Skip to content

Advertisement

You're viewing the new version of our site. Please leave us feedback.

Learn more

Applied Cancer Research

Open Access

Distant metastases in phyllodes tumours of the breast: an overview

Applied Cancer Research201737:15

https://doi.org/10.1186/s41241-017-0028-6

Received: 12 January 2017

Accepted: 5 May 2017

Published: 7 July 2017

Abstract

Phyllodes tumours (PTs) of the breast are uncommon fibroepithelial neoplasms, comprising 0.3 – 1.0% of all primary breast malignancies in Western countries, but accounting for a higher proportion of primary breast tumours in Asian countries. They are graded as benign, borderline or malignant based on the World Health Organisation (WHO) classification, according to a constellation of 5 histologic parameters. While most PTs carry a good prognosis, malignant and occasionally borderline PTs have the potential to metastasize to distant sites. Although events of distant metastasis are few, the prognosis for such patients is dismal, as they are often unresponsive to chemotherapy with high mortality. This review seeks to provide an overview of this rare but important phenomenon of distant metastases in PTs of the breast.

Keywords

Fibroepithelial neoplasmsPhyllodes tumoursMetastasisDistant metastasesPrognosis

Background

Phyllodes tumours (PTs) of the breast are uncommon fibroepithelial neoplasms morphologically characterised by benign double-layered epithelium surrounded by a hypercellular stroma, which together exhibit a leaf-like architecture [1]. They are classified into benign, borderline, and malignant according to the World Health Organisation (WHO) classification, based on the assessment of 5 histologic parameters – stromal cellularity, stromal atypia, mitoses, stromal overgrowth, and tumour margins. PTs comprise 0.3 – 1.0% of all primary breast tumours in Western countries. In Asian countries however, PTs account for a higher proportion of primary breast tumours and can also develop in younger patients [1].

The majority (60.0%–75.0%) of PTs are benign. Benign PTs carry a good prognosis, and are generally well managed with surgery, with a local recurrence rate of about 10.0%–20.0% [24]. Borderline and malignant PTs account for 15.0 – 20.0% and 10.0 – 20.0% of all PTs respectively [1]. Unlike benign PTs, malignant PTs, and occasionally borderline PTs, can behave in a clinically aggressive manner, with local recurrence rates of malignant PTs ranging from 15.0 to 40.0%. Distant metastasis is rare, occurring nearly exclusively in malignant PTs at a rate of 9.0 – 27.0%. Although a rare event, the prognosis of patients with metastasis is very poor, as many are unresponsive to standard chemotherapy with ensuing mortality [4].

As events of distant metastases in PTs are rare, there are limited studies on this clinically important phenomenon. This review seeks to provide a literature overview of PTs with distant metastases.

Rates of metastasis in PTs

A summary of studies containing PTs with distant metastases by various authors can be found in Table 1. The overall rates of distant metastases in PTs range from 1.7 to 27.1% [5, 6], with an average of 5.6%, and vary according to tumour grade. It is highly unlikely for benign PTs to metastasize to distant sites; however, rare exceptions do exist. Reinfuss et al. [7] documented 3 cases of benign PTs that developed metastases, while Mangi et al. [8], Chaney et al. [9], Asoglu et al. [10], and Abdalla et al. [11] each recorded 1 case of metastatic benign PT in their studies. In the study by Mangi and colleagues, the case of benign PT that later metastasized was initially treated with a simple excision. The lesion was 2 cm in size and the surgical margins were <1 mm. Distant metastasis (site not mentioned) developed 36 months later and the patient underwent a total mastectomy and radiotherapy, but eventually still succumbed to the disease. It is also noteworthy that the PT cases by Mangi et al. and Asoglu et al. were categorised as low grade, instead of benign. The average rate of metastasis amongst benign PT is 0.4%, based on literature reports (Table 1). It is acknowledged however, that accurate grading relies on diligent sampling of these usually large tumours, and it is possible that benign PTs that metastasized may have been under-graded.
Table 1

A summary of studies with metastatic PT

Authors, year of publication

No. of cases

Total metastatic rate, % (no. of cases)

Metastatic rate by tumour grade, % (no. of cases)

Site(s) of metastasis

PT-related death rate, % (no. of cases)

Metastatic death rate, % (no. of cases)

Time to metastasis from diagnosis (months)

Time to death (months)

