Malignant phyllodes tumor of the breast with bilateral ductal carcinoma in situ and postoperative distant metastasis: a case report

Introduction

Phyllodes tumors (PTs) is a rare breast neoplasm with varying degrees of malignancy, ranging from benign to malignant, accounting for 0.3% to 1% of primary breast tumors (1,2). The World Health Organization (WHO) classification categorizes phyllodes tumor of the breast (PTB) into benign (60%), borderline (20%), and malignant (20%) subtypes (1). Malignant phyllodes tumor of the breast (MPTB) is exceptionally uncommon, and its etiology remains elusive. Possible associations include concurrent presence with fibroadenoma, and transformation from pre-existing fibroadenoma (3).

Fibroadenomas and PTs are both diseases of the breast, but there are some differences between them. Fibroadenomas are the most common benign tumors of the breast, which can occur from puberty onwards at any age, with a high incidence generally between 15–35 years old (3,4). On the other hand, the age of onset for PTs is generally 40–50 years old, which is older than those of fibroadenomas (1,2,5-7). Fibroadenomas generally grow slowly, with no significant changes over several years. A small portion of fibroadenomas can naturally regress, but there are also some that can rapidly enlarge (3,4). PTs can rapidly enlarge in a short period of time. Fibroadenomas are generally benign (1,2,5-7). However, PTs are generally divided into benign, borderline, and malignant types in pathological diagnosis (4). Mammography reveals circumscribed masses, and sonography can distinguish certain features of PTs from fibroadenomas. However, distinguishing between benign and malignant PTs remains difficult. Additionally, cytological diagnosis, especially of malignant PTs, presents challenges (5-7).

This case report provides a retrospective analysis of a clinically rare case of MPTB. The aim of this case report is to consolidate knowledge about the clinical and imaging manifestations of MPTB by drawing insights from case studies and literature reviews. This could potentially enhance our understanding and contribute to more effective diagnosis and treatment strategies for this complex condition. We present this case in accordance with the CARE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-497/rc).

Case presentation

All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). This case report was approved by the ethics committee of Taizhou Central Hospital (No. 2023L-02-05). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Chief complaints

The patient, a 35-year-old woman, noticed a walnut-sized mass in her left breast in 2022 but neglected the mass without seeking medical attention. During the first half year of 2023, the mass significantly increased in size, prompting her to seek treatment at Taizhou Central Hospital. Upon physical examination in June of 2023, the patient exhibited asymmetrical breast sizes, prominent varicose veins on the skin of the left breast, and a palpable, firm mass measuring approximately 10 cm × 10 cm in the left breast. The mass had unclear boundaries, limited mobility, and a rough surface. Notably, there was no tenderness, skin discoloration, swelling, dimpling, or orange peel-like changes. The right breast showed no palpable abnormalities, and no enlarged lymph nodes were detected in both axillae.

The patient reported no medical history or family history of breast disease. No previous intervention was proceeded before she came to Taizhou Central Hospital.

Breast ultrasound examination

Breast ultrasound revealed a large hypoechoic area in the left breast measuring approximately 5.6 cm in thickness. The lesion displayed irregular shape, unclear boundaries, uneven echogenicity, irregular dark areas, and abundant intratumoral blood flow signals. Surrounding the primary lesion, multiple hypoechoic areas of varying sizes were observed, characterized by irregular shapes and indistinct boundaries. The largest of these measured 2.7 cm × 1.7 cm. Additionally, several hypoechoic areas were detected in the left axilla, with clear boundaries and internal structures, accompanied by minimal blood flow signals. One of these measured 1.6 cm × 0.6 cm and was classified as Grade 4C (Figure 1A) according to Breast Imaging Reporting and Data System (BI-RADS). In the right breast, multiple hypoechoic areas with either clear or unclear boundaries were observed. Among these, two lesions, measuring 1.5 cm × 1.1 cm (located at the 9 o’clock position, displaying an irregular shape and unclear boundary with strong internal echogenic foci) and 0.8 cm × 0.6 cm (also at the 9 o’clock position, exhibiting an irregular shape and unclear boundary), were noted. Notably, no palpable, enlarged lymph nodes were detected in the right axilla, and these findings were classified as BI-RADS Grade 4A.

