title: Anaplasia in pilocytic astrocytoma predicts aggressive behavior.
abstract: The clinical significance of anaplastic features, a rare event in pilocytic astrocytoma (PA), is not fully established. We reviewed 34 PA with anaplastic features (Male = 21, Female = 13; median age 35 y, 5 to 75) among approximately 2200 PA cases (1.7%). Tumors were included which demonstrated brisk mitotic activity [at least 4 mitoses/10 high power fields (400 x )], in addition to hypercellularity and moderate-to-severe cytologic atypia, with or without necrosis. The tumors either had a PA precursor, coexistent (n = 14) (41%) or documented by previous biopsy (n = 10) (29%), or exhibited typical pilocytic features in an otherwise anaplastic astrocytoma (n = 10) (29%). Clinical features of neurofibromatosis type-1 were present in 24% and a history of radiation for PA precursor in 12%. Histologically, the anaplastic component was classified as pilocytic like (41%), small cell (32%), epithelioid (15%), or fibrillary (12%). Median MIB1 labeling index was 24.7% in the anaplastic component and 2.6% in the precursor, although overlapping values were present. Strong p53 staining (3+) was limited to areas with anaplasia (19%), with overlapping values for 1 and 2+ in areas without anaplasia. Median overall and progression-free survivals after diagnosis for the entire study group were 24 and 14 months, respectively. Overall and progression-free survivals were shorter in the setting of prior radiation for a PA precursor (P = 0.007, 0.028), increasing mitotic activity (P = 0.03, 0.02), and presence of necrosis (P = 0.02, 0.02), after adjusting for age and site. The biologic behavior of PAs with high-mitotic rates and those with necrosis paralleled that of St Anne-Mayo grades 2 and 3 diffuse astrocytomas, respectively. In summary, PA with anaplastic features exhibits a spectrum of morphologies and is associated with decreased survival when compared with typical PA.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. rodriguez.fausto@mayo.edu
authors.forename: Fausto J
authors.initials: FJ
authors.lastname: Rodriguez
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Scheithauer
authors.forename: Peter C
authors.initials: PC
authors.lastname: Burger
authors.forename: Sarah
authors.initials: S
authors.lastname: Jenkins
authors.forename: Caterina
authors.initials: C
authors.lastname: Giannini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000708:Anaplasia; D001254:Astrocytoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D008938:Mitosis; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases