Pericytic
tumors are subclassified as
myopericytomas,
myofibromas,
angioleiomyomas, and
glomus tumors according to the current World Health Organization classification. These pericytic
tumors form a continuous morphologic spectrum, including those with combined morphology. However, to our knowledge, no widely accepted criteria for classifying
tumors with combined morphology are available. Recent studies have identified
platelet-derived growth factor receptor-beta (
PDGFRB) gene mutations in a subset of
myofibromas,
myopericytomas, and myopericytomatoses but not in
angioleiomyomas.
NOTCH receptor 3 (NOTCH3) mutations have been reported in a subset of infantile
myofibromatosis. To assess their potential role in classifying pericytic
tumors, we investigated
PDGFRB and NOTCH3 mutations in 41 pericytic
tumors of variable morphology, including some combined forms. Our results show these mutations to be present in a variety of pericytic
tumors, such as
myopericytomas (
PDGFRB, 3/11; NOTCH3, 4/11), myopericytomatoses (1/2; 1/2),
myofibromas (3/6; 0/6),
angioleiomyomas (2/13; 3/13), and
glomus tumors (5/9; 1/9). Point mutations were identified in 3
tumors in
PDGFRB exon 12 (Y562C, S574F, and G576S), 12
tumors in
PDGFRB exon 14 (M655I, H657L, and N666K), and 9
tumors in NOTCH3 exon 25 (A1480S/T, D1481N, G1482S, T1490A, E1491K, G1494S, and V1512A). All
PDGFRB mutations and NOTCH3 G1482S, T1490A, and G1494S mutations were classified as "deleterious/damaging" by ≥4 of 6 pathogenicity prediction tools in silico. Five-mutation-positive
tumors, including 1
myopericytoma-
angioleiomyoma, 2 myopericytomatoses-
myofibroma, 1
myofibroma-
myopericytoma and 1
angioleiomyoma-
myopericytoma, were of combined morphology. Therefore, we found
PDGFRB and NOTCH3 mutations to be detectable in a much wider variety of pericytic
tumors than previously reported and confirmed
myopericytomas,
myofibromas,
angioleiomyomas, and
glomus tumors as members harboring
PDGFRB or NOTCH3 mutations. Our results thus suggest that
PDGFRB or NOTCH3 mutations are not useful for subclassifying members of the pericytic
tumor family.