Figure 1 Preoperative image of the patient. (A) Preoperative B-ultrasonography of breast. (B,C) Preoperative molybdenum target image. (D) Preoperative computed tomography images of the chest.

Mammography examination

The left breast exhibited increased volume, multiple nodules, and masses, with no apparent calcification foci. The skin of the left breast was thickened, and the subcutaneous fat space was unclear. Enlarged lymph nodes were observed in the left axilla. The diagnosis result showed an occupying mass that differed from normal tissue observed in the left breast, which was classified as BI-RADS Grade 4B. In the right breast, a small nodule was identified, which was categorized as BI-RADS Grade 3 (Figure 1B,1C).

Chest computed tomography (CT) examination

The left breast displayed multiple nodules and masses, some of which had fused, with partially unclear boundaries. Local skin thickening and blurred subcutaneous fat space were noted. Enlarged lymph nodes were observed in the left axilla. Scattered small solid nodules were found in both lungs (Figure 1D). The lesion was small and metastasis was not confirmed, and no clinical intervention was given before surgery.

Surgical procedure and gross examination

Considering clinical assessment of a giant malignant breast tumor, the patient was suggested to receive surgery immediately. No biopsy was performed. After exclusion of contraindications to surgery, modified radical mastectomy of both breasts was performed under general anesthesia, and a mass was seen on the cut surface of the left breast mass underneath the nipple and skin by the naked eye, with a size of 9 cm × 8 cm × 6 cm, and a greyish-white, greyish-red, and greyish-yellow section, and a mass was seen in the right breast in the upper outer quadrant of the nipple at a distance of 3.5 cm from the nipple with a size of 2 cm × 1 cm × 1 cm, and a greyish color of the cut surface.

Intraoperative cryostat sectioning

It revealed that the left breast tumor was consistent with soft tissue sarcoma with significant necrosis, while the right breast exhibited hyperplasia with focal ductal epithelium considered atypical hyperplasia.

Pathological findings

Left breast: malignant PT, accompanied by ductal carcinoma in situ (intermediate grade, diameter 0.8 cm), accompanied by hyperplasia and fibroadenoma, and axillary lymph node metastasis 0/8 (Figure 2A,2B).

Figure 2 Immunohistochemical image. (A) Malignant phyllodes tumor in the left breast (Vimentin +, ×200). (B) Intraductal carcinoma in the left breast (estrogen receptor +, ×200). (C) Intraductal carcinoma in the right breast (estrogen receptor +, ×200).

Right breast: ductal carcinoma in situ (low grade, multifocal, maximum diameter 0.7 cm), accompanied by hyperplasia and fibroadenoma, and active ductal epithelial hyperplasia, with axillary lymph node metastasis 0/7 (Figure 2C).

Immunohistochemical findings

The immunohistochemical findings were as follows. The left breast I piece (Figure 2) showed estrogen receptor (ER) (−), progesterone receptor (PR) (−), human epidermal growth factor receptor II gene (CerbB2) (0), Ki-67 (a tumor proliferation-associated antigen) (10%+), B-cell lymphoma-2 (BcL-2) (−), smooth muscle actin (SMA) (stain +), recombinant cluster of differentiation 34 (CD34) (vascular +), soluble protein-100 (S-100) (−), Vimentin (VIM) (+), P53 (tumor suppressor protein, oncogene protein) (−), cytokeratin (CK) (epithelial +), and recombinant tumor protein P63 (−). The left breast showed ER (partial ++), PR (partial +++), CerbB2 (0), Ki-67 (2%+), CK5/6 (stain −), and calponin (muscle epithelial +). The right breast I piece showed ER (small focus +++), PR (small focus +++), CerbB2 (1+), Ki-67 (2%+), P53 (muscle epithelial +), CK5/6 (small focus −), and calponin (muscle epithelial +). The right breast O + H piece showed CK5/6 (small focus −).

