[Undifferentiated and dedifferentiated renal cell carcinomas : Morphomolecular aspects and differential diagnosis in...

Histological subtyping of diverse renal cell carcinomas (RCCs) has seen significant changes during the last two decades. This resulted in the introduction of several new phenotypically and genetically defined entities, many which are also listed in the current WHO classification. Some of these well-defined entities may, under certain circumstances, undergo a process of dedifferentiation resulting in loss of their phenotypic and immunohistochemical features, hence adopting a non-descript anaplastic morphology. Accordingly, the original entity-defining tumor clone might be either totally overgrown and lost or just be missed by sampling the tumor. This final common pathway of dedifferentiation results in several oncological disadvantages and prevents a histology-tailored approach to systemic therapy. In addition, the possibility of inherited cancer as in the case of SDH- and FH-deficient RCC would be easily overlooked if the exact subtyping is not possible. This overview article illuminates the main RCC subtypes that may undergo dedifferentiation and their differential diagnostic approach.