678589 research-article2016
TAI0010.1177/2049936116678589Therapeutic Advances in Infectious DiseaseG Krishnamurthy, H Singh
Therapeutic Advances in Infectious Disease
Review
Gallbladder tuberculosis camouflaging as gallbladder cancer – case series and review focussing on treatment
Ther Adv Infectious Dis 2016, Vol. 3(6) 152–157 DOI: 10.1177/ 2049936116678589 © The Author(s), 2016. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Gautham Krishnamurthy, Harjeet Singh, Jayapal Rajendran, Vishal Sharma, Thakur Deen Yadav, Balan Louis Gaspar, Rakesh Kumar Vasishta and Rajinder Singh
Abstract: Introduction: Gallbladder tuberculosis, in an endemic region, is a common infectious etiology affecting a rare organ. The high prevalence of carcinoma gallbladder in the endemic regions of tuberculosis, like India, poses diagnostic dilemma. Case series: We are reporting three cases of gallbladder tuberculosis mimicking carcinoma gallbladder of which the first two cases were operated with a presumptive diagnosis of malignancy. The third case presented to us after laparoscopic cholecystectomy elsewhere and on evaluation was found to have disseminated tuberculosis. Discussion: The lack of pathognomonic clinical and radiological characters results in histological surprise of gallbladder tuberculosis following surgery performed for other indications like malignancy. In preoperatively diagnosed patients medical management plays pivotal role in management. Surgery is required in symptomatic patients. On the other hand, histologically proven cases following surgical resection require antitubercular therapy. Conclusion: Previous history of tuberculosis or concomitant tuberculosis at other sites may provide clue to the diagnosis of biliary tuberculosis. Antitubercular treatment after surgery plays an important role in preventing further dissemination.
Keywords: gallbladder tuberculosis, carcinoma gallbladder, antitubercular therapy, radical cholecystectomy Introduction Gallbladder tuberculosis is a well-recognised rare infectious disease [Saluja et al. 2007]. In the endemic regions of tuberculosis, this pathology remains a part of differential diagnosis in managing patients with disease of any organ system. [Sia and Wieland, 2011]. The infection, though it primarily affects the lungs, can affect any system and mimic variety of conditions, including malignancy [Pitlik et al. 1984]. Tha gallbladder is relatively immune to tubercular infection [Tauro et al. 2008]. Up to 2010, around 120 cases have been reported in the published English literature [Xu et al. 2011]. Diagnosis based on clinical examination and imaging is challenging [Jain et al. 1995]. The preoperative diagnosis, though rarely made, can save the patient from a radical surgery done for suspected carcinoma gallbladder. High incidence of needle tract seeding in carcinoma gallbladder precludes preoperative tissue sampling to differentiate these two entities [Kumar et al. 2012]. We present three cases of
gallbladder tuberculosis diagnosed postoperatively following histological examination. Two of the patients had radical surgery for presumed carcinoma gallbladder and the other had laparoscopic cholecystectomy for symptomatic gallstone disease. Case 1 A 62-year-old man, a known diabetic patient and recently diagnosed with hypertension, presented with complaints of vague dull aching pain in the right upper quadrant with significant loss of weight and appetite. The patient had pulmonary tuberculosis 10 years back, for which he received full course of first-line antitubercular treatment. General and physical examinations were unremarkable. Routine biochemical investigations were within normal limits except for elevated alkaline phosphatase (ALP – 312 IU/ml). Ultrasound of the abdomen revealed contracted gallbladder with irregular wall thickening (4–6 mm) and associated 19.2 mm
Correspondence to: Harjeet Singh Post Graduate Institute of Medical, Education and Research, Chandigarh 160012, India. harjeetsingh1982@gmail. com Gautham Krishnamurthy, MS, MRCS Harjeet Singh, MS, MCh Jayapal Rajendran, MS Vishal Sharma, MD, DM Thakur Deen Yadav, MS Balan Louis Gaspar, MD Rakesh Kumar Vasishta, MD, FRCPath Rajinder Singh, MS Postgraduate Institute of Medical Education and Research, Chandigarh, India
152 journals.sagepub.com/home/tai
G Krishnamurthy, H Singh et al.
Figure 1. Panel of contrast-enhanced computed tomographic images. (a and b) Arterial phase axial computed tomographic images. (c–f) Portal venous phase axial computed tomographic images. Asymmetrical hypodense areas are seen along the fundus of gallbladder (long thin white arrow in a, b, d, and e) with contiguous involvement of segment 4B and 5 of liver. Hyperdense calculus within gall bladder lumen (long block arrow in e), subcentimetric lymphnodes in portocaval location (thin short arrow in c), and calcified lymphnode in omentum (block short arrow in f) are seen.