Postoperative follow-up and disease progression

The patient was diagnosed of malignant PT with intraductal carcinoma after pathological examinations. The patient recovered well from the surgery and the wound healed well. Postoperative toremifene citrate was administered once a day, one tablet each time (no radiotherapy). Three months (September of 2023) after the operation, the patient found a mass in the left axillary fossa. The physical examination found an enlarged lymph node of about 4.0 cm × 3.0 cm with hard texture, unclear boundary and poor mobility in the left axillary fossa. Repeat breast ultrasound showed a heterogeneous parenchymal occupancy in the left axilla (Figure 3A). Chest CT suggested diffuse metastasis in both lungs after surgery (Figure 3B,3C). The patient was considered to have diffuse metastasis in the left axillary lymph node and both lungs based on the physical examinations and imaging results, but the patient refused pathological examinations and the metastasis could be confirmed. After discovering lung metastases, the patient was suggested of transferring to intensive care unit for treatment. But the patient chose to forgo treatment, and refused the pathological examination and other examinations. Then, the patient had secondary lung infection, and the disease progressed rapidly. The patient passed away at the 4th month post-surgery.

Figure 3 Postoperative image of the patient. (A) Reexamination of breast B-ultrasound images after surgery. (B,C) Postoperative computed tomography images of the chest.

Discussion

MPTB predominantly occurs in middle-aged and elderly women. Some studies suggest that age significantly influences the prognosis of MPTB, with patients aged ≤40 years having a worse prognosis than those aged >40 years (6). Young patients often present with larger tumors. The patient in this case was 35 years old and had a large, diffuse, multinodular mass with partially unclear borders, consistent with the reported characteristics of MPTB. It has been reported that MPTB is seldom accompanied by skin thickening or axillary lymph node enlargement (7). However, in this case, the patient exhibited irregular mass morphology, localized skin thickening, ambiguous subcutaneous fat gaps, and axillary lymph node enlargement. Postoperative pathology suggested that the enlarged lymph nodes were reactive hyperplasia changes, with no clear signs of metastasis. A research report (8) indicates that skin varicose veins are highly suggestive of MPTB, likely due to the large mass causing significant compression of neighboring veins, resulting in venous return obstruction. This case presented with obvious skin varicose veins, further supporting the diagnosis of MPTB.

Before surgery, no biopsy was performed since the clinical assessment diagnosed that was a giant malignant breast tumor. After completing all necessary examinations, the patient underwent surgery directly. Regrettably, a preoperative magnetic resonance imaging (MRI) was not conducted, and the lack of effective communication between the radiologists and the doctors performing the mammography examination posed a challenge to making an accurate diagnosis. This oversight underscored the importance of comprehensive communication and collaboration among medical professionals to enhance diagnostic accuracy. The lack of biopsy was a limitation of this case report.

Prior research (1,6) has demonstrated that MPTB has a high recurrence rate, with most recurrences occurring within two years of diagnosis. Recurrence rates can be as high as 30%, and the tumor is prone to metastasis. Approximately 10–30% of MPTBs develop distant metastases, commonly spreading to the lungs and bones. Axillary lymph node metastasis is rare (9), and gastrointestinal tract metastasis is even rarer (10). In this case, the patient experienced rapid disease progression, developing axillary lymph node metastasis and diffuse lung metastasis merely three months post-surgery. The patient refused treatment and her condition deteriorated swiftly, leading to her demise a mere four months after the surgical intervention.

The aggressive nature of MPTB, especially in younger patients, emphasizes the need for early detection, accurate diagnosis, and timely intervention to improve outcomes and patient survival. MPTB exhibits distinctive characteristics, including infiltrative growth, significant cell polymorphism, and prominent stromal hyperplasia (1,5,7,8,11). The tumor often demonstrates active cell division, with a high nuclear division rate (>10/10 high-power fields). Hemorrhage and necrosis within the tumor are common occurrences (1). Notably, when stromal components excessively proliferate, epithelial components can become challenging to identify. Careful examination of multiple specimens is crucial to avoid misdiagnosis, particularly with interstitial sarcoma (1,5,7,8,11). In this case, intraoperative cryostat sectioning indicated the presence of soft tissue sarcoma with extensive necrosis, suggesting a potential connection to the excessive proliferation of stromal components.

