Original Article
Cytological features contributing to the misclassification of pancreatic neuroendocrine tumors

https://doi.org/10.1016/j.jasc.2016.01.001Get rights and content

Introduction

Pancreatic neuroendocrine tumors are a diverse group of malignant neoplasms of varying biological behavior, with outcomes predicted by tumor differentiation and grade. Initial diagnosis is often made by fine-needle aspiration cytology via endoscopic ultrasound of the pancreas primary. We retrospectively reviewed our institutional experience with pancreatic neuroendocrine cytology diagnosis and evaluated for tumor typing accuracy and causes of misdiagnosis.

Materials and methods

We searched our institutional database (1994-2012) for all pancreas fine-needle aspirations with corresponding pancreatic histology and a neuroendocrine diagnosis. Cases with discrepant cytology and histology diagnoses were reviewed for factors contributing to misclassification.

Results

143 patients were identified with a neuroendocrine diagnosis either by cytology or histology. In the 129 cytology cases classified as positive/neoplastic/suspicious, tumor type was diagnosed correctly in 101 (78%) cases, incorrectly in 17 (13%), and unclassified (epithelioid neoplasm) in 11 (9%). The most common tumor classification error (7 cases) was misclassifying a neuroendocrine tumor as adenocarcinoma on cytology, which in one case led to inappropriate neoadjuvant chemotherapy. Features of neuroendocrine cytology misdiagnosed as adenocarcinoma included cell clustering and anisonucleosis. Features of non-neuroendocrine cytology misclassified as neuroendocrine included abundant acinar cells or problematic interpretation of immunohistochemical stains.

Conclusions

Cytology can accurately identify neuroendocrine differentiation in the majority of cases; nevertheless, there are potential serious pitfalls. Misclassification of a neuroendocrine tumor as adenocarcinoma or vice versa can have significant clinical impact. Clinical and radiological correlation is essential.

Introduction

Pancreatic neuroendocrine (NE) neoplasms represent a biologically diverse group of functional, nonfunctional, and hereditary tumors with behavior ranging from indolent to aggressive. The recent widespread use of high-resolution imaging techniques has identified an increasing number of asymptomatic patients with small, incidentally detected, and nonfunctioning tumors.1, 2 The 2010 WHO classification for tumors of the gastrointestinal tract defined two distinct subgroups of tumor differentiation for pancreatic NE neoplasms: well-differentiated pancreatic NE tumors (WD-PanNETs) and poorly differentiated pancreatic NE carcinomas (PD-NECs) (Table 1). The distinction is based on biological differences, carries crucial prognostic implications, and poses a specific impact on therapeutic strategies. The 2010 WHO classification further designates three tumor grades based on the mitotic rate and Ki67 proliferative index (KI) (Table 1).3 WD-PanNET is a heterogeneous entity and clinical management decisions consider patient symptoms and volume of disease. Currently, the distinction of low versus intermediate grade tumors is not crucial but it may impact some treatment decisions.5 In contrast, PD-NECs have a uniformly aggressive clinical behavior similar to small-cell lung cancer and are generally managed with cytotoxic chemotherapy.6

Cytology may be the primary diagnostic material guiding initial management for these tumors because they are readily accessed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which performs well in localizing small lesions.7, 8 A number of factors influence the cytopathologist’s ability to reliably recognize NE neoplasms, including low incidence, atypical clinical presentation, morphologic mimics, and artifacts associated with the biopsy procedure. Historically, reporting of these tumors has not been straightforward because of the diversity of diagnostic terms across systems of nomenclature and a lack of standards for a primary diagnostic category that conveyed biologic potential.

We aimed to retrospectively review our institutional experience with pancreatic NE cytology diagnosis. We evaluated accuracy in tumor typing, identified factors contributing to misclassification, and examined rates of cytology reporting for tumor differentiation and grade.

Section snippets

Materials and methods

We retrospectively searched the pathology archive at our institution for all pancreas FNA specimens with a corresponding histologic specimen from the same pancreatic anatomic site during the time interval January 1994 through March 2012; all diagnoses were recorded. Patients with a cytology or histology diagnosis of a “tumor”, “neoplasm”, or “carcinoma” of “endocrine” or ”neuroendocrine” type (including islet cell tumor) were selected for inclusion. The search yielded cytology specimens

Results

In the 18-year period studied, 143 patients with cytology and histology samples from the same pancreatic anatomic site and a diagnosis of a tumor, neoplasm, or carcinoma of endocrine/NE type (including islet cell tumor) from either type of specimen were identified. A summary of clinical data for patients with a histologic diagnosis of NE neoplasm is shown in Table 2. The cytology comprised 153 pancreas FNAs (including 10 repeat biopsies). The diagnostic categories were distributed as follows:

Discussion

Cytology, most commonly via EUS-FNA, is sometimes the only pathologic diagnosis for patients with pancreatic lesions. This places considerable responsibility on cytopathologists for providing accurate diagnoses to guide appropriate clinical management. Accuracy for determining a NE neoplasm in this study was 78%. This rate is at the lower range of prior studies (79%-90%) that have used diverse methods of case selection and analytic methods,7, 9, 10 and this could be due to our inclusion of

Funding sources

DK has consulting fees from Wren Laboratories and royalties from American Registry of Pathology and UpToDate.

Conflict of interest disclosures

The authors have no financial disclosures.

Acknowledgments

Cymra McBean and Tanisha Daniel provided administrative assistance for the study and proofreading of the article.

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    Present address: Department of Pathology, Trinity Hospital of Augusta, 2321 Kings Way, Augusta, GA 30904 USA.

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