Skip to main content
NCBI home page
Breast Care logoLink to Breast Care
. 2025 Jan 30;20(2):132–140. doi: 10.1159/000543655

Phyllodes Tumor of the Breast: Histomorphological Transformation to High-Grade Tumor during Pregnancy and Challenging Oncoplastic Surgery

Caroline Ines Preuss a,✉, Peter Schrenk b, Marco Affortunati a, Nina Brandstetter a, Stefanie Schuster b, Heike Kathleen Schwarz c, Bruno Schneeweiss c, Thomas Gitter d, Peter Oppelt a, Andreas Shamiyeh b, Rupert Langer e, Farid Moinfar f,g, Claudia Grosse e, Maria Steinmair e
PMCID: PMC12005692  PMID: 40256671

Abstract

Introduction

Phyllodes tumors of the breast are a very rare tumor entity. There are two different classifications according to AFIP (low-grade and high-grade phyllodes tumors of the breast) and WHO (three subtypes: benign, borderline, and malignant phyllodes tumors). Phyllodes tumors have an increased risk of recurrence. Primary clinical treatment of phyllodes tumors is surgery, although the width of the required resection margins often presents a challenge for surgical management.

Case Presentation

This case report deals with a 24-year-old woman with second recurrence of borderline phyllodes tumor. The challenge of this case lays first in surgical removal of the large tumor by breast-conserving therapy with tumor-free margins and favorable aesthetic outcome. Achieving this goal by tumor-adapted reduction mammoplasty, skin excision, and slide-swing skin flap was challenging. The second exciting aspect of this case is the histomorphology of the tumor and the transformation in vivo from fibroadenoma with stromal atypia in 2021 to the first recurrence with a low-grade phyllodes tumor in 2022 and the further transformation to a high-grade tumor with stromal overgrowth in the second recurrence of phyllodes tumor in 2023 during pregnancy and childbed.

Conclusion

This case of a phyllodes tumor shows how quickly tumor characteristics can change in fast-growing tumors due to transformation from low-grade to high-grade tumor. The influence of pregnancy on this process remains unclear at present. Surgical removal of phyllodes tumors should be performed during pregnancy.

Keywords: Phyllodes tumor, Breast oncoplastic surgery, Pregnancy, Tumor transformation, Breast sarcoma

Established Facts

  • Phyllodes tumors are a very rare and inhomogenous tumor entity.

  • Phyllodes tumors are classified according to WHO and AFIP criteria.

  • Only a few cases of phyllodes tumors during pregnancy and breastfeeding have been described in the literature so far.

  • The primary treatment of phyllodes tumors is surgical tumor resection.

Novel Insights

  • Following tumor transformation of phyllodes tumor in vivo from fibroepithelial tumor with stromal atypia to a low-grade borderline tumor to a high-grade phyllodes tumor with stromal overgrowth during pregnancy and childbed.

  • Challenging surgical procedure because of the giant recurrent tumor mass and patient’s wish of having a breast-conserving surgery. A combination of various oncoplastic surgical techniques was necessary for breast reconstruction and favorable aesthetic outcome.

Introduction

Phyllodes tumors are a rare tumor entity of fibroepithelial breast tumors with an incidence rate of 2.1 per 1 million women [1]. Phyllodes tumors have a broad biological appearance ranging from benign tumors almost like fibroadenomas to high-grade sarcomatous tumors without epithelial components. Phyllodes tumors have a higher risk of local recurrence and malignant phyllodes tumors can lead to distant metastases [2–5].

A multicenter trial in a contemporary cohort of 550 phyllodes tumors shows a deleterious mutation in approximately 10% of women with phyllodes tumors. Only 6.2% of the study patients with phyllodes tumor had a germline genetic testing, although additional 15.6% of patients met NCCN criteria for genetic testing. Deleterious mutation was found in BRCA1, TP53, and variant of uncertain significance in BRCA2 [6].

We are presenting a 24-year-old woman with the second recurrence of a phyllodes tumor of the left breast in 2023. The initial diagnosis of a fibroadenoma with stromal atypia was made in Afghanistan in spring 2021. The histopathological report took phyllodes tumor as differential diagnosis into consideration. Surgical removal of this finding was recommended. The surgical removal took place in Afghanistan in April 2021, after which the patient fled from Afghanistan to Europe. In November 2021, the patient presented to Kepler University Hospital for the first time with pain in her left breast. Since then, breast care has been provided exclusively at the Kepler University Hospital Linz, Austria.

