Differentiation Between Phyllodes Tumor and Fibroadenoma of the Breast: A Radiomics Prediction Model Based on Full-Field Digital Mammography & Digital Tomosynthesis.

OBJECTIVE: To assess the diagnostic performance of FFDM-based and DBT-based radiomics models to differentiate breast phyllodes tumors from fibroadenomas. METHODS: 192 patients (93 phyllodes tumors and 99 fibroadenomas) who underwent mammography were retrospectively enrolled. Radiomic features were respectively extracted from FFDM and the clearest slice of DBT images. A least absolute shrinkage and selection operator (LASSO) regression was used to select radiomics features. A combined model was constructed by radiomics and radiological signatures. Machine learning classification was done using logistic regression based on radiomics or radiological signatures (clinical model). Four radiologists were tested on phyllodes tumors and fibroadenomas with and without optimal model assistance. The area under the receiver operating characteristic (ROC) curve (AUC) was computed to assess the performance of each model or radiologist. The Delong test and McNemar's test were performed to compare the performance. RESULTS: The combined model yielded the highest performance with an AUC of 0.948 (95%CI: 0.889-1.000) in the testing set, slightly higher than the FFDM-radiomics model (AUC of 0.937, 95%CI: 0.841-0.984) and the DBT-radiomics model (AUC of 0.860, 95%CI: 0.742-0.936) and significantly superior to the clinical model (AUC of 0.719, 95%CI: 0.585-0.829). With the combined model aid, the AUCs of four radiologists were improved from 0.808 to 0.914 (p=0.079), 0.759 to 0.888 (p=0.015), 0.717 to 0.846 (p=0.004), and 0.629 to 0.803 (p=0.001). CONCLUSION: Radiomics analysis based on FFDM and DBT shows promise in differentiating phyllodes tumors from fibroadenomas.

Postoperative surgical margin results of the phyllodes tumors from a tertiary hospital.

OBJECTIVE: Phyllodes tumors in the breast are exceptionally uncommon fibroepithelial tumors. In the literature, they are typically categorized as benign phyllodes tumor, borderline phyllodes tumor, and malignant phyllodes tumor. This study aims to assess and present the clinical and surgical outcomes of patients diagnosed with phyllodes tumor. METHODS: The outcomes of patients aged 18 years and above diagnosed with phyllodes tumor between 2006 and 2023 were retrospectively reviewed. Patients were grouped as benign phyllodes tumor and borderline/malignant phyllodes tumor and compared by clinical and surgical results. RESULTS: Of all 57 patients with phyllodes tumor, 64.9% (n=37) were benign phyllodes tumor and 35.1% (n=20) were borderline/malignant phyllodes tumor [22.8% (n=13) borderline phyllodes tumor and 12.3% (n=7) malignant phyllodes tumor]. When the patients were divided into two groups as benign phyllodes tumor and borderline/malignant phyllodes tumor and compared, our cumulative (total) recurrence rate was 14.0%, with final surgical margin width between groups [(0

Microinvasive lobular carcinoma arising in a benign phyllodes tumour - a short report and brief review of the literature.

Lobular carcinoma in situ (LCIS) with microinvasion is a rare entity which is rarely reported in the literature. We describe a case of microinvasive LCIS following excision of a fibroepithelial lesion. The lesion was graded as U3 and M3 on ultrasonography and mammography respectively, and on core needle biopsy was described as a fibroepithelial lesion with 'unusual features'. Microscopic examination revealed a fibroepithelial lesion focally colonised by florid E-cadherin negative LCIS with multiple foci of microinvasive classical lobular carcinoma, which lacked a myoepithelial layer on CK5 and S100 staining.

Coexisting invasive ductal carcinoma arising within a benign phyllodes tumour.

A woman in her 40s presented to the breast clinic with a 2-year history of an enlarging right breast lump. Examination revealed a 10 cm firm mass in the upper outer quadrant of the right breast. MRI and ultrasonography results revealed an 8 cm mass in the right breast and suspicious axillary nodes. Biopsy results of this mass revealed a sclerosed fibroadenoma (B2). Excision of the right breast lump had shown a benign phyllodes tumour, containing an incidental invasive ductal carcinoma and high-grade ductal carcinoma in situ. The patient underwent a right breast cavitectomy and sentinel lymph node biopsy, which revealed no further disease. She received adjuvant radiotherapy, chemotherapy and anti-HER2 treatment, and has remained disease-free at 20-month follow-up. The coexistence of an invasive carcinoma arising within a benign phyllodes tumour is rare. This case report underscores the importance of thoroughly examining excised specimens for phyllodes tumour to exclude malignant components.