calculus. In addition to the asymmetrical mural thickening of 11 mm in fundus and body of gallbladder and cholelithiasis, contrast-enhanced computed tomography showed hypodense area in segment 4b and 5 of liver which raised suspicion of contiguous infiltration (Figure 1). Apart from cystic artery, fat planes with other vascular structures were maintained. Surgical exploration for presumptive diagnosis of carcinoma gallbladder was done. Intraoperatively, there was a hard growth of size 3 × 2 cm2 in the fundus of the gallbladder with contiguous infiltration into segment 4b and 5 of liver. Multiple enlarged periportal, hepatoduodenal, common hepatic and retropancreatic lymphnodes were seen. Hepatic artery and portal veins were free of tumor. The patient underwent radical cholecystectomy. Cut section revealed hard growth of size 3 × 3 cm2 in the fundus of gallbladder infiltrating into the liver and asymmetrical thickening in the body and neck. A single pigment stone of size 2 cm was seen in the lumen (Figure 2(a)–(c)). The histopathological examination exhibited features of granulomatous inflammation consistent with that of gallbladder tuberculosis (Figure 3). Acid fast
bacilli could not be demonstrated. Postoperative course was uneventful. Patient was discharged in satisfactory condition on post-operative day 5. Case 2 A 40-year-old man presented with dull aching pain in the right hypochondrium that had persisted for 5 months. It was associated with significant loss of weight and appetite. He had pulmonary tuberculosis 1 year back for which he took antituberculous treatment for 6 months. Abdominal examination revealed right hypochondrial tenderness. Ultrasonography showed 3.2 × 2.6 cm2 hypoechoic mass in the fundus of the gallbladder. Computed tomography concurred with the findings of enhancing lesion in the gallbladder fundus and loss of fat planes with the liver. There was no significant lymphadenopathy. Intraoperative findings correlated with the imaging of fundal thickening (Figure 2(d)). The patient underwent radical cholecystectomy. The diagnosis of gallbladder tuberculosis was made based on histological examination of the specimen, which showed presence of caseating granuloma and acid fast bacilli. The patient had an unremarkable postoperative period and was discharged on postoperative day 8.
journals.sagepub.com/home/tai 153
Therapeutic Advances in Infectious Disease 3(6)
Figure 2. Case 1 – (a) gross specimen with infiltration of fundal mass into the adjoining liver, (b) solitary pigment gallstone, and (c) thickening present in the body and neck of the gallbladder. Case 2 – (d) gross specimen showing fundal thickening.
Figure 3. (a) H&E image (40×) showing a well-formed granulomas with central area of caseous necrosis (yellow arrow). The adjacent normal liver parenchyma can also be appreciated (black arrows). (b) H&E image (20×) showing a caseating granuloma with peripheral cuff of lymphocytes. The inset shows Ziehl–Neelsen stain which was negative for acid-fast bacilli. H&E, hematoxylin and eosin.
Case 3 A 50-year-old woman attended the outpatient department with complaints of diffuse abdominal pain and abdominal distension for 3 months. She had been operated for symptomatic gallstone disease elsewhere, 9 months back. The preoperative complaints of the patient included right hypochondrial pain and intermittent low grade fever for 4 months. There was no past or family history of tuberculosis. The patient had undergone laparoscopic cholecystectomy with histological diagnosis of chronic cholecystitis. Intraoperative details were not available. She was doing well for 6 months when she developed the above complaints. Abdominal examination revealed ascites. With a presumptive diagnosis of incidental carcinoma gallbladder, the patient was subjected to computed tomography and histological review of the gallbladder specimen. Computed tomography showed no mass at gallbladder fossa. There was moderate ascites with omental fat stranding. Foci of well-formed epithelioid cell granulomas with Langerhans type of giant cell were present at slide re-examination. Acid fast bacilli could not be demonstrated. Endoscopy ultrasound with
fine needle aspiration of the serosal deposits confirmed peritoneal tuberculosis. Patient was started on antitubercular treatment and is doing well after 6 months of follow-up. Discussion Gallbladder tuberculosis is an uncommon entity presenting as a diagnostic dilemma with gallbladder cancer. Similar to our series, it is often discovered after histological evaluation of gall bladder resected for suspected malignancy [Rejab et al. 2013]. Occasionally, diagnosis may be established on preoperative fine needle aspiration for suspected malignancy [Verma et al. 2012]. The reports describing gall bladder tuberculosis are mainly in the form of case reports or small case series indicating that the condition is rare. The rarity of tuberculosis in gallbladder is due to the alkaline nature of gallbladder bile, which has inhibitory effect on Mycobacterium [Abu-Zidan and Zayat, 1999]. The route of spread to gallbladder is either hematogenous or lymphatics [Chen et al. 1999; Collier, 1994]. The cystic duct obstruction and gallstone disease are
154 journals.sagepub.com/home/tai
G Krishnamurthy, H Singh et al. Table 1. Clinical Case series (minimum of 3 cases) of gallbladder tuberculosis published in English literature. Author (year)
Kumar et al. [2000]
Kapoor et al. [2006]
Saluja et al. [2007]
Govindasamy et al. [2011]
Xu et al. [2011]
Number of patients Age (in years) Males Duration of symptoms Pain Fever LOA/LOW Jaundice Lump Tuberculin skin test Abnormal CXR Past TB Other organs Deranged LFT Associated GSD Ultrasonogram
5 53 (36–65) 0 NA 4 0 1 0 1 NA 2 2 NA 0 5 Thickened wall – 4 Mass – 1 GSD – 3 Bilioma – 1 NA
3 40 2 NA 2 1 1 0 1 NA NA NA 2 1 0 NA
3 54 (32–65) 1 2–8 months 3 2 2 2 1 NA NA 0 3 1 1 Mass – 2 IHBRD – 1 Thickened wall – 1
7 46.3 (32–78) 3 0.5–6 months 7 2 3 0 1 1 (2) 1 NA 5 NA NA NA
Computed tomography
5 37.8 1 NA 5 1 1 0 1 NA NA NA 0 NA 4 Mass – 1 Thickened wall – 2 GSD – 4 NA
Mass – 2 Thickened Wall – 1
Mass – 2 IHBRD – 1
Acid fast bacilli present Granuloma Surgery
NA NA 5
1 5 5
NA NA 3
NA NA 3
Thickened wall – 4 Mass – 2 Polyp – 1 Calcification – 1 NA NA 7
CXR, chest X-ray; GSD, gallstone disease; IHBRD, intrahepatic biliary radical dilatation; LFT, Liver Function Test; LOA, loss of appetite; LOW, loss of weight; NA, detail not available; TB, tuberculosis.
