Myeloid Neoplasms with Germline Predisposition

The updated 2016 WHO classification of hematopoietic tumors has a new category: "myeloid neoplasms with germline predisposition." These entities are rare, but are also currently underdiagnosed and underreported. Recognition is critical for appropriate clinical evaluation and therapy, with potential implications for the patient's entire family. The WHO includes 3 categories of myeloid neoplasms with germline predisposition: neoplasms without preexisting conditions, neoplasms with a history of thrombocytopenia, and neoplasms with other organ dysfunction. Specialized molecular testing is frequently necessary to make the diagnosis, as the presence of one of the implicated mutations is not sufficient for diagnosis and should be confirmed with germline DNA evaluation. Many families have unique mutations that are not detected by targeted sequencing panels. Periodic bone marrow (BM) examinations are recommended to assess patients' baseline morphology and rule out evidence of disease progression. Thus, accurate diagnosis requires a careful recording of clinical history, a BM morphology evaluation, and advanced molecular testing.