Materials and Methods

The patient has been treated at the Kepler University Hospital in Linz since November 2021 with the first recurrence of a borderline phyllodes tumor of the left breast until now. The case report is based on the original findings reports from the patient’s medical file. The findings were all obtained as part of routine care and the surgical treatment was also carried out according to current clinical standards.

The histopathological processing of all specimens (core biopsy and surgical specimen) was carried out by the Institute of Pathology and Microbiology at the Kepler University Hospital Linz according to current guidelines for breast pathology. Phyllodes tumors are classified according to WHO [7] and AFIP criteria.

The WHO distinguishes between three subtypes: benign, borderline, and malignant phyllodes tumors, while the AFIP criteria distinguishes between low-grade and high-grade phyllodes tumors of the breast. The surgical specimen of both operations was subject to a second opinion by an external reference pathologist. The surgical reconstruction was performed by the team of the certified Breast Competence Center, Kepler University Hospital Linz, Austria.

Results

First Recurrence: Core Biopsy

When the patient presented in November 2021, a solid mass with central liquid parts and irregular borders with a diameter of 8 mm was found. The lesion was in the upper outer quadrant of the left breast. The core biopsy on the same day revealed a histopathological component of a fibroepithelial tumor, possibly corresponding to a phyllodes tumor with moderately dense stromal cellularity and focal atypia of the stromal cells. Seven mitotic figures per 10 HPF [3 mitoses/mm2] were observed. The patient did not wish to have another operation, so a sonographic follow-up was recommended after 6 months.

After just 2 months, the patient presented again in January 2022 with breast tumor on the left side and stated that the tumor has been growing. Breast ultrasonography showed the tumor to be progressive in size, measuring 20 × 18 mm (8 mm 2 months previously). A surgical excision of the tumor was recommended to the patient.

First Recurrence: Excision Biopsy and Histopathological Report

The excision biopsy was performed in March 2022 by periareolar incision. The tumor was completely excised, but intraoperatively there was a laceration of the tumor with fluid leakage.

In this first recurrence, the histopathological examination no longer revealed a fibroepithelial tumor with atypia of the stromal cells as in the initial histopathological findings. The resection specimen showed the first transformation of the tumor cells into a borderline phyllodes tumor (WHO) or low-grade phyllodes tumor of the breast (AFIP) (Fig. 1, 2). Molecular analysis using next-generation sequencing (Ion Torrent, Thermo Fisher, OACV3 panel) revealed TERT wild type and MED12 wild type in this tumor specimen. After surgery, the patient became pregnant for the first time and did not appear for a sonographic follow-up.

Fig. 1.

Fig. 1.

Open in a new tab

First recurrence: borderline phyllodes tumor (WHO) or low-grade phyllodes tumor of the breast (AFIP): biphasic fibroepithelial neoplasm with leaf-like epithelial pattern and stromal proliferation (hematoxylin-eosin staining, low power magnification).

Fig. 2.

Fig. 2.

Open in a new tab

First recurrence: borderline phyllodes tumor (WHO) or low-grade phyllodes tumor of the breast (AFIP): stroma component with slightly atypical cells (hematoxylin-eosin stain, high power magnification). In this image, no mitoses can be detected.

Second Recurrence: 18th Week of Pregnancy

The next appearance of the patient was in October 2022 in the 18th week of pregnancy with mastodynia and increasing firmness of the left breast. Sonography of the breast showed an 18 mm hypoechoic lesion in the upper outer quadrant of the left breast with a small satellite lesion starting at the cranial edge of the surgical scar.

Due to the pregnancy and the known histopathological findings of a low-grade phyllodes tumor 8 months before, a short-term follow-up after 6 weeks was discussed with the patient. The sonographic follow-up in December 2022 revealed a rapidly progressing tumor measuring 50 × 20 mm in the left breast. The patient was in the 29th week of pregnancy at this time. Surgical excision of the tumor was recommended to the patient, but the patient requested this after her expected date of childbirth in March 2023.

The spontaneous delivery took place on March 23rd, 2023 in the 41st week of pregnancy. There was no histopathological examination of the placenta. The patient was breastfeeding her healthy newborn.

Progress of Second Recurrence during Pregnancy and Delivery

Four weeks postpartum, the patient presented in April 2023 with a massively progressive tumor in the left breast and severe pain. The clinical examination revealed a 10 × 8 cm tumor with pronounced swelling and deformation of the breast (Fig. 3, 4). Stopping breastfeeding and weaning the child was the first step to optimize the initial situation for surgical removal of the tumor and oncoplastic reconstruction.

Fig. 3.

Fig. 3.

Open in a new tab

Phyllodes tumor of the left breast with large tumor mass and swelling in the upper outer quadrant (frontal).

