November 2020 — Cytopathology

The correct answer is solid pseudopapillary neoplasm.

The diagnosis is solid pseudopapillary neoplasm (SPN) of the pancreas. SPN are rare, accounting for 1-2% of pancreatic exocrine neoplasms. They predominately occur in young women but can also be detected in men and older adults. They are found in any location within the pancreas, with a slight predilection for the tail. SPN are frequently identified incidentally by imaging or may present with abdominal pain. Characteristic imaging findings include a well circumscribed mass with variably solid and cystic components. Fine needle aspirates (FNA) are generally moderately to highly cellular and composed of single cells, loosely cohesive groups, and tissue fragments (Figure 1) with layers of cells loosely arranged around a central fibrovascular core (Figure 2). The cells are monomorphic with a variable amount of cytoplasm, which may contain vacuoles, hyaline globules, or cytoplasmic tails. The nuclei are eccentrically located, round to ovoid, and exhibit fine chromatin with grooves and small nucleoli (Figure 2). Extracellular globules of metachromatic material (Figure 1, arrows), foamy histiocytes, and necrotic debris may also be present in the background. The pseudopapillae are highlighted on histologic sections (Figure 3) and contain broad hyalinized or myxoid fibrovascular cores with loosely clinging tumor cells. Immunohistochemically, the tumor cells show nuclear expression of beta-catenin (Figure 4) and may be focally reactive for pan-keratin and synaptophysin.

The cytological differential diagnosis for SPN includes normal pancreatic acinar cells, acinic cell carcinoma (ACC), and neuroendocrine tumor (NET). Normal pancreatic acini are composed of grape-like clusters of cohesive cells, with abundant finely granular cytoplasm and eccentrically located nuclei with small nucleoli, and may surround fibrovascular tissue. Recognition of single cells and fine fibrovascular cores with loosely attached layers of tumor cells with a monomorphic appearance as well as the presence of intracytoplasmic hyaline globules and extracellular matrix material should aid in the distinction. FNA from acinic cell carcinoma demonstrate isolated cells and loose aggregates of uniform cells with granular cytoplasm and round to ovoid nuclei with smooth contours, and unlike SPN, typically contain prominent nucleoli and show some degree of nuclear atypia. Diffuse immunoreactivity for pan-keratin and trypsin distinguish ACC from SPN. ACC may also show focal reactivity for neuroendocrine markers, and nuclear expression for beta-catenin is observed in approximately 10%. FNA from neuroendocrine tumors demonstrate isolated and small clusters of plasmacytoid cells with uniform round to ovoid nuclei and characteristic finely stippled (“salt and pepper”) chromatin. Prominent nucleoli and delicate capillaries may also be observed. In addition to the characteristic nuclear appearance, immunoreactivity for pan-keratin, synaptophysin, and chromogranin as well as non-nuclear expression of beta-catenin helps distinguish NET from SPN.

SPN is considered a tumor of low malignant potential and has an excellent prognosis after surgical resection. Approximately 10-15% locally recur or metastasize.

References
1. Cibas ES, Ducatman BS. Cytology: Diagnostic Principles and Clinical Correlates. Elsevier; 2020.
2. Mody DR, Thrall MJ, Krishnamurthy S. Diagnostic Pathology: Cytopathology. Amirsys; 2018.
3. Arends MJ, Fukayama M, Klimstra DS, et al., editors. WHO Classification of Digestive System Tumours. Lyon, France: IARC Press; 2019.
4. Hooper K, Tracht JM, Eldin-eltoum IA. Cytologic criteria to reduce error in EUS-FNA of solid pseudopapillary neoplasms of the pancreas. J Am Soc Cytopathol. 2017;6(6):228-235.