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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 2  |  Issue : 4  |  Page : 169-172

Gallbladder adenocarcinoma with incidental finding of xanthogranulomatous cholecystitis and tubercular lymphadenitis: A rare case report


Department of Pathology, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India

Date of Submission06-Jun-2022
Date of Decision10-Aug-2022
Date of Acceptance23-Aug-2022
Date of Web Publication13-Oct-2022

Correspondence Address:
Kafil Akhtar
Department of Pathology, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ghep.ghep_17_22

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  Abstract 


Gallbladder carcinoma is the fifth most common gastrointestinal malignancy and the most common malignancy of the biliary system, with a high incidence in the Gangetic belt of India. The 5-year survival rate is nearly 19.0% because of the aggressive nature of the lesion. We report a rare case of a 35-year-old female who presented with complaints of pain in the right upper abdomen with jaundice, bloating, and intolerance to fatty food for 3 months and the lump in the right upper abdomen for 1 month. Ultrasonography and computed tomography were performed which showed a thickening in the fundic region of the gallbladder with infiltration into the liver. Extended cholecystectomy was done, and a diagnosis of well-differentiated adenocarcinoma with xanthogranulomatous cholecystitis with tubercular lymphadenitis was made.

Keywords: Gallbladder carcinoma, tubercular lymphadenitis, xanthogranulomatous cholecystitis


How to cite this article:
Usman SI, Nahid Z, Shams A, Akhtar K. Gallbladder adenocarcinoma with incidental finding of xanthogranulomatous cholecystitis and tubercular lymphadenitis: A rare case report. Gastroenterol Hepatol Endosc Pract 2022;2:169-72

How to cite this URL:
Usman SI, Nahid Z, Shams A, Akhtar K. Gallbladder adenocarcinoma with incidental finding of xanthogranulomatous cholecystitis and tubercular lymphadenitis: A rare case report. Gastroenterol Hepatol Endosc Pract [serial online] 2022 [cited 2022 Nov 27];2:169-72. Available from: http://www.ghepjournal.com/text.asp?2022/2/4/169/358471




  Introduction Top


Many genetic and environmental factors have been linked to carcinoma gallbladder.[1] Chronic infection of the gallbladder and environmental exposure to certain chemicals, heavy metals, and many dietary factors have been proposed to play a role in carcinoma gallbladder.[1] Gallstones are also an important risk factor for the occurrence of carcinoma of the gallbladder. The number of gallstones, size of stones, and their duration are implicated in disease causation as they are responsible for the continuous insult to the mucosa of the gallbladder.[2],[3] Large size solitary gallstones have been found associated with gallbladder carcinoma.[4] Female gender, multiparity, and smoking are other important risk factors.[4],[5]

Xanthogranulomatous cholecystitis is a rare type of chronic cholecystitis characterized by severe proliferative fibrosis and accumulation of lipid-laden macrophages. It is both a mimicker and risk factor for carcinoma of the gallbladder.[6],[7]


  Case Report Top


A 35-year-old female presented to the surgical outpatient department, with complaints of pain in the right upper abdomen for 3 months which was continuous, dull aching, nonradiating, and transiently relieved by analgesics. The pain was associated with bloating and vomiting. She also complained of a progressive lump in the right upper abdomen for 1 month. There was no history of yellowish discoloration of eyes and urine. Her bowel and bladder habits were regular. There was associated history of weight loss and a decrease in appetite.

On general examination, the patient was alert, oriented, and not icteric. On per abdominal examination, an irregular, nontender, nonmobile lump was noted in the right upper quadrant approximately 6 cm × 3.5 cm in size. The liver was not enlarged, but the lump was contiguous with the liver. The overlying skin was completely normal with no signs of ascites.

Her abdominal ultrasonography showed a distended gallbladder with thickened wall and a solitary oval stone of 2 cm in maximum dimension in the lumen. Computed tomography showed a distended gallbladder with asymmetric heterogeneous thickening of the fundic wall measuring 5.5 cm in largest diameter with infiltration in segments 4b and 5 of the liver, suggestive of carcinoma of the gallbladder.

She was mildly anemic with hemoglobin of 10 g/dl. Her liver function tests were within normal limits with serum carbohydrate antigen 19-9 (CA19-9) of 25 units/ml. Extended cholecystectomy was performed with regional lymphadenectomy including aortocaval, interaortocaval, cystic artery, common hepatic artery, and hepatoduodenal ligament lymph nodes.

