Protein kinase-related tumors in the pediatric population

Advanced and widespread molecular techniques have deepened our understanding of mesenchymal lesions, revealing considerable overlap among morphologically defined entities now known to be related to protein kinases (PKs). This paradigm shift is important for understanding oncogenesis and also in terms of treatment options and prognosis. Therefore, it is preferable to stratify these tumors molecularly instead of morphologically, as the different categories have clinical implications. Molecular analyses are an essential and integrated part of the diagnostic workup of tissue specimens, especially those of young patients. Involved PKs range from receptor tyrosine kinases (neurotrophic tyrosine receptor kinase [NTRK]1, 2, 3; anaplastic lymphoma kinase [ALK]; proto-oncogene 1 [ROS1]; proto-oncogene [RET]; and proto-oncogene/hepatocyte growth factor receptor [MET]; etc.) to intracytoplasmic serine/threonine kinases (RAF proteins) activating the same pathways. Morphological patterns vary from infantile fibrosarcoma(-like) to lipofibromatosis(-like), dermatofibrosarcoma protuberans(-like), and malignant peripheral nerve sheath tumor-like. However, there is considerable overlap histopathologically and immunohistochemically. Most of the neoplasms are (myo)fibroblastic in type, consisting of monomorphic cells. A hemangiopericytoma-like vasculature can be a diagnostic clue. The immunophenotype is characterized by variable expression of smooth muscle actin (SMA)/desmin/CD34 or CD34/S100. This review provides updates to understand the currently known spectrum of PK-related lesions, with emphasis on those occurring more rarely, to aid proper diagnoses and treatment. The aim is to contribute to a better holistic classification.