Giant juvenile fibroadenomas with and without prominent pseudoangiomatous stromal hyperplasia (PASH)-like change: clinicopathological and molecular characteristics. Histopathology 2023 Sep;83(3):357-365
Date
05/04/2023Pubmed ID
37140543DOI
10.1111/his.14935Scopus ID
2-s2.0-85156108581 (requires institutional sign-in at Scopus site)Abstract
AIMS: Juvenile fibroadenomas (JFA) are biphasic fibroepithelial lesions (FEL) usually occurring in adolescent female patients. Giant (G) JFA, like other FEL, may exhibit prominent pseudoangiomatous stromal hyperplasia (PASH)-like change. We sought to determine clinicopathological and molecular characteristics of GJFA with and without PASH.
METHODS AND RESULTS: Archives were searched for cases of GJFA (1985-2020). All were stained for androgen receptor (AR), beta-catenin, CD34 and progesterone receptor (PR). Cases were sequenced using a custom 16-gene panel - MED12 (exons 1 and 2), TERT promoter (-124C>T and -146Ctable>T), SETD2, KMT2D, RARA (exons 5-9), FLNA, NF1, PIK3CA (exons 10, 11 and 21), EGFR, RB1, BCOR, TP53, PTEN, ERBB4, IGF1R and MAP3K1. Twenty-seven GJFA from 21 female patients aged 10.1-25.2 years were identified. Size ranged from 5.2 to 21 cm. Two patients had multiple, bilateral and later recurrent GJFA. Thirteen (48%) cases showed prominent PASH-like stroma. All were positive for stromal CD34, negative for AR and beta-catenin and one case showed focal PR expression. Sequencing showed MAP3K1 and SETD2 mutations in 17 samples, with KMT2D, TP53 and BCOR aberrations in 10 (45%), 10 (45%) and seven (32%) cases, respectively. Tumours with a PASH-like pattern had higher prevalence of SETD2 (P = 0.004) and TP53 (P = 0.029) mutations, while those without PASH had more RB1 mutations (P = 0.043). MED12 mutation was identified in one case. TERT promoter mutation was observed in four (18%), including two recurrences.
CONCLUSIONS: Gene mutations along more advanced phases of the proposed FEL pathogenetic pathway in GJFA are unusual, and suggest a mechanism for more aggressive growth in these tumours.
Author List
Jorns JM, Farooq A, Puzyrenko A, Jarzembowski J, Thike AA, Nasir NDM, Ng CCY, Liu W, Lee JY, Lim AH, Guan P, Teh BT, Tan PHAuthors
Jason A. Jarzembowski MD, PhD Sr Associate Dean, CEO CSG, Professor in the Pathology department at Medical College of WisconsinJulie M. Jorns MD Professor in the Pathology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdolescentAngiomatosis
Breast Diseases
Breast Neoplasms
Female
Fibroadenoma
Fibroma
Humans
Hyperplasia
Neoplasms, Fibroepithelial
beta Catenin
