Pure mucinous (colloid) carcinoma of gall bladder: a rare entity

INTRODUCTION

Gallbladder carcinoma is a rather uncommon malignancy. The National Cancer Registry Programme of India showed the incidence of gall bladder carcinoma in north India as 4.5 cases per 1,00,000 in males and 10.1 cases per 1,00,000 in females.¹ In the biliary tract, carcinomas with prominent stromal mucin deposition are rare, and ‘mucinous’ carcinomas in which extracellular mucin constitutes more than 50% of the tumour volume, are even more rare.^2,3 Those tumours in which the mucinous pattern comprises of at least 90% of the tumour are called ‘pure mucinous’ (‘colloid phenotype’) carcinomas and are exceedingly rare in the gallbladder (GB).^2,3 These present in middle to late age group (47 to 78 years), usually don't have a sex predilection, and clinically exhibit symptoms of acute cholecystitis.⁴ Approximately twenty cases of mucinous carcinoma of the GB have been reported so far. We report a very rare case of pure mucinous carcinoma of the GB.

CASE REPORT

A 55 years old female presented with the complaints of jaundice for three months and dull aching pain in right hypochondriac region for 1 week. USG abdomen was done, which showed an irregularly marginated hypoechoic mass in the fundus of gallbladder, thickened wall, as well as echogenic shadowing foci from gallstones, and was suggestive of carcinoma along with cholelithiasis. Cholecystectomy was performed and the specimen was received for histopathological examination. Grossly, the gall bladder was enlarged measuring 12x9x7 cm. External surface was congested and nodular (Figure1a). On cut, a large grey-white tumour was identified measuring 11.6x8.5x6.6 cm. Cut surface was variegated showing mucoid areas along with areas of haemorrhage and necrosis. A single mixed stone was identified at the fundus (Figure 1b).

Haematoxylin and eosin stained section showed a tumour which was entirely composed of pools of extracellular mucin, in which clusters of tumour cells were floating. Individual tumour cells were round to oval with moderate amount of cytoplasm and large, hyperchromatic nuclei. Intracellular mucin vacoules could be appreciated. Signet-ring cells were also present. The surrounding stroma showed extensive desmoplasia. The tumour was involving the muscle coat and was reaching upto the serosa layer of the gall bladder (Figure 2a, 2b, 2c).

Immunohistochemistry for MUC1, CK7, CK20 and CDX2 was applied. On evaluation, it was found to be positive for MUC1 and CK7, and negative for CK20 (ruling out intestinal carcinoma) and CDX2 (ruling out pancreatic mucinous carcinoma) (Figures 3a, 3b, 3c, 3d).

A final diagnosis of ‘pure mucinous (colloid) adenocarcinoma’ of the gallbladder was given.

DISCUSSION

Majority of the carcinomas of the GB are adenocarcinomas of the pancreatobiliary type while other subtypes such as papillary, clear cell and mucinous adenocarcinomas comprise the rest.^2,3 Mucinous carcinomas are tumours in which extracellular mucin constitutes more than 50% of the tumour volume, and is seen as mucin lakes containing scant clusters of floating carcinoma cells.^2,3 These tumours are rare in the GB and, if present, the mucinous pattern usually constitutes 50 to 90% of the tumour, with the rest of the tumour being comprised of conventional adenocarcinoma.^2,3 ‘Pure mucinous (colloid) carcinoma’, i.e. tumours with 90% or more mucinous pattern, as seen in the breast, are exceedingly rare in the gallbladder.^2,3,5 The reported incidence rate varies from 5% to 10.8%.^6-8 About twenty cases of mucinous carcinoma of the GB have been reported so far. However, exactly how many of these had pure mucinous phenotype is unclear. The reported female to male ratio is 1.1 for mucinous carcinomas (versus 3.9 for conventional pancreatobiliary-type GB adenocarcinomas). Perineural invasion has been reported in 73% cases, however, it was not seen in the present case.⁴ In the cases showing perineural invasion, nerve bundles present in mucin pools can be identified by special stains for mucin (Alcian blue, mucicarmine), as well as IHC for mucin (Muc1) and for nerve bundles (S100). Immunophenotypically, mucinous carcinomas of gall bladder differ from intestinal carcinomas by an inverse CK7/20 profile, and from pancreatic mucinous carcinomas by CDX2 negativity (Figure 4).⁴

The risk factors, associated features, natural history and prognosis of mucinous carcinoma of GB are not very well known, owing to their extreme rarity. They are typically large and advanced tumours at the time of diagnosis, with 87% of the cases showing T3 tumours, as opposed to 48% in conventional GB adenocarcinomas, and thus exhibit more-aggressive behavior than conventional GB carcinomas.⁴

They may lead to pseudomyxoma peritonei. Giang et al, in a review of 23 GB carcinomas, discussed the potential pitfall of confusing primary mucinous adenocarcinoma of GB with pseudomyxoma peritonei from a low-grade appendiceal neoplasm disseminated to GB, especially when only the GB is removed.⁹

CONCLUSION

Overall the survival of mucinous carcinoma is significantly worse than that of conventional adenocarcinomas. Moreover, overall survival of patients who have carcinomas with signet-ring cells appears to be worse (6 months) than for pure colloid cases and mixed mucinous ones (14 months).⁴

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

1. 1. National Cancer Registry Programme, Consolidated reports of the population based cancer registries 1990-96. Indian Council of Medical Research, New Delhi, India: 2001.
2. 2. Adsay VN, Klimstra DS. Benign and Malignant Tumours of the gallbladder and extrahepatic biliary tract. In: Odze RD, Goldblum JR, editors. Surgical pathology of the GI tract, liver, biliary tract, and pancreas. 2^nd ed. Philadelphia: Saunders Elsevier. 2009;857-70.
3. 3. Adsay VN. Gallbladder, Extrahepatic biliary tree, and ampulla. In: Mills SE, editor. Sternberg’s diagnostic surgical pathology. 5^th Ed. Lippincott Williams and Wilkins; 2010:1620-4.
4. 4. Dursun N, Escalona OT, Roa JC, Basturk O, Bagci P, Cakir A, et al. Mucinous carcinomas of the gallbladder: clinicopathologic analysis of 15 cases identified in 606 carcinomas. Archives of Pathol Laboratory Med. 2012;136(11):1347-58.
5. 5. Rosen PP, editor. Rosen’s Breast Pathology. 3^rd ed. Lippincott Williams and Wilkins. 2009:515-35.
6. 6. Joo YE, Kim HS, Choi SK, Rew JS, Kim HJ, Kang HK, et al. Case of mucinous adenocarcinoma with porcelain gallbladder. J Gastroenterol Hepatol. 2003;18(8):995-8.
7. 7. Shani M, Hart J, Modan B. Cancer of the biliary system: a study of 445 cases. Br J Surg. 1974;61:98-100.
8. 8. Lack EL. Tumours of the gallbladder and cystic duct. In: Lack EL, ed. Pathology of the Pancreas, Gallbladder, Extrahepatic Biliary Tract, and Ampullary Region. New York, NY: Oxford University Press, Inc; 2003:465-511.
9. 9. Giang TH, Ngoc TTB, Hassell LA. Carcinoma involving the gallbladder: a retrospective review of 23 cases: pitfalls in diagnosis of gallbladder carcinoma. Diagn Pathol. 2012;7:10.