contributory factors [Abu-Zidan and Zayat, 1999]. There is no pathognomonic presentation of gallbladder tuberculosis and clinical presentation may be
positive in patients with gallbladder tuberculosis [Ramia et al. 2006]. Table 1 summarizes the studies reporting 3 or more cases with clinical details in English literature.
(1) Similar to carcinoma gallbladder as seen in our cases, (2) Persistent port site sinus following laparoscopic cholecystectomy [Mansoor et al. 2011], (3) Acute cholecystitis [Cacciarelli et al. 1998], (4) Metastatic gallbladder cancer with umbilical nodules [Goyal et al. 1998], (5) Perforation and bilioma [Hahn et al. 1995], (6) Empyema [Tauro et al. 2008], (7) Multicystic mass [Gulati et al. 2002].
The first two cases in our series are the typical presentation wherein the tuberculosis was detected after surgery for presumed carcinoma gallbladder. In the third case, the peritoneal dissemination is probably after surgery, since such a presentation during the laparoscopic procedure would have made the surgeon entertain the diagnosis of disseminated carcinoma gallbladder and abandon the procedure. Systemic spread of tuberculosis as early as 2 months following splenectomy for splenic tuberculosis has been reported [Yan et al. 2015]. It is difficult to ascertain whether the peritoneal tuberculosis in our third case was part of systemic spread or spillage during surgery in the absence of preoperative and intraoperative details. However, the case highlights
Computed tomographic findings are also variable and include thickening of the gallbladder wall, gallbladder mass and micronodular lesions of the gallbladder [Xu et al. 2011]. Metabolic imaging like positron emission tomography may also be false
journals.sagepub.com/home/tai 155
Therapeutic Advances in Infectious Disease 3(6) the importance of meticulous search for granulomas in histopathology and appropriate postoperative antitubercular treatment for gallbladder tuberculosis to avoid dissemination. The treatment of gallbladder tuberculosis can be broadly classified into those diagnosed preoperatively and those postoperatively. Preoperative diagnosis can be suspected in the presence of history of active or treated tuberculosis complemented by imaging studies [Rouas et al. 2003]. The lack of pathognomonic imaging coupled with possible high incidence of tuberculosis in regions endemic for carcinoma gallbladder makes preoperative diagnosis unlikely [Liu et al. 2016]. Though in extreme suspicion, fine needle aspiration cytology can be performed, the probability of lesion being carcinoma should be still seriously considered [Rana et al. 2016]. This would violate the oncological principle of management of carcinoma gallbladder. However, the benefit of the procedure is in avoiding radical surgery for a benign condition. In an untreated patient diagnosed preoperatively, the treatment includes administration of appropriate medical antituberculous treatment. In the absence of symptoms and gallstones, cholecystectomy is not required. The presence of either will warrant a completion of intensive phase of antitubercular treatment followed by cholecystectomy [Guirat et al. 2011]. This is based on the principle that tuberculosis of abdominal solid viscera requires medical management rather than surgical excision [Wu et al. 2013]. Patients who have recently completed the antitubercular treatment for other sites can be subjected to cholecystectomy for symptoms and gallstones. Postoperative diagnosis based on histology showing acid fast bacilli or suggestive findings in the form of granulomatous inflammation and caseating necrosis will warrant antitubercular therapy. If patient has already received antitubercular therapy, then second-line antitubercular therapy should be administered. The importance of antitubercular treatment to avoid peritoneal or systemic spread of the infection is highlighted by the third case. Awareness among surgeons regarding the probability of gallbladder tuberculosis in patients with risk factors needs to be improved. Risk factors include high endemic regions, active or prior history of pulmonary or extrapulmonary tuberculosis
and immunosuppression. In these cases, skin tuberculin test and partial specimen preservation in saline for tubercle bacilli culture should be done. A positive skin test or culture will improve diagnostic accuracy. Conclusion Gallbladder tuberculosis mimics gallbladder malignancy. In patients having gallbladder masses with prior history of tuberculosis or from endemic regions, a differential diagnosis of gallbladder tuberculosis should be considered. All patients positive for the presence of acid fast bacilli should be subjected to anti-tubercular treatment. Antitubercular drugs should be tailored based on the previous antitubercular treatment, if any. For patients with the presence of histological features suggestive of tuberculosis and negative for the presence of acid fast bacilli, initiation of antitubercular treatment in the setting of risk factors should be considered. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Conflict of interest statement The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
References Abu-Zidan, F. and Zayat, I. (1999) Gallbladder tuberculosis (Case report and review of the literature). Hepatogastroenterology 46: 2804–2806. Cacciarelli, A., Naddaf, S., El-Zeftawy, H., Aziz, M., Omar, W., Kumar, M. et al. (1998) Acute cholecystitis in AIDS patients: correlation of Tc-99 m hepatobiliary scintigraphy with histopathologic laboratory findings and CD4 counts. Clin Nucl Med 23: 226–228. Chen, C., Yang, C., Yeh, Y., Yang, J. and Chou, D. (1999) Pancreatic tuberculosis with obstructive jaundice – a case report. Am J Gastroenterol 94: 2534–2536. Govindasamy, M., Srinivasan, T., Varma, V., Mehta, N., Yadav, A., Kumaran, V. et al. (2011) Biliary tract tuberculosis – a diagnostic dilemma. J Gastrointest Surg 15: 2172–2177. Goyal, S., Goyal, R., Malhotra, V. and Kaushik, K. (1998) Tuberculosis of the gall bladder. Indian J Gastroenterol 17: 108.
