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  • Published: 09 January 2024

Margin status impact on recurrence of phyllodes tumors in high-risk groups: a retrospective observational study

  • Aliyeh Ranjbar 1 ,
  • Vahid Zangouri 1 , 2 &
  • Mansoureh Shokripour 3  

BMC Cancer volume  24 , Article number:  48 ( 2024 ) Cite this article

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Phyllodes tumor (PT) is an fibroepithelial tumor with potential for local recurrence. The optimal margin for surgical resection of PT is still debated, particularly in cases of positive margins. This study aimed to identify the risk factors for phyllodes tumor recurrence and the effect of a free margin on tumor recurrence by considering these risk factors.

Materials and methods

This is a retrospective observational study of patients diagnosed with PT who had undergone surgical management. The data were collected from medical records from 2001 to 2020 in the breast clinic of Shahid Motahhari Clinic of Shiraz. Patients were followed up for at least 3 years after the operation to be checked for local recurrence or distant metastasis at regular intervals.

This retrospective study included 319 patients with PT who underwent surgical management. Of these patients, 83.9% ( n  = 267), 7.6% ( n  = 24), and 8.5% ( n  = 27) were classified as benign, borderline, and malignant, respectively. 8.8% of all patients and 7.6% of non-malignant cases experienced local recurrence, and risk factors for recurrence included oral contraceptive use, smoking, size > 4 cm, stromal overgrowth, and stromal cell atypia. A negative surgical margin decreased the prevalence of recurrence in tumors > 4 cm and with stromal overgrowth significantly.

The study found that a negative margin in all patients did not reduce the recurrence rate in benign and borderline phyllodes tumors, suggesting close follow up as a reasonable alternative. However, a negative margin may be effective in reducing recurrence in certain high-risk groups.

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Introduction

Phyllodes tumors (PT) is a rare fibroepithelial breast tumor with an incidence ranging from 0.3 to 0.9%, primarily affecting women aged between 35 and 55 years [ 1 , 2 , 3 ]. It originates from the periductal stromal cells of the breast and is histologically characterized by increased stromal cellularity with leafy fronds [ 4 ]. The World Health Organization classifies this tumor into benign, borderline, or malignant based on its histological features [ 5 ], with the benign tumor being the most common grade, occurring in 60–75% of cases [ 6 ].

PT is often clinically and behaviorally similar to fibroadenomas of the breast, which are the most common benign breast tumors [ 4 , 7 ]. Mammography and breast ultrasound cannot distinguish phyllodes tumors from fibroadenomas [ 7 , 8 , 9 ], and fine-needle biopsy is often insufficient for diagnosis [ 7 , 10 , 11 , 12 ]. Consequently, phyllodes tumor is often diagnosed after excision, as it has poor preoperative diagnostic accuracy [ 13 ]. Historically, Phyllodes tumors have been known to have a high potential for local recurrence [ 13 , 14 , 15 , 16 ]. Traditionally, surgical margins were considered as the most important predictor of local recurrence, and a free margin of at least 1 cm was recommended to reduce recurrence [ 17 , 18 , 19 ]. However, multiple cohort studies have shown the lack of association between surgical margin width and local recurrence rates, questioning the need for negative margins in benign phyllodes tumors [ 20 , 21 , 22 , 23 ]. Although the National Comprehensive Cancer Network (NCCN) practice guidelines endorse surgical excision without obtaining surgical margins for benign phyllodes tumors [ 24 ]. However, wide-local excision with margins > 1 cm remains a standard practice in borderline and malignant PT [ 24 ].

Currently, the optimal margin for surgical resection of PT is still a topic of debate. In many medical centers, the standard practice for the management of close or positive margins in PT is to perform wide local excision and re-excision [ 25 , 26 ]. There is also evidence suggesting that achieving a clear surgical margin during the initial surgery can reduce the risk of tumor recurrence [ 27 ]. This study aims to identify the risk factors for phyllodes tumor recurrence and the effect of a free margin on tumor recurrence by considering these risk factors.

Patient and study design

This is a retrospective observational study of patients diagnosed with phyllodes tumors who had undergone surgical management. All patients referred to the breast clinic of Shahid Motahhari Clinic in Shiraz between 2001 and 2020 with a final diagnosis of phyllodes tumor was included in the study. The inclusion criteria were age between 18 and 80 years and a final diagnosis of phyllodes tumor. The exclusion criteria were a simultaneous diagnosis of other breast malignancies and serious medical illness that prevents the patients’ follow-up.

It is important to note that patients with malignant PT received adjuvant radiotherapy after surgery, while those with benign and borderline PT did not receive any additional treatment except surgery. Specifically, all patients with malignant PT received adjuvant radiotherapy for 15 sessions, 5 days per week, after surgery.

Data collection

Data were collected from medical records from 2001 to 2020 in the breast clinic of Shahid Motahhari Clinic of Shiraz. The data included age, past medical history, mammographic and ultrasonographic tumor characteristics, type of surgery (local excision, wide excision, mastectomy, re-excision after initial surgery), tumor size, and margin according to pathology reports. Slides were reviewed by a single expert pathologist to review the margin status and determine histological features such as histologic subtype (according to WHO classification), heterogeneous stroma, stromal overgrowth defined as stromal proliferation without epithelial elements observed in at least one low-power field (×4 microscope objective), stromal cell atypia, and mitotic rate. In this study, “Negative margin” means no tumor on ink.

Patient follow-up

All participants were checked for local recurrence (new tumor found in the ipsilateral breast) or distant metastasis at least 3 years after the operation. They were followed up at intervals of 4 months in the first year with ultrasonography and breast examination, and every 6 months in the second year. The duration of follow-up was annually. Additionally, mammography was done annually for patients over 35 years of age.

Statistical analysis

The statistical analysis was done using the Package for the Social Sciences (SPSS) 21 software. Parametric data are presented as mean ± standard deviation. Categorical values were compared using the chi-square or Fisher’s exact chi-square tests, and Student’s t-test was used for the comparison of continuous variables. Recurrence rates and recurrence-free probabilities were estimated using the Kaplan-Meier method. The association of variables with recurrence was evaluated using Cox proportional-hazard regression analysis and summarized with HR and 95% CI. Univariate and multivariate analysis models were used, and only factors found to be associated with recurrence in the univariate analysis were entered into the multivariate model. A p-value < 0.05 was considered statistically significant.

Ethics approval

This study was conducted in accordance with the principles established by the Declaration of Helsinki and obtained the approval of the Ethics Committee of Shiraz University of Medical Sciences (approval ID: IR.SUMS.MED.REC.1400.029).

Over the study period, 341 patients with a diagnosis of PT had undergone breast surgery. A total of 23 patients were excluded from the study, with 18 excluded due to incomplete medical records or follow-up and five due to a diagnosis of breast cancer during the follow-up period. This study comprised 319 patients with a mean age of 36.97 years and a mean follow-up period of 114.97 months.

22% ( n  = 70) of the lesions were sampled by Core needle biopsy (CNB). The most common pathological diagnosis on biopsy was a fibroepithelial lesion, which was present in 51.8% ( n  = 37) of CNBs. The others showed fibroadenomas in 28.6% ( n  = 20), phyllodes tumours in 15.7% ( n  = 11), and fibrocystic change in 2.9% ( n  = 2). The most commonly reported histologic subtype was benign (83.9%). 7.6% and 8.5% of the patients were of borderline and malignant histologic subtypes, respectively. The mean size of the mass was 4.57 cm, and the mean mitotic rate was 2.27 in 10 high-power fields (HPF). The type of breast surgery was mastectomy in 1.9%, breast-conserving surgery in 98.1%. Mastectomy was conducted in patients with malignant PT, characterized by a substantial tumor size occupying over half of the breast space, as it was impractical to achieve a clear margin in BCS. 39.4% of cases underwent second surgery. Totally, 52.8% of the cases had a negative surgical margin, and 47.2% of them had a positive surgical margin. All cases of malignant subtype had a negative surgical margin. In borderline and benign subtypes, 58.3% and 48.6% had a negative surgical margin. The demographics, imaging, and clinicopathologic characteristics of the study cohort are summarized in Table  1 .

From the overall study cohort, 28 (8.8%) reported local recurrence, and 290 (91.2%) did not. Distance recurrence was not found. Recurrence rate in benign, borderline, and malignant cases was 7.5%, 8.3%, and 22.2% respectively.

The relationship between tumor recurrence and tumor margin in all cases, as well as in benign and borderline cases separately was not significant ( p  > 0.05). In benign cases, the recurrence rate was 10.2% for positive margins and 4.6% for negative margins ( P  = 0.082). Similarly, in borderline cases, the recurrence rate was 10% for positive margins and 7.1% for negative margins ( p  = 0.803).

Patients who developed local recurrence experienced higher frequencies of oral contraceptive use, smoking, hyperechoic mass in sonography, malignant subtype, heterogeneous stroma, stromal overgrowth, and stromal cell atypia. Also, the mean size of the mass was larger, and the mean of mitotic rate was higher in patients who developed recurrence compared to the no recurrence group ( p  < 0.05). Cox regression analysis was performed to identify the predictors of local recurrence (Table  2 ). All possible risk factors were analyzed using the univariate regression model. Oral contraceptive use, smoking, hyperechoic mass in sonography, size > 4 cm, malignant subtype, mitotic rate > 2, presence of stromal overgrowth, and stromal cell atypia were the factors associated with recurrence. However, multivariate analysis demonstrated that oral contraceptive use (HR: 3.41; p  = 0.002), smoking (HR: 3.17; p  = 0.027), size > 4 cm (HR: 3.45; p  = 0.005), presence of stromal overgrowth (HR: 2.81; p  = 0.017), and presence of stromal cell atypia (HR: 3.65; p  = 0.026) were the independent predictors of recurrence.

The recurrence-free survival overall and stratified by the presence or absence of risk factors are demonstrated in Fig.  1 . The mean recurrence-free time was 259.99 months (95% CI: 251.43, 268.56 months). The mean time to recurrence was 32.07 months. The recurrence-free probability decreased with time; it was 97.2% after 1 year, 95.3% after 2 years, 92.1% after 3 years. The recurrence occurred in as early as 4 months and as late as 128 months postoperatively. Most of the recurrence (20 cases; 71.4%) occurred in the early postoperative 3 years. The mean recurrence-free survival times stratified by the presence or absence of risk factors are summarized in Table  3 .

figure 1

Kaplan-Meier survival plot of recurrence-free survival. Overall ( A ), and stratified by the presence or absence of risk factors: oral contraceptive use ( B ), smoking ( C ), size of mass ( D ), stromal overgrowth ( E ), and stromal cell atypia ( F )

The results of this study showed that the negative surgical margin decreased the prevalence of recurrence in the size of the mass > 4 cm and the presence of stromal overgrowth significantly ( p  = 0.015, p  = 0.017). The prevalence of recurrence according to surgical margin, stratified by the presence or absence of risk factors, is shown in Figs.  2 and 3 , indicating the recurrence-free survival, stratified by the negative and positive surgical margin in mass size > 4 cm and the presence of stromal overgrowth.

figure 2

Bar charts of prevalence of recurrence according to surgical margin. stratified by the presence or absence of risk factors: oral contraceptive use ( A ), smoking ( B ), size of mass > 4 cm ( C ), stromal overgrowth ( D ), and stromal cell atypia ( E )

figure 3

Kaplan-Meier survival plot of recurrence-free survival. stratified by the negative and positive surgical margin in mass size > 4 cm ( A ), and present of stromal overgrowth ( B )

Fibroepithelial lesions of the breast comprise a group of lesions ranging from fibroadenoma to malignant PT. The key difference in this group is the higher risk of recurrence in PT compared to fibroadenoma. NCCN guidelines were modified in 2021 and now recommend surgical excision without obtaining surgical margins for benign PT [ 24 ]. However, the latest published article suggests that having a free margin in the first surgery may be beneficial for reducing the recurrence rates [ 27 ]. This study aimed to identify the risk factors for PT recurrence and the effect of surgical margin on recurrence in patients with identified risk factors. Results showed a recurrence rate of 8.8%, and several factors, including oral contraceptive use, smoking, tumor size > 4 cm, malignant subtype, mitotic rate > 2, and the presence of stromal overgrowth and stromal cell atypia, were significantly associated with higher recurrence risk. Negative surgical margins may be beneficial in reducing the prevalence of recurrence in masses as large as 4 cm or with stromal overgrowth.

Our study demonstrated a recurrence rate of 8.8% at a median follow-up of 114.97 months. Recent studies have reported recurrence rates for PT ranging from 1.9 to 23.1% [ 20 , 25 , 28 , 29 ]. The differences in recurrence rates across studies could be attributed to variations in the prevalence of malignant PT and other associated risk factors. Our study indicated that the recurrence rates for borderline and benign PT were near. Previous studies have shown that the recurrence of borderline phyllodes tumours is more similar to benign PT than malignant one [ 30 , 31 , 32 ]. Most recent studies have reported recurrence rates for benign phyllodes tumours ranging from 5 to 10%, which is consistent with our findings. A meta-analysis by Lu et al. reported a recurrence rate of 8% for benign phyllodes tumours [ 31 ], and Tan et al. analyzed 440 cases of benign phyllodes tumours and reported a recurrence rate of 10.9% [ 33 ]. However, Moldoveanu et al. and Moo et al. reported lower recurrence rates of 3.7% and 1.9%, respectively [ 20 , 27 ].

The optimal management strategy for positive margins is still unclear. Of the 264 patients in our study with positive margins, just 39.4% ( n  = 104) underwent second surgery. Various studies have shown significant heterogeneity in margin management. Although older studies have recommended resection of tumors with wide margins [ 34 , 35 , 36 ], contemporary studies recommend a wait-and-watch approach [ 22 , 30 , 31 , 37 ]. In some studies, re-surgery in tumors with positive margins has been reported to have no effect on recurrence [ 20 ]. However, considering the low rate of recurrence and potential complications, poor cosmetic outcomes, and additional costs associated with unnecessary interventions, margin revision may not be reasonable for both benign and borderline phyllodes tumours. Nevertheless, due to the possibility of tumor subtype change in subsequent recurrences, re-surgery may be helpful in some patients with identified recurrence risk factors.

Investigating the relationship between clinical and pathological characteristics of patients with PT and their risk of local recurrence is crucial for better personalizing surgical management. Previous studies have identified larger tumor size, presence of heterologous elements, high stromal cellularity, and high mitotic rate as risk factors for local recurrence. In our study, we found that oral contraceptive use for more than 6 months and smoking were also associated with disease recurrence, which has not been mentioned in previous studies. Additionally, we confirmed that larger tumor size, malignant subtype, high mitotic rate, stromal overgrowth, and stromal cell atypia were the risk factors for relapse, which is consistent with the findings of similar studies [ 27 , 38 ]. Our study also revealed that tumors larger than 4 cm had a high risk of recurrence, and achieving a negative margin in this group of patients was significantly associated with a lower risk of recurrence. Notably, patients with stromal overgrowth who achieved a negative margin also had a significantly reduced risk of local recurrence.

Our study had several important limitations that should be acknowledged. First, the study population was small and limited to a single center, which may limit the generalizability of our findings to other populations or settings. Second, the study was retrospective in design, which means that data collection was based on past medical records, and there might be missing or incomplete data. This can introduce bias and limit the accuracy of the data collected. Although the follow-up interval was sufficient to capture most local recurrences, some may have been missed. Third, the radiology information of the patients was not performed by the radiologist of the unit and was extracted based on the report in the file; also, there was significant missing data in the radiology information. Fourth, the statistical methods used in the study might not have fully captured the complexity of the data. Therefore, the results of our study should be interpreted in the context of the available data and with caution. Prospective and multicenter studies are recommended for further investigation of the risk factors related to recurrence. Additionally, developing predictive models for recurrence risk could help identify high-risk patients who may benefit from a second surgery.

Conclusions

The management of benign and borderline phyllodes tumors remains challenging, with local recurrences having a significant impact on patient quality of life and economic consequences. Our study found that achieving a negative margin in all patients did not significantly reduce the recurrence rate. Therefore, careful observation with serial ultrasound imaging and clinical physical examinations may be a reasonable alternative to correcting the margin in most patients with benign and borderline PT. However, achieving a negative margin may be effective in reducing recurrence in certain high-risk groups, such as those with tumors larger than 4 cm or with excessive stromal growth.

Data availability

Data is available from the corresponding author upon reasonable request via email.

Reinfuss M, Mituś J, Duda K, Stelmach A, Ryś J, Smolak K. The treatment and prognosis of patients with phyllodes tumor of the breast: an analysis of 170 cases. Cancer: Interdisciplinary International Journal of the American Cancer Society. 1996;77(5):910–6.

Article   CAS   Google Scholar  

Guerrero MA, Ballard BR, Grau AM. Malignant phyllodes tumor of the breast: review of the literature and case report of stromal overgrowth. Surg Oncol. 2003;12(1):27–37.

Article   PubMed   Google Scholar  

Guillot E, Couturaud B, Reyal F, Curnier A, Ravinet J, Laé M, et al. Management of phyllodes breast tumors. Breast J. 2011;17(2):129–37.

Bennett IC, Khan A, De Freitas R, Chaudary MA, Millis RR. Phyllodes tumours: a clinicopathological review of 30 cases. Aust N Z J Surg. 1992;62(8):628–33. https://doi.org/10.1111/j.1445-2197.1992.tb07534.x . Epub 1992/08/01. PubMed PMID: 1322660.

Article   CAS   PubMed   Google Scholar  

The world Health Organization Histological Typing of Breast Tumors–Second Edition. The World Organization. Am J Clin Pathol. 1982;78(6):806–16. https://doi.org/10.1093/ajcp/78.6.806 . PubMed PMID: 7148748.

Article   Google Scholar  

Zhang Y, Kleer CG. Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates. Arch Pathol Lab Med. 2016;140(7):665– 71. Epub 2016/07/01. https://doi.org/10.5858/arpa.2016-0042-RA . PubMed PMID: 27362571.

Yilmaz E, Sal S, Lebe B. Differentiation of phyllodes tumors versus fibroadenomas: mammographic and sonographic features. Acta Radiol. 2002;43(1):34–9.

PubMed   Google Scholar  

Michaud P, Chave B, Lemaire B, Maitre F, Tescher M. Les tumeurs phyllodes du sein. Rev Fr Gynecol Obstet. 1989;84(12):944–9.

CAS   PubMed   Google Scholar  

Liberman L, Bonaccio E, Hamele-Bena D, Abramson AF, Cohen MA, Dershaw DD. Benign and malignant phyllodes tumors: mammographic and sonographic findings. Radiology. 1996;198(1):121–4.

Vos D, Mastboom W, De Vos R. Phyllodes tumor in the breast. Ned Tijdschr Geneeskd. 1998;142(13):716–21.

Iau P, Lim T, Png D, Tan W. Phyllodes tumour: an update of 40 cases. Ann Acad Med Singapore. 1998;27(2):200–3.

Shet T, Rege J. Cystic degeneration in phyllodes tumor. A source of error in cytologic interpretation. Acta Cytol. 2000;44(2):163–8.

Mangi AA, Smith BL, Gadd MA, Tanabe KK, Ott MJ, Souba WW. Surgical management of phyllodes tumors. Arch Surg. 1999;134(5):487–92. https://doi.org/10.1001/archsurg.134.5.487 . PubMed PMID: 10323420.

Rowell MD, Perry RR, Hsiu JG, Barranco SC. Phyllodes tumors. Am J Surg. 1993;165(3):376–9. https://doi.org/10.1016/s0002-9610(05)80849-9 . PubMed PMID: 8383473.

Sallusti E, Simonelli I, Marzullo A, Peis A, Modesti M. [The breast phyllodes tumor: surgical therapy following histological transformation. Case Report] G Chir. 2004;25(3):95–7. Epub 2004/07/01. PubMed PMID: 15224663.

Gabriele R, Borghese M, Corigliano N, Barbaro M, Conte M. Phyllodes tumor of the breast. Personal contribution of 21 cases. Il Giornale Di Chirurgia. 2000;21(11–12):453–6.

Mishra SP, Tiwary SK, Mishra M, Khanna AK. Phyllodes tumor of breast: a review article. ISRN Surg. 2013;2013:361469. https://doi.org/10.1155/2013/361469 . PubMed PMID: 23577269; PubMed Central PMCID: PMCPMC3615633.

Article   PubMed   PubMed Central   Google Scholar  

Mangi AA, Smith BL, Gadd MA, Tanabe KK, Ott MJ, Souba WW. Surgical management of phyllodes tumors. Arch Surg. 1999;134(5):487–93.

Kılıç MÖ, Terzioğlu SG, Bozkurt B, Dağlar G. Phyllodes Tumor of the breast: analysis of 48 patients. J Breast Health. 2016;12(4):158–64. https://doi.org/10.5152/tjbh.2016.3100 . PubMed PMID: 28331755.

Moo T-A, Alabdulkareem H, Tam A, Fontanet C, Lu Y, Landers A, et al. Association between recurrence and re-excision for close and positive margins versus observation in patients with benign phyllodes tumors. Ann Surg Oncol. 2017;24(10):3088–92.

Ouyang Q, Li S, Tan C, Zeng Y, Zhu L, Song E, et al. Benign phyllodes tumor of the breast diagnosed after ultrasound-guided vacuum-assisted biopsy: surgical excision or wait-and-watch? Ann Surg Oncol. 2016;23:1129–34.

Rosenberger LH, Thomas SM, Nimbkar SN, Hieken TJ, Ludwig KK, Jacobs LK, et al. Contemporary multi-institutional cohort of 550 cases of phyllodes tumors (2007–2017) demonstrates a need for more individualized margin guidelines. J Clin Oncol. 2021;39(3):178.

Genco IS, Purohit V, Hackman K, Ferreira L, Tugertimur B, Hajiyeva S. Benign and borderline phyllodes tumors of the breast: clinicopathologic analysis of 205 cases with emphasis on the surgical margin status and local recurrence rate. Annals of Diagnostic Pathology. 2021;51:151708.

Gradishar WJ, Moran MS, Abraham J, Aft R, Agnese D, Allison KH, et al. Breast cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2022;20(6):691–722.

Nair NS, Chitkara G, Hawaldar RW, Parmar V, Joshi S, Thakkar P, et al. En bloc excision of phyllodes tumor of the breast: radical approach heralds better outcome. Clin Breast Cancer. 2021;21(3):e228–e34.

Toussaint A, Piaget-Rossel R, Stormacq C, Mathevet P, Lepigeon K, Taffe P. Width of margins in phyllodes tumors of the breast: the controversy drags on?—a systematic review and meta-analysis. Breast Cancer Res Treat. 2021;185:21–37.

Moldoveanu D, Iny E, Theriault C, Florea A, Wong SM, Basik M, et al. Margin status and local recurrence in phyllodes tumours of the breast: a Canadian series. Ann Surg Oncol. 2023;30(3):1700–9.

Chao X, Jin X, Tan C, Sun P, Cui J, Hu H et al. Re-excision or wait and watch—a prediction model in breast phyllodes tumors after surgery. Annals of Translational Medicine. 2020;8(6).

Kim YY, Kim H, Kim WY, Chung JH, Lee JB, Woo SU. Under-and Normal-Weight Patients Are More Susceptible to Recurrence of Phyllodes Tumor. The Breast Journal. 2022;2022.

Borhani-Khomani K, Talman M-LM, Kroman N, Tvedskov TF. Risk of local recurrence of benign and borderline phyllodes tumors: a Danish population-based retrospective study. Ann Surg Oncol. 2016;23:1543–8.

Lu Y, Chen Y, Zhu L, Cartwright P, Song E, Jacobs L, et al. Local recurrence of benign, borderline, and malignant phyllodes tumors of the breast: a systematic review and meta-analysis. Ann Surg Oncol. 2019;26:1263–75.

Sharma A, Hyde K, Ferguson D. Benign and Borderline Phyllodes: management and Follow-Up: Phyllodes Management. Archives of Breast Cancer. 2022:398–400.

Tan EY, Hoon TP, Yong WS, Wong HB, Hui HG, Yeo AW, et al. Recurrent phyllodes tumours of the breast: pathological features and clinical implications. ANZ J Surg. 2006;76(6):476–80.

Wei J, Tan Y-T, Cai Y-C, Yuan Z-Y, Yang D, Wang S-S, et al. Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center. Chin J cancer. 2014;33(10):492.

PubMed   PubMed Central   Google Scholar  

Barth RJ. Histologic features predict local recurrence after breast conserving therapy of phyllodes tumors. Breast Cancer Res Treat. 1999;57:291–5.

Parker S, Harries S. Phyllodes tumours. Postgrad Med J. 2001;77(909):428–35.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Ji Y, Zhong Y, Zheng Y, Hu H, Min N, Wei Y, et al. Surgical management and prognosis of phyllodes tumors of the breast. Gland Surg. 2022;11(6):981.

Ravindhran B, Rajan S. Predictive factors of early recurrence in patients with phyllodes tumor of the breast. Eur J Breast Health. 2021;17(1):10.

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Acknowledgements

This study was extracted from the dissertation which was written by Aliyeh Ranjbar for the degree of Doctor of Medicine (thesis no. 20039). The authors would like to thank Shiraz University of Medical Sciences, Shiraz, Iran and also Center for Development of Clinical Research of Nemazee Hospital and Dr. Nasrin Shokrpour for editorial assistance.

The project was funded by Vice Chancellor for Research of the Shiraz University of Medical Science [Grant No. 99-01-01-22758].

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V.Z., A.R., and M.Sh.: conceptualized the data. M.Sh., and A.R.: curated the data. A.R.: wrote the original draft. V.Z.: edited the draft. All authors reviewed the manuscript.

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Correspondence to Vahid Zangouri or Mansoureh Shokripour .

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This study was conducted in accordance with the principles established by the Declaration of Helsinki and obtained the approval of the Ethics Committee of Shiraz University of Medical Sciences (approval ID: IR.SUMS.MED.REC.1400.029). Informed consent was obtained and signed by all study participants prior to recruitment.

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Ranjbar, A., Zangouri, V. & Shokripour, M. Margin status impact on recurrence of phyllodes tumors in high-risk groups: a retrospective observational study. BMC Cancer 24 , 48 (2024). https://doi.org/10.1186/s12885-023-11805-2

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Received : 14 August 2023

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DOI : https://doi.org/10.1186/s12885-023-11805-2

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  • Phyllodes tumour
  • Local recurrence
  • Surgical margins
  • Risk factor

ISSN: 1471-2407

thesis on phyllodes tumor

thesis on phyllodes tumor

  • Vol 11, No 3 (March 24, 2022) /

Surgical management in phyllodes tumors of the breast: a systematic review and meta-analysis

Yufan Wei 1,2# , Yanying Yu 3# , Yashuang Ji 4 , Yuting Zhong 2,5 , Ningning Min 1,2 , Huayu Hu 1,2 , Qingyu Guan 1,2 , Xiru Li 2

1 School of Medicine , Nankai University , Tianjin , China ; 2 Department of General Surgery , The First Medical Center of Chinese PLA General Hospital , Beijing , China ; 3 Eight-Year MD Program, Peking Union Medical College , Chinese Academy of Medical Sciences , Beijing , China ; 4 Department of Galactophore Surgery , Tongzhou District Hospital of Integrated TCM & Western Medicine , Beijing , China ; 5 Medical School of Chinese PLA , Beijing , China

Contributions: (I) Conception and design: X Li, Y Wei; (II) Administrative support: X Li; (III) Provision of study materials or patients: X Li; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

# These authors contributed equally to this work.

Background: Information is still controversial in the studies regarding the current optimal surgical management of phyllodes tumors (PTs) of the breast. Local recurrence (LR) may occur with an upgraded in the pathological grade, influencing the prognosis of patients with PT. This systematic review and meta-analysis aimed to investigate the association of LR risk with margin status and margin width which could have significant implications on the surgical management of PT.

Methods: Independent and comprehensive searches were performed by two authors through five databases including PubMed, Medline, Embase, ScienceDirect and Cochrane Library from January 1990 to October 2021. Studies investigating the association between margin width, margin status and LR rates were considered for inclusion. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed using RevMan5.3 software, and statistical heterogeneity was assessed using the Chi-square test and quantified using the I 2 statistic. Visual inspection of funnel plots was used to judge publication bias.

Results: A total of 34 articles were included in this article, all of which with NOS scores above 5. Regardless of the PT grade, positive margin significantly increased the risk of LR [odds ratio (OR) 3.64, 95% confidence interval (CI): 2.60–5.12]. No significant difference was found in the risk of LR between the margins <1 and ≥1 cm (OR 1.39, 95% CI: 0.67–2.92). For benign and borderline PTs, there were no significant differences of the LR risk between breast-conserving surgery (BCS) and mastectomy (benign OR 0.68, 95% CI: 0.12–3.78; borderline OR 1.14, 95% CI: 0.29–4.51). While the LR risk was significantly increased by BCS for malignant PT (OR 2.77, 95% CI: 1.33–5.74).

Discussion: Different surgical management strategies should be considered for different PT grades. BCS was a feasible option and margins <1 cm was not significantly associated with LR risk for all grade of PT. After BCS, benign PT with positive margin could adopt the “wait and watch” strategy with regular follow-up, while borderline and malignant PTs were expected to underwent re-excision to ensure negative margins. More studies are still needed to clarify and update the existing conclusions and improve the prognosis of PT patients.

Keywords: Phyllodes tumors of the breast; surgical management; margin; local recurrence (LR); systematic review and meta-analysis

Submitted Nov 22, 2021. Accepted for publication Jan 24, 2022.

doi: 10.21037/gs-21-789

Introduction

Phyllodes tumors (PTs) of the breast are uncommon fibroepithelial lesions (FELs), accounting for about 0.3–1% of breast tumors and 2–3% of FELs ( 1 , 2 ). This disease was first reported by Johannes Müller in 1838 and called cystosarcoma phyllodes ( 3 ). Since then, up to 60 names have been reported such as pseudosarcomatoid adenoma and carcinosarcoma. In 1982, the World Health Organization (WHO) officially named it as PT, and divided it into three grades including benign, borderline and malignant. Studies have shown that LR might occur in every grade with the rate of 10–17%, 14–25% and 23–30% respectively. Some recurrent cases could also have an upgrading of the pathological grade ( 4 ). It is of great significance to achieve effective resection of PT for reducing the rate of local recurrence (LR) and prolonging the disease-free survival of patients.

Margin width and status are two important factors affecting the prognosis. Previously, National Comprehensive Cancer Network (NCCN) guidelines recommended a margin of at least 1cm regardless of tumor grade with many studies supporting, including a meta-analysis conducted by Toussaint et al. ( 2 , 5 - 9 ). While some studies investigated that for benign PT, no significant difference of LR between <1 and ≥1 cm margins was found ( 10 ). Thind et al. even indicated that margin <1 cm was also acceptable for borderline and malignant PTs ( 11 ). As for margin status, some studies suggested that positive margin was significantly related to the increase of LR risk ( 12 , 13 ). However, Lu et al. proposed that margin status was only found to be associated with LR risk for malignant PT ( 14 ).

Surgical management of breast-conserving surgery (BCS) and mastectomy is still controversial as the main treatment of PT. Studies have shown that for benign and borderline PT, wide local excision (WLE) can reduce the LR rate from 21–46% to 8–29% ( 15 , 16 ). However, some studies indicated that regular follow-up was adequate since the LR rate of benign PT with positive margin was very low. And re-excision was only suitable for borderline and malignant PTs if safe margin <1 cm ( 17 ). Recently, a retrospective study of 550 cases by Rosenberger et al. found that ensuring a wider margin had nothing to do with reducing the risk of LR. They proposed that re-excision was not necessary for benign PT to ensure negative margin and suggested a revision of NCCN guidelines ( 18 ). In 2021, the fourth edition of NCCN guidelines modified the treatment option of benign PT from WLE to observation after excisional biopsy ( 19 ).

The object of this study is to explore the correlation between margin status, margin width, surgical treatment and LR risk for different grade of PT, supposing to contribute to the formulation of surgical method of PT and improve the prognosis of patients. We presented the following article in accordance with the PRISMA reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-21-789/rc ).

This study has been registered in the International Prospective Register of Systematic Reviews ‘PROSPERO’ database (ID: CRD42021292859).

Eligibility criteria

The literature included in this study contained prospective or retrospective studies of female patients diagnosed pathologically with primary breast PTs. The cases included in the literature should be reviewed by pathologists which clearly report the tumor grade, surgical margins (margin width or margin status), and LR rate. For surgical margins, literature that only reported the surgical process (lumpectomy, WLE, or mastectomy, etc.) without precise definition of margin width and positive or negative criteria for margins should be excluded. If the margin information was only evaluated in patients treated by BCS, then the number of mastectomy cases was subtracted from the total number of cases. If a re-excision was performed, the margin was determined by the information of the last operation. To reduce publication bias, studies only included margin status and with fewer than 50 cases were also excluded. In addition, we only included research articles published in English. All case reports, reviews and comments were excluded.

Search strategy

A three steps search strategy was performed in this study. First, we searched the MeSH terms and free terms of PT, surgical margin and LR in PubMed database, and formulated corresponding search strategies according to the search methods of different databases. A full search strategy was detailed in Appendix 1 . Then, a comprehensive second search was conducted through the five databases including PubMed, Medline, Embase, ScienceDirect, and Cochrane Library for the articles published between January 1990 and October 2021. Finally, the retrieved studies were screened for follow-up research.

Selection of studies

All retrieved articles were uploaded for screening with the duplicate studies deleted. Then, two authors conducted independent screening based on the title and abstract of the literature, and initially deleted the literature that did not meet the inclusion criteria. Finally, the full texts were read in detail and the included studies were confirmed. The disagreement between the two authors in the process of selection was resolved through discussion or discussion with the third author.

Assessment of methodological quality

All the included studies were independently evaluated for methodological quality by two authors using the modified NOS, which mainly included three modules (subject selection, comparability, and exposure/outcome). Scores were assigned in the form of ‘*’. The final score was among 0–9 points.

Data extraction

The two authors independently extracted the data at the same time, and confirmed the final data through comparison and review. The extraction data included the author’s name, publication year, the basic information of the included cases (nationality, age, and the total number of cases), the pathological classification of the cases, the surgical treatment, and the follow-up time to form a table of the features of included literature. The margin status, margin width, the surgical treatment and LR of different grades were extracted for subsequent analysis. All the extracted data was input into the Microsoft Excel database. Funnel plots were drawn to assess the publication bias.

Statistical analysis

The analyses were performed using Review Manager 5.3 (Cochrane Collaboration, Oxford, UK). The odds ratios (OR) were used to compare dichotomous variables and all results were reported with 95% confidence intervals (CIs). The random effects model was used to analyze the pooled data. Sensitivity analysis was carried out by deleting a study every time and checking whether the effect size changed. Statistical heterogeneity between studies was assessed using the Chi-square test and quantified using the I 2 statistic. A significant statistical difference was considered when P<0.05.

Literature search results

A total of 1,089 articles were retrieved in this study with 274 duplicate articles eliminated. By reading the title of the article, searching the full text, and rigorously screening according to the inclusion and exclusion criteria, 34 articles were finally included for subsequent research and analysis. A PRISMA flow diagram summarizing the process of literature selection were presented in Figure 1 . All studies included had a quality score of 5 or higher were considered to have good quality ( Table S1 ).

thesis on phyllodes tumor

Characteristics of the included studies

All 34 articles included in this study were retrospective studies, including 6,431 patients from 1944 to 2019 ( Table 1 ). Among them, 3,898 cases were benign, 1,322 were borderline, and 1,221 were malignant. The age of the patients was the median or average age which ranged from 34 to 51 years old. Surgical treatment included BCS and mastectomy, with 4,779 cases and 803 cases respectively. The median follow-up time was between 19.2 and 120 months.

a , age is represented by the average or the median age of the study. b , the median follow-up time was 15.48 months for benign, 59.88 months for borderline, and 65.05 months for malignant PTs. BCS, breast conservative surgery; M, mastectomy; n/a, not available; PTs, phyllodes tumors.

Margin status

A total of 26 articles evaluated the correlation between surgical margin status (positive or negative) and LR risk. Overall, compared with negative margins, positive margins could significantly increase the risk of LR (OR 3.64; 95% CI: 2.60–5.12) ( Figure 2 ). Ten, eight and eight studies reported LR rates for the benign, borderline and malignant PTs ( Figure S1 ). A positive margin was significantly associated with a high LR risk regardless of tumor grade (benign OR 3.32, 95% CI: 1.18–9.34; borderline OR 2.88, 95% CI: 1.16–7.14 and malignant OR 4.70, 95% CI: 1.63–13.62).

thesis on phyllodes tumor

Margin width

Most studies still use 1 cm as the boundary to explore the impact of margin width on the risk of LR. Pooling of data from 14 studies showed no significant difference in the LR risk between patients with margin ≥1 and <1 cm (OR 1.39, 95% CI: 0.67–2.92) ( Figure 3 ). The subgroup analysis included 10 studies for benign, 9 studies for borderline, and 9 studies for malignant PT. The results showed that there was no significant difference in the LR risk between margin width <1 and ≥1 cm in all subgroup analysis (benign OR 1.19, 95% CI: 0.57–2.48; borderline OR 1.37, 95% CI: 0.42–4.47 and malignant OR 2.15, 95% CI: 0.64–7.19) ( Figure S2 ). The borderline and malignant PTs were combined and analyzed with a total of 13 articles included. No significant difference in the LR risk of the margin width between the two groups was found (OR 1.68, 95% CI: 0.81–3.47) ( Figure S3 ).

thesis on phyllodes tumor

Surgical treatment

A total of 15 studies which contained LR rates for different surgical treatments were extracted. Four, five and six studies reported LR rates for the benign, borderline, and malignant PTs respectively ( Figure 4 ). No significant difference between BCS and mastectomy in benign and borderline PT were found (benign OR 0.68, 95% CI: 0.12–3.78; borderline OR 1.14, 95% CI: 0.29–4.51). But BCS was significantly associated with a higher LR risk for malignant PT (OR 2.77, 95% CI: 1.33–5.74).

thesis on phyllodes tumor

Sensitivity analysis and publication bias

All studies carried out sensitivity analysis and publication bias analysis. Exclusion of Motte et al. or Li et al. , as part of the sensitivity analysis, achieved no statistical significance between positive and negative margin for benign PT (Motte exclusion: OR 2.66, 95% CI: 0.99–7.18; Li exclusion: OR 2.64, 95% CI: 0.85–8.22). After Li et al. or Wen et al. was excluded, the LR risk achieved no statistically difference between different margin status for borderline PT (Li exclusion: OR 2.13, 95% CI: 0.71–6.43; Wen exclusion: OR 2.43, 95% CI: 0.96–6.17). The rest of the analysis showed no significant changes in outcomes. No obvious publication bias was observed in the funnel plots ( Figures S4,S5 ). No significant heterogeneity was statistical in this study.

In this systematic review and meta-analysis grounded on a total of 6,431 patients from 34 studies, we assessed the correlation of margin, surgical treatment and LR risk for different grade of PT.

For benign PT, no significant difference in the LR rate between margin <1 and ≥1 cm and BCS and mastectomy was found, suggesting that BCS even lumpectomy was adequate for benign PT. As for margin status, we found a significant correlation between positive margin and LR risk, indicating that benign PT with positive margin required re-excision to reduce LR risk. Many studies concluded the same results ( 8 , 26 , 46 , 47 ). While some studies suggested that margin status was related to LR only in terms of malignant PT and whether benign PT with positive margins need further resection still required further exploration ( 14 ). Shaaban et al. reviewed cases of benign PT and indicated that positive margins increased the LR rate. However, in view of the low LR rate of benign PT with positive resection margin (12.9%), the strategy of “wait and see” could still be adopted, and re-excision is only applicable for borderline and malignant PTs ( 10 ). Moo et al. performed a study of 246 benign PT patients with positive margins and found no significant difference in LR between patients underwent re-excision and observation ( 33 ). Since the benefits of re-excision on the prognosis of the patient are uncertain and a second operation may bring psychological pressure or cosmetic damage to the patients, “wait and watch” strategy with regular following-up may be an optimal option for benign PT with positive margin.

For borderline PT, we found no significant correlation of LR risk neither with margin width nor surgical treatment, indicating that BCS with a margin less than 1 cm might be feasible for borderline PT. Ogunbiyi et al. also found that margin ≥1 and <1 cm had no significant difference in the LR risk for borderline PT, which was consistent with the result of this study ( 48 ). Thind et al. conducted a systematic review and meta-analysis on borderline and malignant PTs, and proposed that the correlation between margin width and LR was not statistically different as well ( 11 ). However, there were also studies indicated that borderline PT was resemble to malignant PT in terms of chromosomal variation and gene mutation and suggested that borderline PT should be given the same attention as malignant PT in making surgical decision ( 14 , 49 , 50 ). Barth et al. found that 12/50 (24%) borderline PT locally recurred and indicated BCS with negative margins was not enough for borderline PT to meet a good prognosis ( 51 ). Whether the 1 cm margin is sufficient for borderline PT is still controversial with more cases to supplement.

As for malignant PT, no significant difference in the LR rate between margin ≥1 and <1 cm was found which was consistent with the meta-analysis conducted by Thind et al. ( 11 ). Some studies also indicated that there was no real advantage to obtain ≥1 cm margins as thinner surgical excisions did not impact LR and the disease-free survival ( 13 , 28 , 35 ). Neron et al. conducted a multicenter nationwide retrospective study of malignant PT and suggested that a 3 mm threshold was sufficient with no impact of wide margins on overall-survival ( 52 ). However, the vast majority of studies still recommended WLE with margins ≥1 cm and more studies were needed to identify a precise margin threshold ( 12 , 27 , 53 - 55 ). A clearly correlation between positive margin and LR risk was found in terms of margin status. Re-excision was required for malignant PT to obtain negative margin and reduce LR risk ( 12 , 56 , 57 ). In this study, mastectomy was found having a positive impact on LR risk than BCS which was probably linked to the surgical procedure indicated by Neron et al. , that is, en bloc resection along the muscle fascia ( 52 ). Mastectomy should be recommended in the situations where the tumor was too large or if the inability to obtain negative margin to reduce LR risk ( 7 , 58 ).

This study also had some limitations. The studies included were all retrospective studies, and there were only few articles that could be analyzed in the subgroup analysis. Studies are still needed to confirm the reliability of the conclusions. Meanwhile, few studies on <1 and 1–10 mm margins were reported, causing it impossible to evaluate the impact of this threshold on LR risk. In addition, by sensitivity analysis, we found that the correlation between the margin status and LR rate was not statistically significant after the exclusion of some individual studies for benign and borderline PTs. More studies on margin status need to be updated in the future research.

Conclusions

Different surgical management strategies should be considered for different PT grades. Regardless of the tumor grade, there was a significant correlation between positive margin and LR risk. And BCS was a feasible option as margins <1 cm was not significantly associated with LR risk. After BCS, “wait and watch” strategy was adequate for benign PT with positive margin, while borderline and malignant PTs were expected to underwent re-excision to ensure negative margins. Mastectomy was recommended in the situations where the tumor was too large or if the inability to obtain negative margin to reduce LR risk. At present, more retrospective or prospective studies are still needed to clarify and update the existing conclusions and improve the prognosis of PT patients.

