IgG4-cholecystitis is a total masquerader having a similar constellation of signs and symptoms as of gall bladder cancer. Etiopathogenesis of this entity is still not clear, but mostly it is stated that this is manifestation of autoimmune process driven by lymphoplasmacytic interaction in the organ involved.
Depending upon the organ or system involved, it really poses difficulty in making final diagnosis based on clinical and radiological features. To circumvent this dilemma, we need a complete and in-depth understanding of the clinical presentations of IgG4 related diseases. This will eventually lead to decrease unnecessary invasive forms of surgical interventions and ultimately benefits the patient and helps in reducing the futile exercise. It is prudent to put this rare entity in the list of differential diagnosis along with gall bladder cancer whenever any abnormal or suspicious features are there on clinically/ radiologically7.
As per Rui Zhang et al, the incidence of misdiagnosis of IgG4-C is 9.63% 8. This entity is more common in older people having more predilections towards male9. Patients with IgG4 choleycstitis on sonography shows hypoechoic, diffuse, circumferential thickening of the gallbladder Wall. As in our case, sonography showed gall stones along with, asymmetrical thickening of 6 mm in gall bladder.
On CECT scan, it is mainly the delayed enhancement in IgG4 related cholecystitis which helps in differentiating it from gall bladder cancer. In our case, there was asymmetrical thickening of 6 mm along with porcelain bladder.
On MRI, it showed low-signal smooth diffuse gallbladder wall thickening on T2 weighted MR images, and delayed enhancement post-contrast 4,10,11. This thickening or enlargement of organ on imaging is generally due to infiltration of organs by lymphocytes and plasma cells along with coexisting fibrosis. As per Deshpande et al12, the diagnostic criteria for diagnosing IgG4 related diseases are as mentioned in Table 1.
Table 1
Three Major Histopathological Features Associated with IgG4-Related Disease and the Minimal Criteria in a New Organ/Site in the International Pathological Consensus
S.No. | Major histopathological features associated with IgG4-RD | Other histopathological features associated with IgG4-RD are: | Minimal criteria for IgG4-RD in a new organ/site |
1. | Dense lymphoplasmacytic infiltrate | Phlebitis without obliteration of the lumen | Characteristic histopathological findings with an elevated IgG4 plasma cells and IgG4-to-IgG ratio |
2. | Fibrosis, arranged at least focally in a storiform pattern | Increased numbers of eosinophils | High serum IgG4 concentrations |
3. | Obliterative phlebitis | | Effective response to glucocorticoid therapy |
4. | | | Reports of other organ involvement that is consistent with IgG4-RD |
In order to diagnose IgG4 cholecystitis, there should be at least 2 out of 3 major criteria as mentioned above and also presence of more than 50 percent plasma cell per high power field. In our case, all the three major criteria were present. Among minimal criteria as mentioned above, IgG4 positive in 80 plasma cells, but Serum IgG was within normal limit.
But Shin et al reported only 15% plasma cell per high power field in their case study in the background of IgG4 cholecystitis13.
Role of serum IgG4 is also advocated by many studies, but routinely it is not practiced as it is not elevated in all cases of IgG4 related disease and also its accuracy only fits between 40-50% and moreover in developing countries like India, it is difficult to get done due to financial and cost constraints. To differentiate IgG4 or other benign conditions from ca gall bladder, role of Carbohydrate antigen (CA 19-9), Carcino-Embryonic antigen (CEA) and Carbohydrate antigen (CA-125) are more established14. Increased ratio >40% of IgG4/IgG also favours IgG4 related disease and is considered as a salient feature to diagnose IgG4 related disease.
Treatment decision is of paramount importance in suspecting IgG4 related cholecystitis. The main diagnostic ambiguity is with malignancy of gall bladder, as the treatment options for both these diseases are completely different. IgG4 cholecystits is mainly treated by steroids and showed a dramatic response, duration and relapse rate are yet not documented as no randomised controlled trial has not been yet performed. Role of immunomodulators also has been tried in Mayo clinic15. Even if patient requires surgery after steroid treatment, the extent of surgery is definitely less as compared to surgery for gall bladder cancer.
Radical surgery in the form of extended cholecystectomy and regional lymphadenectomy is mainly done for gall bladder cancer. Therefore, a firm and confident diagnosis is required before embarking upon any modality of treatment. Any misdiagnosis will over treat IgG4 cholecystitis at the cost of other post operative surgical complications which can be completely avoided if we have ruled out IgG4 cholecystits in case suspected to have gall bladder cancer.