156 journals.sagepub.com/home/tai
G Krishnamurthy, H Singh et al. Guirat, A., Berjab, H., Ellouz, S., Ayman, T., Tahia, B. and Mohamed, I. (2011) Primitive gallbladder tuberculosis. Virol Mycol 1: 101. Gulati, M., Seith, A. and Paul, S. (2002) Gall bladder tuberculosis presenting as a multiloculated cystic mass on CT. Indian J Radiol Imag 12: 237–238. Hahn, S., Park, S., Shin, W., Kim, C. and Shinn, K. (1995) Gallbladder tuberculosis with perforation and intrahepatic biloma. J Clin Gastroenterol 20: 84–86. Jain, R., Sawhney, S., Bhargava, D. and Berry, M. (1995) Gallbladder tuberculosis: sonographic appearance. J Clin Ultrasound 23: 327–329. Kapoor, S., Sewkani, A., Naik, S., Sharma, S., Jain, A. and Varshney, S. (2006) Myriad presentations of gall bladder tuberculosis. Indian J Gastroenterol 25: 103–104. Kumar, K., Ayub, M., Kumar, M., Keswani, N. and Shukla, H. (2000) Tuberculosis of the gallbladder. HPB Surg 11: 401–404. Kumar, S., Singh, D., Goel, M. and Kushwaha, J. (2012) FNAC site metastasis in gall bladder cancer – a rare presentation. BMJ Case Rep. Epub ahead of print 10 July. DOI: 10.1136/bcr.02.2012.5777. Liu, Y., Wang, K. and Liu, H. (2016) Gallbladder tuberculosis mimicking gallbladder carcinoma: a case report and literature review. Case Reports Hepatol 2016: 3629708.
tuberculosis: false-positive pet diagnosis of gallbladder cancer. World J Gastroenterol 12: 6559–6560. Rana, C., Krishnani, N. and Kumari, N. (2016) Ultrasound-guided fine needle aspiration cytology of gallbladder lesions: a study of 596 cases. Cytopathology. Epub ahead of print 15 March. DOI: 10.1111/cyt.12296. Rejab, H., Guirat, A., Ellouze, S., Trigui, A., Mizouni, A., Triki, H. et al. (2013) Primitive gallbladder tuberculosis: a case report with review of the literature. Ann Ital Chir 84: 1–3. Rouas, L., Mansouri, F., Jahid, A., Zouaidia, F., Saidi, H., Nabih, N. et al. (2003) Gallbladder tuberculosis associated with cholelithiasis. Rev Med Liege 58: 757–760. Saluja, S., Ray, S., Pal, S., Kukeraja, M., Srivastava, D.N., Sahni, P. et al. (2007) Hepatobiliary and pancreatic tuberculosis: a two decade experience. BMC Surg 7: 10. Sia, I. and Wieland, M. (2011) Current concepts in the management of tuberculosis. Mayo Clin Proc 86: 348–361. Tauro, L., Martis, J. and Shenoy, H. (2008) Tuberculosis of gall bladder presenting as empyema. Saudi J Gastroenterol 14: 101. Verma, R., Vij, M. and Pal, L. (2012) Gall bladder tuberculosis masquerading as carcinoma: dilemma resolved by aspiration cytology. Diagn Cytopathol 40: 91–93.
Mansoor, T., Rizvi, S. and Khan, R. (2011) Persistent port-site sinus in a patient after laparoscopic cholecystectomy: watch out for gallbladder tuberculosis. Hepatobiliary Pancreat Dis Int 10: 328–329.
Wu, Z., Wang, W., Zhu, Y., Cheng, J., Dong, J., Li, M. et al. (2013) Diagnosis and treatment of hepatic tuberculosis: report of five cases and review of literature. Int J Clin Exp Med 6: 845–850.
N. A. Collier, L. (1994) Surgery of the Liver and Biliary Tract, 2 edn (ed L.Blumgart). New York: Churchill Livingstone.
Xu, X., Yu, R., Qiu, L., Shen, J., Dong, F. and Chen, Y. (2011) Gallbladder tuberculosis: CT findings with histopathologic correlation. Korean J Radiol 12: 196–202.
Pitlik, S., Fainstein, V. and Bodey, G. (1984) Tuberculosis mimicking cancer – a reminder. Am J Med 76: 822–825. Ramia, J., Muffak, K., Fernandez, A., Villar, J., Garrote, D. and Ferron, J. (2006) Gallbladder
Yan, D., Zhong, C. and Li, L. (2015) Systemic spread of tuberculosis after surgery for a splenic tuberculous abscess without postoperational antituberculosis treatment: a case report. Ther Clin Risk Manag 11: 1697–1700.
