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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 3  |  Page : 365-368
 

Cystosarcoma phyllodes: Pathological enigma: A retrospective review of 162 cases


1 Department of Surgery, Bangalore Medical College and Research Institute, Bangalore, Karnataka, India
2 Department of surgery, Kempegowda Institute of Medical Sciences, Bangalore, Karnataka, India
3 Department of surgical oncology, Kidwai memorial Institute of Oncology, Bangalore, Karnataka, India

Date of Web Publication18-Feb-2016

Correspondence Address:
R P Narayanakar
Department of Surgery, Bangalore Medical College and Research Institute, Bangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.176698

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 » Abstract 

Purpose: Phyllodes tumor (PT) is a rare fibroepithelial neoplasm comprising <1% of all breast tumors. Clinical spectrum ranges from benign (B), borderline (BL), and locally recurrent to malignant (M) and metastatic type. The aim of our study was to analyze the clinicopathological factors, compare treatment options, and evaluate outcome in patients with PT. Methods: We retrospectively reviewed 162 women with PT. The surgical intervention varied from simple excision (lumpectomy)/wide local excision (WLE) in benign cases to simple/modified radical or radical mastectomy (SM/MRM/RM) in malignant and recurrent tumors. Results: Out of 162 patients, B, BL, and M were 95 (58.64%), 29 (18%), and 38 (23.45%), respectively. Mean age, duration of lump, and size were 38 ± 8 years, 28 ± 10 months, and 12 ± 5 cm, respectively. Recurrence rate with B, BL, and M was 15.78%, 41.37%, and 55.26%, respectively (P = 0.00001). As compared to WLE (22%), SM (23.8%), and MRM/RM (14.2%), recurrence was higher with lumpectomy (48.9%) (P = 0.004). Positive correlation was found between recurrence rate with the size of tumor (P = 0.008) and also number of recurrence with holoprosencephaly (P = 0.047). There was no association between the number of recurrences and size of tumor (P = 0.63). Malignant PT was seen in 38 (24%) and distant metastasis was seen in 7 (18%). Mean duration of follow-up was 42 months. Conclusion: WLE with negative margins should be the initial surgery for PT. The role of adjuvant radiotherapy and chemotherapy is uncertain. PT is pathological enigma. Till date, no factors can accurately predict the recurrence and outcome. PT is known for unpredictable behavior and high recurrence rates, hence long-term follow-up is advised.


Keywords: Pathological classification, phyllodes tumor, recurrence, wide local excision


How to cite this article:
Narayanakar R P, Gangaiah D M, Althaf S, Dev K, Kurpad V, Gurawalia J. Cystosarcoma phyllodes: Pathological enigma: A retrospective review of 162 cases. Indian J Cancer 2015;52:365-8

How to cite this URL:
Narayanakar R P, Gangaiah D M, Althaf S, Dev K, Kurpad V, Gurawalia J. Cystosarcoma phyllodes: Pathological enigma: A retrospective review of 162 cases. Indian J Cancer [serial online] 2015 [cited 2019 Jun 26];52:365-8. Available from: http://www.indianjcancer.com/text.asp?2015/52/3/365/176698



 » Introduction Top


Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm that constitutes <1% of all female breast tumors.[1],[2] It was first described by Johannes Muler's in 1838.[3] “Cystosarcoma phyllodes” as a correct term was declared by the World Health Organization (WHO), which has been widely accepted.[4] Although it can occur at any age from adolescents to elderly, in most of the cases occurs between 35 and 55 years of age.[5],[6] It shows a wide range of clinical and pathological behavior. Phyllodes are frequently large in size and may be up to 40 cm in diameter. In most of the patients having unilateral disease, bilateral tumors are rare.[7],[8] Histologically, it is composed of epithelial elements and mesenchymal stroma, the mesenchymal component is a characteristic feature and the presence of high stromal component is associated with aggressive nature of the disease. WHO classified three microscopic types: Benign, borderline (BL), and malignant PT [Table 1].[9]
Table 1: Histopathological criteria for diagnosis of phyllodes tumour

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Even though specific pathological criteria are available for the diagnosis, a definite preoperative diagnosis is still difficult. Clinically, it is very similar to other benign breast masses. Uncertain clinical behavior and preoperative diagnoses results in inappropriate management. Axillary lymph nodes metastases are found only in <1% of patients.[10] The recurrence is the peculiar feature of the phyllodes and still there are no accurate clinicopathological factors that can predict recurrence and mortality.[11] Surgery remains the mainstay of management and options vary from wide local excision (WLE) to mastectomy. Optimal surgery is still a matter of debate, particularly in case of BL and malignant PT. The role of adjuvant radiotherapy and chemotherapy has been controversial.[12],[13],[14],[15]

However, we analyzed the clinicopathological factors, different treatment options, and outcome of treatment in a regional cancer center over a period of 12 years.


