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Xanthogranulomatous cholecystitis (XGC) is a multinodular, focal or diffuse destructive inflammatory lesion of the gall bladder first described in 1970 by Christensen and Ishak as fibroxanthogranulomatous inflammation.[1] It is also known as ceroid granuloma or cholecystic granuloma and occurs as a reaction to bile due to rupture of Rokitansky Aschoff's sinuses.
It is characterized macroscopically by yellowish, tumor like masses in the wall of the gall bladder and microscopically in the early stages, by a collection of foamy macrophages and acute inflammatory cells with later stages showing increasing fibrosis.[2]
XGC is a benign condition, however it may mimic gall bladder carcinoma both radiologically and macroscopically.
Herein we report a case of XGC with coexistent gall bladder carcinoma, wherein preoperatively only the xanthogranulomatous component was detected on fine needle aspiration.
A 64-year female came to the hospital for recurrent right upper abdominal pain on and off for last 1 year. She was a known cardiac patient and had undergone CABG with AVR. An abdominal ultrasound (USG) revealed features suggestive of cholecystitis with cholelithiasis and a right renal cyst. A subsequent Contrast enhanced computed tomography (CECT) revealed an asymmetric heterogeneous enhancing mural thickening in body and fundus of the gall bladder (GB) abutting the first part of duodenum with intramural air fistulous communications and mild pneumobilia. Based on the above findings, a possibility of a neoplastic etiology was suggested.
Subsequently patient underwent an ultrasound guided fine needle aspiration (FNA) of the gall bladder lesion. Air dried smears received in the cytology laboratory were stained with May Grunwald Giemsa (MGG) stain and evaluated under the microscope. Smears consisted of neutrophils, macrophages and plasma cells adherent to blood vessels [Figure 1]a, [Figure 1]e and lying in dispersed fashion. Lying admixed were foam cells [Figure 1]d, Mesothelium like cells [Figure 1]b and numerous multinucleated giant cells [Figure 1]b, [Figure 1]f. Focal calcific material [Figure 1]f and bile pigment [Figure 1]c was also noted. However no granuloma or atypical cells were seen in the smears examined. Based on the above findings a diagnosis of inflammatory lesion- favoring xanthogranulomatous cholecystitis was made.
Figure 1: (a) Network of blood vessels with adhered inflammatory cells. (MGG, 100X). (b) Mesothelium like cell clusters (red arrow) admixed with multinucleated giant cells and inflammatory cells. (MGG, 400X). (c) Bilirubin pigment in macrophages and deposited extracellularly. (MGG,1000x). (d)Foam cells admixed with inflammatory cells. (MGG,400X). (e) Numerous plasma cells admixed with neutrophils and macrophages. (MGG,400X). (f) Calcific material (red arrow) admixed with multinucleated giant cells. (MGG,400X)Patient was planned for radical cholecystectomy. Intaoperatively the duodenum was stuck to the gall bladder with the presence of a cholecysto-enteric fistula and multiple omental adhesions at gall bladder. GB and a part of the omentum were sent to the histopathology laboratory.
On gross examination GB measured 3x2x1 cm with mild wall thickening. Mucosa was partially ulcerated and lumen showed a polypoidal lesion attached to the wall measuring 1x1 cm. The sections cut were stained with Hematoxylin and Eosin (H and E) stain and examined under the microscope.
On microscopic examination, GB showed features of Xanthogranulomatous cholecystitis [Figure 2]b, [Figure 2]c, [Figure 2]e however a microfocus (0.2 cm) of poorly differentiated carcinoma [Figure 2]a was also seen along with dysplastic epithelium and an intra-cystic papillary neoplasm [Figure 2]d.
Figure 2: (a) Microfocus of poorly differentiated carcinoma (H and E, 200x). (b) Plasma cells and multinucleated giant cells (H and E, 400x). (c) Numerous neutrophils, plasma cells and pigment (H and E, 400x). (d) Intracholecystic papillary neoplasm with low grade dysplasia (H and E, 400x). (e) Sheets of Foamy macrophages and lymphoid aggregate (H and E, 400x)Xanthogranulomatous cholecystitis (XGC) is an inflammatory disease of the gall bladder, characterized by focal/diffuse destructive inflammatory process followed by marked proliferative fibrosis along with infiltration of macrophages and foamy cells.[3]
The importance of XGC is that it mimics gall bladder carcinoma (GBC) both preoperatively and intraoperatively, since it can present with pericholecystic infiltration, hepatic involvement and lymphadenopathy.[4]
The correct diagnosis of XGC is important for several reasons, first and foremost because of the high frequency of complications, making early cholecystectomy necessary for this condition.[5]
As FNA is rarely performed for the cytodiagnosis of XGC, there is limited literature and photographs illustrating the same.
Xanthogranulomatous cholecystitis has characteristic cytological findings that may prove useful in differentiating it from a malignant lesion, which it can mimic clinically and radiologically.
There are certain cytological features a cytologist must be aware of while diagnosing Xanthogranulomatous Cholecystitis. The presence of either mesothelium like or foam cells is essential for the diagnosis of XGC. Other supportive features include inflammatory cells, giant cells and a characteristic pink, granular background, as seen with MGG stain.[6]
In the present case on the aspiration smears stained with MGG, we found foam cells, and varying proportion of inflammatory cells (including lymphocytes, neutrophils and plasma cells) adherent to capillary like blood vessels and also in a dispersed fashion. In addition numerous multinucleated giant cells, focal pigment and calcification and few mesothelial like cells were also noted. Few smears showed a pink granular background material.
XGC can not only imitate carcinoma in various ways but can also be associated with primary adenocarcinoma of the gall bladder.[7] When there is an association of XGC and adenocarcinoma, the implications are twofold. First, XGC may obscure the adenocarcinoma, and if only XGC is diagnosed on preoperative or intraoperative FNA cytology, the possibility of a coexistent adenocarcinoma elsewhere in the gall bladder remains.[2]
It is important as a cytologist to be aware of this association, as there is a possibility of missing the malignancy in aspiration smears if the lesion has not been sampled adequately.
In the present case, patient was suspected of having a neoplastic lesion of the gall bladder on CECT but on aspiration smears a preoperative diagnosis of XGC was made, However on histopathology a tiny focus of poorly differentiated carcinoma, was discovered to be coexisting with a XGC. The cytology smears were revisited after the histopathology diagnosis, however no atypical cells were found.
Thus a preoperative guided FNA cytology is an efficient tool to diagnose XGC. However cytology should always be followed by histopathology examination to reveal any microfocus of coexistent carcinoma which may have been missed due to inadequate sampling, as seen in our case.
A cytologist must be aware of the cytological findings of xanthogranulomatous cholecystitis to differentiate it from other nonspecific inflammations.
Although preoperative ultrasound guided FNA is an effective tool in differentiating XGC from malignancy which it mimics radiologically and macroscopically, it has the potential of missing small foci of coexistent malignancy. Therefore it is highly recommended that FNAC be performed from multiple suspicious sites under radiologic guidance and should always be accompanied by histopathology examination to find out any small focus of coexistent carcinoma.
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Xanthogranulomatous Cholecystitis with Coexisting Carcinoma- A Diagnostic Pitfall in Cytology
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CheckDOI: 10.4103/joc.joc_124_21
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