Factors associated with metastasis

Axillary lymph node metastasis, % (no. of cases)

Benign

Borderline

Malignant

Lindquist et al. 1982 [16]

42

9.5 (4/42)

0/3a

0

4/7

Chest wall, liver, lungs, retroperitoneum

50.0 (5/10)

100 (4/4)

Range 0 - 84

PT diagnosis to death: Range 21-84

NAb

NA

Ward and Evans 1986c [19]

26

19.2 (5/26)

-

-

-

Gastrointestinal tract, lung, spleen, thyroid, uterus

26.9 (7/26)

100 (5/5)

NA

PT diagnosis to death: range 6 - 32

Stromal overgrowth

0

Hawkins et al. 1992c [26]

33

24.2 (8/33)

-

-

-

Bone, lung, mesentery, muscle or soft tissue, pleura, skin

21.2 (7/33)

87.5 (7/8)

Median 14 (range 2 - 31)

DMd to death: Median 10 (range 2 - 40) PT diagnosis to death: Median 25 (range 12 - 50)

Severe nuclear pleomorphism, stromal overgrowth, high mitotic count, infiltrating margins, large tumour size, presence of necrosis

NA

Rowell et al. 1993 [30]

18

5.6 (1/18)

0 (0/11)

0 (0/4)

33.3 (1/3)

Lung, muscles

5.6 (1/18)

100 (1/1)

NA

PT diagnosis to death: 23

NA

0

Reinfuss et al. 1996 [7]

170

15.9 (27/170)

3.3 (3/92)

21.1 (4/19)

33.9 (20/59)

Bone, brain, lung

15.9 (27/170)

100 (27/27)

Mean 18 (range 2 - 57)

Mean 4 (range 2 - 11)

NA

0.5 (1/70)

de Roos et al. 1999 [39]

38

10.5 (4/38)

0 (0/15)

0 (0/11)

33.3 (4/12)

NA

10.5 (4/38)

100 (4/4)

NA

Median 17 (range 12 - 125)

Size and grade related to metastatic death

NA

Mangi et al. 1999 [8]

40

2.5 (1/40)

2.9 (1/34)

0 (0/3)

0 (0/3)

NA

2.5 (1/40)

100 (1/1)

36

NA

None

NA

Chaney et al. 2000 [9]

101

7.9 (8/101)

1.7 (1/59)

0 (0/12)

23.3 (7/30)

Brain, lung, pelvis

NA

100 (8/8)

NA

NA

Stromal overgrowth, malignant histology, mastectomy

0

Kapiris et al. 2001e [6]

48

27.1 (13/48)

-

-

27.1 (13/48)

Bone, lung, pleura

35.4 (17/48)

92.3 (12/13)

Median 25.6 (range 6 - 120)

DM to death: mean 16.6 (range 1 - 24)

Tumour size, margins

0

Asoglu et al. 2004 [10]

50

26.0 (13/50)

6.3 (1/16)

33.3 (1/3)

35.5 (11/31)

Abdomen, bone, brain, liver, lung

32.0 (16/50)

100 (13/13)

Mean 53.4, median 36 (range 4 - 77)

DM to death: mean 7 (range 1 - 19)

Stromal overgrowth

2 (1/50)

Chen et al. 2005 [5]

172

1.7 (3/172)

0 (0/131)

8.3 (1/12)

6.9 (2/29)

Lung, soft tissue of neck

NA

100 (3/3)

NA

DM to death: 5 (patient 1), 6 (patient 2). No info on 3rd patient

Stromal cellularity, stromal overgrowth, stromal atypia, mitotic activity, tumour margin, heterologous stromal elements

0

Sotheran et al. 2005 [27]

50

2.0 (1/50)

0 (0/29)

0 (0/12)

11.1 (1/9)

Musculoskeletal chest wall

2.0 (1/50)

100 (1/1)

18

NA

NA

NA

Abdalla et al. 2006 [11]

79

12.7 (10/79)

3.2 (1/31)

11.1 (3/27)

28.6 (6/21)

Bone, brain, lung

12.7 (10/79)

100 (10/10)

Median 14 (range 3 - 36)

DM to death: Mean 5 (range 1 - 11)

Histotypes and resection margins

1.3 (1/79)

Tan et al. 2006 [48]

37

16.2 (6/37)

0 (0/22)

0 (0/9)

100 (6/6)

Bone, lungs, pleura

8.1 (3/37)

