The Pathologic Classification of Neuroendocrine Tumors

Abstract

Neuroendocrine tumors (NETs) arise in most organs of the body and share many common pathologic features. However, a variety of different organ-specific systems have been developed for nomenclature, grading, and staging of NETs, causing much confusion. This review examines issues in the pathologic assessment of NETs that are common among primaries of different sites. The various systems of nomenclature are compared along with new proposal for grading and staging NETs. Although differences persist, there are many common themes, such as the distinction of well-differentiated (low and intermediate-grade) from poorly differentiated (high-grade) NETs and the significance of proliferative rate in prognostic assessment. A recently published minimum pathology data set is presented to help standardize the information in pathology reports. Although an ultimate goal of standardizing the pathologic classification of all NETs, irrespective of primary site, remains elusive, an understanding of the common themes among the different current systems will permit easier translation of information relevant to prognosis and treatment.

Neuroendocrine Carcinomas of the Stomach: Computed Tomography and Pathologic Findings in 32 Patients

“…They account for 6% of gastric neuroendocrine neoplasms, are more common in men (male-tofemale ratio, 2:1), and present at a mean age of 63 years (range, 41 -61 years) (13). Histologically, the NEC component is similar to small cell or large cell NEC of the lung and corresponds to a grade 3 neuroendocrine neoplasm, according to the 2010 WHO classification (2).…”

“…The recent world health organization (WHO) classification in 2010 divided neuroendocrine tumors into three categories that could be applied to all sites within the gastrointestinal tract: grade 1 neuroendocrine neoplasm (low grade), grade 2 neuroendocrine neoplasm (intermediate grade), grade 3 neuroendocrine carcinoma (NEC), small cell carcinoma, and large cell carcinoma (high grade). The proposed grading has three tiers based on proliferation (G1, G2, and G3), with the following definitions of mitotic count and Ki67 index: G1: mitotic count < 2 per 10 high power fields (HPF) or < 3% Ki67 index; G2: mitotic count 2-20 per 10 HPF or 3% -20% Ki67 index; and G3: mitotic count > 20 per 10 HPF or > 20% Ki67 index (2).…”

Ampullary Neuroendocrine Tumor: A Rare Cause of Recurrent Abdominal Pain

“…Carcinoids involving the ampulla of Vater can be derived from cell types of the duodenum, common bile duct or the pancreas. Two main categories of ANET exist: low-grade ANET and high-grade ANET which are distinguished on the basis of their proliferative rates assessed by amount of necrosis, mitotic figures per high power field or Ki67 labeling index [7] [8].…”

“…However, less invasive procedures like local excision and endoscopic resections have also been successfully attempted, especially for ANET less than 2 cm size or in high risk surgical candidates [4] [5] [14]. Extensive debulking surgery should be considered in patients with hormonal hypersecretion, even in the presence of advanced disease (extensive local or distant metastasis) since it has been shown to offer survival rates of up to 80% at 5 years [7]. Our patient had a successful local resection of his tumor, and has been disease free for the past twenty-four months.…”

“…The treatment protocol for ANET remains controversial, as they are rare tumors with an unpredictable biological behavior and prognosis [7]. Since tumor size has not been clearly established to correlate with lymph nodal positivity status, pancreaticoduodenectomy is often recommended as the treatment of choice for tumors of any size with no distant spread [9] [12] [13].…”