Furthermore, MPTB coexisting with other malignant tumor types within the breast is a rare phenomenon. Existing literature reported instances where MPTB is accompanied by ductal carcinoma in situ or coexists with components such as smooth muscle sarcoma, undifferentiated sarcoma, osteosarcoma, chondrosarcoma, or rhabdomyosarcoma (1,5,7,8,11). This coexistence underscores the tumor’s complex nature and highlights the importance of comprehensive pathological examination to identify and differentiate various tumor components accurately.

The intricate histological features of MPTB, coupled with its potential to coexist with diverse malignant elements, pose diagnostic challenges. Accurate diagnosis demands meticulous evaluation, interdisciplinary collaboration, and awareness of the tumor’s diverse presentations. Timely and precise diagnosis is pivotal for guiding appropriate treatment strategies, thereby improving patient outcomes and quality of life.

The coexistence of MPTB with other pathological types of malignant breast tumors is a rare phenomenon, as documented in the previous literatures (11,12). Reports have indicated cases where MPTB is accompanied by ductal carcinoma in situ, smooth muscle sarcoma, undifferentiated sarcoma, osteosarcoma, chondrosarcoma, and rhabdomyosarcoma. This coexistence can occur in distinct ways (1,11,12):

• MPTB may harbor malignant epithelial components, such as ductal carcinoma in situ or invasive ductal carcinoma, within its structure. Clear boundaries between MPTB and coexisting cancer tissues might not be evident, necessitating careful differentiation of their respective sarcomatous and carcinomatous natures.
• MPTB and cancer lesions might be located in different regions of the same breast.
• MPTB and cancer lesions might be situated on different sides of the breast.

In this specific case, MPTB was accompanied by the formation of ductal carcinoma in situ on both sides of the breast, a rare occurrence. The current standard approach for managing MPTB often involves total mastectomy. Ensuring negative surgical margins and implementing adjuvant radiotherapy post-surgery are crucial steps to reduce local recurrence and distant metastasis rates (6,13).

The typical treatment for MPTB involves surgery with the objective of completely removing the tumor, along with a margin of healthy tissue surrounding it to prevent recurrence (1,7,11,14,15). If the tumor is benign, an excisional biopsy might suffice, provided the tumor is completely removed. In the case of a malignant tumor, a wider margin is usually excised. This could be achieved through breast-conserving surgery, such as lumpectomy or partial mastectomy, where a part of the breast is removed (1,7,11,14,15). Alternatively, a mastectomy, which involves the removal of the entire breast, might be performed, especially if a margin of normal breast tissue cannot be preserved with breast-conserving surgery (1,7,11,14,15).

Postoperative radiation therapy may be administered to the area, particularly if it’s uncertain whether the entire tumor was removed (14,15). MPTB differs from more common types of breast cancer in its response to treatment. It is less likely to respond to treatments typically used for breast cancer, such as hormone therapy or standard chemotherapy drugs (1,7,11,14,15). If a malignant PT has metastasized to other parts of the body, it is generally treated similarly to a soft-tissue sarcoma (1,7,11,14,15).

Limitations

This case report, while insightful, has limitations. The limited dataset restricts a comprehensive understanding of MPTB. Molecular and genetic factors were not explored, which is crucial for understanding pathogenesis and prognosis. Furthermore, the patient delayed her time for consulting a doctor, and the hasty operation did not provide preoperative biopsy results, which should be reminded as a “take-away” experience. Finally, the patient was considered to have diffuse metastasis in the left axillary lymph node but the metastasis could be confirmed due to the patient’s refusal on subsequent pathological examinations and treatment. This was a regretful thing for this case report.

