Malignant phyllodes tumor of the breast: case report, tumor characteristics, treatment approach

A 45-year-old female patient was referred to the hospital because of a tumor of the right breast. According to the patient, the tumor was palpable for about 2 years, gradually increasing, with a recent, significant increase of its volume. The patient had not been treated chronically and had a positive family history of breast cancer due to her mother’s illness.

In the physical examination, a large tumor of the right breast was found, measuring approximately 35 × 20 cm. The lymph nodes were not enlarged physically. An ultrasound described wide solid-fluid changes that filled the whole gland, and a phyllodes tumor was suspected. A core needle biopsy was performed, where fibroepithelial hyperplasia was described. There were no suspicious oncological changes in the left breast and no pathological lymph nodes. Metastases were not detected in the carried-out imaging studies. The patient qualified for surgical treatment.

A simple mastectomy was performed with the large pectoral muscle due to muscle infiltration by the tumor. Three lymph nodes of the second group were resected. The tumor size was 30 × 20 × 18 cm, and it was removed with margins of healthy tissues – from the chest, top and bottom with 2-mm margins, and with side margins of 3 and 15 mm. In the histopathological examination, in combination with the immunohistochemical results, a malignant phyllodes tumor was identified. The tumor tissue was of a multicellular nature, with significant mitotic activity (up to 11 mitotic figures in 10 power fields), the presence of extensive necrosis fields, and strong expression of vimentin and the CD34 antigen. No metastases were found in the lymph nodes.

After the operation, the patient qualified for radiotherapy – within 29 days, she received complete radiation on the chest wall and regional lymph nodes on the right side. The dose was 45 Gy in 20 fractions. The postoperative period and the period after radiotherapy were without complications.

Six months after the end of treatment, the patient had left breast and scar after mastectomy ultrasound – a hypogenic mass of 6 mm in diameter, about 2 cm from the medial scar pole, was described, and another one sized 28 × 13 mm in the lower right armpit. Fine needle biopsy was performed – the change in the medial pole region of the wound turned out to be a hematoma. Due to the ambiguous result of biopsy from the armpit, the patient qualified for excision of the lesion. The tumor was excised with the part of the latissimus dorsi, and the resulting skin loss was covered with a full-thickness flap. The operation was performed 1 month after the control ultrasound examination – during this time, the tumor almost doubled its size. In the histopathological examination, a recurrence was confirmed – a lesion of 4.1 × 2.2 × 5 cm in size was described as a malignant phyllodes tumor, which was dissected with the narrowest margin (on the fascial side) 2 mm wide. The tumor infiltrated the skin, creating an ulcer with a diameter of 3 mm.

Five months after the excision of the recurrence, the patient came to the hospital because of a tumor in the left breast, close to the median line, which was painful on palpation. Due to the suspicion of a purulent skin lesion, the patient was treated locally for 1 week – after finding no improvement, the nodule was excised. At the same time, three suspicious lesions were removed from different areas of the chest wall – above and below the scar after mastectomy and from the left breast, with a diameter of 5 mm, 10 mm and 7 mm. In the histopathological examination, all three lesions showed a proliferation of the malignant phyllodes tumor. Another recurrence was excised 20 days later (from a section of the mastectomy scar), with another one 1.5 months later (diameter of 3 mm). After 8 days, another one with a diameter of 7 mm was found on the occasion of the follow-up visit, absent during the previous examination – it was excised with a margin, and in the histopathological examination, once again, there was a recurrence of the malignant phyllodes tumor. After these operations, the patient had no local recurrence for 14 months – then, the patient found a palpable lump in the subcutaneous tissue of the scar after mastectomy. Due to the surgery with subsequent radiotherapy and numerous recurrence procedures, which resulted in significant thinning and soft tissue tension of the anterior chest wall (Figures 1 & 2), the patient qualified for surgery under general anesthesia on the operating block. A fragment of the skin was cut off with the subcutaneous tissue size of 5.5 × 4.8 × 3.5 cm with a lesion inside of 3.5 cm in diameter, and it was diagnosed again as a recurrence of the malignant phyllodes tumor. Due to the lack of skin and a large postoperative wound, plastic surgery was performed with a skin flap from the left side of the chest. The lesion was excised with the narrowest surgical margin of 1 mm. Since then (36 months), no local recurrence has been observed. In the imaging examinations, distant metastases are also not described. More than 5 years have passed since the mastectomy.

Phyllodes tumors are rare breast cancers, first described in 1838 by J Muller. They constitute 0.3 to 1% of all breast tumors [1,2], which is associated with an annual incidence of about 2.1 per million women [2–5]. We observe the peak of illness in women aged 40–50 years (average age 45 years) [1,2,6,7]. They are classified as fibroepithelial tumors, which also include fibroadenoma and hamartoma, and constitute about 2.5% of this group [1].