Acknowledgments

Funding : None.

Reporting Checklist : The authors have completed the PRISMA reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-21-789/rc

Peer Review File : Available at https://gs.amegroups.com/article/view/10.21037/gs-21-789/prf

Conflicts of Interest : All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-21-789/coif ). XL serves as an Editor-in-Chief of Gland Surgery from May 2012 to April 2022. The other authors have no conflicts of interest to declare.

Ethical Statement : The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/ .

  • Zhang Y, Kleer CG. Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates. Arch Pathol Lab Med 2016;140:665-71. [ Crossref ] [ PubMed ]
  • Toussaint A, Piaget-Rossel R, Stormacq C, et al. Width of margins in phyllodes tumors of the breast: the controversy drags on?-a systematic review and meta-analysis. Breast Cancer Res Treat 2021;185:21-37. [ Crossref ] [ PubMed ]
  • J. M. Uber den feineren Ban und Die Formen der Krankaften Geschwulste. Germany: Greiner 1838:54-7.
  • Lakhani S, Ellis I, Schnitt S, et al. World Health Organization Classification of Tumours, Volume 2: Breast Tumours (ed 5). Lyon, France, IARC Press. 2019. Available online: https://www.iarc.who.int/news-events/who-classification-of-tumours-5th-edition-volume-2-breast-tumours/
  • Gradishar WJ, Anderson BO, Abraham J, et al. Breast Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2020;18:452-78. [ Crossref ] [ PubMed ]
  • Mangi AA, Smith BL, Gadd MA, et al. Surgical management of phyllodes tumors. Arch Surg 1999;134:487-92; discussion 492-3. [ Crossref ] [ PubMed ]
  • Kapiris I, Nasiri N, A'Hern R, et al. Outcome and predictive factors of local recurrence and distant metastases following primary surgical treatment of high-grade malignant phyllodes tumours of the breast. Eur J Surg Oncol 2001;27:723-30. [ Crossref ] [ PubMed ]
  • Chen WH, Cheng SP, Tzen CY, et al. Surgical treatment of phyllodes tumors of the breast: retrospective review of 172 cases. J Surg Oncol 2005;91:185-94. [ Crossref ] [ PubMed ]
  • Abdalla HM, Sakr MA. Predictive factors of local recurrence and survival following primary surgical treatment of phyllodes tumors of the breast. J Egypt Natl Canc Inst 2006;18:125-33. [ PubMed ]
  • Shaaban M, Barthelmes L. Benign phyllodes tumours of the breast: (Over) treatment of margins - A literature review. Eur J Surg Oncol 2017;43:1186-90. [ Crossref ] [ PubMed ]
  • Thind A, Patel B, Thind K, et al. Surgical margins for borderline and malignant phyllodes tumours. Ann R Coll Surg Engl 2020;102:165-73. [ Crossref ] [ PubMed ]
  • Kim S, Kim JY, Kim DH, et al. Analysis of phyllodes tumor recurrence according to the histologic grade. Breast Cancer Res Treat 2013;141:353-63. [ Crossref ] [ PubMed ]
  • Jang JH, Choi MY, Lee SK, et al. Clinicopathologic risk factors for the local recurrence of phyllodes tumors of the breast. Ann Surg Oncol 2012;19:2612-7. [ Crossref ] [ PubMed ]
  • Lu Y, Chen Y, Zhu L, et al. Local Recurrence of Benign, Borderline, and Malignant Phyllodes Tumors of the Breast: A Systematic Review and Meta-analysis. Ann Surg Oncol 2019;26:1263-75. [ Crossref ] [ PubMed ]
  • Borhani-Khomani K, Talman ML, Kroman N, et al. Risk of Local Recurrence of Benign and Borderline Phyllodes Tumors: A Danish Population-Based Retrospective Study. Ann Surg Oncol 2016;23:1543-8. [ Crossref ] [ PubMed ]
  • Barth RJ Jr. Histologic features predict local recurrence after breast conserving therapy of phyllodes tumors. Breast Cancer Res Treat 1999;57:291-5. [ Crossref ] [ PubMed ]
  • Chen K, Chen Y, Cartwright P, et al. Optimizing Surgical Treatment for Phyllodes Tumor. Curr Breast Cancer Rep 2018;10:55-61. [ Crossref ]
  • Rosenberger LH, Thomas SM, Nimbkar SN, et al. Contemporary Multi-Institutional Cohort of 550 Cases of Phyllodes Tumors (2007-2017) Demonstrates a Need for More Individualized Margin Guidelines. J Clin Oncol 2021;39:178-89. [ Crossref ] [ PubMed ]
  • Gradishar WJ, Moran MS, Abraham J, et al. Breast Cancer, Version 4.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; [ Crossref ]
  • Chaney AW, Pollack A, McNeese MD, et al. Primary treatment of cystosarcoma phyllodes of the breast. Cancer 2000;89:1502-11. [ Crossref ] [ PubMed ]
  • Sotheran W, Domjan J, Jeffrey M, et al. Phyllodes tumours of the breast--a retrospective study from 1982-2000 of 50 cases in Portsmouth. Ann R Coll Surg Engl 2005;87:339-44. [ Crossref ] [ PubMed ]
  • Tan PH, Jayabaskar T, Chuah KL, et al. Phyllodes tumors of the breast: the role of pathologic parameters. Am J Clin Pathol 2005;123:529-40. [ Crossref ] [ PubMed ]
  • Akin M, Irkorucu O, Koksal H, et al. Phyllodes tumor of the breast; a case series. Bratisl Lek Listy 2010;111:271-4. [ PubMed ]
  • Jung CW, Suh KS, Lee J, et al. Mutation-Free Expression of c-Kit and PDGFRA in Phyllodes Tumors of the Breast. J Breast Cancer 2010;13:257. [ Crossref ]
  • Tsang JY, Mendoza P, Putti TC, et al. E-cadherin expression in the epithelial components of mammary phyllodes tumors. Hum Pathol 2012;43:2117-23. [ Crossref ] [ PubMed ]
  • Spitaleri G, Toesca A, Botteri E, et al. Breast phyllodes tumor: a review of literature and a single center retrospective series analysis. Crit Rev Oncol Hematol 2013;88:427-36. [ Crossref ] [ PubMed ]
  • Wei J, Tan YT, Cai YC, et al. Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center. Chin J Cancer 2014;33:492-500. [ Crossref ] [ PubMed ]
  • Onkendi EO, Jimenez RE, Spears GM, et al. Surgical treatment of borderline and malignant phyllodes tumors: the effect of the extent of resection and tumor characteristics on patient outcome. Ann Surg Oncol 2014;21:3304-9. [ Crossref ] [ PubMed ]
  • Yom CK, Han W, Kim SW, et al. Reappraisal of conventional risk stratification for local recurrence based on clinical outcomes in 285 resected phyllodes tumors of the breast. Ann Surg Oncol 2015;22:2912-8. [ Crossref ] [ PubMed ]
  • Bellezza G, Prosperi E, Del Sordo R, et al. IMP3 Is Strongly Expressed in Malignant Phyllodes Tumors of the Breast: An Immunohistochemical Study. Int J Surg Pathol 2016;24:37-42. [ Crossref ] [ PubMed ]
  • Moutte A, Chopin N, Faure C, et al. Surgical Management of Benign and Borderline Phyllodes Tumors of the Breast. Breast J 2016;22:547-52. [ Crossref ] [ PubMed ]
  • Ruvalcaba-Limón E, Jiménez-López J, Bautista-Piña V, et al. Phyllodes Tumor of the Breast: 307 Treated Cases, the Largest Mexican Experience at a Single Breast Disease Institution. Iran J Pathol 2016;11:399-408. [ PubMed ]
  • Moo TA, Alabdulkareem H, Tam A, et al. Association Between Recurrence and Re-Excision for Close and Positive Margins Versus Observation in Patients with Benign Phyllodes Tumors. Ann Surg Oncol 2017;24:3088-92. [ Crossref ] [ PubMed ]
  • Rodrigues MF, Truong PT, Weir LM, et al. Phyllodes tumours of the breast: The British Columbia cancer agency experience. Cancer Research 2017;77.
  • Tremblay-LeMay R, Hogue JC, Provencher L, et al. How Wide Should Margins Be for Phyllodes Tumors of the Breast? Breast J 2017;23:315-22. [ Crossref ] [ PubMed ]
  • Chng TW, Gudi M, Lim SH, et al. Validation of the Singapore nomogram for outcome prediction in breast phyllodes tumours in a large patient cohort. J Clin Pathol 2018;71:125-8. [ Crossref ] [ PubMed ]
  • Choi N, Kim K, Shin KH, et al. Malignant and borderline phyllodes tumors of the breast: a multicenter study of 362 patients (KROG 16-08). Breast Cancer Res Treat 2018;171:335-44. [ Crossref ] [ PubMed ]
  • Sevinç Aİ, Aksoy SÖ, Güray Durak M, et al. Is the extent of surgical resection important in patient outcome in benign and borderline phyllodes tumors of the breast? Turk J Med Sci 2018;48:28-33. [ Crossref ] [ PubMed ]
  • Mitus JW, Blecharz P, Jakubowicz J, et al. Phyllodes tumors of the breast. The treatment results for 340 patients from a single cancer centre. Breast 2019;43:85-90. [ Crossref ] [ PubMed ]
  • Zhou Z, Wang CC, Sun XJ, et al. Prognostic Factors and Local Recurrence Pattern in Breast Phyllodes Tumors: A Nomogram Based on Retrospective Cohort Study of 404 Cases. Int J Radiat Oncol Biol Phys 2018;99:E60-1. [ Crossref ]
  • Gulben K, Öndeş B, Berberoglu U. Factors Affecting Local Recurrence for Phyllodes Tumors of the Breast: a Retrospective Analysis of 89 Patients in a Single Center. Indian Journal of Surgery 2019. Available online: https://www.semanticscholar.org/paper/Factors-Affecting-Local-Recurrence-for-Phyllodes-of-G%C3%BClben-%C3%96nde%C5%9F/468e0f5d925cd58bcf2f807b7998568c00b3c3e3
  • Li J, Tsang JY, Chen C, et al. Predicting Outcome in Mammary Phyllodes Tumors: Relevance of Clinicopathological Features. Ann Surg Oncol 2019;26:2747-58. [ Crossref ] [ PubMed ]
  • Wen B, Mousadoust D, Warburton R, et al. Phyllodes tumours of the breast: Outcomes and recurrence after excision. Am J Surg 2020;219:790-4. [ Crossref ] [ PubMed ]
  • Genco IS, Purohit V, Hackman K, et al. Benign and borderline phyllodes tumors of the breast: Clinicopathologic analysis of 205 cases with emphasis on the surgical margin status and local recurrence rate. Ann Diagn Pathol 2021;51:151708. [ Crossref ] [ PubMed ]
  • Lim RS, Cordeiro E, Lau J, et al. Phyllodes Tumors-The Predictors and Detection of Recurrence. Can Assoc Radiol J 2021;72:251-7. [ Crossref ] [ PubMed ]
  • Ben Hassouna J, Damak T, Gamoudi A, et al. Phyllodes tumors of the breast: a case series of 106 patients. Am J Surg 2006;192:141-7. [ Crossref ] [ PubMed ]
  • Spanheimer PM, Murray MP, Zabor EC, et al. Long-Term Outcomes After Surgical Treatment of Malignant/Borderline Phyllodes Tumors of the Breast. Ann Surg Oncol 2019;26:2136-43. [ Crossref ] [ PubMed ]
  • Ogunbiyi S, Perry A, Jakate K, et al. Phyllodes tumour of the breast and margins: How much is enough Can J Surg 2019;62:E19-21. [ Crossref ] [ PubMed ]
  • Tan J, Ong CK, Lim WK, et al. Genomic landscapes of breast fibroepithelial tumors. Nat Genet 2015;47:1341-5. [ Crossref ] [ PubMed ]
  • Laé M, La Rosa P, Mandel J, et al. Whole-genome profiling helps to classify phyllodes tumours of the breast. J Clin Pathol 2016;69:1081-7. [ Crossref ] [ PubMed ]
  • Barth JR Jr. Margin negative, breast conserving resection: adequate for benign phyllodes tumors, but inadequate therapy for borderline and malignant phyllodes tumors. Breast Cancer Res Treat 2013;142:463-4. [ Crossref ] [ PubMed ]
  • Neron M, Sajous C, Thezenas S, et al. Surgical Margins and Adjuvant Therapies in Malignant Phyllodes Tumors of the Breast: A Multicenter Retrospective Study. Ann Surg Oncol 2020;27:1818-27. [ Crossref ] [ PubMed ]
  • Narayanakar RP, Gangaiah DM, Althaf S, et al. Cystosarcoma phyllodes: Pathological enigma: A retrospective review of 162 cases. Indian J Cancer 2015;52:365-8. [ Crossref ] [ PubMed ]
  • Mituś J, Reinfuss M, Mituś JW, et al. Malignant phyllodes tumor of the breast: treatment and prognosis. Breast J 2014;20:639-44. [ Crossref ] [ PubMed ]
  • Ramakant P, Chakravarthy S, Cherian JA, et al. Challenges in management of phyllodes tumors of the breast: a retrospective analysis of 150 patients. Indian J Cancer 2013;50:345-8. [ Crossref ] [ PubMed ]
  • Tan PH, Thike AA, Tan WJ, et al. Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol 2012;65:69-76. [ Crossref ] [ PubMed ]
  • Barrio AV, Clark BD, Goldberg JI, et al. Clinicopathologic features and long-term outcomes of 293 phyllodes tumors of the breast. Ann Surg Oncol 2007;14:2961-70. [ Crossref ] [ PubMed ]
  • Papas Y, Asmar AE, Ghandour F, et al. Malignant phyllodes tumors of the breast: A comprehensive literature review. Breast J 2020;26:240-4. [ Crossref ] [ PubMed ]

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Yanhong Zhang , Celina G Kleer; Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates. Arch Pathol Lab Med 1 July 2016; 140 (7): 665–671. doi: https://doi.org/10.5858/arpa.2016-0042-RA

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Context.— Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm with risks of local recurrence and uncommon metastases. The classification proposed by the World Health Organization for PTs into benign, borderline, and malignant is based on a combination of several histologic features. The differential diagnosis between PT and fibroadenoma and the histologic grading of PT remain challenging. In addition, the molecular pathogenesis of PT is largely unknown.

Objective.— To provide an updated overview of pathologic features, diagnostic terminology, and molecular alterations of PT.

Data Sources.— Current English literature related to PT of the breast.

