Clinicopathological characteristics and outcomes of phyllodes tumors in a tertiary care center: a retrospective study

Introduction

Phyllodes tumors (PTs) are rare fibroepithelial breast neoplasm, accounting for approximately 0.3–1% of all breast tumors, with a reported mean age of presentation around 40 (1,2). According to the World Health Organization (WHO), PTs are histologically classified into benign, borderline, and malignant based on multiple histological features including tumor border characteristics, stromal overgrowth, degree of stromal cellularity, degree of stromal atypia, mitosis number, and the presence of malignant heterologous element (3).

Prior studies have shown that the average age of patients ranged between 39 and 40 years. The benign subtype is the most frequently reported, and the average tumor size is approximately 6 cm (4,5). PTs tend to exhibit a lobulated appearance (6).

Surgical excision remains the primary treatment modality, with options including local excision, wide local excision, simple mastectomy, radical mastectomy, and vacuum-assisted surgery. A recent meta-analysis reported that malignant PTs have the highest rate of local recurrence reaching up to 25% (7). Additionally, positive surgical margins have been identified as a major predictor of local recurrence (7,8). Excision with at least 1 cm of negative margin is generally associated with reduced recurrence risk. However, several studies including a systematic review have reported no significant difference in recurrence between <1 and ≥1 cm margins (5,9,10). Postoperative radiotherapy has also been associated with decreased local recurrence rates when compared to surgery alone (7).

Despite global research efforts, data regarding PT behavior in the Saudi Arabian population particularly in the Western region remain limited. This study aimed to investigate the clinicopathological characteristics of PTs at a tertiary care hospital and explore their association with recurrence and other clinical outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-153/rc).

Methods

This is a retrospective study that was conducted at King Abdulaziz University Hospital, a tertiary care center in Jeddah, Saudi Arabia. Ethical approval was obtained from the ethics committee of King Abdulaziz University Hospital (IRB No. 308-24). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The data of the patients who are proven to be diagnosed with PT from January 2015–March 2024 were recruited through the hospital’s electronic records. Informed consent was waived due to the retrospective nature of the study and the use of anonymized data.

Regarding inclusion and exclusion criteria, any patients who were older than 18 years old, diagnosed with PT by a histopathology report were included in the study. Any patients who were younger than 18 years old or patients who lacked a definitive histopathological diagnosis of PT were excluded from the study. A total of 37 patients with PT were included.

Collected variables included demographic data (age, body measurements, family and surgical history), clinical presentation, and radiological findings. Preoperative imaging reports (mammogram and/or ultrasound) were reviewed to determine tumor site, size, morphology, and lymph node status. Information on surgical management categorized as wide local excision, simple mastectomy, or radical mastectomy was collected for each patient who underwent surgery.

Histopathological features were extracted from pathology reports and included: tumor border type (pushing vs. infiltrative), stromal overgrowth, degree of stromal cellularity and atypia, mitotic count, and the presence of necrosis. Surgical margin status and closest margin distance were also recorded.

Tumor size and mitotic count were categorized into three groups: <5, 5–10, and >10. These groupings were selected based on thresholds commonly reported in the literature for risk stratification of PTs. This classification allowed for simplified comparative analysis and clearer interpretation of associations with tumor behavior and recurrence.

Patients were followed up postoperatively, and recurrence was assessed through clinical records and imaging reports. Recurrence was defined as local or systemic tumor reappearance after surgical management. Follow-up duration was calculated from the date of surgery to the date of the last documented clinic visit. In some cases, patients were not under consistent surveillance beyond 24 months but re-presented with symptoms such as a palpable lump, which led to recurrence diagnosis. These return visits were included when calculating total follow-up time for those individuals.

To minimize bias, standardized data extraction forms were used by trained reviewers to ensure consistency and accuracy. All data were cross-verified with multiple sources when available, such as operative notes, pathology reports, and radiology systems, to reduce the risk of misclassification.

Statistical analysis

Data analysis was performed using Statistical Package for the Social Sciences (SPSS) software version 21.0. Descriptive statistics were used to summarize demographic and clinical characteristics. Categorical variables were analyzed using the Chi-squared test, while continuous variables were assessed using the independent t-test after confirming normality assumptions. A P value of <0.05 was considered statistically significant.

