Introduction
Phyllodes tumor (PT) is a rare type of breast tumor, accounting for less than 1% of benign and malignant breast tumors (1). PT is classified as benign, borderline or malignant, with approximately 10% of PT being malignant. Malignant transformation of PT usually occurs in the stromal component, and is rare in the epithelial component. The occurrence of PT and BC involves a twofold pattern: a separate coexistence within an ipsilateral or contralateral breast, and BC occurring in PT. The incidence of breast carcinoma (BC) in PT is thought to be only 1–2% of all PTs (2,3). To the best of our knowledge, 27 PT cases with 28 BCs have been reported in the literature, and 15 out of the 28 BCs were reported to be carcinoma in situ (CIS) (4–29).
A 53-year-old female with a benign PT with a ductal carcinoma in situ (DCIS) within the tumor was evaluated. The literature available was also reviewed.
Results
Macroscopic findings
The macroscopic examination revealed a hard elastic mass, which was encapsulated by thin fibrous tissue and which adhered firmly to the adjacent scar tissue. The tumor comprised 3 discrete PT nodules (Fig. 2). The overall size of the PT was 3.5×3.0×2.7 cm.
Microscopic findings
A histopathological examination showed that the tumor had two components; epithelium and stroma. The stroma consisted of monotonous, uniform and spindle-shaped tumor cells without atypia or mitosis, indicating that the tumor was benign (Fig. 3). The epithelium lined the elongated ductal structures or leaf-like processes protruding into dilated ducts formed by the overgrowth of the stromal component. The epithelium lining the ducts also exhibited benign features in the majority of areas, but, in part, showed significant nuclear atypia and a prominent proliferation in a cribiform pattern, definite features of low to intermediate grade DCIS. The DCIS was ~5 mm in diameter (Fig. 3).
Fig. 4 shows the results of immunohistochemical staining. The DCIS cells were strongly positive for estrogen (ER) and progesterone receptors (PgR), but HER2 expression was negative (score 0).
Post-surgical course
The patient received local irradiation (50 Gy) following surgery and no evidence of recurrence or metastasis was detected in the 2 years following surgery.
The previous cases are shown in Table I. A total of 1 patient had 2 BCs in 2 PTs. The first BC was a DCIS and the second one was a tubular carcinoma (5). The patient ages ranged between 26 and 80 years (average 52.7). Of the 28 PTs, 12 cases were identified as malignant and 14 as benign, with 1 borderline case. The diameters of the tumors ranged between 2.0 and 21 cm (average 8.0). The combined BCs included 15 CISs, 12 invasive BCs, and 1 patient had recurrent PTs twice in combination with a lobular carcinoma in situ (LCIS) at the first recurrence and a tubular carcinoma at the second recurrence. A total of 15 CISs included 10 DCISs and 3 LCISs, and 2 cases presented with both DCIS and LCIS. The CIS sizes were not described in 7 cases, but the majority of the remaining CISs were focal, and the largest CIS was 2.0 cm in diameter. On the other hand, 13 invasive BCs included 7 invasive ductal carcinomas (IDCs), 4 squamous cell carcinomas (SCCs), 1 invasive lobular carcinoma (ILC) and 1 tubular carcinoma. The tumor size was not described in 12 BC cases, and in 1 case the diameter was 2.5 cm. Axillary lymph nodes (AxLNs) were involved in 2 of 7 invasive BC cases reported, but no lymph nodes (LNs) were involved in any of the 7 CIS cases described. The LN involvement noted was metastasized from BCs, but not from PTs.
Discussion
The coexistence of PT and BC includes two patterns; a separate coexistence within an ipsilateral or contralateral breast, and a BC arising within PT. The present case was the latter type, a DCIS arising in a benign PT. To the best of our knowledge, the literature shows a total of 28 BCs arising in PT in 27 patients.
A variety of therapies were applied to the various cases. The present case received a LoEx with a margin of 1 cm from the tumor edge, and local irradiation at a total dose of 50 Gy since the PT tumors locally recurred four times at the same site. Two years have elapsed since the previous surgery and the patient remains disease-free. The additional surgeries included 5 LoExs, 21 mastectomies (MXs), 3 no descriptions, AxLNs were dissected in 10 cases, 12 patients received no Ax dissection (Dx) and 6 were not described. It appears that MX or LoEx was selected according to the size of the PT. MX with AxDx was applied for large PTs, but LoEx was applied for small PTs. Overall, 4 cases received LoEx first and then MX again according to the pathological diagnosis of malignancy or combination with invasive BC (10,12,20,23). AxDx was also applied for large PTs, but no LNs involving PTs were noted in the 10 cases described. AxDx may thus be restricted to patients suspected of having LN involvement by image diagnosis.
Post-surgical radiotherapy (RT), chemotherapy and/or endocrine therapy were applied for large PTs or those with combined invasive BCs. Overall, 1 patient with a 15.5 cm malignant PT with SCC of the breast received chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) following surgery (22), and 1 patient with a benign PT with a diameter of 15 cm received chemotherapy with oral Tegafur for 2 years following surgery. This second patient has been disease-free for 5 years (23). A patient with a 3.3 cm benign PT with AxLN involving a combined invasive BC received chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil (CEF) and local RT following surgery, followed by tamoxifen (TAM), and was disease-free for 3 years (25). A patient with a 21 cm malignant PT with LN involving combined BC received chemotherapy with 4-cycle adriamycin and cyclophosphamide (AC), local RT and TAM, and was disease-free for 11 months (28). A patient with a 12 cm benign PT received TAM alone since the combined DCIS was ER- and PgR-positive, and remained disease-free for 1 year (18). A patient with a recurring benign PT combined with an invasive BC received local RT at 5500 rad following surgery, similar to the present case, and this patient was disease-free for 21 months (5). Notably, a patient was diagnosed with SCC of the breast by FNA biopsy, and post-surgical pathology showed an SCC arising in malignant PT. The patient received preoperative chemotherapy with FEC followed by PTX. However, no post-surgical chemotherapy was administered, and the patient succumbed to PT lung metastasis 40 months following surgery (27). Since no standard therapy for PT has been established, a variety of combinations of surgery, chemotherapy, endocrine therapy and/or RT are applied.
The patient outcomes were described in 12 cases, and the majority of these patients were followed for a number of months or years. A total of 2 patients survived for 5 years following surgery (16,23). A total of 2 patients succumbed to the disease, 1 is mentioned above (27) and 1 developed lung metastasis and succumbed 10 months following surgery (14).
In conclusion, a rare case of a DCIS arising in benign PT is reported. Various types of carcinoma have been reported to arise in PT, such as IDC, ILC, DCIS, LCIS, SCC and tubular carcinoma. The etiological relationship between PT and carcinoma has yet to be elucidated. This type of combination therefore remains to be investigated.