50 (3/6)

NA

Mean 11.3

NA

NA

Cheng et al. 2006 [12]

182

2.2 (4/182)

0 (0/138)

7.7 (1/13)

9.7 (3/31)

Lungs

2.2 (4/182)

100 (4/4)

Mean 14

Mean 6 (range 5 - 9)

None

0

Belkacémi et al. 2008 [13]

443

3.4 (15/443)

0 (0/284)

2.5 (2/80)

16.5 (13/79)

Lung

NA

NA

NA

NA

NA

0.2 (1/443)

Lenhard et al. 2008 [24]

33

9.1 (3/33)

0 (0/13)

0 (0/9)

27.3 (3/11)

Liver, lung

3.1 (1/32) (1 lost follow-up)

50 (1/2) (1 lost follow-up)

Median 40 (range 4 - 56)

26 (DM at diagnosis)

Histopathological classification

0

Guillot et al. 2011 [49]

165

1.2 (2/165)

0 (0/114)

0 (0/37)

14.3 (2/14)

Bone, lung

1.2 (2/165)

100 (2/2)

NA

NA

NA

0

Al-Masri et al. 2012 [40]

43

14.0 (6/43)

0 (0/16)

0 (0/10)

35.3 (6/17)

NA

NA

NA

NA

NA

Expression of stromal CD10

NA

Jang et al. 2012 [50]

164

2.4 (4/164)

0 (0/82)

0 (0/42)

10.0 (4/40)

Bone, lung

1.8 (3/164)

75 (3/4)

NA

NA

NA

NA

Tan et al. 2012 [2]

605

2.0 (12/605)

0 (0/440)

0 (0/111)

22.2 (12/54)

Liver, lung, pleura, soft tissue, vertebra

2.0 (12/605)

NA

NA

NA

NA

NA

Do et al. 2013 [51]

179

2.8 (5/179)

0 (0/103)

0 (0/38)

13.2 (5/38)

NA

2.2 (4/179)

60 (3/5)

NA

NA

None

NA

Sawalhi and Shatti 2013 [20]

42

14.3 (6/42)

0 (0/16)

0 (0/9)

35.3 (6/17)

Bone, intestine, lung, thigh

NA

NA

Mean 15.9

NA

Histological grade

14.3 (6/42)

Spitaleri et al. 2013 [3]

172

2.3 (4/172)

0 (0/68)

0 (0/42)

6.5 (4/62)

NA

2.3 (4/172)

75.0 (3/4)

NA

NA

Young age (<35 years), presence of necrosis, positive surgical margins associated with increased risk of all PT-related events

NA

Ren et al. 2014 [14]

140

7.1 (10/140)

0 (0/80)

6.7 (2/30)

26.7 (8/30)

NA

NA

NA

NA

NA

Tumour grade, expression of Axl and ST6GaINAcII

NA

Wei et al. 2014 [15]

192

6.3 (12/192)

0 (0/80)

6.3 (4/63)

16.3 (8/49)

Bone, liver, lung, pancreas, pleura, soft tissue, thoracic cavity

6.3 (12/192)

100 (12/12)

Median 26 (range 0 - 60)

DM to death: Median 10.0 (range 2.0 - 41.1) PT diagnosis to death: Median 34.3 (range 14.0 - 80.0)

Histotype, margin status

0

Bumpers et al. 2015 [52]

50

2.0 (1/50)

0 (0/40)

0 (0/3)

14.3 (1/7)

Lung

2.0 (1/50)

100 (1/1)

Lung metastasis found at time of presentation

PT diagnosis to death: 4

NA

4 (2/50)

Ramakant et al. 2015 [17]

167

4.2 (7/167)

0 (0/118)f

14.3 (7/49)

Adrenal, bone, brain, duodenum, lung, mediastinal nodes, para-aortic nodes

NA

85.7 (6/7)

Median 7 (range 0 - 156)

NAg

NA

1.2 (2/167) (para-aortic and mediastinal nodes)

Demian et al. 2016 [53]

35

2.9 (1/35)

0 (0/1)

0 (0/13)

4.8 (1/21)

Lung

Lost follow-up

Lost follow-up

NA

NA

-

0

Total

3516

5.6 (196/3516)

0.4 (7/1915)

2.9 (18/612)

20.0 (154/770)