Visit SAGE journals online journals.sagepub.com/ home/tai
SAGE journals
journals.sagepub.com/home/tai 157
TAI0010.1177/2049936116678589Therapeutic Advances in Infectious DiseaseG Krishnamurthy, H Singh
Therapeutic Advances in Infectious Disease
Review
Gallbladder tuberculosis camouflaging as gallbladder cancer – case series and review focussing on treatment
Ther Adv Infectious Dis 2016, Vol. 3(6) 152–157 DOI: 10.1177/ 2049936116678589 © The Author(s), 2016. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Gautham Krishnamurthy, Harjeet Singh, Jayapal Rajendran, Vishal Sharma, Thakur Deen Yadav, Balan Louis Gaspar, Rakesh Kumar Vasishta and Rajinder Singh
Abstract: Introduction: Gallbladder tuberculosis, in an endemic region, is a common infectious etiology affecting a rare organ. The high prevalence of carcinoma gallbladder in the endemic regions of tuberculosis, like India, poses diagnostic dilemma. Case series: We are reporting three cases of gallbladder tuberculosis mimicking carcinoma gallbladder of which the first two cases were operated with a presumptive diagnosis of malignancy. The third case presented to us after laparoscopic cholecystectomy elsewhere and on evaluation was found to have disseminated tuberculosis. Discussion: The lack of pathognomonic clinical and radiological characters results in histological surprise of gallbladder tuberculosis following surgery performed for other indications like malignancy. In preoperatively diagnosed patients medical management plays pivotal role in management. Surgery is required in symptomatic patients. On the other hand, histologically proven cases following surgical resection require antitubercular therapy. Conclusion: Previous history of tuberculosis or concomitant tuberculosis at other sites may provide clue to the diagnosis of biliary tuberculosis. Antitubercular treatment after surgery plays an important role in preventing further dissemination.
Keywords: gallbladder tuberculosis, carcinoma gallbladder, antitubercular therapy, radical cholecystectomy Introduction Gallbladder tuberculosis is a well-recognised rare infectious disease [Saluja et al. 2007]. In the endemic regions of tuberculosis, this pathology remains a part of differential diagnosis in managing patients with disease of any organ system. [Sia and Wieland, 2011]. The infection, though it primarily affects the lungs, can affect any system and mimic variety of conditions, including malignancy [Pitlik et al. 1984]. Tha gallbladder is relatively immune to tubercular infection [Tauro et al. 2008]. Up to 2010, around 120 cases have been reported in the published English literature [Xu et al. 2011]. Diagnosis based on clinical examination and imaging is challenging [Jain et al. 1995]. The preoperative diagnosis, though rarely made, can save the patient from a radical surgery done for suspected carcinoma gallbladder. High incidence of needle tract seeding in carcinoma gallbladder precludes preoperative tissue sampling to differentiate these two entities [Kumar et al. 2012]. We present three cases of
gallbladder tuberculosis diagnosed postoperatively following histological examination. Two of the patients had radical surgery for presumed carcinoma gallbladder and the other had laparoscopic cholecystectomy for symptomatic gallstone disease. Case 1 A 62-year-old man, a known diabetic patient and recently diagnosed with hypertension, presented with complaints of vague dull aching pain in the right upper quadrant with significant loss of weight and appetite. The patient had pulmonary tuberculosis 10 years back, for which he received full course of first-line antitubercular treatment. General and physical examinations were unremarkable. Routine biochemical investigations were within normal limits except for elevated alkaline phosphatase (ALP – 312 IU/ml). Ultrasound of the abdomen revealed contracted gallbladder with irregular wall thickening (4–6 mm) and associated 19.2 mm
Correspondence to: Harjeet Singh Post Graduate Institute of Medical, Education and Research, Chandigarh 160012, India. harjeetsingh1982@gmail. com Gautham Krishnamurthy, MS, MRCS Harjeet Singh, MS, MCh Jayapal Rajendran, MS Vishal Sharma, MD, DM Thakur Deen Yadav, MS Balan Louis Gaspar, MD Rakesh Kumar Vasishta, MD, FRCPath Rajinder Singh, MS Postgraduate Institute of Medical Education and Research, Chandigarh, India
152 journals.sagepub.com/home/tai
G Krishnamurthy, H Singh et al.
Figure 1. Panel of contrast-enhanced computed tomographic images. (a and b) Arterial phase axial computed tomographic images. (c–f) Portal venous phase axial computed tomographic images. Asymmetrical hypodense areas are seen along the fundus of gallbladder (long thin white arrow in a, b, d, and e) with contiguous involvement of segment 4B and 5 of liver. Hyperdense calculus within gall bladder lumen (long block arrow in e), subcentimetric lymphnodes in portocaval location (thin short arrow in c), and calcified lymphnode in omentum (block short arrow in f) are seen.
