|Ahead of print publication
Mucinous carcinoma of the gallbladder- two rare case reports
Mitakshara Sharma1, Ashutosh Rath1, Reena Tomar1, Nita Khurana1, Deepak Ghuliani2
1 Department of Pathology, Maulana Azad Medical College, New Delhi, India
2 General Surgery, Maulana Azad Medical College, New Delhi, India
|Date of Submission||25-Aug-2019|
|Date of Decision||23-Sep-2019|
|Date of Acceptance||05-Feb-2020|
|Date of Web Publication||10-May-2021|
Department of Pathology, Maulana Azad Medical College, New Delhi
Source of Support: None, Conflict of Interest: None
Gallbladder carcinomas are uncommon with female predominance in the sixth or seventh decades. Mucinous carcinomas of the gallbladder are rare with few cases documented in the literature. We present two cases of mucinous carcinoma of the gallbladder one of which was incidentally detected. The first case is a 65-year-old female who was diagnosed clinically with a suspected case of carcinoma of the gallbladder with the help of contrast-enhanced computed tomography. Microscopy showed extensive areas of mucin pools (>90% of the tumor), atypical cells in three-dimensional clusters, and scattered singly in the mucin pools. Immunohistochemistry revealed a strong expression of MUC2 by the tumor cells. The second case is a 60-year-old female who was diagnosed clinically with a case of chronic cholecystitis; however, the cholecystectomy specimen showed a mucinous growth in the fundus and body of the gallbladder, microscopy of which showed extensive mucin pools (>90% of the tumor) along with scattered signet-ring cells. Both the cases were reported as mucinous carcinoma of the gallbladder. Mucinous carcinoma of the gallbladder exhibit more aggressive behavior than conventional gallbladder carcinomas. Documentation of these rare cases will encourage further research to find out their true incidence and adequate management of the patient.
Keywords: Adenocarcinoma, gallbladder carcinoma, mucinous carcinoma gall bladder
| > Introduction|| |
Gallbladder carcinomas are uncommon carcinomas. They have a strong female predominance and are mostly seen in the sixth or seventh decades of life. The incidence of gallbladder cancer is higher in patients with gallstones. Cholelithiasis is present in over 80% of gallbladder carcinomas. Mucinous carcinomas of the gallbladder are extremely rare, and very few cases are documented in the literature. We present two cases of mucinous carcinoma of the gallbladder. One of them was incidentally detected after cholecystectomy.
| > Care Reports|| |
A 65-year-old female presented with pain in the right upper abdomen associated with intermittent episodes of vomiting and gradually increasing swelling in the periumbilical area for 5 years. On physical examination, the abdomen was soft, nontender with a 10 cm × 8 cm lump palpable in the periumbilical area. Contrast-enhanced computed tomography of the abdomen revealed nodular enhancing polypoidal thickening along the wall of the gallbladder with focal infiltration into the adjacent segment of the liver and was suggestive of carcinoma gallbladder. Laparoscopic cholecystectomy was done and the specimen was sent for histopathological examination. On gross examination, gallbladder was measured as 10 cm × 4 cm × 2 cm. On cutting open, a thickened area was seen measuring 2 cm × 2 cm × 0.5 cm in the wall of the fundus of the gall bladder. The wall thickness of the rest of the gall bladder ranged from 0.1 cm to 2 cm. The lumen of the gall bladder was filled with bile and multiple concretions. Grossly, no lymph nodes and liver tissue were identified. Microscopy showed extensive areas of mucin pools (more than 90%), atypical cells in small three-dimensional clusters, and also scattered singly [Figure 1]a. These cells had high nuclear-to-cytoplasmic ratio and hyperchromatic nuclei. A small focus of the gall bladder showed dysplasia. The resected end of the gall bladder was free of tumor. Stain for mucicarmine was positive with variable amounts of tumor cells floating in the pools. Immunohistochemistry revealed a strong expression of MUC2 by the tumor cells in the mucinous areas [Figure 1]b. The case was reported as mucinous carcinoma of the gall bladder. TNM staging was pT1a, Nx, and MX.
|Figure 1: (a) Hematoxylin and eosin stained section showing extensive extracellular mucin pools with scattered tumor cell clusters(Case 1, ×400). (b) Immunohistochemistry, MUC2 showing positive tumor cells in the mucinous areas (arrow, Case 1, ×400). (c) Gross image of the gallbladder of Case 2, showing the mucinous growth in the fundus and body (arrow). (d) Hematoxylin and eosin stained section showing extensive extracellular mucin pools with scattered signet-ring cells (arrow, Case 2, ×400)|
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A 60-year-old female presented with pain upper abdomen for 1 year. General physical and systemic examinations, including per abdominal examination, were unremarkable. Ultrasonography of the abdomen showed features suggestive of chronic cholecystitis with focal wall thickening. With the clinical impression of chronic cholecystitis, cholecystectomy was performed. On gross examination, the gallbladder was measured 7 cm × 4 cm × 2 cm. The mucosal surface showed a mucinous growth over the fundus and body measuring 3.2 cm × 2 cm × 0.5 cm [Figure 1]c. Rest of the gallbladder wall measured was 0.5 cm. No gallstone was identified. Microscopic examination revealed extensive areas of extracellular mucin pools, comprising >90% of the tumor. Scattered singly and in small clusters were signet-ring cells with abundant vacuolated cytoplasm and eccentrically placed hyperchromatic nuclei [Figure 1]d. The resected end of the gallbladder was free of the tumor. The cystic lymph node was not included in the specimen. The tumor was infiltrating the perimuscular connective tissue without any serosal involvement. Thus, the case was reported as mucinous carcinoma of gallbladder with the TNM staging of Pt2, Nx, MX.
