Ductal carcinoma in-situ arising within benign phyllodes tumours

Abstract

Ductal carcinoma in situ arising within a benign phyllodes tumour is a rare neoplasm of the breast. We present a case of a 19-year-old woman who had a right breast lump for six months with the above diagnosis together with a mini-review of the literature. Ultrasound revealed a 5-cm breast lump and core biopsy revealed ductal carcinoma in situ. She underwent wide local excision of the breast lump with clear margins. Final histology confirmed ductal carcinoma in situ within a fibroepithelial lesion consistent with a benign phyllodes tumour. To our knowledge, this is the youngest case of ductal carcinoma in situ arising in a phyllodes tumour to have been reported so far.

Introduction

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

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

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.

Authors	Year	Age (years)	Surgery	Phyllodes grade	Size	Epithelial type	Size	Axillary lymph node involvement
Norris et al.	1967	–	–	–	–	Invasive carcinoma (two cases)	–	–
Cornog et al.	1971	–	–	–	–	Squamous cell carcinoma	–	–
Pietruska et al.	1978	45	–	–	5.5	Invasive carcinoma	–	Negative
Seemayer et al.	1975	27	Mastectomy	Malignant	6.0	Ductal carcinoma in situ	Focal	–
Bassermann et al.	1980	–	–	–	–	Squamous cell carcinoma	–	–
Leong et al.	1980	49	Local excision	Benign	6	Lobular carcinoma in situ	–	–
Leong et al.	1980	51	Mastectomy	Benign	4	Invasive ductal carcinoma	–	Negative
Klausner et al.	1983	60	Mastectomy	Malignant	4	Invasive ductal carcinoma	–	Negative
Cole-Beuglet et al.	1983	60	Local excision	Benign	3	Invasive ductal carcinoma	Focal	Negative
Cole-Beuglet et al.	1983	55	Local excision	Benign	3.5	Ductal carcinoma in situ + lobular carcinoma in situ	–	–
Hunger et al.	1984	57	Mastectomy	Malignant	15.5	Squamous cell carcinoma	–	–
Ishida et al.	1984	41	Mastectomy	Benign	5.6	Invasive ductal carcinoma	Focal	Negative
Grove et al.	1986	71	Mastectomy	Benign	19.0	Ductal carcinoma in situ	2	Negative
Ward et al.	1986	55	Mastectomy	Benign	4.0	Lobular carcinoma in situ	Focal	–
Knudsen et al.	1987	71	Mastectomy	Benign	7.0	Ductal carcinoma in situ + lobular carcinoma in situ	Multi-focal	Negative
Yasumura et al.	1988	47	Mastectomy	Benign	13.0	Invasive ductal carcinoma	Focal	Negative
De Rosa et al.	1989	77	Mastectomy	Benign	5.0	Ductal carcinoma in situ	0.3	Negative
Schwickerath et al.	1992	47	Mastectomy	Malignant	2.0	Ductal carcinoma in situ	–	Negative
Padmanabhan et al.	1997	47	Mastectomy	Malignant	7.5	Lobular carcinoma in situ	Focal	Negative
Naresh	1997	51	Local excision	Borderline	14.0	Ductal carcinoma in situ	Focal	–
Nishimura et al.	1998	80	Local excision	Malignant	10.5	Ductal carcinoma in situ	–	–
Alo et al..	2001	39	Mastectomy	Malignant	9.0	Ductal carcinoma in situ	–	–
Kodama et al.	2003	47	Mastectomy	Benign	17.0	Invasive lobular carcinoma	Focal	Negative
Parfitt et al.	2004	26	Local excision	Benign	3.3	Ductal carcinoma in situ and invasive carcinoma (no special type)	–	Positive (4/13)
Lim et al.	2005	45	Mastectomy	Malignant	12.0	Ductal carcinoma in situ	0.6	–
Tokudome et al.	2005	59	Mastectomy	–	3.5	Invasive carcinoma	Negative	–
Ramdass et al.	2006	69	–	Benign	–	Squamous cell carcinoma	–	–
Nomura et al.	2006	75	Mastectomy	Malignant	3.5	Ductal carcinoma in situ	–	–
Sugie et al.	2007	54	Mastectomy	Malignant	8.0	Squamous cell carcinoma	–	Negative
Korula et al.	2008	51	Mastectomy	Malignant	21.0	Ductal carcinoma in situ and invasive ductal carcinoma	–	Positive (2/12)
Yamaguchi et al.	2008	54	Mastectomy	Benign	15.0	Ductal carcinoma in situ	Focal	–
Macher-Goeppinger et al.	2010	70	Mastectomy	Malignant	6.0	Invasive ductal carcinoma	2.5	Negative
Kuo et al.	2010	24	Mastectomy	Borderline	–	Ductal carcinoma in situ and invasive ductal carcinoma	–	Positive (1/2)
Nio et al.	2010	53	Local excision	Benign	3.5	Ductal carcinoma in situ	0.5	–
Yoshinori Nio et al.	2011	53	Local excision	Benign	3.5	Ductal carcinoma in situ	Focal	–
Gina Shirah et al.	2011	49	Local excision	Benign	5.0	Lobular carcinoma in situ and invasive lobular carcinoma	0.2	–
Prithwijit Ghosh et al.	2015	42	Local excision	Benign	2.2	Ductal carcinoma in situ	–	–
Sharat et al.	2015	23	Local excision	Benign	5.0	Ductal carcinoma in situ	Focal	–
Nancy et al.	2017	70	Local excision	Beenign	2.3	Ductal carcinoma in situ and invasive ductal carcinoma	0.5	Negative

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

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.