala X, Salinas C, Mauriz A, et al. Immunohistochemical expression of the carcinoembryonic antigen in gallbladder cancer]. Rev Med Chil 1991;119:129-36.
• 17 Roa I, Araya JC, Shiraisch T, Yatani R, Wistuba I, Villaseca M, et al. Gallbladder cancer: Immunohistochemical expression of CA-19-9, epithelial membrane antigen, dupan-2 and carcinoembryonic antigen. Rev Med Chil 1992;120:1218-26.
• 18 Albores-Saavedra J, Nadji M, Morales AR, Henson DE. Carcinoembryonic antigen in normal, preneoplastic and neoplastic gallbladder epithelium. Cancer 1983 15;52:1069-72.
• 19 Van Patten K, Parkash V, Jain D. Cadherin expression in gastrointestinal tract endometriosis: Possible role in deep tissue invasion and development of malignancy. Mod Pathol 2010;23:38-44.
• 20 Albores-Saavedra J, Keenportz B, Bejarano PA, Alexander AA, Henson DE. Adenomyomatous hyperplasia of the gallbladder with perineural invasion: Revisited. Am J Surg Pathol 2007;31:1598-604.
• 21 Shirai Y. Histological differentiation of Rokitansky-Aschoff sinus involvement from stromal invasion of carcinoma of the gallbladder. Nihon Geka Gakkai Zasshi 1987;88:970-81.