Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors.
OBJECTIVE
The biologic potential of nonfunctioning pancreatic neuroendocrine tumors (PNETs) is highly variable and difficult to predict before resection. This study was conducted to identify clinical and pathologic factors associated with malignant behavior and death in patients diagnosed with PNETs.


METHODS
We used International Classification of Diseases 9th edition codes to identify patients who underwent pancreatectomy for PNETs from 1998 to 2011 in the databases of 4 institutions. Functioning PNETs were excluded. Multivariate regression Cox proportional models were constructed to identify clinical and pathologic factors associated with distant metastasis and survival.


RESULTS
The study included 128 patients-57 females and 71 males. The age (mean ± standard deviation) was 55 ± 14 years. The body mass index was 28 ± 5 kg/m(2). Eighty-nine (70%) patients presented with symptoms, and 39 (30%) had tumors discovered incidentally. The tumor size was 3.3 ± 2 cm with 56 (44%) of the tumors measuring ≤2 cm. Seventy-three (57%) patients had grade 1 histology tumors, 37 (29%) had grade 2, and 18 (14%) had grade 3. Peripancreatic lymph node involvement was present in 31 patients (24%), absent in 75 (59%), and unknown in 22 (17%). Distant metastasis occurred in 18 patients (14%). There were 12 deaths, including 1 perioperative, 8 disease related, and 3 of unknown cause. With a median follow-up of 33 months, the overall 5-year survival was 75%. Multivariate Cox regression analysis identified age >55 (hazard ratio [HR], 5.89; 95% confidence interval [CI], 1.64-20.58), grade 3 histology (HR, 6.08; 95% CI, 1.32-30.2), and distant metastasis (HR, 8.79; 95% CI, 2.67-28.9) as risk factors associated with death (P < .05). Gender, race, body mass index, clinical symptoms, lymphovascular and perineural invasion, and tumor size were not related to metastasis or survival (P > .05). Three patients with tumors ≤2 cm developed distant metastasis resulting in 2 disease-related deaths.


CONCLUSIONS
Age >55 years, grade 3 histology, and distant metastasis predict a greater risk of death from nonfunctioning PNETs. Resection or short-term surveillance should be considered regardless of tumor size.
NorthShore University HealthSystems, Evanston, IL. Electronic address: jovenel1@yahoo.com.
Jovenel
J
Cherenfant
Susan J
SJ
Stocker
Mistry K
MK
Gage
Hongyan
H
Du
Tiffany A
TA
Thurow
Melanie
M
Odeleye
Scott W
SW
Schimpke
Karen L
KL
Kaul
Curtis R
CR
Hall
Ihab
I
Lamzabi
Paolo
P
Gattuso
David J
DJ
Winchester
Robert W
RW
Marsh
Kevin K
KK
Roggin
David J
DJ
Bentrem
Marshall S
MS
Baker
Richard A
RA
Prinz
Mark S
MS
Talamonti
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018358:Neuroendocrine Tumors / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016016:Proportional Hazards Models; D012189:Retrospective Studies