Introduction

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Phyllodes tumours are fibroepithelial breast tumours; they account for less than 1% of all breast neoplasms.¹ Phyllodes tumours have characteristic epithelial components arranged in clefts, surrounded by a mesenchymal component organised in a leaflike pattern.² Although malignant transformation of the stromal component can occur, a carcinoma arising from the epithelial component is only rarely reported. To date, 41 cases of breast cancer arising from phyllodes tumours have been reported, of which 19 were reported to be ductal carcinoma in situ (DCIS). We present a review and a case discussion of a 19-year-old woman diagnosed with DCIS arising from a phyllodes tumours, the youngest case to date, who was successfully managed with oncoplastic breast conserving surgery.

Case history

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A 19-year-old single nulliparous woman presented with six months’ history of a rapidly enlarging right breast lump. Family history was significant for an aunt with breast cancer at the age of 60 years. On clinical examination, the mass measured 5 cm and was firm, non-tender, mobile and well defined in the upper outer quadrant of the right breast. There were no skin or nipple changes. Examination of the left breast was normal. There were no palpable axillary lymph nodes. Ultrasonography of the right breast revealed a heterogeneous vascular mass with fairly well circumscribed margins in the right breast at 9–10 o'clock 5 cm from nipple, measuring 5 x 2.8 x 5.1 cm (Fig 1). An ultrasound-guided biopsy was performed in view of clinical suspicion and histology showed a low to intermediate grade DCIS. Bilateral mammograms subsequently performed showed a mass with partially obscured borders in the right upper outer quadrant, with a couple of scattered specks of benign coarse calcifications in right breast (Fig 2). There were no other suspicious lesions in either breast. Considering the patient’s age, size of lesion and histology, she was counselled for mastectomy with implant reconstruction. She declined mastectomy and subsequently underwent a wide local excision and sentinel lymph node biopsy via an inframammary fold incision. The usual practice in our centre is to excise breast tissue down to the pectoral fascia. Intraoperative frozen section of two sentinel axillary lymph nodes was negative for malignancy. Parenchymal flaps were mobilised to close the defect. Histopathological examination showed a well-circumscribed fibroepithelial lesion consistent with a benign phyllodes tumours with diffuse involvement of the ductal epithelial component by multiple foci of low to intermediate nuclear grade DCIS (Figs 3 and 4). The fibroepithelial lesion showed focal leaf-like architectural pattern. The epithelial component also displayed features of columnar cell change and usual type ductal hyperplasia. There was no definite evidence of invasive carcinoma. All resection margins were free of malignancy with nearest 0.1 cm from posterior margin. After discussion with the radiation oncologist, in view of the substantial risk considering her age, it was decided to omit adjuvant radiotherapy, accepting that there will be higher risks of local recurrence. She was subsequently started on chemoprevention with tamoxifen. Surveillance ultrasound performed this February revealed no recurrence or new lesions. All genetic screening for hereditary breast cancer syndromes including BRCA1, BRCA2 and PTEN were negative.

Figure 1 Ultrasound scan of the right breast revealing a heterogeneous vascular mass with fairly well-circumscribed margins in the right breast

Figure 2 Bilateral mammography showing a mass with partially obscured borders in the right upper outer quadrant with couple of scattered specks of benign coarse calcifications in right breast

Figure 3 Fibroepithelial tumour with focal leaf-like architecture. There is secondary involvement of the ductal epithelial component by foci of ductal carcinoma in-situ (40 x magnification)

Figure 4 Secondary involvement of the ductal epithelial component of the fibroepithelial tumour by foci of ductal carcinoma in-situ (40 x magnification)

Discussion

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Phyllodes tumours are graded according to their stromal characteristics, namely benign, borderline or malignant,³ with recurrences occurring at a rate of 17%, 25% and 27%, respectively.⁴ The classification is based on histological characteristics of the phyllodes tumours and is used to prognosticate their clinical course. Most series-reported benign phyllodes represented 50–70% of phyllodes tumours.^1,3 DCIS or invasive breast carcinomas can occur in conjunction with phyllodes tumours, but are very uncommon, occurring in only about 1% of patients with phyllodes tumours.⁵

A literature search of PubMed was conducted using the keywords: ‘breast cancer’, ‘phyllodes tumor’, ‘carcinoma in situ’, ‘cystosarcoma phyllodes’ and ‘DCIS’. Only 41 cases of carcinoma arising in patients with phyllodes tumours (Table 1) were identified, of which 19 were DCIS.^5–40

Table 1 Published data on carcinomas arising within phyllodes tumours.

