Table 10.

Vascular tumors.

Tumor	Clinical phenotype	Candidate gene	Protein function or suspected role (if known)	Clinical work-up	References
Infantile hemangioma	• Most common tumor of infancy • Comprised of capillaries and proliferating endothelial cells • Grow rapidly during first few months of life then regress in early childhood	Possible variants in VEGFR2 and TEM8	• Altered VEGF-A and VEGFR2 signaling Constitutive activation of VEGF-dependent VEGFR2 signaling • Sequestration of integrin 1B, inhibition of NFAT transcription and reduction of VEGFR1	• Consider liver US if > 5 cutaneous hemangiomas • Consider evaluation for PHACES if facial segmental hemangioma (brain MRI/MRA, Echocardiogram, eye exam)	(3, 10, 12, 62)
Congenital hemangioma	• Fully formed at birth • Can be rapidly involuting (RICH), partially involuting (PICH), or non-involuting (NICH)	GNAQ GNA11	• Organization of the formation and remodeling of blood vessels. GNAQ mediates signals between G-protein-coupled receptors and downstream effectors Increased RAS/MAPK signaling	• None unless clinically indicated • Large lesions can have transient Kasabach-Merritt phenomenon (screen with CBC, fibrinogen, PT, PTT)	(3, 10, 11)
Pyogenic granuloma	• Post-natal lesion with mean onset around age 6 years • Benign, pedunculated, fragile, and frequently bleed	KRAS, NRAS, HRAS GNAQ, BRAF	• Upregulated RAS/MAPK/ERK signaling	• None unless clinically indicated	(3, 10, 11)
Kaposiform hemangioendothelioma and Tufted angioma	• Vascular neoplasm generally present at birth and enlarges during infancy • Locally aggressive. Associated with Kasabach-Merritt phenomenon	GNA14	• G-protein related signal transduction	• Evaluation for Kasabach Merritt phenomenon (CBC, fibrinogen, PT, PTT) • Imaging of site (MRI) • Oncology consult	(3, 10, 11)
Angiosarcoma	• High-grade malignant neoplasm of endothelial cell origins • Can arise in skin, deep soft tissues, or visceral organs • Can be radiation or lymphedema-associated	PTPRB, PLCG, KDR/VEGFR2 mutations, FLT4/VEGFR3 amplifications MYC amplification (in XRT induced)	• Vascular endothelial growth factor receptors • Proto-oncogene, increased expression of genes involved in cell proliferation	• Imaging of site and for metastatic disease, including brain • PET/CT • Oncology consult	(3, 10, 63, 64)
Epithelioid hemangioendothelioma	• Malignant endothelial tumor with variable clinical behavior • Multifocal lesions can be stable, grow slowly, or rapidly progress and metastasize	WWTR1-CAMTA1 translocation YAP1-TFE3 translocation	• Transcription factor signaling in the hippo pathway	• Imaging of site and for metastatic disease, including brain • Consider PET/CT • Oncology consult	(3, 10, 63, 65)
Familial infantile myofibromatosis	• Fibrous tumor of early childhood • Solitary lesions can regress • Multifocal or generalized lesions can be life threatening	PDGFRβ	• Receptor tyrosine kinase and mitogen for mesenchyme-derived cells, signaling in embryonic development, including recruitment of vascular smooth muscle cells	• Imaging of site and for metastatic disease • Oncology consult	(3, 10, 66, 67)