Conclusions.— Phyllodes tumor shows a wide spectrum of morphology. There are no clearly distinct boundaries between PT and fibroadenoma. Strict histologic assessment of a combination of histologic features with classification can help to achieve the correct diagnosis and provide useful clinical information. The genomic landscapes of PT generated from genomic sequencing provide insights into the molecular pathogenesis of PT and help to improve diagnostic accuracy and identify potential drug targets in malignant PT.

Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm, accounting for 0.3% to 1% of all breast tumors. 1   Phyllodes tumor presents a morphologic continuum from benign to malignant. The classification of PT proposed by the World Health Organization (WHO) into benign, borderline, and malignant is based on a combination of several histologic features, including stromal cellularity, nuclear atypia, mitotic activity, stromal overgrowth, and tumor margin appearance. 2   However, there are no defined criteria or clear cutoffs for individual histologic parameters. Thus, the diagnosis of PTs based on the integration of morphology remains challenging, particularly in the distinction of PTs from fibroadenoma. The majority of PTs behave in a benign fashion, with the risk of local recurrence ranging from 17% in benign PT to 27% in malignant PT. Distant metastasis occurs in up to 22% of malignant PTs. 2   The histologic grading of PT generally correlates with prognosis; however, histologic features have not always been found to be predictive of clinical behavior in individual patients. 3 – 5   Several biomarkers have been reported to be associated with histologic grades and show some prognostic value. However, at present, none of them have been proven to be of clinical value in daily practice. The pathogenesis and molecular biologic features of PT are largely unknown. The most favored theory on the pathogenesis of PT is epithelial-stromal interactions. The most recent genome sequencing studies have identified frequent MDM12 somatic mutations in fibroadenoma and PT, suggesting these 2 entities may share a common origin. 6 – 10   This review will address some of the diagnostic problems that are encountered in routine practice and provide molecular/genetic updates on PTs of the breast.

Phyllodes tumors are biphasic tumors, histologically characterized by a leaflike architecture resulting from an enhanced intracanalicular growth pattern, cleftlike spaces lined by epithelium, and hypercellular stroma. A variety of terms have been used to describe these tumors, the most common being cystosarcoma phyllodes, cellular fibroadenoma, and juvenile fibroadenoma. The term cystosarcoma phyllodes was first introduced by Müller in 1838. 11   It is derived from the Greek words sarcoma , meaning flesh appearance, and phyllon , meaning leaflike. This term may be misleading because the majority of PTs are benign. Cellular fibroadenoma and juvenile fibroadenoma are common benign biphasic tumors recognized as distinct entities; the terms have been used interchangeably. Cellular fibroadenoma has the architecture of a fibroadenoma with prominent cellular stroma. 2   Juvenile fibroadenoma exhibits a pericanalicular growth pattern, gynecomastoid-like epithelial hyperplasia, and an increased stromal cellularity. 12   Juvenile fibroadenomas occur predominantly in adolescents and may grow to enormous sizes. 13   Juvenile fibroadenoma is considered giant when larger than 5 cm.

Phyllodes tumor is classified as benign, borderline, or malignant according to the WHO classification of 2012 ( Table 1 ). 2   Like all morphologic grading systems, this grading scheme is somewhat subjective, especially at the cut points between grades. Of note, PT may contain foci with benign, borderline, and malignant features intermingled within the same neoplasm, making careful gross examination and histologic sampling particularly important. Therefore, given PT's histologic heterogeneity, excision is required to accurately classify and grade PT. Definitions of the histologic features commonly used for evaluation of PT are summarized in Table 2 .

Three-Tiered Grading System for Phyllodes Tumors Based on 2012 World Health Organization Classification

Three-Tiered Grading System for Phyllodes Tumors Based on 2012 World Health Organization Classification

Definitions of Histologic Parameters for Evaluation of Phyllodes Tumors in Core Biopsy and Excisional Specimens

Definitions of Histologic Parameters for Evaluation of Phyllodes Tumors in Core Biopsy and Excisional Specimens

Benign PT comprises 60% to 75% of all PT. The local recurrence rate has been reported to be about 20%. These tumors are characterized by mildly increased stromal cellularity and mild nuclear atypia. Mitoses are rare, usually fewer than 5 per 10 high-power fields (HPF) ( Figure , A). It can be difficult to distinguish benign PT from cellular fibroadenoma because increased stromal cellularity is a prominent feature of both. The distinction between the 2 is important, however, because their treatment and prognosis are different. The leaflike pattern that is typical of PT is not seen in cellular fibroadenoma and, if present, is focal and not well developed. One source of difficulty is the fact that fibroadenoma-like areas can be seen in otherwise typical cases of PT. Histologic heterogeneity in stromal cellularity and structure in PT may further create difficulty in the distinction between PT and cellular fibroadenoma on core biopsy. Numerous studies have attempted to determine which histologic features of PTs are useful in predicting PT on surgical excision and clinical behavior.

A, Benign phyllodes tumor. Leaflike projections of mildly increased stromal cellularity. B, Stromal fragmentation in core biopsy. C, Intratumoral stromal heterogeneity. The stroma is fibrotic in the left lower area and hypercellular in the right upper area in the same tumor. D, Subepithelial stromal condensation. E, Malignant phyllodes tumor. The stroma is markedly cellular and the stromal cells show marked nuclear pleomorphism. There are numerous mitoses. F, Malignant spindle cell proliferation. The presence of a bland epithelial component in the upper right of this core biopsy is typical of malignant phyllodes tumor. G, Borderline phyllodes tumor. The stroma is moderately cellular and the stromal cells show moderate nuclear atypia (hematoxylin-eosin, original magnifications ×40 [A and D], ×20 [B and F], ×10 [C], and ×100 [E and G]).

A, Benign phyllodes tumor. Leaflike projections of mildly increased stromal cellularity. B, Stromal fragmentation in core biopsy. C, Intratumoral stromal heterogeneity. The stroma is fibrotic in the left lower area and hypercellular in the right upper area in the same tumor. D, Subepithelial stromal condensation. E, Malignant phyllodes tumor. The stroma is markedly cellular and the stromal cells show marked nuclear pleomorphism. There are numerous mitoses. F, Malignant spindle cell proliferation. The presence of a bland epithelial component in the upper right of this core biopsy is typical of malignant phyllodes tumor. G, Borderline phyllodes tumor. The stroma is moderately cellular and the stromal cells show moderate nuclear atypia (hematoxylin-eosin, original magnifications ×40 [A and D], ×20 [B and F], ×10 [C], and ×100 [E and G]).

Stromal cellularity is categorized as mild, moderate, or marked, and is assessed in the most cellular area. The threshold for mild stromal cellularity has not been well defined. Jacobs et al 14   have considered mildly increased stromal cellularity as being approximately twice the cellularity of that of normal perilobular stroma, with no or rare stromal nuclei appearing to touch each other. With this definition, they found all core biopsy specimens with mildly increased stromal cellularity (n = 4) were fibroadenomas on excision. Among 20 core biopsy specimens with moderate stromal cellularity, 12 (60%) were fibroadenomas on excision. The data suggest that their threshold for stromal cellularity is low. Lee et al 15   defined the stromal cellularity as mild increase in at least 50% of the stroma in PT compared with a typical fibroadenoma. In their study, the concordance rate for diagnosis of PT on core needle biopsy and surgical specimen was higher (36 of 50; 72%), and the reproducibility of assessment of this feature by 4 pathologists was excellent. In another study by Yasir et al, 16   increased stromal cellularity was defined as the presence of stromal nuclear crowding or overlapping. Although this cutoff seems to be comparable with that for moderate cellularity in other studies, increased stromal cellularity was not a helpful feature in predicting a diagnosis of PT on excision in their study. Although the data on increased stromal cellularity are inconsistent, many studies have found that subepithelial condensation of stromal cells is a common feature of PT and may be the best predictor of PT in core biopsies. 16  

Stromal overgrowth, defined as a stromal proliferation without accompanying epithelial elements in at least 1 low-power field (×4), is a feature of PT. However, stromal overgrowth is absent in benign PT. Several studies found that stromal overgrowth defined as a ×10 field with no epithelium could be useful to diagnose PT on core biopsy. 15 , 16   A leaflike pattern, often seen in PT, can also be present in fibroadenoma and is not useful unless it is diffuse and well developed. Stromal nuclear atypia and infiltrative margin (adipose tissue within stroma) were found to be useful features in the distinction of PT and fibroadenoma on core biopsy, 15 , 16   but another study found that they were of little value. 14  

The mitotic activity of the stromal cells may also help distinguish PT from cellular fibroadenoma. Stromal mitoses have been evaluated in more cellular areas and quantified per 10 HPF. A minority of fibroadenomas have 1 or 2 mitoses per 10 HPF. Mitoses reported by Jacobs et al 14   (>2/10 HPF) and by Jara-Lazaro et al 17   (≥2/10 HPF) might help determine the probability of PT. Similarly, Yasir et al 16   found the average mitotic figures per 10 HPF were 3 and 0.8 in PT and cellular fibroepithelial lesions, respectively. This suggests that a count of 3 or more mitoses per 10 HPF favors PT over fibroadenoma. However, the mitotic count of up to 5/10 HPF has been reported in rare pediatric breast fibroadenomas. 13  

It is clear that PT and fibroadenoma exhibit overlapping histologic features that should not be used in isolation to make a definitive diagnosis. Thus, taking into account several of these features may be a more sensible approach. In a study of 62 cellular fibroepithelial lesions on core biopsy with follow-up excisions, the histologic features of stromal overgrowth at ×10, increased stromal cellularity, stromal fragmentation ( Figure , B), infiltration into fat, stromal heterogeneity ( Figure , C), subepithelial stromal condensation ( Figure , D), and stromal cell nuclear pleomorphism were evaluated. It was found that PT had more features (3.9) on average compared with cellular fibroadenoma (1.4). The findings suggest that presence of any 3 or more of these histologic features on core biopsy favors PT over fibroadenoma. 16  

Despite great efforts toward improving the pathologist's ability to better distinguish fibroepithelial lesions, there is still poor interobserver reproducibility. Studies show that the overall rate of correctly diagnosed fibroadenoma and PT ranges from 40% to 60%. 18 – 20   In a study by Lawton et al, 21   21 fibroepithelial lesions were evaluated among 10 breast pathologists. There was a uniform agreement on only 2 cases (10%). Of the remaining 19 cases, the diagnoses included fibroadenoma, cellular fibroadenoma, PT, and borderline PT. There was fair agreement on the separation of fibroadenoma/cellular fibroadenoma/benign PT from borderline and malignant PT. A number of studies reported that the recurrence rate of fibroadenoma is up to 17%, which is similar to that for benign PT. In addition, studies have shown that expectant management towards benign PTs excised without clear margins may be an acceptable option, given an overall low local recurrence rate and rare recurrence as a high-grade tumor from a benign PT. 22 , 23   These findings suggest that distinction between these 2 entities may not be significant. In core biopsies with morphologic features of fibroadenoma and benign PT, a diagnosis of benign fibroepithelial neoplasm is advocated by some authors and recommended by the WHO classification system. 2  

Malignant PT

Malignant PT is characterized by marked stromal cellularity and nuclear pleomorphism, stromal overgrowth, and more than 10 mitoses per 10 HPF ( Figure , E). The presence of heterologous sarcomatous elements (liposarcoma, chondrosarcoma, and osteosarcoma) alone qualifies a PT as malignant. The differential diagnosis of malignant PT includes sarcomas and metaplastic (sarcomatoid) carcinoma.

The distinction of malignant PT from metaplastic (sarcomatoid) carcinoma is based on the morphology. Like malignant PT, metaplastic (sarcomatoid) carcinoma may also show spindle cells with nuclear pleomorphism, abundant mitoses, and heterologous elements. The presence of leaflike architecture and bland epithelium lining cleftlike spaces is typical of PT ( Figure , F), whereas malignant epithelial elements, if present, are more likely to be metaplastic (sarcomatoid) carcinoma. If there is no epithelial component, particularly on core biopsy, immunohistochemistry may be helpful. A panel of cytokeratins (CKs) (CKAE1/AE3, CK5/6, 34βE12, cam 5.2) and myoepithelial marker p63 24   should be used for the workup because of variable staining patterns in metaplastic (sarcomatoid) carcinomas. The majority of PTs are negative for CKs and p63. 25   In a recent study of 32 PTs, it was found that p63, p40, and CKs can be focally positive in 57%, 29% and 21%, respectively, of malignant PT but not in benign or borderline PT. 26   These results suggest that these markers alone should not be used to differentiate metaplastic (sarcomatoid) carcinoma from malignant PT on core biopsy. CD34 has been reported to be positive in up to 75% of PT and negative in metaplastic (sarcomatoid) carcinoma. 27 – 29   However, CD34 positivity was observed in only 37% to 57% of malignant PTs. Nuclear expression of β-catenin is observed in PT; it is frequently seen in the stromal cells of benign and borderline PT. 30   A small proportion of sarcomatoid carcinoma may also show nuclear staining of β-catenin. When there is histologic and immunohistochemical ambiguity, a diagnosis of malignant spindle cell neoplasm with a descriptive comment is necessary and surgical excision is recommended for further classification because the clinical treatments for these 2 entities are different. Malignant PT is typically treated with complete surgical excision. Routine sentinel lymph node biopsy is not recommended because of rare lymph node metastases. The role of adjuvant radiotherapy and chemotherapy for malignant PT remains uncertain, whereas metaplastic carcinoma is managed by neoadjuvant or adjuvant chemotherapy and surgery including sentinel lymph node biopsy.

Primary sarcoma of the breast is extremely rare. The majority of sarcomas of the breast arise as a component of a malignant PT. Some undifferentiated mammary sarcomas are morphologically indistinguishable from malignant PT on core biopsy, particularly when no epithelial component is present. However, the clinical management of these 2 entities diagnosed on core biopsy is similar. Several studies have demonstrated that patients with primary breast sarcoma had identical disease-free survival and overall survival rates to those of patients with malignant PT. 31   Reports suggest that approximately 10% to 15% of PTs are malignant. Local recurrence rate ranges from 15% to 40%, and 9% to 27% of malignant PTs metastasize to distal organs. Most patients with metastasis do not respond to standard chemotherapy and die within 3 years of the initial treatment.

