Recommendations for Clinical Evaluation, Imaging Studies, Indications for Cytologic Study, and Preprocedural Requirements for Pancreatic FNA
The PSC has proposed recommendations for clinical evaluation, imaging studies, indications for cytological study, and preprocedural requirements for pancreatic FNA [27]. The clinical presentation of pancreatic neoplasia may include newly diagnosed late-onset diabetes mellitus, unexplained pancreatitis in an older individual, development of obstructive jaundice, pruritus, cholestasis, abdominal pain that radiates to the back, anorexia, weight loss, and steatorrhea. Elevated liver enzymes or imaging studies may indicate the presence of metastatic disease and confirm the presence of malignancy.
According to the PSC recommendations, patients with suspected pancreatic neoplasm should receive the following [27]:
1.A thorough history and physical examination. The history should include assessment for risk factors for the development of pancreatic adenocarcinoma, possible familial cancer history, and history of previous malignancy. The history should also include an assessment of risk factors for benign conditions such as pancreatitis.
2.Laboratory studies to assess bilirubin and alkaline phosphatase, and serum tumor markers, carbonic anhydrase (CA19-9), and carcinoembryonic antigen (CEA) should be conducted.
3.All of these patients should undergo imaging studies.
4.Benign conditions such as chronic pancreatitis, primary sclerosing cholangitis, and autoimmune diseases should be excluded. A serum IgG4 would be beneficial to exclude IgG4-related disease.
A number of imaging modalities may be used when assessing patients with clinically suspected pancreatic neoplasia. These include transabdominal US, CT, EUS, magnetic resonance imaging (MRI), magnetic resonance angiography, and magnetic resonance cholangiopancreatography. The indications and utility of these imaging studies will be discussed in detail in the chapter by Morse and Klapman [this vol., pp. 21–33].
The imaging work-up of solid masses is usually performed to determine if the mass is benign or malignant, or possibly of some other morphology. If malignant, the work-up is focused on determining resectability, as described by Morse and Klapman [this vol., pp. 23–28]. Patients with evidence of resectable solid pancreatic masses may be referred directly to surgery without a prior FNA, but this approach is not advocated because of the risk of unusual morphologies. A definitive diagnosis is needed for patients who are not surgical candidates or who need to have neoadjuvant therapy, which is increasingly being used for borderline resectable cases, and FNA is the preferred sampling method in this group of patients.
The work-up of pancreatic cysts is focused on determining if the cyst is mucinous (premalignant) or non-mucinous (serous, developmental, or inflammatory). Pancreatic cysts are usually first evaluated by CT scan. ERCP and EUS can be used for further evaluation. The 2012 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN) of the pancreas, and more recent 2017 revisions to the international consensus Fukuoka guidelines, attempt to standardize the work-up and management of patients with neoplastic mucinous cysts [32] and IPMN [33]. The 2017 guidelines are provided in Figure 1. Briefly, depending upon the size of the mucinous cyst, follow-up and treatment options may differ. Conservative management is recommended for mucinous cysts <3 cm in the absence of high-risk clinical and radiographic findings. High-risk radiographic findings include a solid enhancing lesion within the cyst or a main pancreatic duct ≥10 mm in diameter. High-risk clinical findings include obstructive jaundice and a cystic lesion in the head of the pancreas. Worrisome features include a cyst 3 cm or more in size, enhancing mural nodule <5 mm, thickened/enhancing cyst wall, main pancreatic duct diameter 5–9 mm, a non-enhancing mural nodule, an abrupt change in the caliber of the main pancreatic duct with distal pancreatic atrophy, lymphadenopathy, increased serum level of CA19-9, and cyst growth rate ≥5 mm/2 years [27, 33]. In the absence of high-risk and worrisome features, cysts <1 cm are followed by MRI/CT scans in 6 months and then every 2 years if there is no change; cysts of 1–2 or 2–3 cm are followed by MRI/CT scans in 6 months and then every year for 2 years if there is no change, or 6 months for a year and then yearly, respectively. For young patients with a 2- to 3-cm cyst without worrisome features with prolonged surveillance, surgery should be considered.
Fig. 1. 2017 revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Algorithm for the management of suspected BD-IPMN. aPancreatitis may be an indication for surgery for relief of symptoms. bDifferential diagnosis includes mucin. Mucin can move with change in patient position, may be dislodged on cyst lavage and does not have Doppler flow. Features of true tumor nodule include lack of mobility, presence of Doppler flow and FNA of nodule showing tumor tissue. cPresence of any one of thickened walls, intraductal mucin or mural nodules is suggestive of main duct involvement. In their absence main duct involvement is inconclusive. Abbreviations: BD-IPMN, branch duct intraductal papillary mucinous neoplasm; FNA, fine needle aspiration. Reproduced from Tanaka et al. [33] with permission from Elsevier.
EUS, when available, should be used for preoperative staging in patients with suspected pancreatic carcinoma or cancer of the biliary tract. It is particularly useful when CT or MRI findings are equivocal. EUS appears to be superior for detecting small masses, evaluating for tumor involvement of the superior mesenteric vein and the portal vein, and detecting lymph node metastases [34–36].
Pre-FNA requirements include obtaining informed consent. An informed consent form has to be signed by a competent patient before pancreatic FNA is performed. The possibility of complications such as bleeding, allergic/cardiac/respiratory reaction, and/or perforation should be mentioned in the consent form. An informed consent form should also include an explanation of the FNA procedure and inform patients that the results of the procedure may be non-contributory.
Techniques for Cytological Sampling of Pancreatic Lesions
The PSC published guidelines for sampling of pancreatobiliary lesions. This section will focus only on FNA of pancreatic masses. ERCP-guided brush cytology of the pancreatic duct can be performed for sampling of the main pancreatic duct in which a wire-guided brush is used to collect cells from a strictured pancreatic duct.
A number of imaging modalities may be used to guide pancreatic FNA, including US, EUS, and CT scans. EUS FNA is now the procedure of choice in establishing the diagnosis of a pancreatic lesion. Linear endosonographic instruments are required to target lesions for FNA [37]. Simple aspiration needles (usually 22- or 25-G) are used for the procedure. Both caliber needles yield the same cytologic material [38]. Smaller 25-G needles are preferable for sampling suspected PDAC as they are easier to use. They are also preferred for vascular lesions and aspiration of lymph nodes. Core biopsy and Tru-Cut needles are used for lesions such as stromal cell tumors, panNETs, and