calculus. In addition to the asymmetrical mural thickening of 11 mm in fundus and body of gallbladder and cholelithiasis, contrast-enhanced computed tomography showed hypodense area in segment 4b and 5 of liver which raised suspicion of contiguous infiltration (Figure 1). Apart from cystic artery, fat planes with other vascular structures were maintained. Surgical exploration for presumptive diagnosis of carcinoma gallbladder was done. Intraoperatively, there was a hard growth of size 3 × 2 cm2 in the fundus of the gallbladder with contiguous infiltration into segment 4b and 5 of liver. Multiple enlarged periportal, hepatoduodenal, common hepatic and retropancreatic lymphnodes were seen. Hepatic artery and portal veins were free of tumor. The patient underwent radical cholecystectomy. Cut section revealed hard growth of size 3 × 3 cm2 in the fundus of gallbladder infiltrating into the liver and asymmetrical thickening in the body and neck. A single pigment stone of size 2 cm was seen in the lumen (Figure 2(a)–(c)). The histopathological examination exhibited features of granulomatous inflammation consistent with that of gallbladder tuberculosis (Figure 3). Acid fast
bacilli could not be demonstrated. Postoperative course was uneventful. Patient was discharged in satisfactory condition on post-operative day 5. Case 2 A 40-year-old man presented with dull aching pain in the right hypochondrium that had persisted for 5 months. It was associated with significant loss of weight and appetite. He had pulmonary tuberculosis 1 year back for which he took antituberculous treatment for 6 months. Abdominal examination revealed right hypochondrial tenderness. Ultrasonography showed 3.2 × 2.6 cm2 hypoechoic mass in the fundus of the gallbladder. Computed tomography concurred with the findings of enhancing lesion in the gallbladder fundus and loss of fat planes with the liver. There was no significant lymphadenopathy. Intraoperative findings correlated with the imaging of fundal thickening (Figure 2(d)). The patient underwent radical cholecystectomy. The diagnosis of gallbladder tuberculosis was made based on histological examination of the specimen, which showed presence of caseating granuloma and acid fast bacilli. The patient had an unremarkable postoperative period and was discharged on postoperative day 8.
journals.sagepub.com/home/tai 153
Therapeutic Advances in Infectious Disease 3(6)
Figure 2. Case 1 – (a) gross specimen with infiltration of fundal mass into the adjoining liver, (b) solitary pigment gallstone, and (c) thickening present in the body and neck of the gallbladder. Case 2 – (d) gross specimen showing fundal thickening.
Figure 3. (a) H&E image (40×) showing a well-formed granulomas with central area of caseous necrosis (yellow arrow). The adjacent normal liver parenchyma can also be appreciated (black arrows). (b) H&E image (20×) showing a caseating granuloma with peripheral cuff of lymphocytes. The inset shows Ziehl–Neelsen stain which was negative for acid-fast bacilli. H&E, hematoxylin and eosin.
Case 3 A 50-year-old woman attended the outpatient department with complaints of diffuse abdominal pain and abdominal distension for 3 months. She had been operated for symptomatic gallstone disease elsewhere, 9 months back. The preoperative complaints of the patient included right hypochondrial pain and intermittent low grade fever for 4 months. There was no past or family history of tuberculosis. The patient had undergone laparoscopic cholecystectomy with histological diagnosis of chronic cholecystitis. Intraoperative details were not available. She was doing well for 6 months when she developed the above complaints. Abdominal examination revealed ascites. With a presumptive diagnosis of incidental carcinoma gallbladder, the patient was subjected to computed tomography and histological review of the gallbladder specimen. Computed tomography showed no mass at gallbladder fossa. There was moderate ascites with omental fat stranding. Foci of well-formed epithelioid cell granulomas with Langerhans type of giant cell were present at slide re-examination. Acid fast bacilli could not be demonstrated. Endoscopy ultrasound with
fine needle aspiration of the serosal deposits confirmed peritoneal tuberculosis. Patient was started on antitubercular treatment and is doing well after 6 months of follow-up. Discussion Gallbladder tuberculosis is an uncommon entity presenting as a diagnostic dilemma with gallbladder cancer. Similar to our series, it is often discovered after histological evaluation of gall bladder resected for suspected malignancy [Rejab et al. 2013]. Occasionally, diagnosis may be established on preoperative fine needle aspiration for suspected malignancy [Verma et al. 2012]. The reports describing gall bladder tuberculosis are mainly in the form of case reports or small case series indicating that the condition is rare. The rarity of tuberculosis in gallbladder is due to the alkaline nature of gallbladder bile, which has inhibitory effect on Mycobacterium [Abu-Zidan and Zayat, 1999]. The route of spread to gallbladder is either hematogenous or lymphatics [Chen et al. 1999; Collier, 1994]. The cystic duct obstruction and gallstone disease are
154 journals.sagepub.com/home/tai
G Krishnamurthy, H Singh et al. Table 1. Clinical Case series (minimum of 3 cases) of gallbladder tuberculosis published in English literature. Author (year)
Kumar et al. [2000]
Kapoor et al. [2006]
Saluja et al. [2007]
Govindasamy et al. [2011]
Xu et al. [2011]
Number of patients Age (in years) Males Duration of symptoms Pain Fever LOA/LOW Jaundice Lump Tuberculin skin test Abnormal CXR Past TB Other organs Deranged LFT Associated GSD Ultrasonogram
5 53 (36–65) 0 NA 4 0 1 0 1 NA 2 2 NA 0 5 Thickened wall – 4 Mass – 1 GSD – 3 Bilioma – 1 NA
3 40 2 NA 2 1 1 0 1 NA NA NA 2 1 0 NA
3 54 (32–65) 1 2–8 months 3 2 2 2 1 NA NA 0 3 1 1 Mass – 2 IHBRD – 1 Thickened wall – 1
7 46.3 (32–78) 3 0.5–6 months 7 2 3 0 1 1 (2) 1 NA 5 NA NA NA
Computed tomography
5 37.8 1 NA 5 1 1 0 1 NA NA NA 0 NA 4 Mass – 1 Thickened wall – 2 GSD – 4 NA
Mass – 2 Thickened Wall – 1
Mass – 2 IHBRD – 1
Acid fast bacilli present Granuloma Surgery
NA NA 5
1 5 5
NA NA 3
NA NA 3
Thickened wall – 4 Mass – 2 Polyp – 1 Calcification – 1 NA NA 7
CXR, chest X-ray; GSD, gallstone disease; IHBRD, intrahepatic biliary radical dilatation; LFT, Liver Function Test; LOA, loss of appetite; LOW, loss of weight; NA, detail not available; TB, tuberculosis.
