Whole-exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma

J Pathol Clin Res. 2021 Mar;7(2):113-120. doi: 10.1002/cjp2.190. Epub 2020 Dec 2.


Juvenile papillomatosis (JP) of the breast is a rare benign mass-forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole-exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC-NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC-NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC-NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)-positive breast cancers. We observed JP to harbor a dominant aging-related mutational signature, whereas coexisting DCIS and IDC-NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop.

Keywords: PIK3CA; breast carcinoma; juvenile papillomatosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Breast Neoplasms / complications
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma, Intraductal, Noninfiltrating / complications
  • Carcinoma, Intraductal, Noninfiltrating / diagnosis
  • Carcinoma, Intraductal, Noninfiltrating / genetics*
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • DNA Copy Number Variations*
  • DNA Mutational Analysis
  • Exome Sequencing
  • Female
  • Humans
  • Mutation
  • Papilloma / complications
  • Papilloma / diagnosis
  • Papilloma / genetics*
  • Papilloma / pathology


  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human