Fine needle aspiration cytology of a clear cell (lipid‐rich) pancreatic neuroendocrine tumour in a patient without von Hippel‐Lindau disease

Dear Editor, A pancreatic endocrine neoplasm (PEN) is relatively uncommon, accounting for approximately 2% of all clinically detected pancreatic tumours. A clear cell (or lipid-rich) PEN is an unusual variant of a pancreatic neuroendocrine tumour. Cytological features of this entity have rarely been described in the literature. In the present study, we describe one case of an endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) of a clear cell PEN in a patient without von Hippel-Lindau (VHL) syndrome. Confirmatory immunostains were performed using the cell transfer technique. The relationship between the clear cell PEN and VHL syndrome will be discussed. A 64-year-old male with a history of coronary artery disease was found to have an incidental hyperenhancing, well-circumscribed 1.4-cm nodule in the head of the pancreas on a computed tomography (CT) scan performed at an outside hospital. There were no lesions in the adrenal glands or kidneys. Subsequently, the same lesion was identified by EUS to be hypoechoic with a distinct margin and FNA was performed. Rapid assessment of the sample gave no specific diagnosis. The direct smears showed clusters of cells with relatively uniform nuclei, abundant bubbly cytoplasm and indistinct cell borders (Figure 1a). Stripped nuclei with fine chromatin and small nucleoli were also observed. There were abundant clear microvesicles in the smear background (Figure 1b). The overall cytological features were identical to those of a benign adrenal cortical nodule. However, there is much overlap in the cytomorphological appearance of heterotopic adrenal cortical tissue and clear cell (lipid-rich) PEN. Immunocytochemical stains are invaluable for distinguishing them. Unfortunately, haematoxylin and eosin-stained sections cut from the cell block were acellular. We elected to perform immunostains using the cell transfer technique. The tumour cells were positive for synaptophysin and chromogranin (Figure 2) and negative for inhibin and Melan-A (not shown). The absence of staining for inhibin and Melan-A excluded the possibility of heterotopic adrenal cortical tissue and the positive staining for the neuroendocrine markers synaptophysin and chromogranin proved that this was a clear cell PEN. Because this lesion was small with bland nuclear features and no mitotic figures, it was expected to have an indolent clinical behaviour and therefore no surgical biopsy or excision was performed at that time. Seven months later, the follow-up CT scan at our hospital showed that the tumour measured 1.1 cm, having decreased slightly in size. The reason for the reduction in size is unclear. The other differential diagnoses included acinar cell carcinoma, a solid pseudopapillary tumour (SPPT) and clear cell renal cell carcinoma (RCC). Acinar cell carcinoma typically has marked nuclear atypia with prominent nucleoli. It is positive for trypsin, lipase and amylase and can be focally positive for synaptophysin and chromogranin. SPPT shows myxoid or hyalinized vacular stalks lined by neoplastic cells with nuclear grooves and inconspicuous nucleoli. Intracellular metachromatic hyaline globules are a characteristic feature if present. The tumour cells are positive for CD10 and show nuclear staining for beta-catenin. Aspirates of metastatic clear cell RCC are expected to contain tumour cells with enlarged nuclei with fine, pale chromatin and prominent nucleoli. The cells are positive for RCC marker, CD10 and vimentin. The data regarding the relationship between lipidrich PEN and VHL syndrome remain controversial. Clear cell PEN is commonly associated with VHL syndrome. One previous report demonstrated that clear cell cytoplasm was present in 60% of PENs Correspondence: S. Chen, IU Health Pathology Laboratory, 350 West 11th Street, Room 4088, Indianapolis, IN 46202, USA Tel. : +317-491-6443; Fax: +317-491-6419; E-mail: chen251@iupui.edu