 » Methods Top


This is a retrospective observational study of 162 patients of PT, who were received surgical treatment between 2001 and 2012. All the clinical, investigational, operative, pathology details, and follow-up data were collected from patient records. The surgical interventions done varied from simple excision (lumpectomy) to modified radical or radical mastectomy (SM/RM/MRM). The surgical procedure was chosen based on clinical diagnosis, needle aspiration cytology, and the relative size of tumor compared with breast volume. The statistical analysis was done by using the Chi-square test with Yate correction; a P < 0.05 was considered statistically significant. Mean (standard deviation) was calculated for continuous variables.


 » Results Top


Among the total 162 patients, 95 (58.64%) were benign (B), 29 (18%) were BL, and 38 (23.45%) were malignant (M). The age of the patients ranged from 18 to 75 years, with a mean of 38 ± 8 years. The mean duration of having a lump was 28 ± 10 (2–64) months. The mean tumor size was 12 ± 5 (3–25) cm, among them, 28 (17%) tumors were <5 cm, 81 (50%) were between 5 and 10 cm, and 53 (33%) were >10 cm. Bilateral lesions were seen only in 3 patients (1.9%). All patients presented with single palpable lump in the breast. Fourteen patients had ulcers overlying the lump and 8 had bloody nipple discharge. Axillary lymphadenopathy was noted in 12 cases. The mean duration of follow-up was 3 years (range: 1–5 years).

Various surgical procedures were performed as lumpectomy, WLE, SM/RM/MRM in 49 (30%), 50 (31%), 42 (26%), and 21 (13%), respectively. For the benign phyllodes, lumpectomy was done in 42 (44%), WLE in 35 (37%), and SM in 18 (19%). In BL phyllodes, 14 (48%) patients underwent SM, lumpectomy in 5 (17%), and WLE in 10 (35%). In malignant phyllodes, MRM/RM was done in 21 (55%) patients [Table 2].
Table 2: Type of tumour versus type of surgery and recurrence with type of surgery

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Patients with tumor size <5 cm, all underwent either lumpectomy (57%) or WLE (43%) and lesion of size 5–10 cm, underwent lumpectomy in 33 (41%), WLE in 22 (27%), SM in 12 (15%), and MRM in 14 (17%). Large phyllodes mostly underwent mastectomy either SM (57%) or MRM/RM (13%), only 16 patients (30%) underwent WLE [Table 3].
Table 3: Tumour size versus type of surgery

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The overall recurrence rate in B, BL, and M phyllodes was 16% (15/95), 41.3% (12/29), and 55.6% (21/38), respectively. Recurrence rates were significantly higher in BL (41.3%) and malignant tumor (55.6%) compared to benign tumor (15.7%) (P = 0.00001) [Table 4]. Recurrence rate after lumpectomy (48.9%) was higher compared to WLE (22%), SM (23.8%), and MRM/RM (14.2%) (P = 0.004). On multivariate analysis, the association of recurrence rate with histology and type of surgery was not significant (P = 0.57) [Table 5]. Recurrence rate was higher with larger tumor (>10 cm) (45.28%) compared to smaller tumors of 5–10 cm (23.45%) and <5 cm (17.85%) (P = 0.008). On univariate analysis, the association between recurrence rate and size of the tumor was significant (P = 0.008). The number of recurrences were also higher in malignant phyllodes than benign and BL tumors which were statistically significant (P = 0.047). The association between the number of recurrences and size of the tumor was not significant (P = 0.63) [Table 6]. Systemic recurrences were also noted in 7 (18% of all recurrence) patients and the most common site was the lung (4 patients). Patients with systemic recurrence were died within 1 year after recurrence.
Table 4: Recurrence Rate and number of recurrences versus histologic type

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Table 5: Association of recurrence of tumour according to HPE of tumour and type of surgery

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Table 6: Recurrence Rate and number of recurrences versus size of tumour

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 » Discussion Top


PT of breast has been a challenge for surgeons due to its unpredictable clinical presentation, uncertain pathological behavior, and inaccurate preoperative diagnosis. Its unpredictable clinical course and high recurrence rate makes unique from other breast diseases, which leads to dilemma for treatment plan.[7] Pathologically, it is composed of stromal and epithelial tissue components and the stromal component predominantly determines the aggressive behavior of the tumor.[7] Numerous criteria have been proposed to classify tumor as benign or malignant, but only few were widely accepted. The criteria proposed by Azzopardi and Salvadori et al. were widely accepted and tumors were classified among benign, BL and malignant phyllodes.[16],[17]

