Les tumeurs mixtes endocrines et exocrines du pancréas: Questions biologiques et cliniques

Mixed tumors are defined by the coexistence of at least two distinct neoplastic components within the same tumor. In the case of mixed endocrine tumors, one of the component is of neuroendocrine nature; the other component usually is epithelial and of exocrine nature. This is why the term of adeno-neuroendocrine carcinoma has been recently proposed to substitute that of mixed endocrine tumor. The pancreas is one of the most frequent sites of mixed endocrine tumors in the body. Numerous combinations are possible for mixed endocrine tumors of the pancreas: ductular and neuroendocrine, acinar and neuroendocrine, or even ductular, acinar and neuroendocrine. The pathological diagnosis of mixed endocrine tumor must fulfil strict requirements. At least two neoplastic components must be histologically identifiable; their divergent differentiation must be confirmed by immunohistochemistry; the less abundant component must represent at least 30% of the tumor. Even in these conditions, diagnostic pitfalls may occur and result in an overdiagnosis of mixed tumor. The therapeutic strategy for mixed tumors is not codified. The rule is to take into account the most aggressive component, but its identification is sometimes not so easy. The mechanisms responsible for the emergence of mixed tumors are not well known. In most cases, they are composite tumors, in which all components derive from the same precursor. In the pancreas, mixed tumors are favoured by the extreme plasticity of pancreatic epithelial cells, which are able to trans-differentiate the one into another in response to tissue injuries. Much remains to be done to standardize the management of patients with mixed tumors and to understand the mechanisms involved in their histogenesis.