Fig. 4.

Fig. 4.

Open in a new tab

Phyllodes tumor of the left breast with large tumor mass and swelling in the upper outer quadrant (lateral oblique).

Due to the size of the tumor, the patient was recommended a mastectomy. However, because of her young age and without the prospect of primary reconstruction, the patient rejected mastectomy. A complex breast-conserving, oncoplastic surgical procedure was therefore discussed with the patient.

Oncoplastic Surgery: Tumor-Adapted Reduction Mammoplasty, Skin Excision, Slide-Swing Skin Flap

Breast conserving therapy was planned as tumor-adapted reduction mammoplasty. The tumor mass was enormous with deformation of the breast (Fig. 3–5). Because tumor infiltration of the skin could not be excluded preoperatively in the upper outer quadrant of the left breast, skin excision biopsy ventral of the tumor mass was performed (Fig. 5). The reconstruction of the breast was challenging because of high-volume loss of tissue and an enormous skin defect (Fig. 6). The nipple-areola complex was pedunculated by a superior dermoglandular pedicle.

Fig. 5.

Fig. 5.

Open in a new tab

Phyllodes tumor resection specimen with skin ventral on tumor as seen in the operation theater. The cranial suture marker is in the upper part of the tumor specimen. In the lower part of the specimen, the two suture markings show the retroareolar position.

Fig. 6.

Fig. 6.

Open in a new tab

Intraoperative situs left breast after removal of tumor and before reconstruction and slide-swing skin flap.

The skin defect of the former upper outer quadrant should be closed by a slide-swing skin flap of the partially de-epithelialized, inferior dermoglandular pedicle. The breast volume of the lower quadrants was preserved in contrast to usual reduction mammoplasty.

The reconstruction started with swinging the inferior dermoglandular skin flap to the outer breast quadrant and partial de-epithelialization of the flap (Fig. 7) followed by redefinition of the new inframammary fold and the central fixation of the nipple-areola complex. Figure 8 documents the cosmetic result at the end of the oncoplastic surgery. Figure 9 shows the very pleasant aesthetic outcome after removing the stitches 6 weeks postoperative.

Fig. 7.

Fig. 7.

Open in a new tab

Intraoperative remodeling by inferior dermoglandular skin flap swinged in the former upper outer breast quadrant and redefinition of the new inframammary fold.

Fig. 8.

Fig. 8.

Open in a new tab

Postoperative situs, oncoplastic reconstruction of the left breast.

Fig. 9.

Fig. 9.

Open in a new tab

Aesthetic result 6 weeks postoperatively with small superficial skin dehiscence in the submammary fold.

Transformation of Low-Grade Phyllodes Tumor to High-Grade Phyllodes Tumor with Stromal Overgrowth during Pregnancy and Childbed

The big surprise came after pathological assessment of the surgical specimen of second phyllodes tumor recurrence. The HE sections showed a phyllodes tumor of the breast with high percellular stromal sections and numerous sections with cloverleaf-like structures containing mesenchymal high percellular areas with at least moderately polymorphic or atypical stromal cells. Bizarrely shaped, partly hyperchromatic, and partly vesicular cell nuclei as well as multinucleated tumor cells were present. The majority of the stromal cells showed moderate nuclear atypia, but there were always areas with highly polymorphic or atypical tumor cell nuclei, thus overall high-grade nuclear atypia of the tumor cells. The tumor was sharply demarcated (no infiltrative irregular growth pattern detectable in the present samples). Some samples also clearly showed a so-called stromal overgrowth without an epithelial tumor component. In the present samples, no heterologous differentiation could be identified. The tumor was alternately mitotic; in some areas, the mitotic rate was very low, but focally increased mitotic figures could be detected, with a maximum of 6 mitotic figures in 10 HPF. Here, however, atypical mitotic figures could also be identified in isolated cases. According to AFIP criteria, the findings corresponded to a high-grade phyllodes tumor; according to WHO criteria, the findings corresponded with a borderline phyllodes tumor (Fig. 10–12). Molecular analysis using next-generation sequencing (Ion Torrent, Thermo Fisher, OACV3 panel) revealed TERT wild type and MED12 wild type.

Fig. 10.

Fig. 10.

Open in a new tab

Second recurrence: borderline phyllodes tumor (WHO) or high-grade phyllodes tumor (AFIP) of the breast: there is a loss of the leave-like architecture and atypical stroma cells can be easily appreciated (hematoxylin-eosin stain, low power magnification).

Fig. 12.

Fig. 12.