Both the patients were lost to follow-up.
| > Discussion|| |
Gallbladder carcinoma is a relatively uncommon neoplasm. These tumors have female predominance with a female-to-male ratio of 3–4:1. The female predominance is related to the increased incidence of calculi in women. The average age of presentation is 65 years. Gallbladder carcinomas are associated with gallstones (80%), porcelain gallbladder (10%–20%), abnormal choledochopancreatic duct junction, exposure to carcinogens such as methylcholanthrene, O-aminoazotoluene, and nitrosamines and also have the genetic predisposition. The highest incidences are reported in Indians, Pakistanis, Chileans, Bolivians, Central Europeans, Israelis, and Native Americans and Americans of Mexican origin. The incidence is significantly higher in the northern and eastern parts of India.
The signs and symptoms resemble those of chronic cholecystitis, including pain in the right upper quadrant, obstructive jaundice if the tumor is located in the gallbladder neck or its duct. In the present reports, the first case was finally suspected to be a case of carcinoma, whereas the second case was incidentally detected postcholecystectomy.
Grossly, gallbladder carcinoma usually forms a focal, infiltrating, gray-white mass but may also be seen as a diffuse thickness of the gallbladder wall or a polypoidal growth. Gallbladder carcinoma is usually an incidental diagnosis. Majority cases are not identified on gross examination. However, in the present case, the gallbladder of both the patients showed a thickened area, the second case being grossly mucinous.
Microscopically, many patterns of gallbladder carcinoma are described and published by the World Health Organization (WHO). The most common pattern is well to moderately differentiated adenocarcinoma which comprises short and long tubular glands lined by low cuboidal to tall columnar cells. Adenocarcinomas may sometimes show cribriform or angiosarcomatous patterns.
Mucinous adenocarcinomas are rare and constitute 2.5% of gallbladder carcinoma. There are not much data in the literature regarding the incidence, presentation, clinicopathologic characteristics, and etiopathogenesis of mucinous carcinomas of the gallbladder. Till date, approximately 20 cases of mucinous adenocarcinomas have been reported in the literature.
Mucinous carcinoma is defined by the WHO as those tumors comprising >50% mucinous areas composed of extracellular mucin and seen as mucin lakes containing scant clusters of floating carcinoma cells or signet-ring cells. The abundant mucin makes the tumor appear hypocellular. The mucinous areas usually constitute 50%–90% of the tumor which is admixed with areas of conventional adenocarcinoma. Mucinous carcinomas are of two types as follows: (1) pure mucinous carcinomas with more than 90% mucin and (2) mixed mucinous carcinomas with 50%–90% of mucinous areas among the solid areas of adenocarcinoma. Two histological variants of mucinous adenocarcinomas are also described: (1) the first variant is characterized by neoplastic glands lined by columnar cells with mild-to-moderate nuclear atypia and distended with mucin and (2) the second variant is characterized by small groups of clusters of cells surrounded by abundant mucin. In the present reports, the first case showed tumor cells in three-dimensional clusters and scattered singly, lying in mucin pools, whereas the second case showed abundant mucin pools with predominantly signet-ring cells. The mucin pools made >90% of the tumor area in both cases.
The differential diagnosis of the primary mucinous tumor of the gallbladder includes pseudomyxoma peritoni disseminated to the gallbladder, especially when only the gallbladder is removed and mucinous metaplasia in the gallbladder associated with mucosal ulceration, particularly if stones are present, presenting the appearance of possible pools of surface or submucosal mucin.
Immunohistochemistry helps differentiate mucinous carcinomas from other entities. They differ from conventional gallbladder adenocarcinomas by MUC2 positivity. They can be differentiated from intestinal carcinomas by an often inverse CK7/20 profile, from pancreatic mucinous carcinomas by CDX2 negativity and from mammary colloid carcinomas by a lack of MUC6. Unlike gastrointestinal mucinous carcinomas, they appear to be microsatellite stable.
The prognosis of mucinous carcinoma is significantly worse than that of conventional adenocarcinomas because these are large and advanced tumors at the time of diagnosis and thus exhibit more aggressive behavior.
| > Conclusion|| |
The cases of mucinous carcinoma of the gallbladder are presented because of its extreme rarity. They are typically large and advanced tumors at the time of diagnosis and thus exhibit more aggressive behavior than ordinary gallbladder carcinomas. Overall survival of mucinous carcinoma is significantly worse than that of conventional adenocarcinomas. Emphasis should be laid on documentation of these rare cases, which will further encourage research to find out their nature and true incidence.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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