Idiopathic gigantomastia: newer mechanistic insights implicating the paracrine milieu
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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.
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.
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.
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.
Parathyroid hormone related peptide
Body mass index
Follicle stimulating hormone
Insulin like growth factor-1
Insulin like growth factor-2
Free Tri-iodo thyronine
Free Tetra-iodo thyronine
Thyroid stimulating hormone
Homeostasis model assessment for insulin resistance
Breast imaging reporting and data system
Anti-smooth muscle antigen
Anti-liver kidney muscle antibody
Nipple areola complex
Platelet derived growth factor-alpha
Platelet derived growth factor-beta
Vascular endothelial growth factor
Transforming growth factor-beta
- 17-β E2
<2—normal, 2 to 3—mild insulin resistance, 3 to 5—moderate insulin resistance, >5—severe insulin resistance
We would like to thank Prof. Ashley Grossman for his constructive comments.
L.D. drafted the manuscript and interpreted observations. A.R. was involved in histopathology interpretation and manuscript writing. K.V. was involved in histopathology interpretation and manuscript editing. A.G. assisted surgery of the first case. S.M. assisted surgery of the first case. A.B. edited the manuscript. P.D. conceived the idea and was involved in manuscript writing as well as editing. S.S.T. operated the case and was involved in manuscript editing.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed involving human participants/patients were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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