Open in a new tab

Second recurrence: borderline phyllodes tumor (WHO) or high-grade phyllodes tumor (AFIP) of the breast: atypical cells with mitoses in the stroma rich components (hematoxylin-eosin stain, high power magnification).

Fig. 11.

Fig. 11.

Open in a new tab

Second recurrence: borderline phyllodes tumor (WHO) or high-grade phyllodes tumor (AFIP) of the breast: few areas showed the epithelial component. In the stroma, bizarre cells can be detected with atypical mitoses (hematoxylin-eosin stain, high power magnification).

Discussion

Phyllodes tumors of the breast can occur from adolescence to old age, with high-grade tumors more likely to occur in older patients. The median incidence at first diagnosis is between the 40th and 50th year of life [8, 9]. Breast-conserving surgery is the standard of care, although unfavorable breast-tumor ratio of phyllodes tumors with expecting an unfavorable cosmetic result and the need for wide resection margins can lead to mastectomy [8].

The current recommendation of the National Comprehensive Cancer Network (NCCN) Guidelines version 5.2023 is a complete resection of the tumor with resection margins of at least 1 cm. Mastectomy is only recommended if a poor cosmetic outcome is expected with breast-conserving therapy and if the safety margins of 10 mm cannot be maintained [10].

However, discussions about requirements of resection margins are ongoing. Some results of contemporary studies also provided a new basis for more individualized resection margins in phyllodes tumors [11, 12]. Even in benign phyllodes tumors, the acceptance margins lower than 10 mm is upcoming and may be the new standard of care [11, 13, 14]. However, there is still a lack of prospective data.

Adjuvant radiation for borderline and malignant phyllodes tumors is still controversially discussed – radiation reduces the local recurrence risk but has no influence on disease-free survival [10, 15, 16]. Contemporary guidelines are considering postoperative radiation in certain settings – for example, in case of malignant phyllodes tumors or locally recurrent phyllodes tumors (e.g., NCCN, MD Anderson). Only a few cases of phyllodes tumors during pregnancy and breastfeeding have been described in the literature so far [17–19].

There are two exciting aspects to this case report – the first aspect is that breast-conserving surgery is possible even with an unfavorable breast-tumor ratio if various techniques of oncoplastic surgery are combined. The second aspect in this case is the in vivo transformation of a fibroepithelial tumor with stromal atypia to a low-grade borderline tumor to a high-grade phyllodes tumor with stromal overgrowth. Each step in the transformation process of the tumor could be documented histopathologically in the rapid recurrences and clinical progression of the phyllodes tumor.

Conclusion

This case of a phyllodes tumor shows how quickly tumor characteristics can change in fast-growing tumors due to transformation from low-grade to high-grade tumor. The influence of pregnancy on the rapid second recurrence of the borderline tumor, the rapid progression, and the final transformation to a high-grade phyllodes tumor remains unclear at present.

The surgical removal of a phyllodes tumor – even with low-grade morphology – should be performed generally during pregnancy in order to ensure a breast-conserving surgery with favorable aesthetic outcome and to avoid the risk of losing the entire breast. This case shows impressively that transformation from low-grade to high-grade phyllodes tumor is possible within few months during pregnancy.

After oncoplastic surgery of the left breast and the final histopathological findings of a high-grade phyllodes tumor, the patient decided to undergo a secondary ablation of the breast to achieve maximum oncological safety and to avoid radiation therapy. The mastectomy was performed in July 2023 without complications; the histopathological examination showed no further parts of phyllodes tumor.

Acknowledgments

Authors thank all team members of the Breast Competence Center, Johannes Kepler University Hospital Linz, Austria.

Statement of Ethics

Written informed consent was obtained from the patient for publication of this case report and any accompanying images anonymously. Ethical review board was not necessary because treatment of patient was according to standard treatment and not an experimental one. This case report has a retrospective character and writing on it started after written informed consent by patients. Ethical approval was not required for this study in accordance with local/national guidelines.

Conflict of Interest Statement

Caroline Ines Preuss received honoraria from MSD and AstraZeneca and congress/travel expenses from MSD and Daiichi-Sankyo. Rupert Langer received honoraria from MSD, Astellas, Roche, and AstraZeneca. The other authors have no conflicts of interest to declare.

Funding Sources

There was no funding.

Author Contributions

Conceptualization, project administration, and writing – review original draft: C.I.P. and M.S. Data curation: C.I.P., P.S., M.A., N.B., S.S., H.K.S., T.G., and C.G. Investigation: C.I.P., M.S., and F.M. Resources: P.O., A.S., and R.L. Supervision: C.I.P., R.L., and B.S. Visualization: C.I.P., M.S., and T.G. Writing – review and editing: all authors. All authors have read and agreed to the published version of the manuscript.