 

aAlthough the total number of patients with PT was 46, the study only looked at 10 patients with recurrence and/or distant metastasis, as such, the percentages of benign, borderline, and malignant PT were not tabulated and included in the total metastatic rates of benign, borderline, and malignant PTs

b NA Information was not available

cCases were not specified to be benign, borderline, or malignant

d DM Distant metastasis

eThis study looked only at high-grade malignant PTs

fAs the exact breakdown of benign and borderline cases were not known, these numbers were not computed in the total metastatic rates of benign and borderline PTs

gThe follow-up of each patient was detailed in the study, however the starting time points to death (i.e from diagnosis of PTs, or distant metastases or surgery etc.) were not consistent for all patients, therefore we were not able to tabulate a mean, median or range of time to death

There is potential for borderline PTs to metastasize, although the risk is very low. The rate of metastasis amongst borderline PTs averages around 2.9% (Table 1), as documented in 8 studies [5, 7, 1015].

Although the occurrence of distant metastasis in benign PTs is a rare and aberrant phenomenon, metastases in malignant PTs have been recorded in quite a number of studies (All studies in Table 1). Even though events are still considered uncommon, the average metastatic rate of malignant PT is around 20.0% (Table 1).

Sites of metastasis

Metastasis occurs mostly through the haematogenous route [16]. The most common site of distant metastasis for PT appears to be the lungs. Of the 21 studies which mentioned sites of metastasis, 20 documented patients whose PTs had spread were to the lungs. The second most common site for PT metastasis is the bone, with 12 studies containing patients with bone metastases. A picture of a malignant PT and its lung metastasis is shown in Fig. 1.
Fig. 1

a Primary malignant phyllodes tumour shows a fibroadenomatoid area juxtaposed to more cellular zones with pleomorphic cells. b Higher magnification of the phyllodes tumour displaying malignant stromal cells with stromal overgrowth. c Metastatic phyllodes tumour to the lung, composed only of malignant stromal cells

Although the lungs and skeleton are the usual sites of distant metastasis for PT, almost all other organs have been shown to be afflicted, including the adrenal glands [17], brain [7, 911, 17, 18], gastrointestinal tract [17, 1921], heart [22], kidney [23], liver [2, 10, 15, 16, 24, 25], mesentery [26], pancreas and pleura [15], retroperitoneum [16], soft tissues [2, 5, 15, 26, 27], spleen and thyroid [19], tonsil [28], uterus [19], and vulva [29].

Lymph node metastases are less frequent, although 10.0 – 15.0% of patients may present with clinical lymphadenopathy, they are usually as a result of reactive hyperplasia due to tumour necrosis or infection [11, 30]. In a study conducted by Gullett and colleagues [31], 9.0% of 1035 cases of patients with PT were subjected to an axillary sampling of ≥ 10 lymph nodes but nodal involvement was documented only in 9 patients. Of the 17 studies with information on lymph node metastasis in Table 1, 10 of them recorded no lymph node metastasis. With the exception of Sawalhi and Shatti [20], the remaining 6 studies displayed a lymph node metastatic rate of less than 5.0%. It is therefore not recommended to perform routine axillary dissection [32].

Histologically, the majority of the metastases contain only the stromal elements, without the epithelium [1, 32]. However, two unusual cases of metastatic PTs incorporating epithelial components have been documented by West et al. [33], and Kracht et al. [34]. The former described a case of PT metastasizing to the lungs with the pulmonary lesion containing the stroma, a well-differentiated myxoid fibrosarcoma, and the epithelium, which was mono-layered and appeared to be benign. The second case, recorded by Kracht and colleagues, detailed a malignant PT with liposarcomatous differentiation that metastasized to the lungs. The lung metastasis was a replication of the primary PT, displaying both the benign epithelium (bilayered ductal structures comprising luminal and basal cells) and malignant liposarcomatous stroma.

Prognosis of patients with metastasis in PT

The majority of PTs carry a good prognosis; however, patients who develop distant metastasis tend to have a very dismal clinical outlook, oftentimes leading to death. The time that it takes for distant metastasis to develop can be very varied, from as short as 2 months post-treatment [7, 26], to longer than a decade [17] (Table 1).

As patients with metastatic PTs may not respond well to standard chemotherapy, death often ensues [4]. As many as 15 studies summarized in Table 1 describe a 100.0% mortality rate amongst patients with metastatic PTs. The remaining studies displaying metastatic PT death rates had mortality rates exceeding 50.0%. The time to death is also relatively short, ranging from 1.0 to 41.1 months from the diagnosis of distant metastasis (Table 1).