Of the 19 cases with DCIS, all were female, with ages ranging from 23 to 80 years. To our knowledge, our case is the youngest patient to have been diagnosed with DCIS within a phyllodes tumour. Four cases had concomitant invasive components,^26,32,35 while two other cases had concomitant LCIS.^12,17 Six arose from malignant phyllodes tumours, two from borderline phyllodes tumours and ten from benign phyllodes tumours. However, among the ten cases, only six had pure DCIS from benign phyllodes tumours, ours being the seventh case to be reported in the English literature.^{5,15,19,33,36,39}

The size of the phyllodes tumours ranged widely between 2.0 cm and 21.0 cm, suggesting that DCIS can occur in any palpable phyllodes tumour. Eight cases underwent wide local excision while the rest underwent total mastectomy.

Apart from four cases of DCIS with invasive components, the remainder of the patients with DCIS had negative lymph node involvement or did not undergo axillary lymph nodal sampling or dissection. Three cases reported with positive axillary lymph node involvement had invasive carcinomas.

Stromal overgrowth has been reported with rapidly enlarging phyllodes tumours; epithelial hyperplasia has also been reported to occur in as high as 74% of phyllodes tumours.⁴¹ The best-practice diagnostic guidelines published by the Cancer Reform Strategy Breast Cancer Working Group does not recommend biopsy in women younger than 25 years of age with ultrasound showing typical features of fibroadenoma.⁴² In this patient, however, the clinically rapidly enlarging size and heterogenicity of the lesion on ultrasound were suspicious, hence a biopsy was performed.

Standard treatment for phyllodes tumours involves surgical resection with no need for axillary sampling or dissection. However, adjuvant therapy may be indicated for patients with epithelial malignant change, be it radiotherapy, chemotherapy or endocrine therapy. Patients with DCIS who have had breast-conserving surgery are typically offered adjuvant radiotherapy to reduce local recurrence rates. Young age at diagnosis has been reported to be an independent predictor for local recurrence even after controlling for factors such as tumour size, presence of comedonecrosis and clinical presentation.^43,44

A local study by Tan et al. showed a local recurrence rate of 10.9% for benign phyllodes tumours with no distant metastases.⁴⁵ From this study, the predicted recurrence-free survival from the normogram is more than 0.95 at 10 years for our patient. According to another validated normogram published in the Journal of Clinical Oncology in 2010 for the Western population, the ipsilateral breast tumour recurrence rate is about 0.2 at 10 years.⁴⁶ Based on the University of South California/Van Nuys Prognostic Index, our patient had intermediate-risk DCIS. A 2008 study by Di Saverio showed a 10-year disease-free survival of 86.8% for patients who underwent radiotherapy and 78.5% for those who did not, although this was not significant.⁴⁷ Interestingly, a more recent study by Kim et al. showed that patients with intermediate risk DCIS who did not undergo radiotherapy had no recurrence.⁴⁸ Fortunately, a 2015 analysis assessing 20-year mortality outcomes in patients with DCIS demonstrated no survival benefit to radiation, although it did reduce local recurrence risks significantly.⁴⁹ Radiation-related risks of thyroid, breast, brain, skin cancers, as well as leukaemia in children have been demonstrated in a linear dose–response relationship, with risks of cancer greatest for those exposed early in life, and these risks appear to persist throughout life.⁵⁰ In the Childhood Cancer Survivor Study group, the odds ratio for breast cancer increased linearly with radiation dose, with 11-fold increase for local breast doses of approximately 40 Gy relative to no radiation.⁵¹ A dose–response relationship was also observed by Rubino, who showed that risk of post-radiation sarcoma in breast cancer patients was 30.6 times higher for doses of more than 44 Gy compared with those of less than 15 Gy.⁵² However, boost radiation has also been reported by the Rare Cancer Network study to decrease local recurrence rates, particularly in young women less than 45 years of age with DCIS, with 10-year local relapse-free survival of 86% with boost radiation and 72% without.⁵³ In our case, the patient received chemoprevention with tamoxifen and is still on regular follow-up.

Conclusion

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In conclusion, we present a rare case of DCIS arising within benign phyllodes tumor, which is the youngest reported to date. Adjuvant therapy needs to be further investigated and this group of patients should be followed up long-term given their higher rates of local recurrence.