Poorly Differentiated Neuroendocrine Carcinomas of the Pancreas A Clinicopathologic Analysis of 44 Cases

• Type of Material: Article
• Authors: Olca Basturk, Memorial Sloan-Kettering Cancer Center; Laura Tang, Memorial Sloan-Kettering Cancer Center; Ralph H. Hruban, Sol Goldman Pancreatic Cancer Research Center; Volkan Adsay, Emory University; Zhaohai Yang, Penn State Hershey MC; Alyssa Krasinskas, Emory University; Efsevia Vakiani, Memorial Sloan-Kettering Cancer Center; Stefano La Rosa, Ospedale di Circolo; Kee-Taek Jang, Sungkyunkwan University; Wendy L. Frankel, Ohio State University; Xiuli Liu, Cleveland Clinic; Lizhi Zhang, Mayo Clinic; Thomas J. Giordano, University of Michigan; Andrew M. Bellizzi, University of Iowa Hospitals and Clinics; Jey-Hsin Chen, Indiana University; Chanjuan Shi, Vanderbilt University; Peter Allen, Memorial Sloan-Kettering Cancer Center; Diane L. Reidy, Memorial Sloan-Kettering Cancer Center; Christopher L. Wolfgang, Sol Goldman Pancreatic Cancer Research Center; Burcu Saka, Emory University; Neda Rezaee, Sol Goldman Pancreatic Cancer Research Center; Vikram Deshpande, Massachusetts General Hospital; David S. Klimstra, Memorial Sloan-Kettering Cancer Center
• Language: English
• Date: 2014-04-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 by Lippincott Williams & Wilkins.
• Final Published Version (URL): http://dx.doi.org/10.1097/PAS.0000000000000169
• Title of Journal or Parent Work: American Journal of Surgical Pathology
• ISSN: 0147-5185
• Volume: 38
• Issue: 4
• Start Page: 437
• End Page: 447
• Grant/Funding Information: Ralph H. Hruban and N. Volkan Adsay have a grant from National Institutes of Health (#5P50 CA62924).
• Keywords: UNDIFFERENTIATED CARCINOMA; small cell; Science & Technology; GASTROINTESTINAL-TRACT; pancreas; ETOPOSIDE; GRADE; large cell; DISTINCT; carcinoma; neuroendocrine; SMALL-CELL-CARCINOMA; Surgery; high grade; LUNG-TUMORS; ENDOCRINE NEOPLASMS; Life Sciences & Biomedicine; CISPLATIN; PROGNOSTIC-FACTORS; Pathology; poorly differentiated
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology

Abstract

BACKGROUND:: In the pancreas, poorly differentiated neuroendocrine carcinomas include small cell carcinoma and large cell neuroendocrine carcinoma and are rare; data regarding their pathologic and clinical features are very limited. DESIGN:: A total of 107 pancreatic resections originally diagnosed as poorly differentiated neuroendocrine carcinomas were reassessed using the classification and grading (mitotic rate/Ki67 index) criteria put forth by the World Health Organization in 2010 for the gastroenteropancreatic system. Immunohistochemical labeling for neuroendocrine and acinar differentiation markers was performed. Sixty-three cases were reclassified, mostly as well-differentiated neuroendocrine tumor (NET) or acinar cell carcinoma, and eliminated. The clinicopathologic features and survival of the remaining 44 poorly differentiated neuroendocrine carcinomas were further assessed. RESULTS:: The mean patient age was 59 years (range, 21 to 82 y), and the male/female ratio was 1.4. Twenty-seven tumors were located in the head of the pancreas, 3 in the body, and 11 in the tail. The median tumor size was 4 cm (range, 2 to 18 cm). Twenty-seven tumors were large cell neuroendocrine carcinomas, and 17 were small cell carcinomas (mean mitotic rate, 37/10 and 51/10 HPF; mean Ki67 index, 66% and 75%, respectively). Eight tumors had combined components, mostly adenocarcinomas. In addition, 2 tumors had components of well-differentiated NET. Eighty-eight percent of the patients had nodal or distant metastatic disease at presentation, and an additional 7% developed metastases subsequently. Follow-up information was available for 43 patients; 33 died of disease, with a median survival of 11 months (range, 0 to 104 mo); 8 were alive with disease, with a median follow-up of 19.5 months (range, 0 to 71 mo). The 2- and 5-year survival rates were 22.5% and 16.1%, respectively. CONCLUSIONS: Poorly differentiated neuroendocrine carcinoma of the pancreas is a highly aggressive neoplasm, with frequent metastases and poor survival. Most patients die within less than a year. Most (61%) are large cell neuroendocrine carcinomas. Well-differentiated NET and acinar cell carcinoma are often misdiagnosed as poorly differentiated neuroendocrine carcinoma, emphasizing that diagnostic criteria need to be clearly followed to ensure accurate diagnosis.