Conclusions

To conclude, this case report presents a rare instance of MPTB in a 35-year-old woman, underscoring the significant diagnostic and therapeutic challenges encountered. Despite receiving extensive treatment, the patient experienced rapid disease progression, culminating in her demise four months post-surgery. This case accentuates the complex nature of MPTB, highlighting the urgent need for improved diagnostic techniques, interdisciplinary collaboration, and advanced research. Regretfully, as the patient delayed her time to come for treatment, when the patient was diagnosed, the breast tumor was huge and immediate surgery was needed. Moreover, due to the hasty operation, the preoperative biopsy results were not obtained. When the patient had metastasis at the lung three months post-surgery, she refused other examinations and treatment. This was the limitation of this case report.

We advocate for conducting surgery subsequent to obtaining preoperative biopsy results, as these findings may guide physicians in planning accurate surgical procedure and other treatments. The preoperative assessment, which includes the biopsy, is a crucial step in identifying co-morbidities that could potentially lead to complications during the anaesthetic, surgical, or post-operative period. A comprehensive understanding and accurate diagnosis are essential for tailoring treatments, ultimately enhancing patient outcomes and quality of life for those grappling with this aggressive malignancy.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-497/rc

Peer Review File: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-497/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-497/coif). The 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. All procedures performed in this case were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). This case report was approved by the ethics committee of Taizhou Central Hospital (No. 2023L-02-05). Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

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/.

References

1. Lissidini G, Mulè A, Santoro A, et al. Malignant phyllodes tumor of the breast: a systematic review. Pathologica 2022;114:111-20. [Crossref] [PubMed]
2. Alipour S, Eskandari A, Johar FM, et al. Phyllodes Tumor of the Breast during Pregnancy and Lactation; A Systematic Review. Arch Iran Med 2020;23:488-97. [Crossref] [PubMed]
3. Paxton EG, Mabry H, Alattia L. Transformation of a Benign-Appearing Fibroepithelial Lesion to a Giant Malignant Phyllodes Tumor of the Breast. Cureus 2022;14:e32881. [Crossref] [PubMed]
4. Duman L, Gezer NS, Balcı P, et al. Differentiation between Phyllodes Tumors and Fibroadenomas Based on Mammographic Sonographic and MRI Features. Breast Care (Basel) 2016;11:123-7. [Crossref] [PubMed]
5. 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]
6. 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]
7. Ma XW, Zhang SW, Peng WJ. Research progress in the application of imaging techniques in lobular breast tumors. Oncoradiology 2021;30:218-21.
8. Gu HY, Luo S, Deng XY, et al. MRI imaging analysis of lobular breast tumors with different pathological grades. Journal of Clinical Radiology 2019;38:1194-7.
9. Naal T, Saker S, Coldren D. Lymph Node and Distant Metastases in Phyllodes Tumor of the Breast. Int J Surg Pathol 2023;31:761-4. [Crossref] [PubMed]
10. Ko SY. Malignant phyllodes tumor of the breast with heterologous osteosarcoma and chondrosarcomatous differentiation: A rare case report with imaging findings. Radiol Case Rep 2023;18:1982-8. [Crossref] [PubMed]
11. Fede ÂBS, Pereira Souza R, Doi M, et al. Malignant Phyllodes Tumor of the Breast: A Practice Review. Clin Pract 2021;11:205-15. [Crossref] [PubMed]
12. Jain S, Kaur R, Agarwal R, et al. Bilateral invasive duct carcinoma, phyllodes tumor and multiple fibroadenomas of breast associated with lymph node metastases - rare coexistence. Indian J Surg Oncol 2014;5:186-8. [Crossref] [PubMed]
13. Ostapenko E, Burneckis A, Ostapenko A, et al. Malignant phyllodes tumor of the breast with metastases to the lungs: A case report and literature review. Radiol Case Rep 2022;17:4006-12. [Crossref] [PubMed]
14. Rayzah M. Phyllodes Tumors of the Breast: A Literature Review. Cureus 2020;12:e10288. [Crossref] [PubMed]
15. Shah-Patel LR. Malignant phyllodes breast tumor. Radiol Case Rep 2017;12:645-7. [Crossref] [PubMed]