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Revista Española de Enfermedades Digestivas

versión impresa ISSN 1130-0108

Rev. esp. enferm. dig. vol.104 no.1 Madrid ene. 2012 



Diagnostic protocol for pancreatic neuroendocrine tumors (PNETs)

Protocolo diagnóstico de los tumores neuroendocrinos pancreáticos (TNEP)



Modesto Varas1, Joan Gornals2, José Luis Prieto3 and Julio Iglesias-García4. Grupo de trabajo de Ultrasonografía Endoscópica de la SEPD

1Unit of Echoendoscopy. Centro Médico Teknon and Hospital Universitario del Valle Hebrón. Barcelona, Spain.
2Unit of Endoscopy. Hospital Universitario de Bellvitge. Hospitalet de Llobregat, Barcelona, and Centro Médico Teknon. Barcelona, Spain.
3Unit of Digestive Diseases. Hospital Punta Europa. Algeciras. Cádiz, Spain.
4Department of Digestive Diseases. Hospital Clínico Universitario de Santiago de Compostela. A Coruña, Spain





The advent of endoscopic ultrasonography (EUS) or echoendoscopy (EE) represented a breaking point in the localization and diagnosis of PNETs (1-4) (insulinomas, gastrinomas, glucagonomas, non-functioning, etc.) as it provided a high yield (sensitivity around 90%, specificity at 98%) (5-10) only second to EUS-FNA (almost 100%) (10-15).

New EUS-related technologies such as contrast media and elastography have also improved PNET localization (16-22) with percentages matching those obtained with EUS-FNA.

A recent paper states that contrast agents (S: 95%) substantially improve conventional EUS findings (21).

Therefore, diagnostic EUS should be now considered seriously for PNET assessment (10) in addition to elastography, contrast media, both things, or even FNA (22).

Furthermore, novel imaging techniques other than US (23), CT (24,25), and MRI (25,26), including PET (FDG & DOPA) and PET-CT, may be used for the localization and staging of PNETs, particularly when no primary tumor has been found (27-32) (Table I).

When CT will not find a PNET, EUS does so in 91% of cases (34). According to several papers EUS is superior to MDCT (Multiple Detector Computerized Tomography) (8,21,33,34).

PET-CT may be a match for Octreoscan (31) for tumors other than insulinomas, and only PET-CT is superior to Octreoscan when tumors with a high Ki-67 proliferation index are considered (32), with sensitivity approaching 100% when it comes to finding a primary tumor and its related metastases (35-38).

Once a tumor is precisely located its staging must ensue in order to decide on its appropriate management (surgical or otherwise) and to define a prognosis according to histopathology (Figs. 1 and 2) (39).

We have moved from the classical TNM system to the WHO histological classification (40):

- Well differentiated: benign, smaller than 2 cm, confined to the pancreas, fewer than 2 mitoses per 10 HPFs, Ki-67 below 2%, and chromogranin A +. No vascular invasion.

- Uncertain behavior: confined to the pancreas and one or more of the following: a) larger than 2 cm; b) 2-10 mitoses; c) Ki-67 above 2%; and d) vascular invasion and perineural permeation.

- Well-differentiated endocrine carcinoma: low malignity. Macroscopic local invasion and/or metastasis (malignant). No vascular invasion.

- Poorly-differentiated endocrine carcinoma: high malignity, over 10-20 mitoses per 10 HPFs. Ki-67 above 15-20%. Vascular invasion.

For instance, in a series of 139 NF-PNETs incidentally identified (mean size: 3 cm) and then operated upon, 19% were classified as benign, 52% as with uncertain behavior, and 28% as malignancies. Mean 3-year follow-up of 80% (112 cases) revealed an actuarial survival of 89, 92.5, and 50%, respectively, at 5 years (44).



A: angiography; US: ultrasonography; EUS: endoscopic ultrasonography; IUS: intraoperative ultrasonography; EUS-FNA: endoscopic ultrasonography-guided fine-needle aspiration; MRI: magnetic resonance imaging; SRS: octreoscan; CT: computerized tomography; MDCT: multidetector computerized tomography; PET: positron emission tomography; PET-CT: PET with computerized tomography; ICC: immunocytochemistry; I: insulinoma; G: gastrinomas; PNET: pancreatic neuroendocrine tumor or apudoma; NF-PNET: non-functioning PNET; MEN: multiple endocrine neoplasia; VHL: von Hippel-Lindau disease; R: review; C: cystic; CE: contrast-enhanced.



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Modesto Varas.
Unit of Echoendoscopy.
Centro Médico Teknon.
Marquesa de Vilallonga, 12.
08017 Barcelona. Spain.

Received: 29-04-11.
Accepted: 01-09-11.

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