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CASE REPORT
Year : 2016  |  Volume : 19  |  Issue : 2  |  Page : 94-97

Variants of gallbladder adenocarcinomas: Five case reports


1 Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Department of Pathology, B. R. Singh Hospital, Sealdah, Kolkata, West Bengal, India

Date of Web Publication12-Jul-2016

Correspondence Address:
Debjit Banerjee
Department of Pathology, B. R. Singh Hospital, Eastern Railway, Sealdah, Kolkata, West Bengal
India
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DOI: 10.4103/1118-8561.186036

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  Abstract 

Conventional adenocarcinomas comprise of about 90% of all gallbladder neoplasms; among them, pancreatobiliary is the most common phenotype followed by intestinal and gastric foveolar types. Papillary variant is the second most common form of adenocarcinoma affecting the gallbladder. Mucinous adenocarcinoma and signet-ring cell carcinoma are rarer variants with grave prognoses. We report five cases of gallbladder neoplasms with four different histopathological features. (1) To report the rare neoplasms of the gallbladder for the future researches on their histopathology-based targeted therapy. (2) To describe the clinico-pathogical characteristics of the rare variants of gallbladder neoplasm.

Keywords: Gallbladder, mucinous adenocarcinoma, papillary adenocarcinoma, signet-ring cell


How to cite this article:
Das S, Banerjee D, Mondal S, Tayal P. Variants of gallbladder adenocarcinomas: Five case reports. Sahel Med J 2016;19:94-7

How to cite this URL:
Das S, Banerjee D, Mondal S, Tayal P. Variants of gallbladder adenocarcinomas: Five case reports. Sahel Med J [serial online] 2016 [cited 2019 Oct 18];19:94-7. Available from: http://www.smjonline.org/text.asp?2016/19/2/94/186036


  Introduction Top


Gallbladder carcinoma is a relatively uncommon neoplasm that has geographical and ethnic variations in its incidence. The highest incidences are reported in Indians, Pakistanis, Chileans, Bolivians, Central Europeans, Israelis, and Native Americans and Americans of Mexican origin.[1] The overall age-adjusted incidence rates of gallbladder carcinomas in India are 1.0 for men and 2.3 for women per 100,000 population, With great regional variations. The incidence is significantly higher in Northern and Eastern parts of India, reaching up to 6.6 per 100,000 population in New Delhi, the capital and a Northern state in India.[2] Most patients diagnosed with gallbladder carcinoma are in the sixth or seventh decade of life.[3] Important risk factors for the disease include genetic backgrounds, gallstones, and abnormal choledochopancreatic junctions. The signs and symptoms are not specific, often resembling those of chronic cholecystitis. Right upper-quadrant pain is common. If the tumor is located in the gallbladder neck or its duct, obstructive jaundice may present clinically. Gallbladder carcinoma usually forms an infiltrating, gray-white mass. Some carcinomas cause diffuse thickness of the gallbladder wall while some are polypoidal or adenomatous in appearance. Most cases are not detectable on gross examination.[4]

Most gallbladder carcinomas are conventional adenocarcinomas. Among them, the pancreatobiliary is the most common subtype, followed by intestinal-type.[3] Papillary variant of adenocarcinoma is the second most common subtype affecting the gallbladder. However, its true incidence is yet unknown.[3] Both pancreatobiliary and papillary cancers have good prognoses. Other variants, mucinous adenocarcinoma, and adenosquamous carcinoma of gallbladder are mentioned only in case reports. We report five cases of adenocarcinomas, one conventional adenocarcinoma intestinal-type, one papillary adenocarcinoma biliary-type, one papillary adenocarcinoma intestinal-type, one mucinous adenocarcinoma, and one signet-ring cell adenocarcinoma detected on histology.


  Case Reports Top


Case 1

A 58-year-old woman presented with progressively increasing icterus and anorexia for 3 months. Ultrasound revealed an enlarged gallbladder with thickened wall. Serum total bilirubin was 4.7 mg/dl, with direct fraction being 3.9 mg/dl. Open cholecystectomy was done. Gallbladder measured 7.4 cm × 5.2 cm × 3.7 cm. The wall was thickened (thickness 2.1 cm) at the fundus and body areas. The respective mucosa was rough and irregular. Sections revealed neoplastic glands lined by single layer of well-differentiated intestinal-type of epithelium with occasional goblet cells [Figure 1]. Serosa was infiltrated by the tumor. Occasional tumor emboli were noted within venous channels. There was no evidence of hepatic, nodal or distant metastatic involvement. The tumor was staged as Stage II according to tumor-node-metastasis (TNM) classification.
Figure 1: Neoplastic glands lined by single layer of well-differentiated intestinal-type epithelium with occasional goblet cells

