ABSTRACT
The term carcinoid tumors originally covered gastroenteropancreatic endocrine tumors, which were divided according to their embryological origin into foregut carcinoids (broncho-pulmonary, thymic, stomach, duodenum, upper jejunum, pancreas), midgut carcinoids (lower jejunum, ileum, appendix, and cecum), and hindgut carcinoids (colon, rectum) (1). This classification does not relate to the natural history and clinical behavior of these tumors, so a revised classification was proposed taking into account tumor location, tumor size, angioinvasion, hormone production, histological grade, and proliferative index (2). Using this classification the digestive neuroendocrine (NE) tumors are divided into well-differentiated tumors (WDEC) comprising carcinoid tumors of the gastrointestinal tract and endocrine pancreatic tumors (EPT) and poorly differentiated endocrine carcinomas (PDEC). NE tumors are usually diagnosed at a late stage, when the patients has disseminated disease and hormonal symptoms. The work-up of these patients includes CT/MRT, octreotide scintigraphy, hormonal screening, and analysis of tumor biopsies. The histopathological examination aims at classifying the tumor with respect to origin and biological behavior. Immunohistochemical staining for amine and peptide hormones and synaptic vesicle proteins can be helpful in defining the origin of the tumor (3). Analysis of growth pattern, degree of NE differentiation, and proliferative capacity may provide
prognostic information (4). Such analysis includes evaluation of tumor cell growth, degree of cellular/nuclear atypia as well as presence, or absence, of necrosis; these factors are then weighed into a histological grade (G1G3) scale. The NE differentiation is evaluated by antibodies against proteins of the neurosecretory granules (chromogranin A, synaptophysin) or cytosolic markers (neuron specific enolase, PGP 9.5). WDEC are immunopositive for all markers in the majority of tumor cells, while PDEC often lack the granular markers with cytosolic markers retained. The proliferative capacity can be assessed by counting of mitoses, but is more reliably estimated by analyzing the fraction of tumor cells that express the Ki67 antigen (4). Following the histopathological analysis, NE tumors can be broadly divided into WDEC with good, or intermediate, prognosis and PDEC with sinister prognosis. Other factors, e.g., angiogenic capacity, expression of adhesion molecules, and specific genetic changes, may prove to be prognostic tools in the future and also indicators of responsiveness to medical treatment.
