Objective: The primary objective was to characterise the paracrine milieu in three subjects with apparently idiopathic gigantomastia and to study the relative expression of implicated factors in these pathological specimens as compared to tissue samples from normal breast, gynecomastia and breast cancer.
Background: 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.
Design: Three subjects with gigantomastia unrelated to puberty or pregnancy were found to be negative for known causes for the same. Hence, they were subjected to reduction mammoplasty in one and core biopsy in the other two patients. Histopathological examination and immunohistochemistry for ER, PR and Her-2-Neu were performed in all specimens. Quantitative immunofluorescence for aromatase, IGF2, EGFR, TGF-β, PDGFR-a, β, IGF1 and PTHrP was performed not only in patient samples but also in representative tissue from normal breast, benign (gynecomastia) and malignant(breast cancer) specimens. Relevant positive and negative controls were used for validation.
Results: Herein, we describe three patients of idiopathic gigantomastia, including a postmenopausal female. Both are extremely rare and there are only few studies that have attempted to characterise their etiopathogenesis. Serum markers of autoimmunity, incriminated hormones and growth factors analysed, were normal in all the cases. Tissue expression of aromatase, IGF2, EGFR, TGF-β, PDGFR-a and β were found to be upregulated whereas IGF1 and PTHrP were comparable to normal breast.
Conclusion: The 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.