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Case 2

A 53-year-old female, with a history of icterus and vomiting, and a total bilirubin of 2.2 mg/dl, underwent cholecystectomy. The gallbladder measured 7.3 cm × 3.8 cm × 2.1 cm. Maximum wall thickness was 1.8 cm, with papillary excrescences into the lumen arising from the body of the gallbladder. Histologically the tumor was composed of well-formed papillae lined by moderately differentiated neoplastic cells with a biliary phenotype [Figure 2]. Serosa was uninvolved. No nodal or distant metastatic spread was noted. The TNM staging of the tumor was Stage I.
Figure 2: Well-formed papillae lined by moderately differentiated neoplastic cells with a biliary phenotype

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Case 3

A 61-year-old male presented with progressive icterus and right upper quadrant pain for 2 months. Total bilirubin was 4.3 mg/dl. Ultrasonography detected a mass filling the gallbladder lumen showing fingerlike projections [Figure 3]a. Cholecystectomy was done. Gallbladder measured 5.6 cm × 3.8 cm × 2.3 cm. The lumen was filled with a polypoidal growth (3.2 cm × 1.7 cm) arising from the body of gallbladder. Microscopically well-formed papillae, with fibrovascular cores, lined by tall columnar intestinal-type cells identified. Many goblet cells are also seen [Figure 3]b. The tumor invaded the muscularis, but not the serosa. No evidence of nodal or distant metastasis was documented. The tumor was staged as Stage I.
Figure 3: (a) Papillary adenocarcinoma showing fine fingerlike projections into the lumen. (b) Papillae, with fibrovascular cores, lined by tall columnar intestinal-type cells along with many goblet cells

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Case 4

A 57-year-old female, with cachexia and repeated vomiting for 3 months was radiologically detected with thickened gallbladder wall. Cholecystectomy revealed an enlarged gallbladder (7.1 cm × 4.2 cm × 2.9 cm) with thickened wall (maximum wall thickness 1.9 cm). The mucosal surface was glistening and grayish-white. Microscopically, a tumor was detected composing of few scattered glands and many discohesive cells with hyperchromatic and pleomorphic nuclei, floating in lakes of extracellular mucin [Figure 4]a. The mucin was periodic acid-Schiff (PAS) positive [Figure 4]b. Occasional signet-ring cells were also identified. Serosa was infiltrated by the tumor cells, but the liver bed was free. No lymph node or distant metastasis was documented. The tumor was staged as Stage II.
Figure 4: (a) Few scattered glands and many discohesive cells with hyperchromatic and pleomorphic nuclei, floating in lakes of extracellular mucin. (b) Extracellular mucin showing periodic acid-Schiff positivity

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Case 5

A 49-year-old female presenting with repeated episodes of right upper quadrant abdominal pain and vomiting of 4 months duration was clinically and radiologically diagnosed with cholelithiasis. Serum total bilirubin was 2.1 mg/dl. Routine laparoscopic cholecystectomy was done. Gallbladder measured 5.2 cm × 3.1 cm × 1.8 cm. Wall was thickened. Maximum wall thickness was 1.4 cm. The mucosa was smooth and glistening. Histopathological examination revealed pools of extracellular mucin with variable amounts of tumor cells floating in the pools. The neoplastic cells were discohesive with hyperchromatic and pleomorphic nuclei. Abundant intracellular mucin pushed the nuclei toward the periphery, in majority of the neoplastic cells, giving them a signet-ring appearance [Figure 5]. The tumor cells were seen infiltrating the serosa, but no liver invasion was noted. The tumor was staged as Stage II.
Figure 5: Abundant intracellular mucin pushing the nuclei toward the periphery in majority of the neoplastic cells, giving them a signet-ring appearance

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  Discussion Top


Conventional adenocarcinoma of pancreatobiliary type is the most common type of malignant neoplasm involving the gallbladder.[3] Although microscopic foci of intestinal differentiation often co-exist in cases of gallbladder adenocarcinoma, epithelial neoplasms composed wholly or predominantly of cells with an intestinal phenotype are unusual in the gallbladder.[5] Two morphological variants of invasive adenocarcinoma of the intestinal-type have been previously described.[6] The first variant consists of glands predominantly lined with goblet cells, absorptive columnar cells, and a variable number of neuroendocrine and Paneth cells. The second variant is composed of branching tubular glands and papillary components, closely resembling colonic adenocarcinoma and contains fewer goblet cells than the first type.[7] The histological feature of our case is consistent with the small intestinal variant of adenocarcinoma of the gallbladder.