While multivariable modeling was not performed due to the limited sample size, confounding was addressed through stratified subgroup analysis. Specifically, recurrence and tumor grade were analyzed across various levels of pathological features to explore independent associations.

Subgroup analyses were conducted by stratifying patients based on tumor size, mitotic activity, margin type, and stromal features. Chi-square tests were used to compare recurrence and tumor grade across these groups. Formal interaction testing was not performed due to the sample size.

Missing values were recorded as “not available” (N/A) and retained in the dataset. SPSS handled these using pairwise deletion. No imputation was performed. The proportion of missing data was small and did not affect the results.

No formal sensitivity analyses were performed due to the limited sample size. All statistical comparisons were conducted using predefined variable groupings based on literature thresholds.

Results

A total of 37 female patients were diagnosed with PTs between January 2015 and March 2024 at a tertiary care hospital. Patient ages ranged from 19 to 86 years with a mean of 43.7 years and a median of 42 years.

The most common presenting complaint was a breast lump, reported by 26 patients (70.3%). Seven patients (18.9%) presented with breast pain, and 1 (2.7%) reported bloody nipple discharge. Tumors were more commonly located in the left breast (48.6%), followed by the right (40.5%), with 4 patients (10.8%) having bilateral involvement.

Tumor size ranged from 1.5 to 22 cm, with both the mean and median sizes reported as 9 cm. Histologically, 12 tumors (32.4%) were classified as benign, 14 (37.8%) as borderline, and 11 (29.7%) as malignant. Tumor size was categorized as <5, 5–10, and >10 cm. Mitotic activity was categorized as <5, 5–10, and >10 mitoses per 10 high power fields. Stromal cellularity was categorized as mild, moderate, or marked. Significant differences were observed among the three groups with respect to mitotic activity, stromal cellularity, tumor borders, stromal overgrowth, stromal atypia, and necrosis (P<0.05) (Table 1). All patients underwent surgical treatment either with breast-conserving surgery or mastectomy with or without reconstruction.

The median follow-up duration for the entire cohort was 9.5 months with a mean of 13.4 months. While the mean follow-up duration was 13.4 months, follow-up periods varied widely among patients. Notably, three individuals were diagnosed with recurrence more than 24 months post-surgery, specifically at 32, 37, and 43 months. These patients were not under regular surveillance but re-presented with symptoms prompting re-evaluation. Their return visits were documented and included retrospectively in the total follow-up calculation. This highlights the variability of real-world follow-up patterns and the potential for late recurrence.

The overall recurrence rate was 18.9% (7 out of 37 patients). Histological analysis showed that only margin type (pushing vs. infiltrative) was significantly associated with recurrence (P=0.01), while other variables such as tumor size, cellularity, mitotic count, and surgical margin status were not statistically correlated with recurrence (Table 2). Table 3 provides a detailed summary of the patients who experienced recurrence, including tumor subtype, pathological features, margin status, time to recurrence, and the site of recurrence. Among the seven recurrent cases, four were malignant, two borderline, and one benign. The recurrence was local in five patients and systemic in two. Three patients were found to have malignant heterologous elements, including osteosarcoma, myxoid liposarcoma, and well-differentiated liposarcoma. Notably, none of these patients experienced recurrence during the follow-up period.

Discussion

PTs are rare fibroepithelial neoplasms, comprising less than 1% of all breast tumors (1). The World Health Organization classifies these tumors into benign, borderline, and malignant categories based on their microscopic features (11). Current treatment guidelines, including those from the Monroe Dunaway Anderson (MD Anderson), Cancer Center and the National Comprehensive Cancer Network (NCCN), recommend wide local excision with at least 1 cm clear margins (12,13). Additionally, various studies have highlighted the importance of achieving a clear margin of at least 1 cm with a mastectomy being performed if a clear margin cannot be attained (14,15). Despite optimal surgical management, local recurrence remains a clinical concern (16).

This study sought to explore the different histopathological characteristics of PTs and evaluate their outcomes among 37 female patients diagnosed with PT in our tertiary hospital over 8 years. It is widely recognized that the age of diagnosis for PT varies significantly, however, the median age of diagnosis has been reported to be around 45 years of age which is older than the age range typically observed in fibroadenoma (FA) (17-19). The median age of presentation for our patients was 42 years ranging from 19 to 86 years, which was similar to a study done by Wang et al. that had an average of 40.7 years but had shown a different range from just 12 to 74 years (20). However, a study done by Atalay et al. showed a much younger age of presentation with an average of just 26 years old (21).