Borderline PT

According to the WHO definition, PTs that don't possess all the features for malignancy are classified as borderline; this division is arbitrary. Borderline PT may have a circumscribed or focally invasive border, frequent mitoses (5–9/10 HPF), moderate stromal cellularity, and stromal atypia ( Figure , G). Stromal overgrowth is usually absent. Borderline PT has not been extensively investigated compared with benign and malignant PT. The lower limit for diagnosis of borderline PT is not well defined. Moderate stromal cellularity, nuclear atypia, and focal infiltrative border are the features that can be seen in both benign and borderline PTs. It appears that mitotic activity is an important parameter for the diagnosis of borderline PT. The mitosis cutoff for the diagnosis of borderline PT has been clearly defined as 5 to 9/10 HPF in the WHO classification of 2012. In a study by Ang et al, 32   the gene expression profiling of 29 PTs showed that 2 histologically classified borderline cases had expression profiles similar to those of the benign and malignant groups. These 2 cases showed moderate stromal cellularity and atypia, focally infiltrative borders. The mitoses were 2/10 HPF in the profiled with benign group and an average of 6/10 HPF in the profiled with malignant group. This observation suggests that mitotic activity may be an important parameter among the histologic features. Further histologic and molecular correlation studies will help in redefining the features for tumor grading. The percentage of borderline PT ranges from 12% to 26% in different large series. Its local recurrence rate has been reported to be 14% to 25%. There are rare reports of borderline PTs metastasizing, although these events have not been well characterized.

The molecular correlations of histologic grade and malignant behavior and the genetic alterations driving PT development remain unclear.

The most favored theory on the pathogenesis of PT is epithelial-stromal interactions. Morphologic association of leaflike fronds with subepithelial stromal condensation hints at the close relationship between epithelial and stromal elements in PT. This observation is supported by the findings of the stromal expression of β-catenin and insulin-like growth factors (IGF-I and II) 30 , 33   and the epithelial overexpression of Wnt5a in benign/borderline PT. Furthermore, activation of the Wnt signaling pathway in the epithelium may promote stromal overgrowth.

Multiple immunohistochemistry markers have been studied in an attempt to improve the classification of PT and to predict its outcomes. Studies have shown that p53, Ki67, CD117, 34 , 35   EGFR, 36   p16, 37   and VEGF 38   (being the lowest in benign PT and the highest in malignant PT) are associated with histologic grades of PT, but none has been proven to be clinically useful. Among these markers, p53 expression and Ki67 index were reported in some studies 39 , 40   to be significantly associated with disease-free and overall survivals, but other studies 41 , 42   found no association with recurrence or clinical behavior. PAX3 and SIX1 expression by immunohistochemistry 43   and gene-expression analysis 44   has recently been identified in borderline and malignant PTs and correlates with a poor clinical outcome.

Recent studies have focused on defining a molecular classification of PT. Comparative genomic hybridization studies show recurrent chromosome imbalances including +1q, −6q, −13q, −9p, −10p, and +5p. Although currently no chromosomal aberrations were found to be specific to PT, Lae et al 45   reported that low-grade (benign) and high-grade (borderline/malignant) PTs segregate in 2 genetic groups based on genomic alterations, with high-grade PT consistently showing 1q gain and 13q loss and low-grade PT showing few or no alterations. Similar chromosomal changes were identified by Jones et al 46   in their array-GCH analysis in 126 PTs. We must note, however, that Lv et al 47   found the gain of 1q did not correlate with grades, and Lu et al 48   reported that 1q gain was found mainly in benign PTs (6 of 12; 50%), underscoring the need for more conclusive investigations. Loss of 13q in PT suggests that the RB1 gene localized in these regions could be relevant to PT oncogenesis or progression. 45   In addition, frequent deletions of 9p21 associated with loss of p16 INK4A protein expression were identified in borderline/malignant PT. 46  

Gene expression–based classification of PT has been proposed in recent studies. Vidal et al 49   analyzed the expression of 105 breast cancer–related genes in 75 fibroepithelial lesions. The overall profile of benign PT was found more similar to fibroadenomas and the majority of benign and borderline PT was identified as normallike by intrinsic breast cancer subtyping, whereas malignant PT was identified as claudin-low and basal-like. Similar to metaplastic carcinomas, malignant PT showed enrichment for cancer stem cell–related biological processes. 50   In another study by Ang et al, 32   a heat map generated from 29 genes showed 3 distinct groups of benign, borderline, and malignant tumors, consistent with histologic classifications. The discrepancy in these studies is largely due to the smaller size of cohort studies with smaller numbers of borderline and malignant PT, and may also reflect differences in the criteria used for classifying PT. Recent genome sequencing studies provide insights into the molecular pathogenesis of breast PTs and identify the potential opportunities for personalized treatment in malignant PT. Recurrent mediator complex subunit 12 ( MED12 ) somatic mutations, frequently (50%–70%) in uterine leiomyomas, has been recently identified in fibroadenomas (59%–67%) and PTs (45%–67%). In addition, MED12 is frequently mutated in all PTs. 6 , 7 , 9 , 51 , 52   These findings suggest both entities may share genetic etiology, and MDM2 mutation is an early event of fibroadenoma and PT pathogenesis. In a recent study by Tan et al, 10   exome sequencing of 22 PTs and targeted sequencing of 100 fibroepithelial tumors exhibited the genetic landscapes of fibroepithelial tumors, with frequent MED12 (73%) and RARA (32%) mutations in both fibroadenoma and all grades of PT. Of note, mutations in FLNA (28%), SETD2 (21%), and KMT2 (9%) were observed only in PT, suggesting a role in driving PT development. Genome-wide analysis of DNA copy number variations and genomic sequencing have demonstrated significant numbers of amplifications and deletions. In addition to the loss of function mutation in p53, deleterious mutations in Rb1 and NF1, mutations in PIK3CA and ERBB4, and high-level copy number variations of EGFR were detected in borderline/malignant tumors. 10   Cani et al 52   reported that p53, RB1, and NF1 mutations and EGFR 52 , 53   and IGF1R gene amplifications were detected in only the malignant tumors. These genetic alterations are likely responsible for acquisition of malignant characteristics and aggressive biologic behavior in PT. EGFR and IGF1R may be promising therapeutic targets.

In summary, PTs are rare fibroepithelial neoplasms with potential for local recurrence and distant metastasis. Histologic classification of PT into benign, borderline, and malignant is challenging in some cases, and the histologic classification does not correlate well with biological behavior. Distinction between fibroadenoma and PT is important but may be difficult on core biopsy. PTs show intratumoral morphologic and genetic heterogeneity, which may contribute to their unpredictable clinical behavior and the difficulty in classifying them histologically. Expression-based and genomics-based classifications of breast fibroepithelial tumors may help with the diagnosis and grading of PT, when used in combination with histologic criteria, and provide clinically useful prognostic information. The genomic landscapes of PT generated from genomic sequencing provide insights into molecular pathogenesis of PT and help to improve diagnostic accuracy and identify potential drug targets in malignant PT. However, most published studies have a limited number of samples, in particular a smaller number of borderline and malignant tumors. Further studies including a large series of well-characterized PT with follow-up data are needed.

Author notes

The authors have no relevant financial interest in the products or companies described in this article.

Competing Interests

Presented in part at the 2nd Princeton Integrated Pathology Symposium; February 9, 2015; Plainsboro, New Jersey.

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At the time the article was created Frank Gaillard had no recorded disclosures.

At the time the article was last revised Mohammad Taghi Niknejad had no financial relationships to ineligible companies to disclose.

  • Cystosarcoma phyllodes
  • Cystosarcoma phylloides
  • Phyllodes tumours
  • Phyllodes tumors

Phyllodes tumor , also known as cystosarcoma phyllodes , is a rare fibroepithelial tumor of the breast which has some resemblance to a fibroadenoma . It is typically a large, fast growing mass that forms from the periductal stroma of the breast 13 .

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Epidemiology, clinical presentation, radiographic features, treatment and prognosis, history and etymology, differential diagnosis.

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Phyllodes tumors account for less than 0.3-1% of all breast neoplasms 13 . It is predominantly a tumor of adult women, with very few examples reported in adolescents. The occurrence is most common between the ages of 40 and 60, before menopause (peak incidence ~45 years). This is about 15 years older than the typical age of patients with fibroadenoma.

Patients typically present with a painless, rapid growing breast mass for which imaging is requested. Average sizes can vary from 3 to 5 cm at presentation 13 .

Its original term cystosarcoma phyllodes was coined in view of its leaflike growth pattern 13 . A phyllodes tumor may be considered benign, borderline, or malignant depending on histologic features including stromal cellularity, infiltration at the tumor edge, and mitotic activity. At histologic analysis, the tumor can resemble a giant fibroadenoma  with both epithelial and stromal components being seen.

Fine needle aspiration is inaccurate, and even core biopsy has moderate sensitivity due to tumor heterogeneity causing inadequate sampling ref .

The tumors can be quite large at presentation. Imaging alone is not adequate to differentiate phyllodes tumor from fibroadenoma 13 . Phyllodes tumor are frequently classified as BI-RADS 4 tumor 14 .

Mammography

Typically seen as non-specific large rounded oval or lobulated, generally well-circumscribed, lesions with smooth margins. A radiolucent halo may be present. Calcification (typically coarse and plaque-like) may be seen in a very small proportion 13 . 

General sonographic features are non-specific and can mimic that of a fibroadenoma 7 .

On ultrasound, an inhomogeneous, solid-appearing mass is the most common manifestation. A solid mass containing single or multiple, round or cleft like cystic spaces and demonstrating posterior acoustic enhancement strongly suggests the diagnosis of phyllodes tumor. Vascularization is usually present in the solid components 13 .

In practice, most lesions are indistinguishable from fibroadenomas on both mammography and ultrasound. This is why interval enlargement of a "fibroadenoma" is seen as an indication for a needle biopsy. Large lesions (i.e. >4 cm) may qualify for excision out of hand because needle biopsy may not be representative of the pathology in the whole lesion.

As with mammography, they are typically seen as oval, round, or lobulated masses with circumscribed margins. Signal characteristics can vary with histological grade 11 but in general, are:

  • T1: usually of low signal 8
  • T2: can be variable ranging from homogenous low 8 to high 4-5  signal
  • T1 C+ (Gd): the solid components enhance after contrast administration
  • dynamic contrast: the kinetic curve pattern can be gradual slow or have rapid enhancement

An inhomogeneous signal may rarely result in the context of accompanying hemorrhage or cystic spaces 9 . Some suggest the inhomogeneous signal as indicative of benignity 10 .

It is a locally invasive tumor. Treatment is usually with surgical excision. Large tumors may even require a full mastectomy. Both benign and malignant phyllodes tumors have a tendency to recur if not widely excised. Malignant degeneration is seen in 5-25% 4  ( malignant phyllodes tumor ).

After wide local excision, there is relatively frequent local recurrence (up to 25%) and up to 10% can metastasize. The mode of metastases in such cases is by hematogenous route. 

The name is derived from the Greek word: "phullon"   meaning "leaf" .  Phyllodes tumors were first described in 1838 by Johannes Muller as "cystosarcoma phyllodes" .

For ultrasound and MRI appearances consider 6,8 :

  • fibroadenoma of the breast : calcification is more common
  • primary sarcoma of the breast
  • periductal stromal tumor  of the breast : the main distinction being the lack of leaf-like processes 
  • 1. Ralph Weissleder. Primer of Diagnostic Imaging. (2007) ISBN: 9780323040686 - Google Books
  • 2. Buchberger W, Strasser K, Heim K, Müller E, Schröcksnadel H. Phylloides Tumor: Findings on Mammography, Sonography, and Aspiration Cytology in 10 Cases. AJR Am J Roentgenol. 1991;157(4):715-9. doi:10.2214/ajr.157.4.1654022 - Pubmed
  • 3. Yabuuchi H, Soeda H, Matsuo Y et al. Phyllodes Tumor of the Breast: Correlation Between MR Findings and Histologic Grade. Radiology. 2006;241(3):702-9. doi:10.1148/radiol.2413051470 - Pubmed
  • 4. Lifshitz O, Whitman G, Sahin A, Yang W. Radiologic-Pathologic Conferences of the University of Texas M.D. Anderson Cancer Center. Phyllodes Tumor of the Breast. AJR Am J Roentgenol. 2003;180(2):332. doi:10.2214/ajr.180.2.1800332 - Pubmed
  • 5. Farria D, Gorczyca D, Barsky S, Sinha S, Bassett L. Benign Phyllodes Tumor of the Breast: MR Imaging Features. AJR Am J Roentgenol. 1996;167(1):187-9. doi:10.2214/ajr.167.1.8659370 - Pubmed
  • 6. Feder J, de Paredes E, Hogge J, Wilken J. Unusual Breast Lesions: Radiologic-Pathologic Correlation. Radiographics. 1999;19 Spec No(suppl_1):S11-26; quiz S260. doi:10.1148/radiographics.19.suppl_1.g99oc07s11 - Pubmed
  • 7. Chao T, Lo Y, Chen S, Chen M. Sonographic Features of Phyllodes Tumors of the Breast. Ultrasound Obstet Gynecol. 2002;20(1):64-71. doi:10.1046/j.1469-0705.2002.00736.x - Pubmed
  • 8. Wurdinger S, Herzog A, Fischer D et al. Differentiation of Phyllodes Breast Tumors from Fibroadenomas on MRI. AJR Am J Roentgenol. 2005;185(5):1317-21. doi:10.2214/AJR.04.1620 - Pubmed
  • 9. Balaji R & Ramachandran K. Magnetic Resonance Imaging of a Benign Phyllodes Tumor of the Breast. Breast Care (Basel). 2009;4(3):189-91. doi:10.1159/000220604 - Pubmed
  • 10. Kinoshita T, Fukutomi T, Kubochi K. Magnetic Resonance Imaging of Benign Phyllodes Tumors of the Breast. Breast J. 2004;10(3):232-6. doi:10.1111/j.1075-122X.2004.21316.x - Pubmed
  • 11. Yabuuchi H, Soeda H, Matsuo Y et al. Phyllodes Tumor of the Breast: Correlation Between MR Findings and Histologic Grade. Radiology. 2006;241(3):702-9. doi:10.1148/radiol.2413051470 - Pubmed
  • 12. Tan H, Zhang S, Liu H et al. Imaging Findings in Phyllodes Tumors of the Breast. Eur J Radiol. 2012;81(1):e62-9. doi:10.1016/j.ejrad.2011.01.085 - Pubmed
  • 13. Plaza M, Swintelski C, Yaziji H, Torres-Salichs M, Esserman L. Phyllodes Tumor: Review of Key Imaging Characteristics. Breast Dis. 2015;35(2):79-86. doi:10.3233/BD-150399 - Pubmed
  • 14. Duman L, Gezer N, Balcı P et al. Differentiation Between Phyllodes Tumors and Fibroadenomas Based on Mammographic Sonographic and MRI Features. Breast Care (Basel). 2016;11(2):123-7. doi:10.1159/000444377 - Pubmed

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Fibroepithelial tumors

Phyllodes tumor.

