Bilateral synchronous juvenile breast papillomatosis: A case report and review of the literature

Abstract

Juvenile papillomatosis (JP) is a rare benign breast disorder primarily affecting young women. It is characterized by atypical papillary duct hyperplasia and multiple cysts, and was first described as a distinct clinicopathologic entity in 1980.

We report the case of an 17-year-old woman with no significant personal or family history of breast cancer, who presented with a sero-hemorrhagic nipple discharge from the right breast for four years. Clinical examination revealed no palpable masses.

Ultrasound and MRI revealed a dilated galactophoric duct surrounded by cystic lesions in the upper outer quadrant of the right breast and at the junction of the inner quadrants of the left breast, consistent with bilateral juvenile papillomatosis.

The patient underwent a right breast pyramidectomy. Histopathological examination showed cystic dilatation of the galactophoric ducts on a fibrous breast parenchyma, with moderate hyperplasia without atypia, suggestive of the diagnosis.

Breast-conserving surgery is planned for the left breast.

Juvenile papillomatosis is an exceptionally rare benign breast lesion occurring in young women. Radiological imaging is essential for lesion detection, while histopathological examination remains the gold standard for diagnosis.

Introduction

Juvenile papillomatosis of the breast is histologically characterized by a fibrotic stroma and multiple cysts producing a “Swiss cheese” appearance, associated with a florid epithelial proliferation that may occasionally show cytologic atypia [1].

It is a rare condition that primarily affects young females, occurring before the age of 20 years in approximately 69% of cases [2].

Breast carcinoma is reported in about 15% of patients at the time of diagnosis [1]. Furthermore, a risk of malignant transformation may exist when associated hyperplasia is present [3].

The most common location within the breast is the retroareolar region. Ultrasound can be helpful in evaluating this lesion, however, a definitive diagnosis requires histological confirmation through biopsy.

Management is often challenging because of the young age of the patients and the need to adopt the most conservative therapeutic approach possible.

Case presentation

We report the case of an 17-year-old female with no significant past medical history, including no personal or family history of breast cancer.

She presented with a five-year history of unilateral sero-hemorrhagic nipple discharge from the right breast.

On admission, the patient was hemodynamically and respiratory stable and afebrile.

Breast examination revealed a right-sided, single-duct serohemorrhagic nipple discharge that was elicited upon expression, without any palpable mass in either breast.

Laboratory investigations were within normal limits, including a normal white blood cell count and a negative C-reactive protein level.

Breast ultrasound demonstrated focal bilateral ductal ectasia, involving the inner quadrants of the left breast and the retro-areolar region of the right breast, extending into the supero lateral quadrant, with associated adjacent cystic lesions (Fig. 1).

Fig. 1.

Focal ductal ectasia (White arrow), involving the retroareolar region of the right breast, extending into the supero lateral quadrant, with associated adjacent cystic lesions (Black arrow).

Breast MRI confirmed focal bilateral ductal dilatation in the inner quadrants of the left breast and the retroareolar region of the right breast, extending into the superolateral quadrant, associated with peripheral cystic dilatations, and moderate, diffuse wall enhancement along the dilated ducts (Fig. 2).

Fig. 2.

Focal bilateral ductal dilatation in the inner quadrants of the left breast and the retroareolar region of the right breast, extending into the superolateral quadrant, associated with peripheral cystic dilatations, and moderate, diffuse wall enhancement along the dilated ducts.

The patient underwent a right pyramidectomy. Macroscopically, the lesion had a “Swiss cheese” appearance. Histopathological examination revealed cystic dilatation of the galactophoric ducts, with foci of cylindrical and apocrine metaplasia on a fibrous breast parenchyma, as well as moderate hyperplasia without atypia, suggestive of the diagnosis (Fig. 3).

Fig. 3.

Pyramidectomy specimen: Macroscopically, the lesion had a “Swiss cheese” appearance.

Postoperative recovery was uneventful. The patient is scheduled for conservative treatment of the contralateral breast.

Discussion

Juvenile papillomatosis (JP) of the breast is a rare benign lesion [4], occurring predominantly in young women, usually before the age of 25, although cases in older patients and in males have also been reported [5].

The etiology of JP remains unclear. Hormonal imbalance secondary to an alteration of the hypothalamic–pituitary–ovarian axis has been proposed as a possible contributing factor in cases where hormonal or pharmacological induction cannot be excluded [6].

Juvenile papillomatosis was probably first described by Kiaer et al. [7] in 1979 under the term “extreme duct papillomatosis”. In 1980, Rosen et al. [8] reported this entity as juvenile papillomatosis or the so-called “Swiss cheese disease”.

JP is associated with atypical hyperplasia in approximately 40% of cases, and intraductal necrosis has been reported in about 15% of cases, highlighting the potential risk of malignant transformation [9].

