Correspondence and Reprint requests : Dr. Vandana Jain,Assistant Professor, Division of Pediatric Endocrinology,Department of Pediatrics, All India Institute of Medical SciencesNew Delhi-110029, India.

[Received September 1, 2008; Accepted November 3, 2008]

Clinical Brief

Bilateral Breast Enlargement in a Male Toddler: AnUnusual Cause

Rajni Sharma and Vandana Jain

Division of Pediatric Endocrinology and Department of Pediatrics, All India Institute of Medical Sciences, NewDelhi, India

ABSTRACT

We report a case of a two and a half yr old boy who presented with complaint of bilateral asymmetrical breast enlargementsince infancy. On examination, he had features of neurofibromatosis type 1 (NF1). Complete endocrinological evaluation wasnormal. Trucut biopsy of the breast revealed overgrowth of fibrocollagenous and adipose tissue without hyperplasia of breastparenchyma. Thus a diagnosis of NF1 with pseudogynecomastia was made. [Indian J Pediatr 2009; 76 (11) : 1164-1166]E-mail: drvandanajain@gmail.com

Key words: Key words: Key words: Key words: Key words: Neurofibromatosis1; Gynecomastia; Pseudogynecomastic; Prepubertal

Enlargement of the breasts in young prepubertal boys isvery uncommon. Exogenous estrogen exposure,medications affecting androgen metabolism, testiculartumors, germ cell tumors, congenital adrenalhyperplasia (11 α hydroxylase deficiency) andfeminizing adrenal tumors have all been described asrare causes for this, however, no definite cause can befound in the majority of such cases.1 Here, we presentthe case of a two and a half yr old boy presenting withcomplaint of bilateral breast enlargement since infancyand present his diagnostic work up.

REPORT OF CASE

A two and a half year old boy, product ofnonconsanguineous marriage, presented to thepediatric endocrine clinic of our tertiary care hospitalwith the complaint of bilateral non progressive breastenlargement noted since late infancy. There was nocomplaint of pain or tenderness in the breasts or anydischarge from the nipples. There was no history ofexposure to estrogen creams, intake of drugs orcontaminated milk or meat, no history of jaundice orabdominal distension and no history of headache,visual disturbances or vomiting. In the family, theparents and sibling were asymptomatic and there was

no history of gynecomastia. One paternal uncle hadlarge birth marks on his body. There was history of milddelay in acquisition of motor and language milestonesbut presently child was able to walk without supportand speak 15-20 words.

On examination, his height, weight and body massindex were normal for age. He had 6 cafe au lait spotsmore than 5 mm in size on the back and trunk, frecklingin the axilla and anterior bowing of the left leg. He hadbilateral breast enlargement (Fig. 1). The breasts wereasymmetrically enlarged (right 2.5×2.5 cm, left 4×4 cm),

Fig. 1. Patient with bilateral breast enlargement , café au laitspots on trunk and anterior bowing of the left leg.

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Bilateral Breast Enlargement in a Male Toddler: an Unusual Cause

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had uniform consistency without any palpable focalmass and did not transilluminate. There was notenderness or nipple discharge and the overlying skinwas normal. He had no other sign of sexualmaturation. The genital examination was normal witha stretched penile length of 4 cm and testicular volumeof 3 ml bilaterally with a smooth contour. Therespiratory, cardiac and abdominal examination wasnormal. His development quotient was 80 in motor andlanguage domains.

The ophthalmological examination for Lischnodules in the iris and optic nerve glioma in thefundus was negative. Magnetic resonance imaging ofthe brain was also normal. Skeletal survey showedthinning of cortex and bowing of left tibia. Bone age ofthe child was 2 yr. Ultrasonography of the breastsrevealed ill defined breast tissue with no cyst or focallesion and ultrasonography of the testes showedbilaterally normal-sized testes with no focal lesion.Ultrasonography abdomen showed no adrenal mass.

Liver function, renal function tests and electrolyteswere normal. A detailed endocrine work up was donewhich showed Follicle Stimulating Hormone of 0.680U/L, Luteinising Hormone of 0.13 U/L, prolactin 16.04ng/ml, T4 7.74 μg/dl , TSH 4.94 mIU/L, testosterone0.02 ng/ml and estradiol 8.0 pg/ml (all within nomalprepubertal range). The tumor markers, humanchorionic gonadotrophin and alpha fetoprotein werealso undetectable. Trucut biopsy of the left breast masswas done which showed overgrowth offibrocollagenous and adipose tissue. No neuralelements or breast parenchymal tissue was detected. Anexcision biopsy would definitely have been moreinformative but was refused by the parents as they wereapprehensive about a surgery at such young age.

Thus, the final diagnosis was neurofibromatosistype 1 with pseudogynecomastia due to proliferation offibrocollagenous and adipose tissue. This diagnosiswas explained to the parents and the need for regularfollow up and eventual surgical excision of the lesionswas impressed upon them.