Joshua J.X. Li, M.B.Ch.B.

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thesis on phyllodes tumor

Phyllodes tumours

Affiliation.

  • 1 Department of Surgery, University Hospital of Wales, Cardiff, Wales, UK.
  • PMID: 11423590
  • PMCID: PMC1760996
  • DOI: 10.1136/pmj.77.909.428

Phyllodes tumours are rare fibroepithelial lesions that account for less than 1% of all breast neoplasms. With the non-operative management of fibroadenomas widely adopted, the importance of phyllodes tumours today lies in the need to differentiate them from other benign breast lesions. All breast lumps should be triple assessed and the diagnosis of a phyllodes tumour considered in women, particularly over the age of 35 years, who present with a rapidly growing "benign" breast lump. Treatment can be by either wide excision or mastectomy provided histologically clear specimen margins are ensured. Nodal metastases are rare and routine axillary dissection is not recommended. Few reliable clinical and histological prognostic factors have been identified. Local recurrence occurs in approximately 15% of patients and is more common after incomplete excision. It can usually be controlled by further surgery. Repeated local recurrence has been reported without the development of distant metastases or reduced survival. Approximately 20% of patients with malignant phyllodes tumours develop distant metastases. Long term survival with distant metastases is rare. The role of chemotherapy, radiotherapy, and hormonal manipulation in both the adjuvant and palliative settings remain to be defined.

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  • Aged, 80 and over
  • Breast Neoplasms / diagnosis*
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  • Neoplasm Recurrence, Local
  • Phyllodes Tumor / diagnosis*
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Cancer therapies show promise in combating tuberculosis

Published: March 25, 2024

Author: Brandi Wampler

Female professor wearing blue cardigan and black and white shirt stands in research lab.

What could cancer teach us about tuberculosis? That’s a question Meenal Datta has been chasing since she was a graduate student.

Once the body’s immune system is infected with tuberculosis, it forms granulomas — tight clusters of white blood cells — in an attempt to wall off the infection-causing bacteria in the lungs. But more often than not, granulomas do more harm than good.

Charged with analyzing the similarities between granulomas and tumors, Datta discovered that both are structurally and functionally abnormal. In 2015, she and other researchers looked at the vascular structures of granulomas and showed that they are compromised and leaky just like tumor blood vessels, which limits drug delivery and successful treatment in both diseases.

“It was the first time we showed definitively that there was this pathophysiological similarity between these two diseases that present with different causes and symptoms,” said Datta, assistant professor of aerospace and mechanical engineering at the University of Notre Dame. “Cancer doesn’t sound anything like an infectious disease. And yet, here are two different diseases with the same problem of dysfunctional blood vessels.”

Now a study from the same team at the University of Notre Dame, Massachusetts General Hospital and the National Institutes of Health has identified a combination of medications that may improve blood flow within granulomas, benefiting drug delivery. Published in the Proceedings of the National Academy of Sciences, the study leverages decades of cancer research to study tuberculosis-affected lung tissue and improve treatment.

“Much like in tumors, many of the blood vessels in granulomas are compressed or squeezed shut — just like if you stepped on your garden hose,” said Datta, the first author on the study. “In cancer, we know that happens because of the growing tumor mass and the supportive protein scaffolding it puts down, called matrix. We thought maybe the same thing was happening in tuberculosis.”

The study confirmed that a similar phenomenon is occurring in granulomas — too much cell mass and protein scaffolding. This impaired function makes blood flow through blood vessels nearly impossible, crippling the ability to get a medication to the tuberculosis disease site.

Datta and her collaborators used losartan, an affordable drug used to treat high blood pressure. However, it also has the beneficial side effect of reducing the amount of matrix being created inside a granuloma, thus opening the compressed blood vessels and restoring blood flow.

Researchers then combined losartan with bevacizumab, a drug used by cancer patients to stop the overproduction of poorly formed blood vessels. With this two-pronged medicinal approach, Datta and the team were able to make the granuloma blood vessels function and behave more normally.

When the researchers applied the host-directed therapies losartan and bevacizumab along with antibiotics, they showed improved drug delivery and antibiotic concentration within granulomas.

Additionally, Datta’s graduate student Maksym Zarodniuk analyzed genome sequencing data produced by the team, and found that even without antibiotics, there was a reduction in tuberculosis bacteria within the granulomas.

“When we gave just those host-directed therapies, we were getting good treatment benefit even without adding the antibiotics. Those therapies were promoting the body’s inflammatory response to fight against the bacteria, which we did not expect,” Datta said.

For Datta, this study caps off a stretch of tuberculosis research that started when she began her doctoral research at Massachusetts General Hospital and Harvard Medical School in 2011, and has spanned multiple phases of her career. Tuberculosis, although largely controlled in the U.S., is still considered one of the deadliest infectious diseases worldwide.

“The advantage of the host-directed therapies we selected is that these agents or very similar drugs of the same class are already approved by regulatory agencies around the globe, and they are affordable,” Datta said. “We hope that our preclinical results will be found compelling enough to start a clinical trial to benefit tuberculosis patients.”

Today, Datta’s lab at the University of Notre Dame primarily focuses its research on understanding glioblastoma , a rare treatment-resistant brain cancer. Datta said that being an engineer allows her to cross into other areas of research and with a different perspective, making an excellent case for the importance of multidisciplinary research.

“I do believe that really is an advantage of being an engineer. It’s easier for me to sometimes make connections between contexts that seem disparate,” Datta said. “We depend on our life science and clinical colleagues to walk through those details, but engineers are very good at approaching complex problems from a simplified systems approach.”

The study, “Normalizing granuloma vasculature and matrix improves drug delivery and reduces bacterial burden in tuberculosis-infected rabbits,” was funded by the Bill & Melinda Gates Foundation and the National Institutes of Health. Datta is an affiliated member of Notre Dame’s Berthiaume Institute for Precision Health , Eck Institute for Global Health , Harper Cancer Research Institute , Lucy Family Institute for Data and Society , NDnano and Warren Center for Drug Discovery . Datta is an assistant professor in the following doctorate programs: aerospace and mechanical engineering, bioengineering, and materials science and engineering.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, [email protected]

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  • v.17(10); 2022 Oct

Malignant phyllodes tumor of the breast with metastases to the lungs: A case report and literature review

Edvin ostapenko.

a National Cancer Institute, Santariskiu str. 1, Vilnius LT-08660, Lithuania

b Faculty of Medicine, Vilnius University, Vilnius, Lithuania

Arvydas Burneckis

Andrej ostapenko, audronė skaisgirytė, valerijus ostapenko, associated data.

The data used to support the findings of this study are included within the article.

Phyllodes tumors (PTs) are rare fibroepithelial neoplasms of the breasts. Approximately 10%-15% of PTs are malignant, and 9%-27% of patients with malignant PTs, develop metastatic disease. The lungs are the most common target organ for distant metastasis of PT. We report a case of 44-year-old female with a malignant PT. It had recurred locally 3 times, and 3 relapses occurred 13 months after the first diagnosis, presenting multiple metastases to the lungs by CT scan. The patient underwent radiation therapy, and palliative chemotherapy with doxorubicin was initiated. Two courses of doxorubicin therapy were administered, but the patient expired 16 months after PT diagnosis. We present a rare case of malignant PT with local recurrences, lung metastases, and poor patient outcome. Although malignant breast PTs have an unfavorable prognosis, adjuvant radiotherapy combined with margin-negative resection may be associated with decreased local recurrence and distant metastasis rates. Future research should include randomized clinical trials or well-designed prospective matched studies to clarify the effectiveness of treatments of PTs.

Introduction

Phyllodes tumors (PTs) are rare neoplastic lesions that are comprised of both stromal and epithelial components, and they account for approximately 0.3%-1% of breast tumors in women [1] . The term “phyllodes” which means leaf-like, describes the typical papillary projections that are seen on pathologic examination. They were originally called “cystosarcoma phyllodes” by Johannes Müller in 1838 [2] . World Health Organization (WHO) presented classification of tumors of the breast, introduced the term phyllodes tumors, criteria for diagnosis and grading of PT. PTs are subdivided into benign (60%-75%), borderline (15%-20%), or malignant (10%-20%), based on the assessment of 5 features: the degree of stromal cellular atypia; the mitotic activity per 10 high-power fields (HPFs); infiltrative or circumscribed tumor margins; the presence or absence of stromal overgrowth (ie, the presence of pure stroma devoid of epithelium); and the nature of the tumor border [3] . The average tumors size ranges from 4 to 5 cm. When PTs are larger than 10 cm in diameter, they have been classified as “giant” PTs, which account for about 20% of all PTs [4] . In 1931, the first case of a malignant PT with metastases to the lungs was reported, which revealed that these tumors could exhibit malignant behavior [5] . Recent literature reports that 10%-15% of PTs are malignant and approximately 9%-27% of patients with malignant phyllodes tumor have metastasis to distant organs with spreading hematogenously to most frequent sites as lungs, bones, brain, and liver [6] . Recurrence or metastasis of breast PTs predicts a shorter survival time, less than 2 years after diagnosis [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] .

In this report, we describe a rare case of malignant PT of the breast with local recurrences and subsequent metastases to the lungs, we provide a review of the literature, and we discuss treatment modalities.

Case report

A 44-year-old female patient from Lithuania presented to the National Cancer Institute (NCI) complaining of a mass in her left breast that had grown rapidly in the last 12 months. The patient experienced menarche at the age of 16, gave birth to 2 children. No significant signs were observed in the patient's medical or family history. On physical examination, the patient was a well-developed woman with an obvious left-sided breast mass. At the time of presentation, the left breast mass measured 11 cm × 7 cm × 8 cm in greatest dimension. Axillary, mediastinal, or clavicular lymphadenopathy was not observed. The patient's right breast was normal upon palpation. Mammography showed a high-density, smoothly contoured masses with well-circumscribed margins in the left breast measuring 7.8 × 4.3 cm, 4.5 × 2.8 cm, and 3.6 × 2.8 cm ( Fig. 1 ). A core needle biopsy was performed on the same day. The left breast biopsy results revealed malignant neoplasms with carcinomatous and sarcomatous elements. The cells showed marked pleomorphism with >10 mitoses/10HPF. The patient underwent partial mastectomy. Detailed descriptions are shown in ( Table 1 ). Pathological examination confirmed a malignant PT ( Fig. 2 ). Postoperative recovery was without complications with a well-healing wound.

Fig 1

Mammogram of the left breast. There is a high-density, smoothly contoured formations (7.8 × 4.3 cm, 4.5 × 2.8 cm, and 3.6 × 2.8 cm), with circumscribed margins in left region of the breast.

Fig 2

Malignant phylloid tumor with 2 distinct components: on the right side classical phylloid tumor with overgrowth of cellular stroma and intraductal leaf-like structures; on the left side diffuse sarcoma-type growth of highly atypical cells (HE staining).

Three months after the surgery, the patient became aware of a soft tissue mass growing at the partial mastectomy scar. Upon physical examination, postsurgical changes consistent with a left partial mastectomy and a new parasternal 6 cm nonmobile, nontender mass fixed to the medial portion of the scar were observed. No palpable axillary lymphadenopathy was noted.

Core needle biopsy of the breast mass revealed recurrent malignant PT. The patient underwent left mastectomy. The postoperative recovery was uneventful. Pathological examination revealed recurrence of malignant phyllodes tumor with atypical osteoid formation ( Fig. 3 ). After multidisciplinary discussion among breast surgeon, medical oncologist, and radiologist, the patient underwent adjuvant radiotherapy. After adjuvant radiotherapy, the patient had routine follow-up.

Fig 3

Diffuse sarcoma-like growth of highly atypical spindle cells, foci of atypical osteoid formation (HE staining).

After approximately one month, breast ultrasound revealed 4.1 × 3.4 cm mass above the mastectomy scar and 3.8 × 2.3 cm mass subpectoral. Core needle biopsy of the breast mass revealed a recurrence of malignant PT. Computed tomography (CT) scan of the chest, abdomen, and pelvis did not reveal any pulmonary metastatic disease or any other significant findings in the abdomen. The patient underwent left side axillary tumor, m. pectoralis major, and m. serratus anterior resection. Pathological examination showed high grade (G3) malignant phyllodes tumor with sarcomatous elements and spread in the soft tissues and veins ( Fig. 4 ). Three weeks later, the patient returned to the hospital with chest pain, dyspnea, and cough. The CT scan showed multiple lesions ( Fig. 5 ) in both lungs and axillary recurrence. The patient received 2 courses of palliative chemotherapy (60 mg/m 2 doxorubicin hydrochloride on days 1-2). Palliative chemotherapy was stopped because of intolerable nausea, dyspnea, and grade 3 anemia with further need for blood transfusions. The patient expired 16 months after the PT diagnosis.

Fig 4

The histological picture with higher degree of atypia, giant cell component of the tumor (HE staining).

Fig 5

Contrast-enhanced CT of the chest. (A) Lung windows demonstrate a multiple well-defined pulmonary nodules on both sides of the lungs.

Phyllodes tumors of the breast are rare fibroepithelial neoplasms and exhibit a wide range of clinical behaviors. PT and fibroadenoma (FA) are both fibroepithelial lesions, but their management differs. FA may be safely followed without further investigation, whereas PT requires surgical excision. Multidisciplinary approach is very important to distinguish PT from FA in patients with diagnosed fibroepithelial lesions. There are rare cases documented in literature of a FA transformation to a PT. There are 2 possibilities that could account for a core biopsy proven FA being rediagnosed as a PT: the first possibility is misdiagnosis at core biopsy due to their overlapping pathologic appearance, or the second possibility, more rarely, the progression of a FA into a PT [22] . There is no accurate imaging or clinical predictor of which lesion will transform. The majority of PT occur in women between the ages of 35 and 55 years, whereas a FA is the most common solid breast mass in a woman under the age of 30 but can be seen in older women as well [22] . In men, phyllodes tumors usually occur in association with gynecomastia. PT is reported rarely in men [23] . PTs can be caused by genetic syndromes, such as Li-Fraumeni syndrome (germline TP53 mutation), which is related to breast cancers, brain tumors, soft tissue sarcomas, and rarely other types of tumors [24] . Malignant PTs have a higher risk of metastatic disease, whereas benign and borderline tumors demonstrate a proclivity for local recurrence and rarely metastasize [25] . Koh et al. [26] showed that a combination of large tumor size (≥90 mm) ant the presence of malignant heterologous elements had a statistically significant association with the development of distant metastasis. Most frequently, malignant PTs metastasize to the lung, bones, brain, and liver [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] . Few rare distant metastatic sites are the adrenal glands [20] , kidney [13] , skin [27] , ovary [28] , heart [29] , pleura [30] , oral cavity [31] , duodenum [32] , pancreas [33] , tonsillar [12] , and para-aortic nodes [34] . Once patients with malignant PT develop metastasis, their prognosis is extremely poor. The median survival ranged from 5 to 30 months [35] . Our patient expired 16 months after the diagnosis of PT.

