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Size and heterologous elements predict metastases in malignant phyllodes tumours of the breast

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Abstract

Phyllodes tumours (PTs) of the breast are uncommon fibroepithelial neoplasms comprising 0.3–1.0% of all primary breast tumours. The majority of PTs are benign and generally well managed with surgery. However, malignant PTs, and occasionally borderline PTs, can behave in a clinically aggressive manner by metastasizing to distant organs. Although distant metastasis is rare, the prognosis of patients with metastasis is dismal as many are unresponsive to standard chemotherapy and the risk of death is high. In this study, we correlated clinicopathological parameters to survival outcomes in a cohort of patients diagnosed with malignant PTs in our institution. The study cohort comprised 83 cases of malignant PTs diagnosed at the Department of Anatomical Pathology, Singapore General Hospital from 1994 to 2015. Clinicopathological features and follow-up were obtained from hospital records. Metastasis-free survival (MFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared between groups using the log-rank test. Cox regression was carried out to identify factors predictive for metastasis. Mean and median age of patients was 48 years (range 21–71 years). Tumour size measured from 30 to 220 mm (mean 90 mm, median 77 mm). Follow-up data was available for 68 patients. Mean and median follow-up was 90 and 57 months, respectively, with a maximum of 291 months. Distant metastasis occurred in 16 out of 68 patients (23.5%). The most common site of metastasis was the lung. Malignant heterologous elements were observed in 16 (19.3%) cases. Individual clinicopathological parameters had no impact on outcome. On Kaplan-Meier analysis, women with large tumours and presence of malignant heterologous elements showed trends for poorer MFS (p = 0.217 and p = 0.566, respectively). However, the combination of large tumours (≥ 90 mm) containing malignant heterologous elements disclosed significantly worse MFS (p = 0.043) and a trend for poorer OS (p = 0.238). On multivariate analysis, large tumours harbouring malignant heterologous elements independently predicted metastasis (95% CI 1.041–12.517, HR 2.434, p = 0.049). Our study demonstrates that tumour size and presence of malignant heterologous elements predicted metastasis in malignant PTs. Further work needs to be done in determining if protein biomarkers and genomic aberrations are able to additionally refine metastatic risk and define therapeutic targets.

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References

  1. Tan PH, Tse G, Lee A, Simpson JF, Hanby AM (2012) Fibroepithelial tumours. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ. WHO classification of tumours of the breast. IARC, Lyon, p 142-145

  2. Zhang Y, Kleer CG (2016) Phyllodes tumor of the breast: histopathologic features, differential diagnosis, and molecular/genetic updates. Arch Pathol Lab Med 140(7):665–671. https://doi.org/10.5858/arpa.2016-0042-RA

    Article  PubMed  Google Scholar 

  3. Mituś JW, Blecharz P, Walasek T, Reinfuss M, Jakubowicz J, Kulpa J (2016) Treatment of patients with distant metastases from phyllodes tumor of the breast. World J Surg 40(2):323–328. https://doi.org/10.1007/s00268-015-3262-7

    Article  PubMed  Google Scholar 

  4. Tan PH, Thike AA, Tan WJ, Thu MM, Busmanis I, Li H et al (2012) Predicting clinical behaviour of breast phyllodes tumours: a nomogram based on histological criteria and surgical margins. J Clin Pathol 65(1):69–76. https://doi.org/10.1136/jclinpath-2011-200368

    Article  PubMed  Google Scholar 

  5. Tan BY, Acs G, Apple SK, Badve S, Bleiweiss I, Brogi E et al (2016) Phyllodes tumours of the breast: a consensus review. Histopathology 68(1):5–21. https://doi.org/10.1111/his.12876

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tan PH, Jayabaskar T, Chuah KL, Lee HY, Tan Y, Hilmy M et al (2005) Phyllodes tumors of the breast: the role of pathologic parameters. Am J Clin Pathol 123(4):529–540. https://doi.org/10.1309/U6DV-BFM8-1MLJ-C1FN

    Article  PubMed  Google Scholar 

  7. Hawkins RE, Schofield JB, Fisher C, Wiltshaw E, McKinna JA (1992) The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes. Cancer 69(1):141–147

    Article  CAS  PubMed  Google Scholar 

  8. de Roos WK, Kaye P, Dent DM (1999) Factors leading to local recurrence or death after surgical resection of phyllodes tumours of the breast. Br J Surg 86(3):396–399

    Article  PubMed  Google Scholar 

  9. Kapiris I, Nasiri N, A'Hern R, Healy V, Gui GP (2001) 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 27(8):723–730. https://doi.org/10.1053/ejso.2001.1207

    Article  CAS  PubMed  Google Scholar 

  10. Warrier S, Hwang S, Gibbings K, Carmalt H, O'Toole S (2015) Phyllodes tumour with heterologous sarcomatous differentiation: case series with literature review. Int J Surg Case Rep 11:91–94. https://doi.org/10.1016/j.ijscr.2015.02.009