contributory factors [Abu-Zidan and Zayat, 1999]. There is no pathognomonic presentation of gallbladder tuberculosis and clinical presentation may be
positive in patients with gallbladder tuberculosis [Ramia et al. 2006]. Table 1 summarizes the studies reporting 3 or more cases with clinical details in English literature.
(1) Similar to carcinoma gallbladder as seen in our cases, (2) Persistent port site sinus following laparoscopic cholecystectomy [Mansoor et al. 2011], (3) Acute cholecystitis [Cacciarelli et al. 1998], (4) Metastatic gallbladder cancer with umbilical nodules [Goyal et al. 1998], (5) Perforation and bilioma [Hahn et al. 1995], (6) Empyema [Tauro et al. 2008], (7) Multicystic mass [Gulati et al. 2002].
The first two cases in our series are the typical presentation wherein the tuberculosis was detected after surgery for presumed carcinoma gallbladder. In the third case, the peritoneal dissemination is probably after surgery, since such a presentation during the laparoscopic procedure would have made the surgeon entertain the diagnosis of disseminated carcinoma gallbladder and abandon the procedure. Systemic spread of tuberculosis as early as 2 months following splenectomy for splenic tuberculosis has been reported [Yan et al. 2015]. It is difficult to ascertain whether the peritoneal tuberculosis in our third case was part of systemic spread or spillage during surgery in the absence of preoperative and intraoperative details. However, the case highlights
Computed tomographic findings are also variable and include thickening of the gallbladder wall, gallbladder mass and micronodular lesions of the gallbladder [Xu et al. 2011]. Metabolic imaging like positron emission tomography may also be false
journals.sagepub.com/home/tai 155
Therapeutic Advances in Infectious Disease 3(6) the importance of meticulous search for granulomas in histopathology and appropriate postoperative antitubercular treatment for gallbladder tuberculosis to avoid dissemination. The treatment of gallbladder tuberculosis can be broadly classified into those diagnosed preoperatively and those postoperatively. Preoperative diagnosis can be suspected in the presence of history of active or treated tuberculosis complemented by imaging studies [Rouas et al. 2003]. The lack of pathognomonic imaging coupled with possible high incidence of tuberculosis in regions endemic for carcinoma gallbladder makes preoperative diagnosis unlikely [Liu et al. 2016]. Though in extreme suspicion, fine needle aspiration cytology can be performed, the probability of lesion being carcinoma should be still seriously considered [Rana et al. 2016]. This would violate the oncological principle of management of carcinoma gallbladder. However, the benefit of the procedure is in avoiding radical surgery for a benign condition. In an untreated patient diagnosed preoperatively, the treatment includes administration of appropriate medical antituberculous treatment. In the absence of symptoms and gallstones, cholecystectomy is not required. The presence of either will warrant a completion of intensive phase of antitubercular treatment followed by cholecystectomy [Guirat et al. 2011]. This is based on the principle that tuberculosis of abdominal solid viscera requires medical management rather than surgical excision [Wu et al. 2013]. Patients who have recently completed the antitubercular treatment for other sites can be subjected to cholecystectomy for symptoms and gallstones. Postoperative diagnosis based on histology showing acid fast bacilli or suggestive findings in the form of granulomatous inflammation and caseating necrosis will warrant antitubercular therapy. If patient has already received antitubercular therapy, then second-line antitubercular therapy should be administered. The importance of antitubercular treatment to avoid peritoneal or systemic spread of the infection is highlighted by the third case. Awareness among surgeons regarding the probability of gallbladder tuberculosis in patients with risk factors needs to be improved. Risk factors include high endemic regions, active or prior history of pulmonary or extrapulmonary tuberculosis
and immunosuppression. In these cases, skin tuberculin test and partial specimen preservation in saline for tubercle bacilli culture should be done. A positive skin test or culture will improve diagnostic accuracy. Conclusion Gallbladder tuberculosis mimics gallbladder malignancy. In patients having gallbladder masses with prior history of tuberculosis or from endemic regions, a differential diagnosis of gallbladder tuberculosis should be considered. All patients positive for the presence of acid fast bacilli should be subjected to anti-tubercular treatment. Antitubercular drugs should be tailored based on the previous antitubercular treatment, if any. For patients with the presence of histological features suggestive of tuberculosis and negative for the presence of acid fast bacilli, initiation of antitubercular treatment in the setting of risk factors should be considered. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Conflict of interest statement The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
References Abu-Zidan, F. and Zayat, I. (1999) Gallbladder tuberculosis (Case report and review of the literature). Hepatogastroenterology 46: 2804–2806. Cacciarelli, A., Naddaf, S., El-Zeftawy, H., Aziz, M., Omar, W., Kumar, M. et al. (1998) Acute cholecystitis in AIDS patients: correlation of Tc-99 m hepatobiliary scintigraphy with histopathologic laboratory findings and CD4 counts. Clin Nucl Med 23: 226–228. Chen, C., Yang, C., Yeh, Y., Yang, J. and Chou, D. (1999) Pancreatic tuberculosis with obstructive jaundice – a case report. Am J Gastroenterol 94: 2534–2536. Govindasamy, M., Srinivasan, T., Varma, V., Mehta, N., Yadav, A., Kumaran, V. et al. (2011) Biliary tract tuberculosis – a diagnostic dilemma. J Gastrointest Surg 15: 2172–2177. Goyal, S., Goyal, R., Malhotra, V. and Kaushik, K. (1998) Tuberculosis of the gall bladder. Indian J Gastroenterol 17: 108.