The classification of benign, borderline, and malignant subtypes was established based on histopathological parameters including stromal cellularity, stromal atypia, stromal proliferation and overgrowth, rate of mitosis, and the presence of tumor necrosis (4,22). According to our analyzed data, we found that amongst the 37 patients that had a confirmed diagnosis of PT between January 2015 and March 2024, the majority of the patients were borderline at 37.8%, followed by benign at 32.4% malignant at 29.7% (Table 1), in contrast to other studies that had reported different incidence of the types. Including a study done by Sawalhi et al. in 2013 in Jordan, included 42 cases of PT with the majority being malignant (40%) followed by benign at 38%, and finally borderline being the minority reporting in only 9 (21%) of the cases (4). Also, Yuniandini et al. reported that of the 69 patients that were included, the majority of the PT patients were found to be malignant (55.07%) (23). Meanwhile, a study done in Tunisia involving 106 patients over a 10-year period by Ben Hassouna et al. showed that the majority (58.40%) had a benign PT and only 15.09% were borderline PT (24).

According to our analyzed data, there was a slight discrepancy in the site of the tumor, as 44.82% were on the right side, 41.37% on the left, and 13.79% were bilateral.

In terms of recurrence, our study identified a recurrence rate of 18.9%, which varies compared to findings from other countries. For example, a study by Wen et al. reported a recurrence rate of 7.3%, while a study by Sotheran showed a rate of 14%. In contrast, a study by Ravindhran et al. reported a higher recurrence rate of 29.8% (25-27). Infiltrative tumor margins were the only pathological feature significantly associated with recurrence “(P=0.01)”. Other variables, including surgical margin status and stromal cellularity, did not show a statistically significant association. This finding contrasts with several previous studies that identified margin status and high stromal cellularity as key predictors of recurrence (28-30). For instance, Tan et al. developed a prognostic nomogram incorporating stromal atypia, mitotic count, stromal overgrowth, and surgical margins to predict recurrence-free survival (31).

Interestingly, our analysis showed margin status to be an insignificant factor relating to recurrence “(P=0.63)”, previous literature that had identified negative margin to be a crucial factor in reducing recurrence (31-33). The low number of recurrence events in our study may limit the statistical power to detect additional associations, as similarly observed in other small-cohort studies (4,14,34). Recent evidence by Neron et al. suggests that margins ≥3 mm are necessary and sufficient for local control in malignant phyllodes tumors, and that margins >8 mm offer no additional benefit compared with 3–7 mm (35). This supports the growing consensus that excessively wide margins may not be necessary, particularly in low-resource or breast-conserving contexts.

Our study has several limitations. The retrospective design and single-center setting may limit the generalizability of the findings. Additionally, the absence of centralized pathological review could introduce variability in tumor grading and potential misclassification bias, possibly affecting the accuracy of histologic categorization and outcome associations. Retrospective data collection also carries the risk of selection bias and incomplete data capture, which may influence the reported recurrence rates. Moreover, some patients were lost to follow-up before completing the standard 24-month surveillance period, which may have influenced the calculated mean follow-up duration and led to underestimation of late recurrence events. Although the 37 patients provide valuable preliminary insights, the relatively small cohort may limit the statistical power of the study and the generalizability of the findings. Larger, multicenter studies are warranted to validate these results. Despite these limitations, this study provides important local data on PTs and underscores the need for broader prospective investigations to clarify histologic predictors and optimize management strategies in the Saudi population.

Conclusions

Our findings suggest that PTs exhibiting focal infiltration are associated with an increased risk of recurrence. Conversely, margin status and stromal cellularity do not demonstrate a significant correlation with tumor recurrence. To enhance the reliability and generalizability of these observations, further multi-center studies with larger sample sizes are recommended.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-153/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-153/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-153/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-153/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. This study was approved by the ethical committee of King Abdulaziz University Hospital (IRB No. 308-24), and was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Informed consent was waived due to the retrospective nature of the study and the use of anonymized data.

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/.

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