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

Basturk, Olca MD*; Tang, Laura MD, PhD*; Hruban, Ralph H. MD; Adsay, Volkan MD; Yang, Zhaohai MD, PhD§; Krasinskas, Alyssa M. MD; Vakiani, Efsevia MD, PhD*; La Rosa, Stefano MD; Jang, Kee-Taek MD, PhD#; Frankel, Wendy L. MD**; Liu, Xiuli MD, PhD††; Zhang, Lizhi MD‡‡; Giordano, Thomas J. MD§§; Bellizzi, Andrew M. MD∥∥; Chen, Jey-Hsin MD, PhD¶¶; Shi, Chanjuan MD##; Allen, Peter MD***; Reidy, Diane L. MD†††; Wolfgang, Christopher L. MD, PhD†,‡‡‡; Saka, Burcu MD; Rezaee, Neda MD†,‡‡‡; Deshpande, Vikram MD§§§; Klimstra, David S. MD*

The American Journal of Surgical Pathology: April 2014 - Volume 38 - Issue 4 - p 437–447
doi: 10.1097/PAS.0000000000000169
Original Articles

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.

Departments of *Pathology


†††Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY

Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center

‡‡‡Department of Surgery, Johns Hopkins University, Baltimore, MD

Department of Pathology, Emory University, Atlanta, GA

§Department of Pathology, Penn State Hershey MC, Hershey

Department of Pathology, University of Pittsburgh, Pittsburgh, PA

**Department of Pathology, Ohio State University, Columbus

††Department of Pathology, Cleveland Clinic, Cleveland, OH

‡‡Department of Pathology, Mayo Clinic, Rochester, MN

§§Department of Pathology, University of Michigan, Ann Arbor, MI

∥∥Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA

¶¶Department of Pathology, Indiana University, Indianapolis, IN

##Department of Pathology, Vanderbilt University, Nashville, TN

§§§Department of Pathology, Massachusetts General Hospital, Boston, MA

Department of Pathology, Ospedale di Circolo, Varese, Italy

#Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Presented in part at the 102nd annual meeting of the United States and Canadian Academy of Pathology in Baltimore, MD, in March 2013.

Conflicts of Interest and Source of Funding: Supported in part by the National Cancer Institute Specialized Program in Research Excellence (SPORE) CA62924. R.H.H. and N.V.A. have a grant from National Institutes of Health (#5P50 CA62924); Z.Y. has received honoraria from UpToDate Inc.; W.L.F. has been an alliance for Clinical Trials in Oncology and received honoraria from Frozen Section Library: Pancreas: Springer; D.S.K. was on the speaker’s bureau for Novartis and has received honoraria from UpToDate. For the remaining authors none were declared.

Correspondence: David S. Klimstra, MD, Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (e-mail:

© 2014 by Lippincott Williams & Wilkins.