The median age of presentation is 45 years which is slightly higher than our series (38 ± 8 years).[5],[16] The mean duration of presentation also varies with different countries which may be related to illiteracy, ignorance, poverty, and hesitation. In our study, it was 28 (2–64) months. The incidence of different histological variants reported varies in different studies. The incidence of benign phyllodes is 35–64% while for malignant tumors it is about 25%.[5],[8],[18] This trend was seen similar in our series. The suitable surgical procedure for phyllodes is as same as for the soft tissue sarcomas. However, the WLE is the minimal requirement to get the negative margins and minimize the recurrence. The adequate margin should be 1 cm in all three dimensions. The risk of margin positivity is higher with local surgery in comparison with radical which led to higher recurrence. The recurrence in benign cases may due to misdiagnosis with fibroadenoma that favors to only lumpectomy. In our series, the recurrence rate with lumpectomy (48.9%) was higher compared to WLE (22%), SM (23.8%), and MRM/RM (14.2%) (P = 0.004). That is why even though benign phyllodes are proportionately higher than BL and malignant phyllodes, the rate of recurrence is lower. The overall recurrence rate in phyllodes is reported as 19%, which is 10% lower than our series.[19] The mean duration of recurrence after treatment is variable. In our series, most of the recurrences occurred within 2 years.

The local recurrence is highest in malignant phyllodes as reported in few series as 20–40%.[5],[6] The systemic metastasis is also reported as 25–40%.[20],[21],[22],[23] In our series, systemic metastasis was seen in 7 (4.3%) patients and the lung was the most common site. The survival of these patients is very poor; mean survival was 4 months.

It is due to high mitotic rate, stromal atypia, and infiltrating margins. The rate of malignancy increases with age. In our series, we found that the age of malignant phyllodes cases was between 48 and 54 years. There must be a high index of suspicion when treating older women, and carcinoma must be ruled out. In our series, more than half of malignant phyllodes had local recurrence that proves the type of surgery performed; incomplete resection and histology are the crucial factors to predict the recurrence.

The fine needle aspiration cytology has low sensitivity to differentiate the type of histology as reported (72%) and the core needle biopsy is rarely advised for that due to low clinical suspicion of malignancy.[7] Role of imaging is debatable in diagnosis. Phyllodes and fibroadenomas have few similar mammographic and sonographic features. On mammography, PT have smooth, round to oval margin with lobulation. PT on ultrasonography shows lobulation, heterogeneous, hypoechoic internal echoes, and calcifications are absent.[24] Sonography cannot distinguish between different types of phyllodes tumors.[25] Hence, with inappropriate diagnosis, it is difficult to decide the type of surgery.

The size of lesion also affects the recurrence. The risk of incomplete resection is higher with larger tumors which led to higher recurrence. In our series, recurrence rate was higher with larger tumor size (>10 cm) (45.28%) compared to 5–10 cm (23.45%) and <5 cm (17.85%) (P = 0.008). The number of recurrences is also more with larger tumors and malignant histology. In our series, three or more recurrences occurred only with malignant phyllodes. Hence, the large and malignant phyllodes need more aggressive treatment, and surgery must be tailored according to the size and pathology of tumor. On multivariate analysis in our series, the relation of recurrence rates with histopathology of tumor to type of surgery was not statistically significant.

The incidence of axillary lymphadenopathy is reported as 20–25% (Bhargav et al., Chen et al. 2005), higher than our series (10%). Metastatic axillary lymph nodes were not found in our series, but it is reported as <1%.[7],[26] The decision to proceed with axillary lymph node dissection (ALND) should be according to age of patient, size, and characteristics of primary tumor and lymph nodes. Still, the role of ALND is not well defined.

The role of adjuvant radiotherapy and chemotherapy is not established. The adjuvant radiotherapy is considered for the high-risk phyllodes tumors such as large, unfavorable histological features, and recurrent.[27] Although the adjuvant chemotherapy with various regimes is in practice, the survival advantage is not yet proved. In our series, doxorubicin and ifosfamide were used in metastatic cases, which did not improve survival.

Phyllodes are the challenge to treat due to difficulty in making correct clinical and accurate preoperative diagnosis. WLE with negative margins should be the initial surgery for all PT. Mastectomy reduced local recurrence but failed to prevent distant recurrence in malignant phyllodes. Malignant phyllodes recurred more commonly than benign tumor after local excision. Type of surgery and pathology of tumor played a major role in outcome. Till date, there are no accurate clinicopathological factors that can predict the recurrence and mortality. The role of adjuvant radiotherapy and chemotherapy is uncertain, only considered in recurrent, malignant, and metastatic patients. ALND is rarely indicated. It is known for their unpredictable behavior and high recurrence rate, hence long-term follow-up is advised.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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