Idiopathic gigantomastia: newer mechanistic insights implicating the paracrine milieu

Endocrine. 2019 Nov;66(2):166-177. doi: 10.1007/s12020-019-02065-x. Epub 2019 Sep 9.

Abstract

Purpose: Gigantomastia refers to pathological breast enlargement usually occurring in the peripubertal or peripartum period. Idiopathic gigantomastia, however, is a rare entity with hypotheses citing local expression of hormones and growth factors in causing this disease, none of which have been systemically analysed. The purpose of this study was to delve deeper into the mechanistic pathways causing this condition.

Methods: Herein, we describe three patients of idiopathic gigantomastia, all of whom had had normal puberty and uneventful pregnancies. Further, one of the patients had postmenopausal gigantomastia which is extremely rare, with only four cases described in the literature. Serum markers of autoimmunity, incriminated hormones and growth factors analysed, were normal in all the cases. Breast tissue specimens were subjected to histopathological examination and immunohistochemistry for ER, PR and Her-2-Neu. Quantitative immunofluorescence for aromatase, IGF2, EGFR, TGF-β, PDGFR-α, β, IGF1 and PTHrP was also performed.

Results: Of these, the tissue expression of aromatase, IGF2, EGFR, TGF-β, PDGFR-α and β were found to be upregulated, whereas IGF1 and PTHrP were comparable to normal breast.

Conclusion: This observation that paracrine overexpression of these factors is responsible for the pathogenesis of apparently idiopathic gigantomastia may have therapeutic ramifications in the future for patients with this debilitating condition.

MeSH terms

  • Breast / abnormalities*
  • Breast / metabolism*
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Hypertrophy / metabolism*
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / metabolism
  • Parathyroid Hormone-Related Protein / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • IGF1 protein, human
  • IGF2 protein, human
  • Parathyroid Hormone-Related Protein
  • Transforming Growth Factor beta
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • ErbB Receptors

Supplementary concepts

  • Gigantomastia