The clinical picture is usually a well-defined, hard, painless mass that is movable relative to the skin. Pathologies of the nipple in this type of cancer are rare (but described) [4,5,8]. Lesions are usually located in the upper, outer breast quadrant [9,10]. Phyllodes tumors are composed of two types of cells – epithelial origin, as well as surrounding and overgrowing stromal cells, organized into leaf-like structures. Stromal cells are responsible for the malignant features of the tumor and are the main element that differentiates phyllodes tumors from fibroadenomas [8,11,12]. In 2003, the WHO proposed the division of phyllodes tumors into benign, borderline and malignant. Incidence is estimated at 60, 20 and 20%, respectively [13] (according to some sources, the percentage of benign tumors reaches as much as 85–90%, but it is possible that these statistics are related to the underdiagnosis of malignant lesions [2]). The characteristics of the tumor indicating the degree of its malignancy are mitotic activity, the nature of margins, the degree of cellular atypia and the presence of stromal hyperplasia [2,12,14]. The 5-year survival rate for a malignant phyllodes tumor is 60 to 80% [4].

Phyllodes tumors are characterized by a high percentage of local recurrences – more than 20% regardless of the tumor subtype (17, 25 and 27% for benign, borderline and malignant changes, respectively), exceeding 30% (according to some sources up to 60% [4]) after surgery with a positive margin of resection [6]. In addition, at local recurrence, the tumor may become more malignant [15,16]. It is estimated that about 10% of phyllodes tumors (0, 4 and 22% of benign, borderline and malignant, respectively) spread to other organs, mainly to the lungs and bones, but cases of dissemination to other organs have been described [1,6,10,13,15]. Histologically, distant metastases of this tumor are made only of malignant stromal cells, responsible for the ability of the tumor to spread, without epithelial elements [12,15]. The average survival time after the detection of distant metastases is 30 months (4–17 months according to some authors [17]) [4,5]. Currently, the treatment of choice is surgery (the most common method is simple mastectomy), and for smaller tumors, the treatment choice is breast-conserving surgery. There are no indications for resection of the armpit lymph nodes, because this spreads through the blood, whereas the lymph nodes can be enlarged (in about 20% of patients) and have a reactive character in the majority of cases [5,10,12,18,19]. The key element for the effectiveness of surgical treatment is negative margins, at least 1 cm (a positive surgical margin is the most important risk factor for local recurrence, along with the primary tumor size [9,14]). However, when a smaller margin is obtained, it is recommended to observe the resection site without urgently removing the scar. Unfortunately, due to the lack of pathognomonic features in imaging studies [5,8,20] and low incidence, in many cases a phyllodes tumor is not properly recognized in the preoperative procedure and is enucleated or dissected locally as fibroadenoma, which is associated with the lack of free margins and a significant increase in the risk of local recurrence [4,5].

Radiotherapy is the only routine treatment in adjuvant therapy. It is recommended for patients with a high risk of recurrence – with malignant tumors, large in size, with positive margins of resection, and after breast-saving surgery in the case of border and malignant tumors. However, postoperative radiotherapy does not change the incidence of distant metastases or survival time – it only reduces the risk of local recurrence [5,6,15,19]. Radiotherapy does not prolong survival. There are too few studies with radiotherapy in malignant phyllodes tumors to recommend this treatment as a standard of care.

In the treatment of this type of tumor, the use of chemotherapy and hormone therapy remains controversial. There is a lack of randomized trials on a large group of patients, and those that are available provide contradictory information and do not prove the benefits of this form of therapy clearly [14,16,21]. It is true that in the case of phyllodes tumors, receptors that could react to hormonal treatment have been detected, but they are found only on epithelial-type cells, and not on stromal cells, which are responsible for the malignant nature of these tumors [14,16,21]. Generally, the role of chemotherapy is negligible in this type of tumor. From all data, there is only one work, with 28 patients included, that showed a little effect on survival time [22]. Therefore, we should wait for more studies to find this treatment as a benefit for patients.

Phyllodes tumors are unpredictable tumors – usually they increase in size rapidly, but there are cases where they grow slowly over the years only to suddenly accelerate the rate of growth and gain the ability to metastasize after malignant transformation [10,16].

In the presented case, the patient did not develop metastases, but there were many recurrent lesions, often in a form that, at first glance, did not raise suspicion of malignancy. Therefore, the safest procedure seems to be excision with a margin of healthy tissues (if possible) of any lesion that occurs near the primary tumor, even if, at some point, it will require us to perform plastic procedures (especially in patients after radiotherapy). This is also justified in the case of benign tumors, due to cases of increased malignancy of local recurrence and the possibility of deep infiltration of tissues. However, fine needle biopsy and core needle biopsy are not justified completely, because both methods have a high false-negative rate (as much as 25–30% USG guided core-needle biopsy) [4,20].

In malignant cases, there is usually a fast growth of recurrences – in our case, it happened that just 1 week after the previous examination, a malignant lesion of more than 5 mm in diameter appeared. This requires us to place special emphasis on the regularity of the controls, make patients aware of the disease type and get the best possible cooperation, as they should undertake thorough, regular self-examination and report any observed abnormality of the skin to the treating physician. In our opinion, aggressive surgical treatment of all, even small, lesions, close to the scar, gives a chance for a long period without recurrences or metastasis. The course of the patient’s disease emphasizes the purposefulness and effectiveness of aggressive surgical treatment. Leaving even small abnormalities within the scar just to observation is not good practice; surgeons should try to remove all, even unclear abnormalities. This article shows that postoperative controls in malignant phyllodes tumors should be very often, and only by often controls and rapid surgery are we able to extend time to local recurrence and metastasis. Therefore, we suggest to change postoperative time controls in our protocols.