Granulomatous inflammation still fooling surgeons

Dear Sir,

Xanthogranulomatous cholecystitis is very often mistaken for gall bladder malignancy and only on histopathological examination is the ambiguity resolved. Where draining lymph nodes are enlarged, the diagnosis is tilted more in favour of malignancy than a benign process. Clinicians may easily mistake xanthogranulomatous inflammation for carcinoma. Our case, similar to one published in this journal ¹ had the added complication of enlarged regional lymph nodes.

A 50-year-old woman presented to our surgical outpatient department complaining of pain in the right hypochondrium for the previous six months. She acknowledged suffering from tuberculosis (TB) 18 years before, for which she had taken a full course anti-tubercular regimen and was deemed cured. Her systemic examination was normal. On computed tomography, the gall bladder showed enhancing thickening (11 mm) of the fundus along with loss of fat planes in segment IV of the liver. Pericystic and regional lymph nodes were markedly enlarged. In view of these findings, an impression of a neoplastic lesion was made. A radical cholecystectomy along with regional lymph node dissection and segment IV and V liver resection were performed. Gross pathological examination of the surgically excised specimens revealed two pigment stones within the gall bladder whose wall was thickened (0.8–1 cm) and had an ulcerated mucosal lining. The infiltration did not involve the underlying liver. The lymph nodes were enlarged and congested but without evidence of tumour deposits. Histological examination of ulcerated areas of the gall bladder wall showed subepithelial aggregates of foamy macrophages (Figure 1a and 1b), with a lympho-plasmacytic infiltrate and the presence of multinucleated giant cells with marked fibrosis of the wall. Focal pyloric metaplasia was also present. Even after extensive examination of further sections, no dysplasia or evidence of malignancy was identified. Well-defined, non-necrotising granulomata and multinucleated giant cells (Figure 1c and 1d) were seen in the lymph nodes. Subcapsular sinuses were filled with sinus histiocytes. Likewise, no metastatic tumour or lymphoma infiltrate was identified. Thus, a diagnosis of xantho-granulomatous cholecystitis and granulomatous lymphadenitis was tendered. OPEN IN VIEWER

Figure 1.

(a) Section (100 × H&E) shows partially ulcerated mucosa with chronic inflammatory cell infiltrate. The muscle layer fibres are widely separated, dispersed due to diffuse infiltration by foamy macrophages along with giant cell reaction spreading transmurally up to the adventitia. (b) Higher magnification (400 × H&E) shows sheets of foamy macrophages many of which have engulfed bile (brown-yellowish looking cytoplasm). (c) Section from lymph node shows replacement of lymphoid architecture by numerous well-defined granulomas occupying whole of the lymphoid parenchyma. Langhans giant cells are also seen. (d) Higher magnification (400×) showing a Langhans giant cell (horseshoe arrangement of nuclei) in the periphery of an epithelioid cell granuloma.

Xanthogranulomatous cholecystitis was coined in 1981 as a specific entity by Ishak et al.^2,3 It is characterised by focal to diffuse thickening of the gall bladder wall.^3,6 There is invariably accumulation of foamy macrophages, lymphocytes and plasma cells. Multinucleated giant cells are also seen frequently. ² The inflammatory process is associated with marked fibrotic proliferation, which apart from distorting the architecture also leads to infiltration into surrounding structures giving a false impression of malignancy, intraoperatively as well as on radiological imagery.^2–4 The pathogenesis is still elusive, though most accepted theories believe it is due to bile entering into the interstitium of the gall bladder wall, inciting an inflammatory response.^4,5 Involvement of the adjacent tissue is the major complication, making the differentiation from carcinoma difficult. The problem is further accentuated when regional lymph nodes are enlarged, as seen in our case, which has only rarely been reported in the literature. ⁴ The only modality, shown to delineate the two diagnoses, is a frozen section sample examination.^4,5 We therefore stress that where there is a doubt of malignancy, a frozen section examination must be performed. This is mandatory, both to save patients from unsatisfactory routine cholecystectomy where a radical procedure is indicated, as well as unnecessary radical cholecystectomy and extended hepatectomy, where no malignancy is found, as of course is the case where TB is discovered. ⁶ This is especially important in India where TB is common but still has a social stigma and patients tend to hide the disease.