On gross examination, the gallbladder was distorted, 6 cm × 4 cm × 1 cm in size, and completely fused with liver parenchyma. The cut section showed a creamish white nodular growth of size 5 cm × 3.5 cm × 3 cm grossly involving the liver parenchyma. All the lymph nodes were bisected into two and examined. On microscopic examination, ill-formed glands with compressed lumina lined by atypical cells infiltrating the muscularis propria were seen [Figure 1]. The tumor cells in acinar configuration showed increased nuclear-to-cytoplasmic ratio, hyperchromasia, and pale eosinophilic cytoplasm surrounded by loose fibrocollagenous stroma [Figure 2] with foci of clusters of foamy histocytes and dense transmural chronic inflammatory infiltrate [Figure 3]. There was no lymphovascular, perineural invasion, and liver parenchyma margins were not involved by tumor cells. All the lymph nodes were free from tumors, but surprisingly, the cystic artery lymph node showed well-formed epithelioid cell granulomas with Langhan's giant cells, histiocytes, and dense chronic inflammation [Figure 4]. Ziehl–Neelsen stain for acid-fast bacilli was found to be negative. A diagnosis of well-differentiated adenocarcinoma (pT1bN0Mx) with xanthogranulomatous cholecystitis with tubercular lymphadenitis was given.
Figure 1: On microscopic examination, ill-formed glands with compressed lumina lined by atypical cells infiltrating the muscularis propria were seen. Hematoxylin and Eosin ×5

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Figure 2: The tumor cells in acinar configuration showed increased nuclear-to-cytoplasmic ratio, hyperchromasia, and pale eosinophilic cytoplasm surrounded by loose fibrocollagenous stroma. Hematoxylin and Eosin ×10

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Figure 3: Section from the tumor area also showed foci of clusters of foamy histocytes and dense transmural chronic inflammatory infiltrate. Hematoxylin and Eosin ×10

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Figure 4: Cystic artery lymph node showed well-formed epithelioid cell granulomas with Langhan's giant cells, histiocytes, and dense chronic inflammation. Hematoxylin and Eosin ×10

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Our patient was prescribed 9-month regimen of four antitubercular drugs comprising isoniazid, rifampicin, ethambutol, and pyrazinamide along with six cycles of 5-fluorouracil-based chemotherapy. She is fine after 6 months of follow-up period.


  Discussion Top


Xanthogranulomatous cholecystitis is an uncommon form of cholecystitis with an overall incidence of 1.3%–1.9%, but the incident is exceptionally high in India that is 8.8%.[8] About 2%–15% of cases are associated with carcinoma gallbladder suggesting a causal association.[8],[9]

Pathogenesis of this uncommon disease includes the gallstone-induced insult to gallbladder mucosa and rupture of Rokitansky–Aschoff sinuses which result in the spreading of inflammation to adjacent structures.[10] Degradation of bile results in phagocytosis of insoluble cholesterol and bile salts by histiocytes forming lipid-laden macrophages. The extensive inflammatory process causes fibrosis and adhesions to adjacent structures mimicking carcinoma.[7],[10]

Preoperative differentiation of xanthogranulomatous cholecystitis and carcinoma gallbladder is difficult. Long recurrent abdominal pain, diffusely thick gallbladder, and cholelithiasis favor xanthogranulomatous cholecystitis, while focal thickening of gallbladder wall along with local organ infiltration on imaging and history of anorexia and weight loss favors the diagnosis of gallbladder carcinoma. Lymph nodes can be enlarged in both cases.[11] This differentiation is important as the extent of surgical resection is different in both cases. Our patient was diagnosed as gallbladder carcinoma preoperatively, and to our surprise, it was also associated with xanthogranulomatous cholecystitis with tubercular lymphadenitis.

Gallbladder carcinoma is the most common biliary epithelial malignancy, and India contributes to 10.0% of the global gallbladder cancer burden.[12] This malignant lesion can occur due to polyps and adenoma-carcinoma progression, but dysplasia-carcinoma sequence is most commonly seen. It may take up to 10 years for the progression of metaplasia to dysplasia and additional 5 years for the development of carcinoma in situ.[13],[14]

Gallbladder tuberculosis is a rare disease. The alkaline nature of bile does not allow the growth of mycobacteria, but it can mimic gallbladder carcinoma. The mode of spread can be both hematogenous and lymphatics.[15] Although our patient did not have tuberculosis of the gallbladder, one of the resected nodes showed clusters of epithelioid cell granulomas. This patient did not have any prior history of tuberculosis or history of contact.

The outcome of gallbladder carcinoma is not good, and the overall survival rate is <5.0%.[16] Postoperatively, the patient should be given concurrent radiotherapy and chemotherapy to improve survival. Fluorouracil (5-FU) is the most commonly used drug with proven safety and efficacy in several trials.[17] Our patient was also given 5-FU-based chemotherapy along with antitubercular treatment and did not develop any significant complications during 6 months of follow-up period. Many targeted therapies are under trial for gallbladder carcinoma, but there has been no major improvement in the survival of patients. Till date, combination therapy remains the standard care for advanced disease.[18] Even after cholecystectomy, patients aged more than 65 years at the time of diagnosis, adenocarcinoma with >3 cm in size, increasing tumor spread, and lymph node involvement are poor survival predictors.[19] Studies have also shown that survival is poor in gallbladder carcinoma associated with acute cholecystitis.[20] Our patient was diagnosed in the early stage of malignancy with no lymph node involvement but with associated xanthogranulomatous cholecystitis and tubercular lymphadenitis, which are additional risk factors of malignancy that can harm the overall survival and recovery of the patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sharma A, Sharma KL, Gupta A, Yadav A, Kumar A. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update. World J Gastroenterol 2017;23:3978-98.  Back to cited text no. 1
    