Factors associated with metastasis

In 2012, a nomogram for predicting PT recurrences was developed by Tan and colleagues [2], based on the assessment of 4 predictive factors, namely, stromal atypia, mitoses, overgrowth, and surgical margins (AMOS). This nomogram was subsequently validated in two small case series [35, 36]. Its widespread use in clinical practice is limited by the rarity of PTs in general. Nevertheless, it is being further validated in 2 larger cohorts [37, 38]. Although several studies have looked into the various factors that may predict distant metastasis of PTs, none were successfully established and universally recognised as reliable predictors of PT metastasis, in part due to the limited number of such events. One of the earlier studies by Ward and Evans [19], which examined 26 cases of cystosarcoma phyllodes (synonymous with PTs), found that stromal overgrowth was significantly associated with metastasis (p = 0.0014). Stromal overgrowth as a predictor of PT metastasis was also supported by 4 other studies [5, 9, 10, 26].

Other clinico-pathological predictive factors for distant metastasis include severe nuclear pleomorphism [26], mitotic activity [5, 26], positive surgical margins [3, 5, 6, 11, 15, 26], large tumour size [6, 26, 39], presence of necrosis [3, 26], tumour grade [9, 11, 14, 15, 20, 24, 39], stromal cellularity and atypia, heterologous stromal elements [5], and young age [3].

Studies investigating the predictive value of biomarkers for PT metastasis have also been performed. Al-Masri and colleagues [40] studied the expression of CD10 in 43 cases of PTs and found that positive CD10 expression was significantly associated with the development of distant metastasis (p < 0.05). Ren et al. [14] also noted in their study that positive expression of Axl (p = 0.006) and ST6GalNAcII (p = 0.015) correlated significantly with distant metastasis in PT. In another study by Tan et al. [41], high stromal cytoplasmic expression of Six1 was shown to be independently associated with distant metastasis and local recurrence (p = 0.044).

Recent molecular developments in PTs have revealed insights into the pathogenesis of PTs, in particular the identification of recurrent mediator complex subunit 12 (MED12) somatic mutations, found in fibroadenomas and all grades of PTs [4245]. Mutations in FLNA (28.0%), SETD2 (21.0%) and KMT2D (9.0%) were also discovered, which are believed to contribute to tumour progression in PTs [46]. Currently, the genomic features of primary PTs and their metastases are not well understood. Molecular studies on malignant PTs are few [47], and to the best of our knowledge, no studies have focused on comparing the genomic profiles of primary PTs and their metastases.

Conclusions

The clinical behaviour of PTs can be very unpredictable, as seemingly benign PTs can recur as malignant PTs and develop distant metastasis, while cases with malignant histology may never exhibit metastatic behaviour at all. However, it is clear that malignant PTs stand the highest risk of developing distant metastases, compared to borderline and benign PTs. The most common sites of distant metastasis are the lungs and skeleton; however nearly all other organs have been shown to be affected as well. Patient prognosis is extremely poor after metastatic spread, with death oftentimes ensuing. Several factors, such as stromal overgrowth, have been shown to be significantly associated with the occurrence of distant metastasis, although there are still no established robust pathological characteristics to predict which cases of PTs are at risk of developing distant metastasis. Future work investigating the predictive factors of distant metastases in PTs will be another step closer in identifying patients who are at higher risk of developing distant metastasis, in order to optimize their management.

Abbreviations

DM: 

Distant metastasis

PT: 

Phyllodes tumour

WHO: 

World Health Organisation

Declarations

Acknowledgements

Not applicable.

Funding

Not applicable.

Availability of data and materials

Not applicable.

Authors’ contributions

VK drafted the manuscript. AAT contributed to the content of the manuscript and also revised it. PHT revised it critically for important intellectual context and gave final approval of the version to be published.

