Prepubertal borderline phyllodes tumour—decision-making and issues for consideration of a very rare paediatric entity: a case report and literature review

Introduction

Background

Phyllodes tumours are an extremely rare cause of breast lumps, accounting for less than 1% of all breast tumours (1).

Rationale and knowledge gap

To the best of our knowledge, only a handful of cases of prepubertal phyllodes tumours are reported in the literature. Of the reported cases in the literature, most patients were post-pubertal, with a median age of 17 years quoted for the juvenile population and 50 years for the adult population (2).

Objective

In this report, we describe a case involving a 10-year-old girl presenting with a non-tender breast mass with a borderline phyllodes tumour identified on histology. We additionally highlight the lack of an established paediatric care pathway for phyllodes tumours. We present this case in accordance with the CARE reporting checklist (available at https://asj.amegroups.com/article/view/10.21037/asj-24-17/rc).

Case presentation

A 10-year-old prepubertal female of African descent was referred by her general practitioner to our symptomatic breast unit with a rapidly progressing discrete lump in her left breast. The patient first brought it to her mother’s attention 6–7 weeks before presentation. She had no previous history of trauma or infections in the area. She had no past medical history and was otherwise well. There was no family history of breast cancer. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the guardian of the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

A well-circumscribed painless mass was evident in the left breast, spanning approximately 10 cm on palpation, with no associated skin or nipple changes. Examination of her right breast and both axillae were unremarkable. An ultrasound of her left breast showed a mass measuring at least 8.2 cm × 4.7 cm with internal vascularity. It was reported as a possible juvenile fibroadenoma. No lymphadenopathy was identified on the ultrasound of the left axilla. An ultrasound of her right breast was performed for comparison and showed normal developing glandular tissue with no focal masses evident.

Because of her young age and concordant clinical and radiological examinations, and in consensus with her mother, an ultrasound-guided core biopsy was omitted. Less than a week following her initial presentation, the patient underwent a left breast excisional biopsy under general anaesthetic. The decision to proceed straight to surgery was made on account that, as a child, she would not tolerate a core biopsy under local anaesthetic in the outpatient setting. As this was a very large mass in a pre-pubertal breast bud, special consideration and care was taken during dissection not to disturb the normal breast tissue. The tumour was shelled out with relative ease along a clear fascial plane. The tumour was not adherent to surrounding structures and had a well-defined capsule. Intraoperative clinical photography was taken with consent obtained from the guardian of the patient, see Figure 1. The patient recovered well and was discharged home the same day.

Figure 1 Well-circumscribed encapsulated left breast mass following excision.

The specimen measured 8.0 cm × 8.0 cm × 5.5 cm in size and weighed 199 g at the time of excision. It was a well-encapsulated mass with a clear plane separating it from surrounding normal tissue. The cut surface revealed a septating mass that was grossly homogeneous. It was sectioned at 10 mm intervals and sampled. A well-circumscribed epithelial-stromal neoplasm was identified with moderate stromal hypercellularity and moderate atypia of the stromal component. Scattered stromal mitosis were present (up to 5 per mm²). No stromal overgrowth or malignant heterologous elements were reported. The final pathology report confirmed a borderline phyllodes tumour. Figure 2 outlines the respective pathological specimens of the phyllodes lesion. The pathological specimens show well circumscribed biphasic tumour, leaf-like architecture, hypercellular stroma with moderate nuclear atypia and stromal mitoses.

Figure 2 The respective pathological specimens of the phyllodes lesion. (A) Well circumscribed biphasic tumour comprising stromal cells and benign epithelium (hematoxylin and eosin, ×2). (B) Leaf-like architecture (hematoxylin and eosin, ×10). (C) Hypercellular stroma with moderate nuclear atypia (hematoxylin and eosin, ×20). (D) White arrow identifying two black circles encompassing two stromal mitoses (hematoxylin and eosin, ×40). (E) Stromal mitoses, higher magnification (hematoxylin and eosin, 40 high power field).

This case was discussed at the breast tumour multi-disciplinary meeting (MDM). The consensus was that this patient did not require further surgery, as the tumour was fully excised along a distinct fascial plane and the capsule was not breached intraoperatively. She will be seen annually for the following three to five years for physical examination with ultrasound imaging implemented if clinical findings of concern. She has been advised to be vigilant for any signs of recurrence.

