PanNETs, immunostains synaptophysin, chromogranin, and the proliferation marker Ki-67 can be extremely helpful. Ki-67 is of importance in the histologic grading of PanNETs, but its utility in cytological preparations remains to be determined [59]. Strong nuclear staining for beta-catenin is diagnostic for SPNs in the pancreas.
Fig. 2. Flowchart depicting an algorithmic approach to pancreatic lesions for diagnostic purposes.
Cystic lesions of the pancreas exhibit a specific distinctive mutational profile for each subtype. SCNs have VHL mutations, CTNNB1 mutation is diagnostic of SPNs, MCNs have mutations involving the RNF43, KRAS, TP53, and SMAD4 genes, and IPMNs have mutations involving the genes KRAS, RNF43, GNAS, P53, and SMAD4 [60, 61].
Algorithmic Approach to Cytological Evaluation of Pancreatic Masses
Indications for pancreatic FNA are the presence of a solid or cystic mass. It is important to distinguish benign, indolent, or inflammatory processes which may be treated with observation, compared to neoplastic processes which require surgery or neoadjuvant or adjuvant chemotherapy. An algorithmic approach in the evaluation of pancreatic lesions includes clinical history, radiographic findings, cytological findings, and ancillary studies to yield the most clinically relevant interpretation of the aspirated material (Fig. 2).
Some of the pancreatic tumors show certain age and gender predilections as MCNs occur in middle-aged women and pancreatoblastoma is a childhood tumor. Imaging findings are very informative as to whether the mass is cystic or solid. This information determines the cytopathological algorithm. Different entities are considered on the radiographic information depending on whether the mass is solid, solid and cystic, entirely cystic, or cystic with connection to the pancreatic ductal system. If the lesion is solid, entities such as chronic pancreatitis, lobular atrophy, adenocarcinoma, pancreatic endocrine tumor, ACC, and metastases are some of the main differential diagnoses that are considered. Any solid tumor that undergoes cystic degeneration may present radiographically as a solid and cystic lesion. Tumors that present as solid and cystic lesions include PanNETs and SPNs. Purely cystic lesions include MCNs, serous cystadenoma, side branch IPMN, and pseudocysts. When a dilated main pancreatic duct is present or a connection of the cyst to the ductal system is demonstrated, a diagnosis of IPMN may be made. Gross evaluation of the material aspirated is very useful, especially in cystic lesions. Evaluation of the smears starts at a low-power examination where the cellularity, architecture, and background information are collected. At intermediate power, assessments made at low power are confirmed and architectural patterns can be further analyzed. At high power, nuclear and cytological features and mitotic figures are appreciated. Ancillary studies include immunohistochemistry, flow cytometry for suspected lymphoma, cyst fluid analysis for CEA, amylase, and occasionally for k-RAS mutations and loss of heterozygosity.
Disclosure Statement
The author has no conflicts of interest to disclose.
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