Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis and is classified into two subtypes: type 1 (associated with systemic IgG4-related disease) and type 2 (not associated with IgG4). Diagnosis is based on a combination of clinical, imaging, serological, and histological findings.

We present the case of a 52-year-old woman who was referred to our department for endoscopic ultrasound (EUS) evaluation due to an enlargement of the pancreatic head. The reported lesion has been identified in recent imaging studies (CT, MRI) performed due to painless obstructive jaundice. Serologically, a markedly elevated serum IgG4 level was recorded, while tumor markers CEA and CA19-9 were within normal limits. Medical history revealed a possibly underdiagnosed IgG4-related ocular disease; the patient had undergone surgical excision of the lacrimal gland three years earlier, due to severe inflammation and vision impairment. The histological exams revealed dense lymphoplasmacytic infiltrate, storiform fibrosis and IgG4-positive lymphoplasmacytic infiltration with IgG4+/IgG plasma cell ratio <20%.

EUS revealed diffuse, homogeneous and hypoechoic enlargement of the head, uncinate, isthmus, and part of the body of the pancreas, without clear features of an infiltrative neoplasm. The pancreatic duct appeared thin yet visible, whereas the intrapancreatic portion of the common bile duct was narrow with upstream dilatation. Endoscopic ultrasound-guided biopsy showed extensive fibrosis with scattered lymphocytic aggregates, numerous small tubular formations, and scattered plasma cells without IgG4 expression.

A presumptive diagnosis of type 1 AIP was made based on the medical history, imaging features and elevated serum IgG4, despite certain atypical findings. Corticosteroid therapy was initiated, leading to rapid clinical and biochemical improvement and marked regression of the imaging findings. 

Nonetheless, symptoms relapsed during corticosteroid tapering. The patient, subsequently, appeared with jaundice, blared vision and arthralgia. Following consultation with a rheumatologist, a shared decision was made to initiate rituximab and a substantial improvement was observed. The patient remains under close surveillance with blood tests and frequent clinical assessment. 

This case demonstrates the diagnostic problems associated with autoimmune pancreatitis in the absence of histological IgG4 confirmation, underlining the need for a multifactorial approach, particularly when a relevant medical history is present. In uncertain cases, where the diagnosis is unclear, particularly when the traditional diagnostic criteria are not entirely satisfied, the therapeutic response can support the diagnosis.