156 journals.sagepub.com/home/tai
G Krishnamurthy, H Singh et al. Guirat, A., Berjab, H., Ellouz, S., Ayman, T., Tahia, B. and Mohamed, I. (2011) Primitive gallbladder tuberculosis. Virol Mycol 1: 101. Gulati, M., Seith, A. and Paul, S. (2002) Gall bladder tuberculosis presenting as a multiloculated cystic mass on CT. Indian J Radiol Imag 12: 237–238. Hahn, S., Park, S., Shin, W., Kim, C. and Shinn, K. (1995) Gallbladder tuberculosis with perforation and intrahepatic biloma. J Clin Gastroenterol 20: 84–86. Jain, R., Sawhney, S., Bhargava, D. and Berry, M. (1995) Gallbladder tuberculosis: sonographic appearance. J Clin Ultrasound 23: 327–329. Kapoor, S., Sewkani, A., Naik, S., Sharma, S., Jain, A. and Varshney, S. (2006) Myriad presentations of gall bladder tuberculosis. Indian J Gastroenterol 25: 103–104. Kumar, K., Ayub, M., Kumar, M., Keswani, N. and Shukla, H. (2000) Tuberculosis of the gallbladder. HPB Surg 11: 401–404. Kumar, S., Singh, D., Goel, M. and Kushwaha, J. (2012) FNAC site metastasis in gall bladder cancer – a rare presentation. BMJ Case Rep. Epub ahead of print 10 July. DOI: 10.1136/bcr.02.2012.5777. Liu, Y., Wang, K. and Liu, H. (2016) Gallbladder tuberculosis mimicking gallbladder carcinoma: a case report and literature review. Case Reports Hepatol 2016: 3629708.
tuberculosis: false-positive pet diagnosis of gallbladder cancer. World J Gastroenterol 12: 6559–6560. Rana, C., Krishnani, N. and Kumari, N. (2016) Ultrasound-guided fine needle aspiration cytology of gallbladder lesions: a study of 596 cases. Cytopathology. Epub ahead of print 15 March. DOI: 10.1111/cyt.12296. Rejab, H., Guirat, A., Ellouze, S., Trigui, A., Mizouni, A., Triki, H. et al. (2013) Primitive gallbladder tuberculosis: a case report with review of the literature. Ann Ital Chir 84: 1–3. Rouas, L., Mansouri, F., Jahid, A., Zouaidia, F., Saidi, H., Nabih, N. et al. (2003) Gallbladder tuberculosis associated with cholelithiasis. Rev Med Liege 58: 757–760. Saluja, S., Ray, S., Pal, S., Kukeraja, M., Srivastava, D.N., Sahni, P. et al. (2007) Hepatobiliary and pancreatic tuberculosis: a two decade experience. BMC Surg 7: 10. Sia, I. and Wieland, M. (2011) Current concepts in the management of tuberculosis. Mayo Clin Proc 86: 348–361. Tauro, L., Martis, J. and Shenoy, H. (2008) Tuberculosis of gall bladder presenting as empyema. Saudi J Gastroenterol 14: 101. Verma, R., Vij, M. and Pal, L. (2012) Gall bladder tuberculosis masquerading as carcinoma: dilemma resolved by aspiration cytology. Diagn Cytopathol 40: 91–93.
Mansoor, T., Rizvi, S. and Khan, R. (2011) Persistent port-site sinus in a patient after laparoscopic cholecystectomy: watch out for gallbladder tuberculosis. Hepatobiliary Pancreat Dis Int 10: 328–329.
Wu, Z., Wang, W., Zhu, Y., Cheng, J., Dong, J., Li, M. et al. (2013) Diagnosis and treatment of hepatic tuberculosis: report of five cases and review of literature. Int J Clin Exp Med 6: 845–850.
N. A. Collier, L. (1994) Surgery of the Liver and Biliary Tract, 2 edn (ed L.Blumgart). New York: Churchill Livingstone.
Xu, X., Yu, R., Qiu, L., Shen, J., Dong, F. and Chen, Y. (2011) Gallbladder tuberculosis: CT findings with histopathologic correlation. Korean J Radiol 12: 196–202.
Pitlik, S., Fainstein, V. and Bodey, G. (1984) Tuberculosis mimicking cancer – a reminder. Am J Med 76: 822–825. Ramia, J., Muffak, K., Fernandez, A., Villar, J., Garrote, D. and Ferron, J. (2006) Gallbladder
Yan, D., Zhong, C. and Li, L. (2015) Systemic spread of tuberculosis after surgery for a splenic tuberculous abscess without postoperational antituberculosis treatment: a case report. Ther Clin Risk Manag 11: 1697–1700.
Visit SAGE journals online journals.sagepub.com/ home/tai
SAGE journals
journals.sagepub.com/home/tai 157
