Ovarian germ cell tumor/mastocytosis with KIT mutation: A unique clinicopathological entity

Most tumors are sporadic and originated from somatic mutations. Some rare germline mutations cause familial tumors, often involving multiple tissues or organs. Tumors from somatic mosaicism during embryonic development are extremely rare. We describe here a pediatric patient who developed both an ovarian germ cell tumor and systemic mastocytosis. Targeted DNA next-generation sequencing analysis revealed similar genomic changes including the same KIT D816V mutation in both tissues, suggesting a common progenitor cancer cell. The KIT mutated cells are likely from early embryonic development during germ cell migration. A literature search found additional eight similar cases. These diseases are characterized by pediatric-onset, all-female, neoplastic proliferation in both gonad and bone marrow, and a common oncogenic cause, that is, KIT mutation, constituting a clinically and genetically homogenous disease entity. Importantly, the association of germ cell tumors with hematopoietic neoplasms suggests that the primordial germ cells are the primitive hematopoietic stem cells, a much-debated and unsettled question.