Immunoglobulin G4, Autoimmune Pancreatitis and Pancreatic Cancer

Abstract

Background: Immunoglobulin G4 (IgG4)-related diseases are a group of diseases characterized by enlargement of the affected organs, elevation of serum IgG4, massive infiltration of affected organs with lymphocytes and plasma cells with IgG4 positivity and tissue fibrosis. Type I autoimmune pancreatitis is one form of IgG4-related disease. For IgG4-related diseases, various localizations are described for up to 10% of malignancies. The aim of our study was to examine IgG4 serum levels and pancreatic tissue with respect to the simultaneous presence of autoimmune pancreatitis in patients with pancreatic cancer. Methods: IgG4 serum levels were examined In 106 patients with histologically confirmed pancreatic cancer. The level of 135 mg/dl was considered as the normal value. Pancreatic tissue was histologically examined with respect to the presence of markers of autoimmune pancreatitis. Results: A higher IgG4 level than the cut-off value of 135 mg/dl was proven in 11 patients with pancreatic cancer. Of these 11 patients, 7 had levels twice the normal limit (65.6%). Autoimmune pancreatitis was diagnosed in these individuals. In the case of 1 patient, it was basically an unexpected finding; another patient was initially diagnosed with autoimmune pancreatitis. Repeated biopsy of the pancreas at the time of diagnosis did not confirm the presence of tumour structures, therefore steroid therapy was started. At a check-up 6 months after starting steroid therapy, the condition of the patient improved subjectively and IgG4 levels decreased. However, endosonographically, malignancy was suspected, which was subsequently confirmed histologically. This patient also demonstrated an IgG4 level twice the normal limit. Conclusion: IgG4-related diseases can be accompanied by the simultaneous occurrence of malignancies, which also applies to autoimmune pancreatitis. Chronic pancreatitis is considered a risk factor for pancreatic cancer. It cannot be reliably confirmed whether this also applies to autoimmune pancreatitis. In accordance with other works, however, it is evident that, despite the described high sensitivity and specificity for IgG4 elevation in the case of autoimmune pancreatitis, even levels twice the normal limit are demonstrable in some individuals with pancreatic cancer, without the presence of autoimmune pancreatitis. We believe that patients with IgG4-related disease, including autoimmune pancreatitis, must be systematically monitored with respect to the potential presence of malignancy.

Simultaneous occurrence of autoimmune pancreatitis and pancreatic cancer in patients resected for focal pancreatic mass

“…Serum markers of AIP (notably serum IgG4) are often helpful in diagnosis of both conditions[ 12 ]. However, IgG4 levels exceeding twice the upper limit of normal were found in a considerable proportion of patients with pancreatic cancer and thus this marker cannot be used alone to exclude the diagnosis of malignancy[ 13 ]. In cases where the presence of pancreatic cancer cannot be ruled out with certainty, pancreatic resection is indicated.…”

“…In our opinion, this represents the largest ever published group of patients with co-occurrence of PC and AIP. Pancreatic cancer in patients with AIP has so far been documented only in individual cases[ 13 , 17 - 20 ]. Recently, two patients with both AIP and PC were described in a study that examined serum IgG4 level in 106 patients with histologically confirmed pancreatic cancer[ 13 ].…”

Dilemmas in autoimmune pancreatitis. Surgical resection or not?

“…Serum IgG4 levels alone are unsuitable for distinguishing AIP from pancreatic cancer; serum IgG4 level > 140 mg/dl has a sensitivity of 76 % and specifi city of 93 % in diagnosing of AIP (9). Notably, 5 % of healthy persons and approximately 10 % of the patients with pancreatic cancer have slightly (about 2-fold) elevated IgG4 (9,25,26). Increasing the cutoff to 280 mg/dl decreases sensitivity, but improves specifi city to 99 % in diagnosis of AIP (16).…”

Surgical treatment of chronic pancreatitis: the state of the art

“…Аналогично, в случае компрессии желчных протоков следует ожидать увеличения показателей холестаза. В случае подозрения на аутоиммунную природу показано определение IgG и IgG4 [6]. При подозрении на злокачественность следует контролировать уровень CА-19-9.…”