Cytopathologic diagnosis of oncocytic type intraductal papillary mucinous neoplasm: Criteria and clinical implications of accurate diagnosis

Abstract

Background: Cytologic findings of pancreatic oncocytic-type intraductal papillary mucinous neoplasms (IPMNs)/intraductal oncocytic papillary neoplasms (IOPNs) are largely unknown.

Methods: Five IOPNs encountered by the authors were analyzed.

Results: Four IOPNs were located in the pancreatic head, and 1 was located in the pancreatic body/tail in 2 men and 3 women ages 56 to 84 years (mean age, 66 years). Radiologic diagnoses included pancreatic ductal adenocarcinoma (PDAC) in 2 patients, invasive cancer associated with IPMN in 1 patient, IPMN versus mucinous cystic neoplasm in 1 patient, and cystic mass in 1 patient. Cytologic findings included: hypercellular smears (4 of 5 cases) containing well formed clusters of oncocytic cells (5 of 5 cases) with prominent, slightly eccentric nucleoli (4 of 5 cases), predominantly arranged in sheets/papillary units (5 of 5 cases), with punched-out intercytoplasmic spaces (4 of 5 cases), and with occasional 3-dimensional groups and focal necrosis (3 of 5 cases). The intracytoplasmic mucin and thick extracellular mucin typical of other IPMNs were observed only in 2 cases and were very limited. The mean size on resection was 4.5 cm. Invasion was observed in 3 cases (0.1, 0.3, and 2.0 cm) of tubular-type IPMN. Initial cytologic evaluation was performed by the authors in 4 of 5 cases, which were diagnosed as IOPN (n = 3) and IPMN versus cystic PDAC (n = 1). One case was initially misdiagnosed as PDAC and, on resection, proved to be noninvasive IOPN.

Conclusions: Cytologic features of IOPNs are classical, similar to their histologic counterparts, and differ significantly from other IPMN subtypes. Because of their highly complex appearance, they are often radiologically misdiagnosed as PDAC; thus, failure to recognize their characteristic features on fine-needle aspiration may lead to inappropriate treatment. Patients with IOPN have an incomparably better prognosis than patients with ordinary PDAC, even when their neoplasms are invasive.

Keywords: cytology; fine-needle aspiration; intraductal oncocytic papillary neoplasm (IOPN); intraductal papillary mucinous neoplasm (IPMN); oncocytic; oncocytic intraductal papillary mucinous neoplasm; pancreas.

Figure 1

(A) A hypercellular smear is composed of numerous sheets of epithelial cells (Diff-Quik stain). (B) Large, complex papillary units have an “antler-like” branching pattern similar to that observed in fibroadenoma of the breast (Papanicolaou stain). (C) Magenta-colored fibrovascular cores traversed some tumor cell clusters (Diff-Quik stain). (D) A hypercellular smear is composed of crowded sheets and singly dispersed oncocytic tumor cells (Diff-Quik stain).

Figure 2

(A) A smear composed of oncocytic cells arranged in large, flat sheets with prominent nucleoli is shown (Diff-Quik stain). (B) Tumor cells have round to oval nuclei, prominent nucleoli, and abundant pink cytoplasmic granules, as highlighted in the inset (Papanicolaou stain). (C) Case 2 had large vesicular nuclei with slightly eccentric, prominent nucleoli and more nuclear contour irregularity than that observed in B (Papanicolaou stain). (D) Oncocytic features of the tumor cells are easily identifiable on this ThinPrep slide (Papanicolaou stain).

Figure 3

Rigid, punched-out, intercellular spaces are visible on (A) Diff-Quik–stained and (B) Papanicolaou-stained smears and give a vaguely cribriform appearance to cell clusters. (C) Identical punched-out spaces are observed in this resected oncocytic intraductal papillary mucinous neoplasm composed of complex, branching, edematous papillae lined by oncocytic epithelium (H&E stain). (D) Intracytoplasmic pink mucin is observed in occasional tumor cells, as highlighted in the inset (Papanicolaou stain).

Figure 4

Case 1 was an oncocytic intraductal papillary mucinous neoplasm that was misdiagnosed as pancreatic ductal adenocarcinoma on cytology. (A) Smears revealed crowded sheets of oncocytic cells (Diff-Quik stain). (B) Thick, colloid-like mucin was present and contained necrotic debris and clusters of atypical cells with prominent cytoplasmic vacuoles (Papanicolaou stain). (C) Occasional 3-dimensional groups with high nuclear-to-cytoplasmic ratio and irregular nuclear contours highly concerning for adenocarcinoma were present (Papanicolaou stain). (D) A corresponding cell block revealed numerous papillae with hyalinized fibrovascular cores lined by atypical oncocytic cells and no adenocarcinoma component (H&E stain).

Figure 5

Case 5 was an oncocytic intraductal papillary mucinous neoplasm that had an invasive adenocarcinoma component identified on resection. (A) Smears reveal numerous 3-dimensional clusters of oncocytic cells with background necrotic debris (Diff-Quik stain). (B) There is marked nuclear pleomorphism and single-cell necrosis (Papanicolaou stain). (C) Prominent nucleoli and nuclear irregularity were striking in some areas (Papanicolaou stain). (D) A cell block revealed multiple, broad papillae with striking basophilic edema lined by oncocytic cells with occasional intranuclear inclusions (inset) and large, hyperchromatic nuclei (H&E stain).

Figure 6

Case 5 was an oncocytic intraductal papillary mucinous neoplasm that had an invasive adenocarcinoma component identified on resection. (A) This wholemount slide reveals the intraductal location of a complex papillary neoplasm. (B) Papillae are lined by large oncocytic cells with (C) multiple, minute foci of microinvasive adenocarcinoma (see inset) and (D) lymph node metastasis (H&E stain).