The majority of cases of acute pancreatitis are associated with partial or complete biliary tract obstruction, alcoholism, infectious agents (toxoplasmosis and ­adenovirus), or trauma including prior Fine-needle aspiration (FNA) [3, 4]. Most patients with acute pancreatitis are diagnosed and treated clinically. Fine-needle aspiration is rarely needed in such cases. It is more often the patient with active chronic pancreatitis and a mass lesion on work up who is sent for FNA. The management of acute pancreatitis focuses on treating the etiological cause [4].

A number of etiologies exist for chronic pancreatitis including obstruction of the ductal system, alcoholism, hyperparathyroidism, hereditary diseases, polyarteritis nodosa, viral infections, toxins, and tuberculosis [6]. Chronic pancreatitis has an as yet incompletely defined relationship with cystic fibrosis. KRAS mutations are found in a significant number of cases of chronic pancreatitis [7]. Chronic pancreatitis presents with abdominal pain of variable severity which may result in surgery. Extensive, late phase chronic pancreatitis can result in both endocrine and exocrine function deficiency. Imaging studies of chronic pancreatitis utilizing contrast enhanced computed tomography (CT) examination demonstrate parenchymal atrophy and scarring with pancreatic duct dilatation and often pancreatic stones [8]. The presence of calcification favors chronic pancreatitis over malignancy . While chronic pancreatitis may globally affect the gland, approximately 30 % of cases demonstrate focal pancreatic enlargement [6]. Fine-needle aspiration is rarely used for the investigation of chronic pancreatitis when clinical and imaging findings strongly indicate that diagnosis. When focal pancreatic enlargement is present, workup to exclude malignancy is required and FNA is the initial diagnostic procedure of choice.

Autoimmune pancreatitis (AIP) represents a manifestation of a systemic disease characterized by fibrosclerosis at a number of body sites including sclerosing mediastinitis, retroperitoneal fibrosis, sclerosing cholangitis, Riedel thyroiditis, and sclerosing sialadenitis among others [10–13]. These entities appear to be linked by increased numbers of IgG4 producing plasma cells. In autoimmune pancreatitis increased numbers of IgG4 producing plasma cells are identified and are diagnostically important [10]. Autoimmune pancreatitis can clinically and by imaging be easily confused with pancreatic adenocarcinoma requiring tissue examination to separate the two entities [11, 14, 15]. The cytological diagnosis of autoimmune pancreatitis is often not possible by cytology alone. Cellblock preparations with tissue fragments or small core biopsies are helpful in making the diagnosis. Immunohistochemical stains for IgG and IgG4 may be supportive of the diagnosis if IgG4 is overwhelmingly positive compared to IgG, but caution is warranted in using these markers for a definitive diagnosis due to the difficulty in interpreting these stains, which often have high background, and the absence of criteria for such a diagnosis. However, a suggestion… of the diagnosis may be sufficient for clinical management. Serology for IgG4 and/or a trial with corticosteroids may be performed prior to surgical intervention [16, 17].

Pseudocyst generally represents a sequelae of acute or chronic pancreatitis or trauma [20–22]. Pseudocysts represent liquefactive necrosis of the pancreatic substance and surrounding adipose tissue. They may obtain massive proportions with extension beyond the pancreas proper. The term pseudocyst is used to indicate that these lesions lack an epithelial cyst lining and the intraluminal contents are bloody, necrotic, or cloudy. Some become secondarily infected. The pseudocyst fluid is high in amylase, which is a finding that helps to support the diagnosis when analyzing biochemical cyst fluid analysis results since all pseudocysts demonstrate a high amylase level, generally in the thousands U/L [23, 24]. Cyst fluid carcinoembryonic antigen (CEA) is not elevated with rare exception.

Lymphoepithelial cysts appear to be the pancreatic homologue for the morphologically similar branchial cleft cyst. Pancreatic lymphoepithelial cysts are often multiloculated and lined by squamous epithelium associated with abundant lymphoid tissue in the wall [26–28]. The lymphoid component may be so prominent as to be associated with germinal center formation. Aspirated cyst contents are usually thick and grumous producing tissue for direct smears . Occasionally, cyst contents are liquid and may be tested for CEA and amylase. Amylase is low as is CEA, but occasionally CEA is elevated [29], which may produce a diagnostic pitfall, especially when the squamous component is so degenerated as to appear to be desiccated mucin.

Intrapancreatic accessory spleen may closely resemble a pancreatic neoplasm on imaging studies since it presents as a round mass in the pancreatic tail, the most common presentation of a neuroendocrine tumor [31]. Microscopically, the splenic tissue has a normal architecture with reactive white pulp. The cells are smaller than neuroendocrine tumor cells and do not display the eccentric plasmacytoid cytoplasm of neuroendocrine tumor cells. Cellblock preparation of tissue fragments and CD8 staining highlights the diagnostic splenic endothelial cells [32, 33].