Colorectal Poorly Differentiated Neuroendocrine Carcinomas (NECs) and Mixed Adenoneuroendocrine Carcinomas (MANECs): Insights into the Diagnostic Immunophenotype and Search for Prognostic Markers
Stefano La Rosa, Alessandro Marando, Carlo Capella. Ospedale di Circolo, Varese, Italy; University of Insubria, Varese, Italy
Background: Colorectal NECs and MANECs are well recognized entities generally known for their biological aggressiveness and poor patient survival. However, a few published papers have highlighted the existence of a subgroup of tumors with a better survival than expected but, to date, there are no established parameters which usefully identify this category.
Design: In order to better characterize such neoplasms and to identify prognostic indicators, 27 NECs and 12 MANECs were investigated for the following parameters: presence of necrosis, cytologic subtype (small, large, intermediate cell types), lymphovascular invasion, perineural invasion, infiltrative or expanding type of growth, size, level of colonic wall invasion, peritumoral lymphoid infiltration, staging according to UICC and ENETS, expression of transcription factors (TTF1, ASH1, CDX2, PAX5), stem cell markers (CD117 and CD34), and cytokeratin 7 and 20.
Results: Neoplasms were more frequently localized in the right colon and were diagnosed at stage III or IV, independently of the scheme used (UICC or ENETS). The mean follow up time was 36 months. 26/39 (67%) patients died of disease and, in particular, 70% of patients with NECs and 58% with MANECs. 7 patients were alive free of disease after a mean follow-up time of 104 months and other 2 patients died for unrelated causes after a mean follow up time of 190 months. No significant different patient survival was observed between NECs and MANECs. Neoplasms showed a heterogeneous spectrum of morphological and immunohistochemical features, but only large cell subtype, significant peritumoral lymphoid reaction, CD117 immunoreactivity and vascular invasion were significantly correlated with prognosis at univariable analysis. Furthermore, only vascular invasion was an independent prognostic marker at multivariable analysis. In addition to these prognostic features, neoplasms showed different expression of transcription factors, stem cell markers and cytokeratins.
Conclusions: Colorectal NECs and MANECs are a heterogeneous group of tumors showing different morphological features and immunophenotype that should be considered for discriminating among possible differential diagnoses. Among different parameters, the evaluation of vascular invasion seems useful to identify different prognostic categories.
Monday, March 19, 2012 2:00 PM
Platform Session: Section H, Monday Afternoon