DISCUSSION

Neurofibromatosis type 1 (NF 1) or von Reckling-hausen’s disease is an autosomal dominant conditionwith a prevalence of 1 in 4000. It results from anabnormality of neural crest differentiation andmigration during the early stages of embryogenesis andcan affect virtually every system and organ in the body.2 Diagnosis of NF 1 is based on the presence of at least 2of the following: six or more café au lait spots of more than5 mm in size in prepubertal and 12.5 mm in

postpubertal individuals; two or more neurofibromas orone plexiform neufibroma; freckling in the axilla oringuinal region; optic glioma ; two or more Lischnodules (iris hamartomas); sphenoid dysplasia orthinning of long bone cortex with or withoutpseudoarthrosis; or a first degree relative with NF 1.3

Our patient fulfilled 3 of these criteria.

Gynecomastia in males is most commonly seen inthe neonatal, pubertal or geriatric age group due toincreased availability of estrogen. It is very rarely seenin mid-childhood and prepubertal age group. Thecauses to be excluded are testicular tumors (Leydig orSertoli cell), germ cell tumors (either gonadal orextragonadal), feminising adrenal tumors, exposure toexogenous estrogens in skin creams or milk and meatfrom animals treated with them and intake of drugs thataffect the metabolism of androgens or increaseconversion of androgens to estrogen. Rare causesinclude hyperaromatase syndrome consisting ofincreased peripheral aromatase activity resulting inestrogen production 1 and congenital adrenalhyperplasia (11 α hydroxylase deficiency).

NF 1 frequently causes cerebral gliomas and can beassociated with isosexual precocious puberty in bothmales and females. Breast development in females maybe due to the isosexual precocity or neurofibromas.4

Males with NF1 may rarely present with breastenlargement which can be either true gynecomastia orpseudogynecomastia. We found case reports of truegynecomastia in 3 adolescents and 2 prepubertal maleswith NF1.5,6,7 Histopathology of the breast in 4 of thesepatients had revealed a very characteristic finding ofpseudoangiomatous stromal hyperplasia with presenceof multinucleated giant cells lining the pseudovascularspaces.5, 6

The term pseudogynecomastia implies breastenlargement without proliferation of both the ductalepithelial and stromal components of the breast.8

Gynecomastia in prepubertal age group is quiteuncommon but pseudogynecomastia is even rarer andis usually associated with NF1. Very few cases havebeen described in literature and the histologic findingshave been reported as lipomatous or neurofibromatousproliferation of the mammary region.8,9,10 This histologyis in keeping with the many variations of neoplasticand hamartomatous proliferation of nerves and theirsupporting mesenhyme that occur in neurofibro-matosis. The spectrum of lesions described in patientswith NF1 ranges from pure fibromas to Schwannomasand perineurial fibroblastomas.

In the present patient, trucut biopsy of the breastshowed fibrocollagenous and lipomatous tissue withno neural elements. However, it is possible that neuralelements might have been missed as excisional had notbeen done. As neurofibromas are known to occasionally

Rajni Sharma and Vandana Jain

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differentiate into neurofibrosarcomas or malignantSchwannomas, we plan to keep the child under regularfollow up and convince the parents for surgicalexcision of the lesions.

Contributions : Both RS and VJ worked up the case, did theliterature search and drafted the manuscript. VJ will act asguarantor.

Role of Funding Source : None

Conflict of Interest : None

REFERENCES

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2. Riccardi VM. Neurofibromatosis: past, present and future.N Engl J Med 1991; 324: 1283-1285.

3. Fienman NL. Pediatric Neurofibromatosis: Review. Compr

Ther 1981; 7: 66.4. Fienman NL, Yakovac WC. Neurofibromatosis in child-

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neurofibromatosis with features of pseudoangiomatousstromal hyperplasia with giant cells. Report of two cases.Virchows Arch 2001; 438: 513-516.

6. Zamecnik M, Michal M, Gogora M et al. Gynecomastia withpseudoangiomatous stromal hyperplasia and multinu-cleated giant cells: Association with neurofibromatosis type1. Virchows Arch 2002; 441: 85-87.

7. Campbell AP. Multinucleated stromal giant cells inadolescent gynecomastia. J Clin Path 1992; 45; 443-444.

9. Curran JP, Coleman RO. Neurofibromata of the chest wallsimulating prepubertal gynecomastia. Clinical Pediatrics1977; 16:1064-1066.

8. Lipper S, Willson CF, Copeland KC. Pseudogynecomastiadue to Neurofibromatosis- A light microscopic andultrastructural study. Hum Path 1981;12:755-759.

10. Murat A, Kansiz F, Kabakus N et al. Neurofibroma of thebreast in a boy with neurofibromatosis type 1. J ClinImaging 2004; 28: 415-417.