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Pilgrim CH, Groeschl RT, Christians KK, Gamblin TC. Modern perspectives on factors predisposing to the development of gall bladder cancer. HPB (Oxford) 2013;15:839-44.  Back to cited text no. 2
    
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Singh BP, Khan WF, Rathore YS, Pol MM. Incidental carcinoma gallbladder: Incidence, risk factors, and factors affecting survival-5-year experience from a tertiary care institute. J Gastrointest Cancer 2020;51:980-7.  Back to cited text no. 3
    
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Alvi AR, Siddiqui NA, Zafar H. Risk factors of gallbladder cancer in Karachi-a case-control study. World J Surg Oncol 2011;9:164.  Back to cited text no. 4
    
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Murray FE, Logan RF, Hannaford PC, Kay CR. Cigarette smoking and parity as risk factors for the development of symptomatic gall bladder disease in women: Results of the Royal College of General Practitioners' oral contraception study. Gut 1994;35:107-11.  Back to cited text no. 5
    
6.
Saritas AG, Gul MO, Teke Z, Ulku A, Rencuzogullari A, Aydin I, et al. Xanthogranulomatous cholecystitis: A rare gallbladder pathology from a single-center perspective. Ann Surg Treat Res 2020;99:230-7.  Back to cited text no. 6
    
7.
Benbow EW. Xanthogranulomatous cholecystitis. Br J Surg 1990;77:255-6.  Back to cited text no. 7
    
8.
Hale MD, Roberts KJ, Hodson J, Scott N, Sheridan M, Toogood GJ. Xanthogranulomatous cholecystitis: A European and global perspective. HPB (Oxford) 2014;16:448-58.  Back to cited text no. 8
    
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Zhuang PY, Zhu MJ, Wang JD, Zhou XP, Quan ZW, Shen J. Xanthogranulomatous cholecystitis: A clinicopathological study of its association with gall bladder carcinoma. J Dig Dis 2013;14:45-50.  Back to cited text no. 9
    
10.
Roberts KM, Parsons MA. Xanthogranulomatous cholecystitis: Clinicopathological study of 13 cases. J Clin Pathol 1987;40:412-7.  Back to cited text no. 10
    
11.
Rajaguru K, Mehrotra S, Lalwani S, Mangla V, Mehta N, Nundy S. New scoring system for differentiating xanthogranulomatous cholecystitis from gall bladder carcinoma: A tertiary care centre experience. ANZ J Surg 2018;88:34-9.  Back to cited text no. 11
    
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Dutta U, Bush N, Kalsi D, Popli P, Kapoor VK. Epidemiology of gallbladder cancer in India. Chin Clin Oncol 2019;8:33.  Back to cited text no. 12
    
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Lazcano-Ponce EC, Miquel JF, Muñoz N, Herrero R, Ferrecio C, Wistuba II, et al. Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin 2001;51:349-64.  Back to cited text no. 13
    
14.
Marks EI, Yee NS. Molecular genetics and targeted therapeutics in biliary tract carcinoma. World J Gastroenterol 2016;22:1335-47.  Back to cited text no. 14
    
15.
Krishnamurthy G, Singh H, Rajendran J, Sharma V, Yadav TD, Gaspar BL, et al. Gallbladder tuberculosis camouflaging as gallbladder cancer – Case series and review focussing on treatment. Ther Adv Infect Dis 2016;3:152-7.  Back to cited text no. 15
    
16.
Goetze TO. Gallbladder carcinoma: Prognostic factors and therapeutic options. World J Gastroenterol 2015;21:12211-7.  Back to cited text no. 16
    
17.
Mallick S, Benson R, Haresh KP, Julka PK, Rath GK. Adjuvant radiotherapy in the treatment of gall bladder carcinoma: What is the current evidence. J Egypt Natl Canc Inst 2016;28:1-6.  Back to cited text no. 17
    
18.
Chaturvedi A, Kumar V, Gupta S. Molecular oncology of gall bladder cancer. Indian J Surg Oncol 2021;12:57-64.  Back to cited text no. 18
    
19.
Zhu J, Wu Y, Xiao W, Li Y. Survival predictors of resectable gallbladder carcinoma: An analysis of the surveillance, epidemiology, and end results database. Am Surg 2022; 31:34-8.  Back to cited text no. 19
    
20.
Bosch DE, Salipante SJ, Schmidt RA, Swanson PE, Bryan A, SenGupta DJ, et al. Neutrophilic inflammation in gallbladder carcinoma correlates with patient survival: A case-control study. Ann Diagn Pathol 2022;56:151845.  Back to cited text no. 20
    


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



 

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