Papillary gallbladder adenocarcinoma is a distinct clinical entity that represents about 5% of all malignant gallbladder tumors.[8] Patients typically present with symptoms similar to cholelithiasis, which may be secondary to the large papillary growth that fills the gallbladder lumen.[9] The indexed cases presented with symptoms of right upper quadrant pain, icterus, and vomiting. Papillary variant of adenocarcinoma presents most commonly with large granular or cauliflower-like masses filling and distending the lumen of gallbladder. Histologically, they are characterized by predominance of branching papillae lined by malignant cuboidal to columnar cells with variable differentiation. Focal intestinal differentiation with collections of goblet, endocrine or Paneth cells, and focal mucinous differentiation has also been noted.[3] In fewer cases, biliary phenotype was documented. In the indexed cases, the gallbladders were distended by papillary excrescences filling the lumen. On microscopy, branching papillae lined by low columnar cells with variable atypia and focal mucinous differentiation was noted in one case, and papillae lined by multiple layers of moderately differentiated biliary epithelium is seen in the other. Papillary variant is said to have better prognosis than the conventional one.[8]

Mucinous differentiation is a quite common secondary component in otherwise conventional adenocarcinomas.[10] By definition, mucinous adenocarcinomas have more than 50% areas composed of extracellular mucin.[3] Two histological variants – one characterized by neoplastic glands distended with mucin and lined by columnar cells with mild to moderate nuclear atypia, and the second variant is characterized by small groups of clusters of cells surrounded by abundant mucin.[10] Some studies said mucinous variants have a worse prognosis than the conventional adenocarcinoma of gallbladder, as they mostly present with advanced stage disease. In our case, thickened glistening gallbladder wall showed clusters of atypical cells floating in pools of PAS positive extracellular mucin.

Signet-ring cell carcinoma is even more uncommon tumor of the gallbladder; only few case reports have previously been published.[11] However, prognosis of gallbladder carcinoma is poor. Owing to the location of the gallbladder, dissemination of the tumor to the adjacent tissues is usually present at the time of diagnosis. Most patients are not suitable for curative surgery because of the advanced stage of the disease.[12] Our cases presented with Stage II disease, without any hepatic or metastatic involvement.


  Conclusion Top


Gallbladder carcinomas are a leading cause of cancer mortality in South-east Asia, especially in India. A greater number of rare variants of gallbladder carcinomas with poorer prognoses are being detected in this part of the world. Reporting of these variants must be encouraged so that the true incidence rates of them can be obtained, which will emphasize future clinical researches on histology-based targeted therapy.

Acknowledgments

We would like to thank all the patients and their attendants for their consistent co-operation, and wish them all a better healthy life.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: Geographical distribution and risk factors. Int J Cancer 2006;118:1591-602.  Back to cited text no. 1
    
2.
Kapoor VK, McMichael AJ. Gallbladder cancer: An 'Indian' disease. Natl Med J India 2003;16:209-13.  Back to cited text no. 2
    
3.
Albores-Saavedra J, Scoazec JC, Wittekind G. Carcinoma of the gallbladder and extra hepatic bile ducts in World Health Organization classification of tumours. Pathology and Genetics of Tumours of the Digestive System. Lyon: IARC Press; 2000. p. 205-14.  Back to cited text no. 3
    
4.
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.  Back to cited text no. 4
    
5.
You Y, Bui K, Bui MM, Malafa M, Coppola D. Histopathological and immunophenotypical features of intestinal-type adenocarcinoma of the gallbladder and its precursors. Cancer Control 2014;21:247-50.  Back to cited text no. 5
    
6.
Albores-Saavedra J, Cruz-Ortiz H, Alcantara-Vazques A, Henson DE. Unusual types of gallbladder carcinoma. A report of 16 cases. Arch Pathol Lab Med 1981;105:287-93.  Back to cited text no. 6
    
7.
Albores-Saavedra J, Nadji M, Henson DE. Intestinal-type adenocarcinoma of the gallbladder. A clinicopathologic study of seven cases. Am J Surg Pathol 1986;10:19-25.  Back to cited text no. 7
    
8.
Albores-Saavedra J, Tuck M, McLaren BK, Carrick KS, Henson DE. Papillary carcinomas of the gallbladder: Analysis of noninvasive and invasive types. Arch Pathol Lab Med 2005;129:905-9.  Back to cited text no. 8
    
9.
Kim MJ, Kim KW, Kim HC, Kim SY, Park SH, Kim AY, et al. Unusual malignant tumors of the gallbladder. AJR Am J Roentgenol 2006;187:473-80.  Back to cited text no. 9
    
10.
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. Arch Pathol Lab Med 2012;136:1347-58.  Back to cited text no. 10
    
11.
Nishida T, Iwasaki H, Johzaki H, Tanaka S, Watanabe R, Kikuchi M. A human gall-bladder signet ring cell carcinoma cell line. Pathol Int 1997;47:368-76.  Back to cited text no. 11
    
12.
Misra S, Chaturvedi A, Misra NC, Sharma ID. Carcinoma of the gallbladder. Lancet Oncol 2003;4:167-76.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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