Discussion

Key findings

Here we report a rare case of prepubertal borderline phyllodes tumour, where a patient developed a rapidly growing mass in their breast initially presumed to represent a benign fibroadenoma.

Strengths and limitations

A phyllodes tumour represents a rare fibroepithelial tumour of the breast characterised by stromal overgrowth (3). Unlike the majority of breast carcinomas, these tumours arise from the connective tissues surrounding the vessels, ducts and lobules of the breast (3-5). Phyllodes tumours are infrequently encountered, accounting for less than 1% of all breast neoplasms (4,6). The primary differential diagnosis for phyllodes is benign fibroadenoma. Both present clinically as well-circumscribed, painless, mobile masses, generating a diagnostic challenge. No clinical guidance relating to the management of paediatric phyllodes has been established for a lack of standardised care pathway.

Explanation of findings

Phyllodes tumours are classified as benign, borderline or malignant based on histological features per the World Health Organisation with benign tumours representing approximately 60% to 75% of all phyllodes cases (4,7). Differentiation between the subtypes of phyllodes tumours includes features relating to mitotic atypia, stromal atypia and stromal overgrowth (8).

The majority of phyllodes cases occur in middle-aged females, with incidence peaking in women over 40 years (9,10). Their aetiology is poorly understood. It has been postulated that trauma, pregnancy, lactation and elevated oestrogen activity may be implicated in their growth (3,11,12). While the majority of phyllodes tumours occur de novo, fibroadenoma transformation to phyllodes has been reported (13). Malignant phyllodes tumours are reported to be the second most common malignant paediatric breast tumour (14). Race has been implicated in these tumours, with black children having a higher incidence of breast carcinoma (15).

Breast lumps that are >2 cm in size or rapidly increasing in size with ultrasound features suggestive of fibroadenoma should raise suspicion of a phyllodes tumour (16). In keeping with current practice, all individuals presenting to our service with a breast mass undergo triple assessment; history and examination, imaging and if indicated, biopsy. Features which may raise suspicion of a phyllodes tumour are a rapidly enlarging breast mass, superficial vein dilatation and tautness of the overlying skin. Axillary lymphadenopathy often occurs (17), however Leraas et al. have shown a decreased frequency of nodal examination in paediatric patients compared to their adult counterparts (2). It is our opinion that children should not undergo nodal sampling unless there are palpable or radiologically visible axillary nodes that are suspicious in nature.

Other symptoms thought to be indicative of a malignant process, such as abnormal nipple discharge, ulceration and retraction, are scarcely encountered (18). It is, therefore, unsurprising that early differentiation between the phyllodes tumour and fibroadenoma poses a challenge to clinicians of differing speciality expertise involved in assessing undifferentiated breast masses.

Comparison with similar research

For paediatric patients, ultrasound is the mainstay of imaging for breast masses, primarily due to its superiority in assessing dense breast tissue without radiation exposure (19,20). On ultrasound, phyllodes tumours may appear as a hypoechoic or mixed echogenic, partially indistinct, or partially circumscribed mass (21,22). Ultrasound can display primarily cystic components (23), the presence of which can be suggestive of malignant tumours. Definitive grading requires histological analysis (24). According to the National Cancer Care Network (NCCN) 2023 guidelines (25), mammography should be completed for all individuals over the age of thirty if there is suspicion of a phyllodes tumour. The role of mammography in paediatric cases is unclear, and the majority of the paediatric cases reported in the literature employed ultrasound alone (16,26). Mammography in these tumours often yields lobulated dense masses with circumscribed or partly indistinct margins, and calcifications (if present) are often large (18). Magnetic resonance imaging provides the most detailed imaging, with T2-weighted imaging more sensitive in comparison to T1-weighted. Reports of T2-weighted imaging in the setting of phyllodes tumours describe lobulated masses with hyperintense fluid with concurrent hyperintensity in surrounding tissues (27).

