title: A neurogenic tumor containing a low-grade malignant peripheral nerve sheath tumor (MPNST) component with loss of p16 expression and homozygous deletion of CDKN2A/p16: a case report showing progression from a neurofibroma to a high-grade MPNST.
abstract: Development of malignant peripheral nerve sheath tumors (MPNSTs) is a stepwise process that involves the alteration of many cell cycle regulators and the double inactivation of the NF1 gene. Inactivation of the TP53 gene and deletion of the CDKN2A/p16 gene are known to play an important role in the process. Herein, we present a 19-year-old man with a familial history of neurofibromatosis type 1, in whom the tumor arose from the intercostal nerve and showed 3 components: a neurofibroma, a low-grade MPNST, and a high-grade MPNST. Loss of p16 expression and homozygous deletion of the CDKN2A/p16 gene were observed in both the low-grade and the high-grade MPNST. In contrast to low-grade MPNSTs, high-grade MPNSTs generally tend to lose expression of p16 and harbor homozygous deletion of the CDKN2A/p16 gene. Loss of p16 expression and homozygous deletion of the CDKN2A/p16 gene in low-grade MPNST in our case might be related to its progression to high-grade MPNST. To the best of our knowledge, this is the first study correlating the p16 expression status and CDKN2A/p16 gene alteration in low-grade MPNSTs.
authors.affiliation: Department of Pathology, Shizuoka Saiseikai General Hospital Shizuoka, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tajima
authors.affiliation: Department of Pathology, Fujieda Municipal General Hospital Fujieda, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Koda
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D018450:Disease Progression; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D060787:Neoplasm Grading; D009442:Neurilemmoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D009455:Neurofibroma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D019635:Neurosurgical Procedures; D010641:Phenotype; D018714:Radiotherapy, Adjuvant; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: CDKN2A/p16 gene; Malignant peripheral nerve sheath tumor; high grade; homozygous deletion; immunohistochemistry; low grade; neurofibromatosis type 1; p16