Competing interests

The authors declare that they have no competing interest.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Not applicable.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Division of Pathology, Singapore General Hospital

References

  1. Lakhani S, Ellis I, Schnitt S, Tan P, van de Vijver M, editors. WHO Classification of Tumours of the Breast. 4th ed. Lyon: International Agency for Research on Cancer; 2012.Google Scholar
  2. Tan P, Thike A, Tan W, Thu M, Busmanis I, Li H, et al. Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol. 2012;65(1):69–76.View ArticlePubMedGoogle Scholar
  3. Spitaleri G, Toesca A, Botteri E, Bottiglieri L, Rotmensz N, Boselli S, et al. Breast phyllodes tumor: a review of literature and a single center retrospective series analysis. Crit Rev Oncol Hematol. 2013;88(2):427–36.View ArticlePubMedGoogle Scholar
  4. Zhang Y, Kleer C. Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates. Arch Pathol Lab Med. 2016;140(7):665–71.View ArticlePubMedGoogle Scholar
  5. Chen W, Cheng S, Tzen C, Yang T, Jeng K, Liu C, et al. Surgical treatment of phyllodes tumors of the breast: retrospective review of 172 cases. J Surg Oncol. 2005;91(3):185–94.View ArticlePubMedGoogle Scholar
  6. Kapiris I, Nasiri N, A'Hern R, Healy V, Gui G. 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(8):723–30.View ArticlePubMedGoogle Scholar
  7. 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. 1996;77(5):910–6.View ArticlePubMedGoogle Scholar
  8. Mangi A, Smith B, Gadd M, Tanabe K, Ott M, Souba W. Surgical management of phyllodes tumors. Arch Surg. 1999;134(5):487–92.View ArticlePubMedGoogle Scholar
  9. Chaney A, Pollack A, McNeese M, Zagars G, Pisters P, Pollock R, et al. Primary treatment of cystosarcoma phyllodes of the breast. Cancer. 2000;89(7):1502–11.View ArticlePubMedGoogle Scholar
  10. Asoglu O, Ugurlu M, Blanchard K, Grant C, Reynolds C, Cha S, et al. Risk factors for recurrence and death after primary surgical treatment of malignant phyllodes tumors. Ann Surg Oncol. 2004;11(11):1011–7.View ArticlePubMedGoogle Scholar
  11. Abdalla H, Sakr M. Predictive factors of local recurrence and survival following primary surgical treatment of phyllodes tumors of the breast. J Egypt Natl Canc Inst. 2006;18(2):125–33.PubMedGoogle Scholar
  12. Cheng S, Chang Y, Liu T, Lee J, Tzen C, Liu C. Phyllodes tumor of the breast: the challenge persists. World J Surg. 2006;30(8):1414–21.View ArticlePubMedGoogle Scholar
  13. Belkacémi Y, Bousquet G, Marsiglia H, Ray-Coquard I, Magné N, Malard Y, et al. Phyllodes tumor of the breast. Int J Radiat Oncol Biol Phys. 2008;70(2):492–500.View ArticlePubMedGoogle Scholar
  14. Ren D, Li Y, Gong Y, Xu J, Miao X, Li X, et al. Phyllodes tumor of the breast: role of Axl and ST6GalNAcII in the development of mammary phyllodes tumors. Tumour Biol. 2014;35(10):9603–12.View ArticlePubMedGoogle Scholar
  15. Wei J, Tan Y, Cai Y, Yuan Z, Yang D, Wang 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):492–500.PubMedPubMed CentralGoogle Scholar
  16. Lindquist K, Van H, Weiland L, Martin J. Recurrent and metastatic cystosarcoma phyllodes. Am J Surg. 1982;144(3):341–3.View ArticlePubMedGoogle Scholar
  17. Ramakant P, Selvamani, Therese M, Paul M. Metastatic malignant phyllodes tumor of the breast: an aggressive disease-analysis of 7 cases. Indian J Surg Oncol. 2015;6(6):363–9.View ArticlePubMedPubMed CentralGoogle Scholar
  18. Rowe J, Prayson R. Metastatic malignant phyllodes tumor involving the cerebellum. J Clin Neurosci. 2015;22(1):226–7.View ArticlePubMedGoogle Scholar