Definitive diagnosis is established through histopathological analysis from excisional biopsy. Core biopsy of these lesions is insufficient for adequate differentiation with a high false negative rate cited in the literature (28,29). The difficulty in distinction lies with the fact that fibroadenomas may show cellular stroma, a feature shown to be more associated with phyllodes tumours (30). Microscopically, phyllodes tumours exhibit leaf-like architecture with an enhanced intracanalicular growth pattern alongside the presence of both stromal and epithelial cells (4,31). In our case, stromal hypercellularity was identified with scattered mitoses and cellular atypia, favouring a phyllodes tumour over fibroadenoma. Stromal proliferation in phyllodes tumour is more prominent in periductal areas and less uniform when compared to fibroadenomas (32). Macroscopically, haemorrhage can be evident (4), as was demonstrated in this case.

Definitive treatment for phyllodes tumours is surgical (33). For benign tumours, excisional biopsy including complete mass removal is accepted (34). In the setting of borderline and malignant tumours, wide local excision with a minimum margin of 1 cm is recommended (34,35). Total mastectomy may be required in the setting of malignant, repeatedly recurrent or extremely large tumours (25,36). As described in this case, it was decided that excision en-masse without breach of the capsule along the fascial plane was sufficient. Any further margins would have necessitated a mastectomy for this child with all the detrimental effects of it in such a critical pre-pubertal age. As such, it was decided in the breast MDM that this resection was sufficient and she is to be followed up for surveillance, along with education of parents on signs of recurrence.

Implications and actions needed

The most pertinent issue that became apparent to us from this case is the lack of an established paediatric pathway for juvenile patients diagnosed with phyllodes tumours. As discussed, these tumours are an extremely rare occurrence in the paediatric population with less than 25 cases reported in the literature (16,26). To our knowledge, no dedicated paediatric pathway exists to date. Some bodies of evidence suggest paediatric treatment should be in keeping with adult pathways, however a recent publication by the NCCN highlighted the importance of weighing the benefits of adjuvant therapies (i.e., radiation) when dealing with paediatric phyllodes tumours (2). Given the extensive range of adverse side effects, both in the immediate period during treatment and later in adulthood, careful consideration is owed to determining the most suitable course of treatment for each individual case.

Regardless of subtype there is a high risk of local recurrence (37). Recurrence in borderline cases is reported in >15% of cases, of which >20% are ultimately of borderline histology again. Over 25% of recurrent cases are malignant in nature. Interestingly, a higher local recurrence rate amongst borderline phyllodes than malignant has been reported (38), which is potentially due to the extent of surgical excision. Irrespective of patient factors, local recurrence may occur depending on histological grade, resection margins and number of tumours. There is no significant difference reported in long-term survival between adult and paediatric patient populations (38).

For individuals with phyllodes tumours the NCCN (25) recommend clinical follow-up for 3 years following surgical intervention as most cases of recurrence occur within three years of initial treatment (35). In cases of adult borderline or malignant phyllodes more frequent imaging; biannual ultrasound for 2 years then yearly until 5 years along with annual mammography is recommended. In the above paediatric case, we propose a minimum of 3-year follow-up consisting of annual physical examination with ultrasound imaging if clinically indicated. MDM opinion and patient factors were considered during the decision-making process. The rationale is based on recurrence being the highest within the first 2 years from the first presentation and the rapidly growing nature of the tumors in this case. Consideration of the presence of certain clinicopathological features has important clinical implications in prognostic factors of recurrence: margin status, tumour border, tumour necrosis, stromal overgrowth and moderate or severe stromal atypia and hypercellularity (36).

We pose the question as to whether the proposed three years of follow-up is adequate for females who have yet to undergo the hormonal changes associated with puberty? No specific guidelines exist regarding paediatric phyllodes tumours exist; current guidelines do not differentiate between adult and paediatric phyllodes management (2). Clinical behaviour and histopathology must be considered in paediatric management pathways. Special consideration of psychosocial implications of frequent physical examination and imaging in this young cohort is necessary.

Conclusions

This case report describes a rare, very large breast tumour in a 10-year-old female child and highlights the issues and challenges of managing these large lesions in pre-pubertal breasts. It highlights lack of specific guidelines and various psychosocial considerations in patients of such a young age. Parental involvement in the decision-making process, management and surveillance was and will continue to be crucial to the outcome of this patient.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://asj.amegroups.com/article/view/10.21037/asj-24-17/rc

Peer Review File: Available at https://asj.amegroups.com/article/view/10.21037/asj-24-17/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://asj.amegroups.com/article/view/10.21037/asj-24-17/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the guardian of the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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