The role of family history in the risk of breast cancer associated with JP has frequently been emphasized. Rosen et al. [3] reported that 28% of patients had a family history of breast cancer, most often on the maternal side. Positive family history associated with recurrent or bilateral JP has therefore been suggested as a risk factor for the development of invasive breast carcinoma [[9], [10], [11]].

A recent study by Guillet et al. [5] identified mutations in genes such as PIK3CA, AKT1, and ATM, suggesting a possible genetic link between JP, positive family history, and the subsequent risk of breast cancer. However, these mutations are not specific to JP and further studies are needed to confirm their pathogenic role.

Clinically, JP often presents similarly to a fibroadenoma [5]. It usually manifests as a unilateral breast mass discovered within the previous six months. The mass is typically firm, smooth or lobulated, mobile, sometimes painful, and most frequently located in the upper outer quadrant of the breast [3]. The average size is approximately 3 cm [[2], [3], [4], [5], [6], [8], [9], [7], [10], [11], [12]]. Nipple discharge may occasionally be present [3].

Mammography, although rarely performed in young patients, may reveal an ill-defined area of increased density, sometimes with a stellate appearance, associated with microcalcifications. These microcalcifications may be polymorphic, punctate, coarse and round, irregular, or even vermicular, and may appear scattered or clustered [13].

On ultrasound, JP typically appears as an irregular hypoechoic area containing clustered cysts, within which microcalcifications may occasionally be identified [14].

On magnetic resonance imaging (MRI), JP generally appears as a lobulated mass with low signal intensity on T1-weighted sequences and multiple small internal cystic lesions visible on T2-weighted sequences. These cystic components are considered the most specific imaging feature and are usually associated with a benign enhancement pattern on dynamic sequences [15].

Synchronous or metachronous bilateral lesions of juvenile papillomatosis have sometimes been reported, and in rare cases the tumors may be multifocal and bilateral [][16].

From a pathological perspective, gross examination typically reveals multiple cystic lesions of variable size embedded within a fibrotic stroma, producing the characteristic “Swiss cheese” appearance [17]. Histologically, the presence of cysts associated with florid epithelial ductal hyperplasia is a constant finding.

Understanding the relationship between these lesions and the associated risk of breast cancer is essential for determining appropriate management.

Hartmann et al. [18] evaluated the relative risk of breast cancer associated with different histological breast lesions: 1.27 % for non-proliferative lesions, 1.88 % for proliferative lesions without atypia (including moderate to florid hyperplasia, papilloma, radial scar, or sclerosing adenosis), and 4.24 % for proliferative lesions with atypia.

Patients considered at high risk of developing breast carcinoma typically present with at least one of the following features: a family history of breast cancer, atypical proliferative lesions, bilateral or multifocal disease, or recurrent juvenile papillomatosis [16].

The recommended management consists of wide local excision of the lesion in order to obtain a complete histological evaluation. Two situations may arise following definitive pathological examination: if malignancy is identified, a second radical surgical procedure may be required; if no malignancy is found, close clinical and radiological follow-up is recommended [16].

In multidisciplinary discussion, it was decided not to perform additional surgery despite non–tumor-free margins, as the patient did not present any significant oncological risk factors [16].

In younger patients, management should be considered on a case-by-case basis, as no clear guidelines currently exist and the priority remains the exclusion of malignancy [16].

In the case of our patient, she underwent a pyramidectomy, and the pathological examination showed no evidence of atypia. A second conservative surgery of the contralateral breast was planned, followed by close surveillance.

Currently, there is no consensus in the literature regarding the optimal follow-up strategy for patients with juvenile papillomatosis [16].

Regarding imaging surveillance, decisions in young patients should be individualized. Magnetic resonance imaging (MRI) may be particularly useful due to its high sensitivity. However, in the absence of associated risk factors for breast neoplasia, simple ultrasound follow-up may be considered in these young patients [16].

Conclusion

Juvenile papillomatosis should be considered in the differential diagnosis of breast masses in adolescents and young women, particularly when ultrasonography demonstrates clustered cystic lesions.

Careful evaluation of family history of breast cancer and histological assessment for epithelial atypia is essential due to the potential risk of subsequent breast carcinoma.

Recent studies have reported PIK3CA and AKT1 genetic mutations, suggesting a possible role in the pathogenesis of the disease.

Complete surgical excision remains the treatment of choice, followed by regular clinical follow-up to detect recurrence or possible malignant transformation.

Authors contribution

KL Is the corresponding author, she participated in the organization and writing of the article. Professor MB supervised the working and validated the figures.

Professor and chief of department of radiology MB and MM red and allowed the article for publication.

All authors read and approved the final manuscript.

Availability of data and materials

The data sets are generated on the data system of the CHU Hassan II of Fes, including the biological and radiological data.

Patient consent

Written informed consent was obtained from the patient. A copy of the written consent is available for review by the Editor-in-Chief of this journal.