  19. Ward R, Evans H. Cystosarcoma phyllodes. A clinicopathologic study of 26 cases. Cancer. 1986;58(10):2282–9.View ArticlePubMedGoogle Scholar
  20. Sawalhi S, Al-Shatti M. Phyllodes tumor of the breast: a retrospective study of the impact of histopathological factors in local recurrence and distant metastasis. Ann Saudi Med. 2013;33(2):162–8.View ArticlePubMedGoogle Scholar
  21. Choi D, Chi H, Lee S, Kwon Y, Park S, Sim S, et al. A Rare Case of Phyllodes Tumor Metastasis to the Stomach Presenting as Anemia. Cancer Res Treat. 2016;doi: 10.4143/crt.2016.188.
  22. Mačák J, Hurník P, Dvořáčková J, Mačáková J. An isolated metastasis to the heart from a malignant phyllodes tumor with osteosarcomatous differentiation. Cesk Patol. 2014;50(4):146–9.PubMedGoogle Scholar
  23. Karczmarek-Borowska B, Bukala A, Syrek-Kaplita K, Ksiazek M, Filipowska J, Gradalska-Lampart M. A rare case of breast malignant phyllodes tumor with metastases to the kidney: case report. Medicine (Baltimore). 2015;94(33):10.View ArticleGoogle Scholar
  24. Lenhard M, Kahlert S, Himsl I, Ditsch N, Untch M, Bauerfeind I. Phyllodes tumour of the breast: clinical follow-up of 33 cases of this rare disease. Eur J Obstet Gynecol Reprod Biol. 2008;138(2):217–21.View ArticlePubMedGoogle Scholar
  25. Hassan S, Ud D, Kayani N. Malignant phyllodes tumor in an 11-year-old girl with fatal clinical outcome. A case report. Breast Dis. 2016;36(1):61–4.View ArticlePubMedGoogle Scholar
  26. Hawkins R, Schofield J, Fisher C, Wiltshaw E, McKinna J. The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes. Cancer. 1992;69(1):141–7.View ArticlePubMedGoogle Scholar
  27. Sotheran W, Domjan J, Jeffrey M, Wise M, Perry P. Phyllodes tumours of the breast--a retrospective study from 1982-2000 of 50 cases in Portsmouth. Ann R Coll Surg Engl. 2005;87(5):339–44.View ArticlePubMedPubMed CentralGoogle Scholar
  28. Sano R, Sato E, Watanabe T, Oshima H, Ando A, Masaki M, et al. Phyllodes tumor metastasis to the tonsil with synchronous undifferentiated carcinoma. Int J Surg Case Rep. 2014;5(6):290–3.View ArticlePubMedPubMed CentralGoogle Scholar
  29. Ajenifuja O, Kolomeyevskaya N, Habib F, Odunsi A, Lele S. Phyllodes tumor of the breast metastasizing to the vulva. Case Rep Oncol Med. 2015;2015:589547.PubMedPubMed CentralGoogle Scholar
  30. Rowell M, Perry R, Hsiu J, Barranco S. Phyllodes tumors. Am J Surg. 1993;165(3):376–9.View ArticlePubMedGoogle Scholar
  31. Gullett N, Rizzo M, Johnstone P. National surgical patterns of care for primary surgery and axillary staging of phyllodes tumors. Breast J. 2009;15(1):41–4.View ArticlePubMedGoogle Scholar
  32. Tan B, Acs G, Apple S, Badve S, Bleiweiss I, Brogi E, et al. Phyllodes tumours of the breast: a consensus review. Histopathology. 2016;68(1):5–21.View ArticlePubMedPubMed CentralGoogle Scholar
  33. West T, Weiland L, Clagett O. Cystosarcoma phyllodes. Ann Surg. 1971;173(4):520–8.View ArticlePubMedPubMed CentralGoogle Scholar
  34. Kracht J, Sapino A, Bussolati G. Malignant phyllodes tumor of breast with lung metastases mimicking the primary. Am J Surg Pathol. 1998;22(10):1284–90.View ArticlePubMedGoogle Scholar
  35. Nishimura R, Tan P, Thike A, Tan M, Taira N, Li H, et al. Utility of the Singapore nomogram for predicting recurrence-free survival in Japanese women with breast phyllodes tumours. J Clin Pathol. 2014;67(8):748–50.View ArticlePubMedGoogle Scholar
  36. Chng T, Lee J, Lee C, Li H, Tan M, Tan P. Validation of the Singapore nomogram for outcome prediction in breast phyllodes tumours: an Australian cohort. J Clin Pathol. 2016;69(12):1124–6.View ArticlePubMedGoogle Scholar