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hallin M, Thway K (2017) Phyllodes tumor with heterologous liposarcomatous differentiation. Int J Surg Pathol 25(5):435–437. https://doi.org/10.1177/1066896917696750

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  13. Patil Okaly GV, Devadass CW, Metikurke SH (2015) Malignant phyllodes tumor with heterologous differentiation: a rare case report. J Cancer Res Ther 11(3):651. https://doi.org/10.4103/0973-1482.137996

    Article  PubMed  Google Scholar 

  14. Tomas D, Bujas T, Stajduhar E, Kirac P, Mijić A, Kruslin B (2007) Malignant phyllodes tumor with associated osteosarcomatous, chondrosarcomatous, and liposarcomatous overgrowth. APMIS 115(4):367–370. https://doi.org/10.1111/j.1600-0463.2007.apm_588.x

    Article  PubMed  Google Scholar 

  15. Inyang A, Thomas DG, Jorns J (2016) Heterologous liposarcomatous differentiation in malignant phyllodes tumor is histologically similar but immunohistochemically and molecularly distinct from well-differentiated liposarcoma of soft tissue. Breast J 22(3):282–286. https://doi.org/10.1111/tbj.12567

    Article  CAS  PubMed  Google Scholar 

  16. Lyle PL, Bridge JA, Simpson JF, Cates JM, Sanders ME (2016) Liposarcomatous differentiation in malignant phyllodes tumours is unassociated with MDM2 or CDK4 amplification. Histopathology 68(7):1040–1045. https://doi.org/10.1111/his.12898

    Article  PubMed  Google Scholar 

  17. Liu SY, Joseph NM, Ravindranathan A, Stohr BA, Greenland NY, Vohra P et al (2016) Genomic profiling of malignant phyllodes tumors reveals aberrations in FGFR1 and PI-3 kinase/RAS signaling pathways and provides insights into intratumoral heterogeneity. Mod Pathol 29(9):1012–1027. https://doi.org/10.1038/modpathol.2016.97

    Article  CAS  PubMed  Google Scholar 

  18. Barnes L, Pietruszka M (1978) Rhabdomyosarcoma arising within a cystosarcoma phyllodes: case report and review of the literature. Am J Surg Pathol 2(4):423–429

    Article  CAS  PubMed  Google Scholar 

  19. Silver SA, Tavassoli FA (1999) Osteosarcomatous differentiation in phyllodes tumors. Am J Surg Pathol 23(7):815–821

    Article  CAS  PubMed  Google Scholar 

  20. Austin RM, Dupree WB (1986) Liposarcoma of the breast: a clinicopathologic study of 20 cases. Hum Pathol 17(9):906–913

    Article  CAS  PubMed  Google Scholar 

  21. Chen WH, Cheng SP, Tzen CY, Yang TL, Jeng KS, Liu CL et al (2005) Surgical treatment of phyllodes tumors of the breast: retrospective review of 172 cases. J Surg Oncol 91(3):185–194. https://doi.org/10.1002/jso.20334

    Article  PubMed  Google Scholar 

  22. Chaney AW, Pollack A, McNeese MD, Zagars GK, Pisters PW, Pollock RE et al (2000) Primary treatment of cystosarcoma phyllodes of the breast. Cancer 89(7):1502–1511

    Article  CAS  PubMed  Google Scholar 

  23. Abdalla HM, Sakr MA (2006) Predictive factors of local recurrence and survival following primary surgical treatment of phyllodes tumors of the breast. J Egypt Natl Canc Inst 18(2):125–133

    PubMed  Google Scholar 

  24. Lenhard MS, Kahlert S, Himsl I, Ditsch N, Untch M, Bauerfeind I (2008) Phyllodes tumour of the breast: clinical follow-up of 33 cases of this rare disease. Eur J Obstet Gynecol Reprod Biol 138(2):217–221. https://doi.org/10.1016/j.ejogrb.2007.08.002

    Article  PubMed  Google Scholar 

  25. Sawalhi S, Al-Shatti M (2013) Phyllodes tumor of the breast: a retrospective study of the impact of histopathological factors in local recurrence and distant metastasis. Ann Saudi Med 33(2):162–168. https://doi.org/10.5144/0256-4947.2013.162

    Article  PubMed  Google Scholar 

  26. Ren D, Li Y, Gong Y, Xu J, Miao X, Li X et al (2014) Phyllodes tumor of the breast: role of Axl and ST6GalNAcII in the development of mammary phyllodes tumors. Tumour Biol 35(10):9603–9612. https://doi.org/10.1007/s13277-014-2254-9

    Article  CAS  PubMed  Google Scholar 

  27. Wei J, Tan YT, Cai YC, Yuan ZY, Yang D, Wang SS et al (2014) 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 33(10):492–500. https://doi.org/10.5732/cjc.014.10048

