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Endocrine

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Idiopathic gigantomastia: newer mechanistic insights implicating the paracrine milieu

  • Liza Das
  • Ashutosh Rai
  • Kim Vaiphei
  • Akhil Garg
  • Subair Mohsina
  • Anil Bhansali
  • Pinaki DuttaEmail author
  • Satyaswarup TripathyEmail author
Clinical Management of Endocrine Diseases
  • 11 Downloads

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.

Abbreviations

PTHrP

Parathyroid hormone related peptide

BMI

Body mass index

E2

Estradiol

LH

Luteinising hormone

FSH

Follicle stimulating hormone

IGF1

Insulin like growth factor-1

IGF2

Insulin like growth factor-2

GH

Growth hormone

fT3

Free Tri-iodo thyronine

fT4

Free Tetra-iodo thyronine

TSH

Thyroid stimulating hormone

HbA1c

Glycated hemoglobin

HOMA-IR

Homeostasis model assessment for insulin resistance

BIRADS

Breast imaging reporting and data system

TPO

Thyroid peroxidase

ANA

Anti-nuclear antibodies

SMA

Anti-smooth muscle antigen

LKM

Anti-liver kidney muscle antibody

AMA

Anti-mitochondrial antibody

CEA

Carcinoembryonic antigen

α-FP

Alpha fetoprotein

NAC

Nipple areola complex

IHC

Immunohistochemistry

ER

Estrogen receptor

PR

Progesterone receptor

Her-2-Neu

Herceptin

IF

Immunofluorescence

PDGFR-α

Platelet derived growth factor-alpha

PDGFR-β

Platelet derived growth factor-beta

VEGF

Vascular endothelial growth factor

TGF-β

Transforming growth factor-beta

IG

Idiopathic gigantomastia

Normal values

17-β E2

7.6–42.6 pg/ml

Progesterone

<1 ng/ml

LH

2.4–12.6 mIU/ml

FSH

3.5–12.5 mIU/ml

GH

<1 ng/ml

Prolactin

5–25 ng/ml

fT3

2.3–4.2 pg/ml

T4

0.89–1.76 ng/dl

TSH

0.4-4.2 mIU/l

TPO

<34 IU/ml

HbA1c

<5.7%

CA125

0–35

CA19-9

0–27

CEA

3.8–5.5

α-FP

0–5.8

IGF1

64–262 ng/ml

HOMA-IR

<2—normal, 2 to 3—mild insulin resistance, 3 to 5—moderate insulin resistance, >5—severe insulin resistance

Notes

Acknowledgements

We would like to thank Prof. Ashley Grossman for his constructive comments.

Author contribution

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.

Ethical approval

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

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12020_2019_2065_MOESM1_ESM.docx (1.2 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Liza Das
    • 1
  • Ashutosh Rai
    • 2
  • Kim Vaiphei
    • 3
  • Akhil Garg
    • 4
  • Subair Mohsina
    • 4
  • Anil Bhansali
    • 1
  • Pinaki Dutta
    • 1
    Email author
  • Satyaswarup Tripathy
    • 4
    Email author
  1. 1.Department of Endocrinology, PGIMERChandigarhIndia
  2. 2.Department of Translational and Regenerative Medicine, PGIMERChandigarhIndia
  3. 3.Department of Pathology, PGIMERChandigarhIndia
  4. 4.Department of Plastic surgery, PGIMERChandigarhIndia

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