  37. Cristando C, Li H, Almekinders M, Tan PH, Brogi E, Murray M. Validation of the Singapore Nomogram for Outcome Prediction in a US-Based Population of Women with Breast Phyllodes Tumors (PT). 2017. United States & Canadian Academy of Pathology 106th Annual Meeting. http://www.nature.com/modpathol/journal/v30/n2s/pdf/modpathol2016241a.pdf. Accessed 09 Feb 2017.
  38. Chng TW, Gudi M, Li HH, Tan PH. Validation of the Singapore Nomogram for Outcome Prediction in Breast Phyllodes Tumors in a Large Patient Cohort. 2017. United States & Canadian Academy of Pathology 106th Annual Meeting. http://www.nature.com/modpathol/journal/v30/n2s/pdf/modpathol2016241a.pdf. Accessed 09 Feb 2017.
  39. de Roos W, Kaye P, Dent D. Factors leading to local recurrence or death after surgical resection of phyllodes tumours of the breast. Br J Surg. 1999;86(3):396–9.View ArticlePubMedGoogle Scholar
  40. Al-Masri M, Darwazeh G, Sawalhi S, Mughrabi A, Sughayer M, Al-Shatti M. Phyllodes tumor of the breast: role of CD10 in predicting metastasis. Ann Surg Oncol. 2012;19(4):1181–4.View ArticlePubMedGoogle Scholar
  41. Tan W, Thike A, Bay B, Tan P. Immunohistochemical expression of homeoproteins Six1 and Pax3 in breast phyllodes tumours correlates with histological grade and clinical outcome. Histopathology. 2014;64(6):807–17.View ArticlePubMedGoogle Scholar
  42. Lim W, Ong C, Tan J, Thike A, Ng C, Rajasegaran V, et al. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet. 2014;46(8):877–80.View ArticlePubMedGoogle Scholar
  43. Ng C, Tan J, Ong C, Lim W, Rajasegaran V, Nasir N, et al. MED12 is frequently mutated in breast phyllodes tumours: a study of 112 cases. J Clin Pathol. 2015;68(9):685–91.View ArticlePubMedGoogle Scholar
  44. Yoshida M, Sekine S, Ogawa R, Yoshida H, Maeshima A, Kanai Y, et al. Frequent MED12 mutations in phyllodes tumours of the breast. Br J Cancer. 2015;112(10):1703–8.View ArticlePubMedPubMed CentralGoogle Scholar
  45. Cani A, Hovelson D, McDaniel A, Sadis S, Haller M, Yadati V, et al. Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors. Mol Cancer Res. 2015;13(4):613–9.View ArticlePubMedPubMed CentralGoogle Scholar
  46. Tan J, Ong C, Lim W, Ng C, Thike A, Ng L, et al. Genomic landscapes of breast fibroepithelial tumors. Nat Genet. 2015;47(11):1341–5.View ArticlePubMedGoogle Scholar
  47. Gatalica Z, Vranic S, Ghazalpour A, Xiu J, Ocal I, McGill J, et al. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast. Oncotarget. 2016;7(2):1707–16.PubMedGoogle Scholar
  48. Tan E, Tan P, Yong W, Wong H, Ho G, Yeo A, et al. Recurrent phyllodes tumours of the breast: pathological features and clinical implications. ANZ J Surg. 2006;76(6):476–80.View ArticlePubMedGoogle Scholar
  49. 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.View ArticlePubMedGoogle Scholar
  50. Jang J, Choi M, Lee S, Kim S, Kim J, Lee J, et al. Clinicopathologic risk factors for the local recurrence of phyllodes tumors of the breast. Ann Surg Oncol. 2012;19(8):2612–7.View ArticlePubMedGoogle Scholar
  51. Do S, Kim J, Kang S, Lee J, Lee J, Nam S, et al. Expression of TWIST1, Snail, Slug, and NF-κB and methylation of the TWIST1 promoter in mammary phyllodes tumor. Tumour Biol. 2013;34(1):445–53.View ArticlePubMedGoogle Scholar
  52. Bumpers H, Tadros T, Gabram-Mendola S, Rizzo M, Martin M, Zaremba N, et al. Phyllodes tumors in African American women. Am J Surg. 2015;210(1):74–9.View ArticlePubMedGoogle Scholar
  53. Demian G, Fayaz S, El-Sayed E, Nazmy N, Samir S, George T, et al. Phyllodes tumors of the breast: analysis of 35 cases from a single institution. J Egypt Natl Canc Inst. 2016;28(4):243–8.View ArticlePubMedGoogle Scholar

Copyright

© The Author(s) 2017

Advertisement