Answer: Malignant mixed germ cell tumor with intratubular granulomatous reaction to ITGCN

Histology: The tumor shows a mixed pattern with teratoma , embryonal carcinomas and granulomas which have a uniform distribution which fits within the architecture of pre-existing seminiferous tubules. A component of the teratoma is atypical cartilage with hyperchromatic pleomorphic nuclei. Adjacent to this tumor are small rounded structures which have the overall size and shape of seminiferous tubules involved to varying degrees by granulomatous reaction. In some tubules, one can still appreciate malignant cells of intratubular germ cell neoplasia (ITGCN) with an associated granulomatous reaction within the center of the tubules. In other tubules, the granulomatous reaction is so extensive that it obscures the germ cells of ITGCN and by itself could be consistent with idiopathic granulomatous orchitis.

Discussion: There are several issues in this case. In terms of the malignant appearing cartilage, in a post-pubertal male it is of no clinical significance whether either the epithelial component (such as glands) or the mesenchymal component (such are cartilage) have cytologic malignancy as long as they are not sheeting out greater than a 4X field without intervening other teratomatous elements. Consequently, the finding of small foci of malignant appearing cartilage is not sufficient to render a diagnosis of a chondrosarcoma arising in a teratoma. Rather, it is just atypical teratomatous element which has no further significance beyond the lesion being a malignant teratoma because it is a teratoma arising in a post-pubertal male. Even teratomas composed of totally benign appearing tissues in a post-pubertal male would have the same designation as a malignant teratoma. The other feature in this case is the granulomatous reaction adjacent to the invasive germ cell tumor. There is an entity idiopathic granulomatous orchitis in which virtually all the seminiferous tubules are replaced by non-necrotizing granulomatous inflammation. This entity appears to be an autoimmune reaction to one’s own germ cells. The other situation where one can get a granulomatous reaction within the seminiferous tubules is seen in the current case where the granulomatous reaction is to intratubular germ cell neoplasia. This is analogous to what one can see with seminoma that is invasive which can have an associated granulomatous reaction. In most cases such as in the current one, this granulomatous reaction to intratubular germ cell neoplasia accompanies an invasive germ cell tumor such that this granulomatous reaction has no clinical significance. However, in a case where there is only intratubular germ cell neoplasia and an associated granulomatous reaction it is critical to recognizing the underlying cells of ITGCN so it’s not mistaken for idiopathic granulomatous orchitis.