cytology yield and lesions suspicious for autoimmune pancreatitis. The EUS-FNA procedure can be difficult to perform due to vessel interposition, duodenal stenosis, bleeding, and tumor firmness. Prior gastric surgery or bypass will limit accessibility of the device to the pancreas. A 22-G beveled needle called Procore (Echo Tip) is available for use with the EUS device that produces a core-like tissue fragment.
Mucinous cysts are aspirated using a 22-G needle due to the high viscosity of the cyst fluid. Serous cystadenomas and cystic NETs should be aspirated with a 25-G needle as the cyst fluid is not viscous. Pseudocysts should be aspirated with a 22- or 19-G needle in order to evacuate the entire lesion, which may become contaminated by FNA. Mural nodules and any adjacent masses can be aspirated after the cyst fluid is aspirated. The cyst fluid is centrifuged and may be sent for CEA and DNA mutational analysis.
Standardized Terminology and Nomenclature
The PSC has developed a set of guidelines for the terminology and nomenclature of pancreatobiliary disease [28]. The proposed terminology recommends a six-tiered system comprising non-diagnostic, negative, atypical, neoplastic (benign and other), suspicious, and positive (Table 3).
Non-diagnostic specimens are those that provide no diagnostic or useful information. This may be due to technical or sampling issues. Absence of epithelial cells should not be presumed to be non-diagnostic as sampling from pancreatic pseudocysts and mucinous cysts can be acellular. Clinical and radiographic information is helpful in these instances. In the presence of any cellular atypia, the non-diagnostic category should not be used. Cytological interpretation can be limited by the amount of material aspirated or by preparation artifact such as tissue entrapped in a blood clot precluding cytological evaluation. The presence of only gastrointestinal contaminants or normal pancreatic tissue in the context of a well-defined pancreatic mass are some examples that should be included in this category.
A negative cytology is a sample that contains adequate tissue to define a lesion that is identified on radiology. It may indicate benign entities like acute, chronic, and autoimmune pancreatitis, pseudocyst, ectopic, and intrapancreatic splenule and lymphoepithelial cyst.
Atypical categories include cases with features that are more than reactive changes, low cellularity, premalignant (dysplastic) changes, and cases assigned due to observer caution. The cytological specimen may contain cells with morphological features beyond recognizable normal or reactive changes. An atypical diagnosis raises the possibility of a neoplasm, especially a low-grade neoplasm. The “neoplastic” category is separated into “benign,” which includes neoplasms such as serous cystadenoma, and “other,” which includes premalignant lesions such as mucinous cysts, IPMN, and low-grade malignant tumors such as PanNETs and SPN.
The PSC guidelines use the term “suspicious for malignancy” to cover a range of atypias falling just short of that necessary for a definitive diagnosis of malignancy. These specimens lack sufficient diagnostic features for a definitive diagnosis. Other information, such as clinical, imaging, or ancillary test findings, must be correlated with the cytologic findings before surgical intervention can be undertaken.
The positive category includes malignant neoplasms such as PDAC, ACC, poorly differentiated neuroendocrine carcinomas, pancreatoblastoma, lymphoma, and metastases. This category is used when unequivocal features of malignancy are identified.
Table 3. Standardized terminology for pancreatic cytology by the PSC
FNA Biopsy Follow-Up and Treatment Options for Patients with Pancreatobiliary Lesions
This work group focused on developing management recommendations based on the proposed terminology [30]. This section summarizes those recommendations.
Recommendations based on the recommended diagnostic categories are as follows:
Non-Diagnostic
The PSC recommends a repeat FNA procedure when the first attempt yields a non-diagnostic cytology sample. The clinical team may elect to proceed to laparotomy without repetition depending on the radiographic and clinical findings for obtaining a Tru-Cut needle biopsy. If the first attempt was via brushings, it can be repeated by brushings or EUS-FNA. If the first attempt was by percutaneous FNA then it may be most reasonable to use EUS-FNA for the second attempt. If the first attempt was EUS-FNA, reassessment of the EUS findings and other imaging should be undertaken, followed by a review of the FNA line of approach [30]. Repeat aspiration of a cystic lesion of the pancreas should be carefully considered due to there being up to 14% risk of associated infection.
Negative
A negative cytology may indicate benign entities like acute, chronic, and autoimmune pancreatitis, pseudocyst, ectopic and intrapancreatic splenule, and lymphoepithelial cyst. If cytopathology is diagnostic of a specific benign entity, then the treatment is aimed to treat that particular entity. However, if the negative cytology diagnosis is descriptive without a specific benign entity diagnosis, it should not be taken to be synonymous with a benign lesion. The multidisciplinary team should evaluate the clinical presentation, radiographic findings, and cytopathology, and should reassess the component that is discrepant. False negative interpretations are not uncommon in pancreatic EUS-FNA due to sampling and interpretive errors. If the lesion is clinically suspicious, FNA may be repeated to collect diagnostic material.
Atypical
Cytologic specimens categorized as atypical demonstrate cytologic and architectural alterations that are greater than reactive atypia, but less than that of suspicious for malignancy. It is not trivial to repeat pancreatic FNAs diagnosed as atypical as there are a number of individuals involved and use of expensive equipment makes the resource utilization and costs of operative biopsy even greater. The appropriate course of action is dependent on a multidisciplinary review, the functional status of the patient, and the wishes of the patient after clinical consultation [30]. An atypical interpretation on cytology may require additional diagnostic tests such as loss of immunohistochemical staining for the Dpc4/SMAD4 suppressor gene and detection of mutant KRAS that may contribute to management decisions when imaging is suspicious for adenocarcinoma. Ancillary tests such as fluorescent in situ hybridization (FISH) and next-generation sequencing have shown promise in improving diagnostic sensitivity for the detection of malignancy [39, 40]. The related malignancy risk of the atypical category for EUS-FNAs of solid pancreatic masses is 25–100% (mean 58%) [41–43].
Neoplastic: Benign
The major lesion in this category is serous cystic neoplasm (SCN), which can either be observed or treated by resection. If imaging, cytology, and cyst fluid biochemistry (CEA and amylase) support an interpretation of an SCN, the patient can be conservatively managed with observation. However, if the patient is symptomatic and there is evidence of significant growth, which increases the risk of hemorrhage and rupture, it is resected.
Neoplastic: Other
Pancreatic Neuroendocrine Tumor. PanNETs can either be managed conservatively by observation or by surgery, depending upon the clinical scenario.