Primitive neuroectodermal tumors and related lesions

Abstract

Primitive neuroectodermal tumors (PNET) form part of the heterogeneous group of small round (blue) cell tumors of childhood and adolescence. This group also contains conventional neuroblastoma, rhabdomyosarcoma, lymphoma, and Ewings sarcoma [36, 37, 40]. Purely for practical reasons, Dehner introduced the distinction between central PNET (cPNET) and peripheral PNET (pPNET), as he was well aware that little knowledge was available concerning the actual biology of these neoplasms and of their interrelationships [12]. This classification applies knowledge of neuroectodermal derivatives to the PNET. The neuroectoderm generates the brain and spinal cord, on the one hand, and the entire autonomic nervous system, dorsal root ganglia, adrenal medulla, and part of the neuroendocrine system, on the other, among many other derivatives. It must be stressed that this division of the PNET does no have any clinicopathologic or prognostic implications. In this chapter only pPNET will be discussed. Peripheral primitive neuroectodermal tumors constitute a group of uncommon tumors with similar histology, and are aggressive and poorly differentiated neoplasms, occurring mainly in children and young adults. These tumors originate in the soft tissues or bone, outside the central or sympathetic nervous system, and are composed of undifferentiated, small, round, hyperchromatic tumor cells. pPNET and Ewings sarcoma form a special group within the small round (blue) cell tumors. Several common characteristics have been discovered that distinguish them from other small round (blue) cell tumors, namely a unique chromosomal translocation, t(11;22)(q24;12), and the expression of a membrane glycoprotein, known as the MIC2 gene product (see Chap. 7: Genetics and Molecular Biology of Soft Tissue Tumors). In addition to pPNET of soft tissue and Ewings sarcoma of bone, there are also osseous pPNET and extraskeletal Ewings sarcoma [4]. It was also noted that extraskeletal Ewings sarcoma and some atypical forms of Ewings sarcoma of bone display neuroectodermal features. Because of these shared phenotypical and genotypical characteristics, very typical for Ewings sarcoma and pPNET, it is now generally accepted that these two neoplasms are related to each other. They are thought to correspond to distinct neural crest lineages or tumors arrested at different stages of development. pPNET is the most differentiated and can be considered the neural variant of Ewings sarcoma [5, 10, 13, 27, 31]. According to the Ewings sarcoma/pPNET classification proposed by Schmidt [31], diagnosis of pPNET is reserved to those cases that express at least two different neural markers and/or Homer-Wright rosettes, the others being termed Ewings sarcoma. This classification has proven to be useful [7]. Due to the identification of the common non-random chromosome rearrangements in Ewings sarcoma, peripheral primitive neuroectodermal tumor, Askin tumor, and neuroepithelioma, these tumors are now considered entities of the Ewings sarcoma family of tumors (ESFT).