Funding Statement

There was no funding.

Data Availability Statement

The patient’s medical file is available.

References

  • 1. Bernstein L, Deapen D, Ross RK. The descriptive epidemiology of malignant cystosarcoma phyllodes tumors of the breast. Cancer. 1993;71(10):3020–4. [DOI] [PubMed] [Google Scholar]
  • 2. 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. [DOI] [PubMed] [Google Scholar]
  • 3. Chaney AW, Pollack A, McNeese MD, Zagars GK, Pisters PW, Pollock RE, et al. Primary treatment of cystosarcoma phyllodes of the breast. Cancer. 2000;89(7):1502–11. [DOI] [PubMed] [Google Scholar]
  • 4. Lerwill MF, Lee AHS, Tan PH. Fibroepithelial tumours of the breast-a review. Virchows Arch. 2022;480(1):45–63. [DOI] [PubMed] [Google Scholar]
  • 5. Tan BY, Acs G, Apple SK, Badve S, Bleiweiss IJ, Brogi E, et al. Phyllodes tumours of the breast: a consensus review. Histopathology. 2016;68(1):5–21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Rosenberger LH, Thomas SM, Nimbkar SN, Hieken TJ, Ludwig KK, Jacobs LK, et al. Germline genetic mutations in a multi-center contemporary cohort of 550 phyllodes tumors: an opportunity for expanded multi-gene panel testing. Ann Surg Oncol. 2020;27(10):3633–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Tan PH, Ellis I, Allison K, Brogi E, Fox SB, Lakhani S, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology. 2020;77(2):181–5. [DOI] [PubMed] [Google Scholar]
  • 8. Karim RZ, Gerega SK, Yang YH, Spillane A, Carmalt H, Scolyer RA, et al. Phyllodes tumours of the breast: a clinicopathological analysis of 65 cases from a single institution. Breast. 2009;18(3):165–70. [DOI] [PubMed] [Google Scholar]
  • 9. Abusalem OT, Al-Masri A. Phyllodes tumors of the breast. Mater Sociomed. 2011;23(4):200–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Sars C, Sackey H, Frisell J, Dickman PW, Karlsson F, Kindts I, et al. Current clinical practice in the management of phyllodes tumors of the breast: an international cross-sectional study among surgeons and oncologists. Breast Cancer Res Treat. 2023;199(2):293–304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. 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):178–89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12. Thind A, Patel B, Thind K, Isherwood J, Phillips B, Dhaliwal K, et al. Surgical margins for borderline and malignant phyllodes tumours. Ann R Coll Surg Engl. 2020;102(3):165–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Ogunbiyi S, Perry A, Jakate K, Simpson J, George R. Phyllodes tumour of the breast and margins: how much is enough. Can J Surg. 2019;62(1):E19–e21. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. Shaaban M, Barthelmes L. Benign phyllodes tumours of the breast: (Over) treatment of margins: a literature review. Eur J Surg Oncol. 2017;43(7):1186–90. [DOI] [PubMed] [Google Scholar]
  • 15. Zeng S, Zhang X, Yang D, Wang X, Ren G. Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: a systematic review and meta-analysis. Mol Clin Oncol. 2015;3(3):663–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Wong RX, Koh YS, Wong FY, Kusumawidjaja G, Ng WL, Yeo RMC, et al. The impact of radiotherapy and histological risk factors on outcomes in malignant phyllodes tumors. Clin Breast Cancer. 2020;20(6):e695–700. [DOI] [PubMed] [Google Scholar]
  • 17. Liang MI, Ramaswamy B, Patterson CC, McKelvey MT, Gordillo G, Nuovo GJ, et al. Giant breast tumors: surgical management of phyllodes tumors, potential for reconstructive surgery and a review of literature. World J Surg Oncol. 2008;6:117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Schmidt M, Ozalinskaite A, Popovic M, Humenikova M, Fersis N. Phylloidestumor in der Gravidität: Fallvorstellung und Literaturrecherche. Senologie Z für Mammadiagnostik Therapie. 2016;13(02):A119. [Google Scholar]
  • 19. Kallam AR, Kanumury V, Korumilli RM, Gudeli V, Polavarapu H. Massive benign phyllodes tumour of breast complicating pregnancy. J Clin Diagn Res. 2017;11(5):Pd08–pd09. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The patient’s medical file is available.

Articles from Breast Care are provided here courtesy of Karger Publishers

RESOURCES