    PubMed  PubMed Central  Google Scholar 

  28. Ward RM, Evans HL (1986) Cystosarcoma phyllodes: a clinicopathologic study of 26 cases. Cancer 58(10):2282–2289

    Article  CAS  PubMed  Google Scholar 

  29. Asoglu O, Ugurlu MM, Blanchard K, Grant CS, Reynolds C, Cha SS et al (2004) Risk factors for recurrence and death after primary surgical treatment of malignant phyllodes tumors. Ann Surg Oncol 11(11):1011–1017. https://doi.org/10.1245/ASO.2004.02.001

    Article  PubMed  Google Scholar 

  30. Spitaleri G, Toesca A, Botteri E, Bottiglieri L, Rotmensz N, Boselli S et al (2013) Breast phyllodes tumor: a review of literature and a single center retrospective series analysis. Crit Rev Oncol Hematol 88(2):427–436. https://doi.org/10.1016/j.critrevonc.2013.06.005

    Article  PubMed  Google Scholar 

  31. Al-Masri M, Darwazeh G, Sawalhi S, Mughrabi A, Sughayer M, Al-Shatti M (2012) Phyllodes tumor of the breast: role of CD10 in predicting metastasis. Ann Surg Oncol 19(4):1181–1184. https://doi.org/10.1245/s10434-011-2076-6

    Article  PubMed  Google Scholar 

  32. Tan WJ, Thike AA, Bay BH, Tan PH (2014) Immunohistochemical expression of homeoproteins Six1 and Pax3 in breast phyllodes tumours correlates with histological grade and clinical outcome. Histopathology 64(6):807–817. https://doi.org/10.1111/his.12329

    Article  PubMed  Google Scholar 

  33. Lim WK, Ong CK, Tan J, Thike AA, Ng CC, Rajasegaran V et al (2014) Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet 46(8):877–880. https://doi.org/10.1038/ng.3037

    Article  CAS  PubMed  Google Scholar 

  34. Ng CC, Tan J, Ong CK, Lim WK, Rajasegaran V, Nasir ND et al (2015) MED12 is frequently mutated in breast phyllodes tumours: a study of 112 cases. J Clin Pathol 68(9):685–691. https://doi.org/10.1136/jclinpath-2015-202896

    Article  CAS  PubMed  Google Scholar 

  35. Yoshida M, Sekine S, Ogawa R, Yoshida H, Maeshima A, Kanai Y et al (2015) Frequent MED12 mutations in phyllodes tumours of the breast. Br J Cancer 112(10):1703–1708. https://doi.org/10.1038/bjc.2015.116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nagasawa S, Maeda I, Fukuda T, Wu W, Hayami R, Kojima Y et al (2015) MED12 exon 2 mutations in phyllodes tumors of the breast. Cancer Med 4(7):1117–1121. https://doi.org/10.1002/cam4.462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Piscuoglio S, Murray M, Fusco N, Marchiò C, Loo FL, Martelotto LG et al (2015) MED12 somatic mutations in fibroadenomas and phyllodes tumours of the breast. Histopathology 67(5):719–729. https://doi.org/10.1038/npjbcancer.2016.35

    Article  PubMed  PubMed Central  Google Scholar 

  38. Tan J, Ong CK, Lim WK, Ng CC, Thike AA, Ng LM et al (2015) Genomic landscapes of breast fibroepithelial tumors. Nat Genet 47(11):1341–1345. https://doi.org/10.1038/ng.3409

    Article  CAS  PubMed  Google Scholar 

  39. Nozad S, Sheehan CE, Gay LM, Elvin JA, Vergilio JA, Suh J et al (2017) Comprehensive genomic profiling of malignant phyllodes tumors of the breast. Breast Cancer Res Treat 162(3):597–602. https://doi.org/10.1007/s10549-017-4156-1

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Pathology, Singapore General Hospital, 20 College Road, Academia, Diagnostics Tower Level 7, Singapore, 169856, Singapore

    Valerie Cui Yun Koh, Aye Aye Thike, Nur Diyana Md Nasir & Puay Hoon Tan

  2. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, MD10, 4 Medical Drive, Singapore, 117594, Singapore

    Valerie Cui Yun Koh, George Wai Cheong Yip, Boon Huat Bay & Puay Hoon Tan

  3. Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore

    Aye Aye Thike & Puay Hoon Tan

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  1. Valerie Cui Yun Koh
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Correspondence to Puay Hoon Tan.

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This is a retrospective study involving human formalin-fixed paraffin-embedded tissues, and has been approved by the SingHealth Centralised Institutional Review Board (CIRB). This article does not contain any studies with animals performed by any of the authors.

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A waiver for informed consent was approved by the SingHealth CIRB. The SingHealth CIRB operates in accordance with the ICH/Singapore Guideline for Good Clinical Practices, and with the applicable regulatory requirement(s).

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Koh, V.C.Y., Thike, A.A., Nasir, N.D.M. et al. Size and heterologous elements predict metastases in malignant phyllodes tumours of the breast. Virchows Arch 472, 615–621 (2018). https://doi.org/10.1007/s00428-017-2257-1

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  • DOI: https://doi.org/10.1007/s00428-017-2257-1

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