The role of cytopathology in the management of patients with pancreatic tumours - special focus on neuroendocrine tumours

The pancreas being a deep-seated organ, the development of a minimally invasive technique such as endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) has been a revolution in assessing a symptomatic or incidentally discovered pancreatic lesion.  The first challenge and aim of this dissertation is the optimization of the technical aspects not only at a pre-analytical level outside the pathology lab, but also the first steps inside the lab in a cost-efficient way with a low-non-diagnostic rate.  In addition, the actual non-diagnostic rate in our institution using the described methodology will be assessed to compare it to the previous published one, discussing advantages and inconveniences of rapid on-site evaluation (ROSE) in our local setting.

Adenocarcinomas and neuro-endocrine tumours are the most frequent mass lesions encountered in the pancreas. Especially the first one has a disastrous outcome with a very short survival time when diagnosed in a late stage.  Therefore, it is mandatory to get a precise diagnosis as soon as possible.  EUS and EUS-FNA are therefore mandatory in the diagnostic algorithm for mass lesions of the pancreas.  They are also very important for staging these tumors being able to sample suspicious lymph nodes and liver metastasis.

Neuroendocrine tumours of the pancreas (PNET), on the other hand, have a more indolent course, even if metastatic, depending on their differentiation grade.  One of the elements used to grade a resected PNET and mandatory in the WHO and ENETS classification is the proliferation index measured with the Ki67 labelling index (Ki67 LI).  Although, there are well-defined grade cut-offs for surgical specimens correlating with survival data, this is not the case for cytological specimens obtained by EUS-FNA.  PNETs being less frequent, representing only 1 to 2 % of pancreatic neoplasms, it is difficult to study a large cohort with a long-follow-up to define a survival related grading system.   The second aim of this dissertation is to assemble such a group and to confirm reproducibility and accuracy of the Ki67 count.

Furthermore, new developments in the field of EUS and EUS-FNA will be reviewed, such as different gauge needles to optimize the material obtained and newly described prognostic molecular markers such as ATRX/DAXX which might also, in addition to the Ki67 LI, help to determine the prognosis of a given tumour at diagnosis.