Surgery is the mainstay of treatment for breast PTs. Lu et al. [36] showed in a recent meta-analysis of 54 retrospective studies with 9234 patients that a positive surgical margins increased the risk of local recurrence: 8% for benign, 13% for borderline, and 18% for malignant PTs. Jang et al. [37] retrospectively reviewed 164 patients with PTs and found that the main prognostic factor for local recurrence of PTs was the presence of tumor cells on the resection margin. They also found, that the width of the resection margin did not confer a local recurrence risk. According to the newest 3.2022 guidelines of the Nation Comprehensive Cancer Network (NCCN), the recommendation for the treatment of PT is local surgical excision with tumor-free margins of 1 cm or greater for malignant and borderline PT. Narrow surgical margins are not an absolute indication for mastectomy when partial mastectomy fails to achieve a margin width ≥1 cm. Total mastectomy is only necessary if negative margins cannot be obtained by lumpectomy or partial mastectomy. While for benign PT excisional biopsy includes complete mass removal, but without the intent of obtaining surgical margins. Since phyllodes tumors rarely metastasize to the ALNs, surgical axillary staging or ALN dissection is not necessary unless the lymph nodes are pathologic on clinical examination [24] .

Currently, there is no consensus regarding the role of radiotherapy in malignant PT. Comprehensive Cancer Network (NCCN) 3.2022 guidelines recommend consideration of radiotherapy for malignant PTs only in the setting of local recurrence (level 2 B evidence) [24] . However, Barth et al. [38] in a prospective, multi-institutional study, revealed that margin-negative resection combined with adjuvant radiotherapy is very effective for local control of borderline and malignant phyllodes tumors. 39 According to Chao et al. [39] meta-analysis of 17 retrospective studies with 696 patients, found that radiotherapy is effective in achieving local disease control and preventing metastasis. Belkacemi et al. [40] reported that in 159 patients with malignant and borderline phyllodes tumors, radiotherapy significantly decreased local recurrence rate ( P = . 02). Accordingly, margin-negative resection combined with adjuvant radiotherapy could be the new gold standard for borderline and malignant PT's.

Adjuvant chemotherapy effects in PTs treatment are lacking because of insufficient data from large prospective studies. In our literature review of patient with distant metastasis to the lungs, the most frequent chemotherapy was with Doxorubicin and ifosfamide [ 7 , 10 , [17] , [18] , [19] ]. In 6 studies [ 8 , 12 , [14] , [15] , [16] , 20 ] adjuvant chemotherapy was not given due to controversial effects or patient's request, detailed descriptions are shown in ( Table 2 ). Moon et al. [10] showed complete remission of lung metastasis and no evidence of locoregional or distant metastasis 3 years after mastectomy with axillary lymph node dissection and adjuvant chemotherapy with doxorubicin and ifosfamide. Koukourakis et al. [9] revealed that the combination of cisplatina with nab-paclitaxel and liposomal doxorubicin chemotherapy had acceptable toxicity and was highly effective in eradicating metastatic lesions. Within 2 years of follow-up, the patients were free of disease and treatment-related toxicities. The Comprehensive Cancer Network (NCCN) guidelines recommend that treatment of distant metastasis with PT following the NCNN Soft Tissue Sarcoma Clinical Practice Guidelines version 2.2022. Preferred regimens: (doxorubicin, ifosfamide, mesna/ifosfamide, epirubicin, mesna) [24] .

Study characteristics, adjuvant treatment, and follow-up of 16 patients with PT and distant metastasis to the lungs

We present a rare case of malignant PT with local recurrences, lung metastases and poor patient outcome. Although malignant breast PTs have an unfavorable prognosis, adjuvant radiotherapy combined with margin-negative resection may be associated with decreased local recurrence and distant metastasis rates. Future research should include randomized clinical trials or well-designed prospective matched studies to clarify the effectiveness of treatments of PTs.

Author contribution

Drs E.O. and V.O. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: E.O. and A.O. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: E.O. and A.O. Critical revision of the manuscript for important intellectual content: all authors. Study supervision: V.O. and A.B.

Ethical approval

Ethical approval was not required for this study.

Data availability

Patient consent.

Complete written informed consent was obtained from the patient for the publication of this study and accompanying images.

Competing Interests: All authors declare no conflict of interest.

Funding: The authors received no financial support for the research, authorship and publication of this article.

IMAGES

  1. (PDF) Phyllodes tumor: A clinicopathologic and immunohistochemical

    thesis on phyllodes tumor

  2. (PDF) Phyllodes Tumor with Sarcomatous transformation

    thesis on phyllodes tumor

  3. Phyllodes Tumor of Breast

    thesis on phyllodes tumor

  4. (PDF) A massive malignant phyllodes tumor

    thesis on phyllodes tumor

  5. Benign phyllodes tumor with classic leaf-like fibroepithelial

    thesis on phyllodes tumor

  6. Histopathology criteria for phyllodes tumor according to WHO

    thesis on phyllodes tumor

VIDEO

  1. montaje de Escarabajo Violin (Mormolyce phyllodes)

  2. Fibroadenoom versus Phyllodes tumor

  3. 21 February 2024

  4. Phyllodes tumor / Cystosarcoma Phyllode in hindi

  5. Dr Sandeep Vaghela Case of Phyllodes tumours of breast

  6. NBE- APPROACH TO PHYLLODES BREAST TUMOR AND IT'S MANAGEMENT- DR. MJ PAUL

COMMENTS

  1. Phyllodes Tumors: A Scoping Review of the Literature

    Purpose: Phyllodes tumors are rare tumors of the breast, with most literature being retrospective with limited guidelines on the management of these patients. Scoping review was performed to highlight themes and gaps in the available literature. Methods: A scoping review of the literature was performed as per PRISMA-ScR guidelines with titles, abstracts, and full texts reviewed in duplicate.

  2. Current clinical practice in the management of phyllodes tumors of the

    Introduction. Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified according to their morphology as benign, borderline or malignant [1, 2].They entail a broad range of pathological and clinical features and therefore regarded as a spectrum of fibroepithelial neoplasms rather than a single entity.

  3. Malignant Phyllodes Tumor of the Breast: A Practice Review

    Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm, representing 0.3 to 1% of all breast tumors . Such cases are classified into benign, borderline, and malignant (mPT) according to a combination of several histologic features. The rarity of these lesions, particularly malignant PTs, contributes to the challenge in defining ...

  4. Management of phyllodes tumor: A systematic review and meta-analysis of

    Phyllodes tumors are histopathologically classified as benign, borderline, and malignant. Currently, surgical excision with a clear margin is the standard treatment for phyllodes tumors [2]. However, local recurrence can occur after excision [3]. The surgical margin, clinicopathological risk factors, and adjuvant radiotherapy may affect disease ...

  5. Phyllodes Tumors of the Breast: A Literature Review

    Phyllodes tumors (PTs) of the breast are an infrequent fibroepithelial neoplasm that accounts for less than 1% of all breast neoplasm. The incidence of PTs is low 0.3%-0.9% of all breast tumors [ 1, 2 ]. PTs were initially described by Muller in 1838 as Cystosarcoma phyllodes. Phyllodes derive from the Latin Phyllodium which means 'leaf-like ...

  6. PDF Management of Phyllodes Breast Tumors

    The mainstay of treatment for phyllodes tumors remains excision with a safe surgical margin, taking advantage breast conserv-ing surgery where amenable. For borderline or malignant phyllodes tumors or in cases of local tumor recurrence, mastec-tomy, and immediate breast reconstruction may become the preferred option.

  7. Malignant phyllodes tumor of the breast: treatment and prognosis

    Abstract. Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast (MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant radiotherapy have been controversial. We report a single institution's experience with MPTB.

  8. Margin status impact on recurrence of phyllodes tumors in high-risk

    Phyllodes tumors (PT) is a rare fibroepithelial breast tumor with an incidence ranging from 0.3 to 0.9%, primarily affecting women aged between 35 and 55 years [1,2,3].It originates from the periductal stromal cells of the breast and is histologically characterized by increased stromal cellularity with leafy fronds [].The World Health Organization classifies this tumor into benign, borderline ...

  9. Full article: Phyllodes tumor of the breast: diagnosis, management and

    Introduction. Phyllodes tumor is a very rare tumor of the breast, incidence being between 0.3% and 0.9% of all breast tumors. Citation 1 They are most commonly found in women aged between 40 and 50 years. Citation 2 The World Health Organization (WHO) has published guidelines classifying this tumor into benign, borderline or malignant according to the histological features such as stromal ...

  10. Phyllodes Tumor of the Breast: Ultrasound-Pathology Correlation

    Phyllodes tumor of the breast is a rare, yet clinically significant, fibroepithelial neoplasm accounting for 1% of all breast neoplasms [].Women classically present with a rapidly growing palpable abnormality that triggers a diagnostic imaging workup [].Phyllodes tumors are biphasic, composed of both epithelial and stromal components [], and have a characteristic leaflike architecture with ...

  11. Surgical management in phyllodes tumors of the breast: a systematic

    Introduction. Phyllodes tumors (PTs) of the breast are uncommon fibroepithelial lesions (FELs), accounting for about 0.3-1% of breast tumors and 2-3% of FELs (1,2).This disease was first reported by Johannes Müller in 1838 and called cystosarcoma phyllodes ().Since then, up to 60 names have been reported such as pseudosarcomatoid adenoma and carcinosarcoma.

  12. Phyllodes Tumor of the Breast

    Phyllodes tumor of the breast is an infrequently encountered fibroepithelial neoplasm, which accounts for 0.3% to 1% of all tumors.[1] Phyllodes tumor presents a morphologic continuum from benign to malignant. Based on histologic features, including nuclear atypia, stromal cellularity, mitotic activity, tumor margin appearance, and stromal overgrowth, the World Health Organization (WHO ...

  13. Phyllodes Tumor of the Breast: Histopathologic Features, Differential

    Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm, accounting for 0.3% to 1% of all breast tumors. 1 Phyllodes tumor presents a morphologic continuum from benign to malignant. The classification of PT proposed by the World Health Organization (WHO) into benign, borderline, and malignant is based on a combination of several histologic features, including stromal cellularity ...

  14. Integrating single-cell and spatial transcriptomes reveals ...

    Background: Breast phyllodes tumours (PTs) are a unique type of fibroepithelial neoplasms with metastatic potential and recurrence tendency. However, the precise nature of heterogeneity in breast PTs remains poorly understood. This study aimed to elucidate the cell subpopulations composition and spatial structure and investigate diagnostic markers in the pathogenesis of PTs.

  15. Phyllodes tumors: Types, Symptoms & Treatment

    What are phyllodes tumors of the breast? A phyllodes tumor is a rare type of tumor that develops in the connective tissue of your breast. When you think of your breast tissue, you probably think more of the fatty tissue that makes up the volume of your breast, or the glandular tissue that produces milk.The connective tissue is the fibrous, supportive tissue that holds these other tissues in place.

  16. Phyllodes tumor

    Epidemiology. Phyllodes tumors account for less than 0.3-1% of all breast neoplasms 13. It is predominantly a tumor of adult women, with very few examples reported in adolescents. The occurrence is most common between the ages of 40 and 60, before menopause (peak incidence ~45 years). This is about 15 years older than the typical age of ...

  17. Pathology Outlines

    Borderline phyllodes tumor. Behavior intermediate between benign and malignant phyllodes tumors ( Histopathology 2016;68:5 ) Higher risk of local recurrence than benign phyllodes tumor. Risk of metastasis present but very low. Malignant phyllodes tumor. 23 - 30% risk of local recurrence ( Histopathology 2016;68:5 ) 9% risk of distant metastasis.

  18. The response of phyllodes tumor of the breast to anticancer therapy: An

    Introduction. Phyllodes tumor (PT) was first described in 1838 by the German physician Johannes Müller as cystosarcoma phyllodes ().The name 'phyllodes' derives from the Latin Phyllodium and means 'leaf-like' which relates to its morphology under the microscope ().Phyllodes tumors of the breast (PTB) are rare, accounting for less than 1% of breast neoplasms overall which translates ...

  19. Phyllodes Tumors of the Breast

    Phyllodes tumors (or phylloides tumors) are rare breast tumors that start in the connective (stromal) tissue of the breast, not the ducts or glands (which is where most breast cancers start). Most phyllodes tumors are benign and only a small number are malignant (cancer). Phyllodes tumors are most common in women in their 40s, but women of any ...

  20. Phyllodes tumours

    Phyllodes tumours are rare fibroepithelial lesions that account for less than 1% of all breast neoplasms. With the non-operative management of fibroadenomas widely adopted, the importance of phyllodes tumours today lies in the need to differentiate them from other benign breast lesions. All breast l …

  21. [Retracted] Phyllodes Tumor of Breast: A Review Article

    1. Introduction. Phyllodes tumors are rare fibroepithelial lesions. They make up 0.3 to 0.5% of female breast tumors [ 1] and have an incidence of about 2.1 per million, the peak of which occurs in women aged 45 to 49 years [ 2, 3 ]. The tumor is rarely found in adolescents and the elderly.

  22. Phyllodes Tumor of Breast: A Review Article

    1. Introduction. Phyllodes tumors are rare fibroepithelial lesions. They make up 0.3 to 0.5% of female breast tumors [ 1] and have an incidence of about 2.1 per million, the peak of which occurs in women aged 45 to 49 years [ 2, 3 ]. The tumor is rarely found in adolescents and the elderly.

  23. Cancer therapies show promise in combating tuberculosis

    "Much like in tumors, many of the blood vessels in granulomas are compressed or squeezed shut — just like if you stepped on your garden hose," said Datta, the first author on the study. "In cancer, we know that happens because of the growing tumor mass and the supportive protein scaffolding it puts down, called matrix.

  24. Malignant phyllodes tumor of the breast with metastases to the lungs: A

    Introduction. Phyllodes tumors (PTs) are rare neoplastic lesions that are comprised of both stromal and epithelial components, and they account for approximately 0.3%-1% of breast tumors in women .The term "phyllodes" which means leaf-like, describes the typical papillary projections that are seen on pathologic examination.