Retrospective analysis of core-needle and vacuum-assisted breast biopsies of B3 fibroepithelial lesions and correlation with results in subsequent surgical specimens.

BACKGROUND: Fibroepithelial lesions (FEL) are a heterogeneous group of biphasic tumours that include fibroadenomas (FA) and the rare entity of benign phyllodes tumors (PT) as well as cases where distinction between these two entities is not possible. The histologic distinction between benign PT and cellular FA is still a diagnostic challenge, especially in core-needle biopsy (CNB) or vacuum-assisted biopsy (VAB). Guidelines are not clearly established regarding the management of FEL in CNB or VAB. In this study, we addressed the frequency of B3 FEL diagnosed in CNB or VAB and compared the final histopathological findings in the excision specimens to evaluate up- or downgrading. METHODS: We identified 117 female patients with the preoperative diagnosis of FEL (B3), PT, or FEL in combination of pure epithelial B3 lesions in CNB or VAB. Clinico-pathological information as well as data on subsequent surgical excision were available for all patients. RESULTS: PT was diagnosed in 9 (14.8%) and FEL (B3) in 52 (85.2%) cases. Additionally, 56 patients with FA in combination with an additional B3 lesion were identified. Most FEL (B3)/PT initial diagnoses were made in CNB (55.6% of PT; 84.6% of FEL). After the initial biopsy, 7 of 9 (77.8%) patients with initial diagnosis of benign or borderline PT in CNB/VAB and 40 of 52 (77.0%) patients with initial diagnosis of FEL (B3) in CNB/VAB underwent open excision (OE). 4 of 9 cases (44.4%) initially diagnosed as PT were verified, whereas 2 of 9 (22.2%) were downgraded to FA. 20 of 52 cases (38.5%) initially diagnosed as FEL (B3) were downgraded to FA, whereas 11 of 52 cases (21.2%) were diagnosed as benign or borderline PT. One FEL (B3) case was upgraded to malignant PT. CONCLUSION: Most PT and FEL (B3) diagnoses on CNB/VAB underwent surgical removal. In the final pathological findings of cases classified primarily as FEL (B3), the majority were downgraded to FA, one quarter were upgraded to PT, and a small subset remained as combined FA/PT. In clinical daily practice, we recommend individualized decision-making considering different options (clinical follow-up or removal of the lesion depending on the whole context) in a multidisciplinary preoperative conference.

Deep learning-assisted distinguishing breast phyllodes tumours from fibroadenomas based on ultrasound images: a diagnostic study.

OBJECTIVES: To evaluate the performance of ultrasound-based deep learning (DL) models in distinguishing breast phyllodes tumours (PTs) from fibroadenomas (FAs) and their clinical utility in assisting radiologists with varying diagnostic experiences. METHODS: We retrospectively collected 1180 ultrasound images from 539 patients (247 PTs and 292 FAs). Five DL network models with different structures were trained and validated using nodule regions annotated by radiologists on breast ultrasound images. DL models were trained using the methods of transfer learning and 3-fold cross-validation. The model demonstrated the best evaluation index in the 3-fold cross-validation was selected for comparison with radiologists' diagnostic decisions. Two-round reader studies were conducted to investigate the value of DL model in assisting 6 radiologists with different levels of experience. RESULTS: Upon testing, Xception model demonstrated the best diagnostic performance (area under the receiver-operating characteristic curve: 0.87; 95% CI, 0.81-0.92), outperforming all radiologists (all P < .05). Additionally, the DL model enhanced the diagnostic performance of radiologists. Accuracy demonstrated improvements of 4%, 4%, and 3% for senior, intermediate, and junior radiologists, respectively. CONCLUSIONS: The DL models showed superior predictive abilities compared to experienced radiologists in distinguishing breast PTs from FAs. Utilizing the model led to improved efficiency and diagnostic performance for radiologists with different levels of experience (6-25 years of work). ADVANCES IN KNOWLEDGE: We developed and validated a DL model based on the largest available dataset to assist in diagnosing PTs. This model has the potential to allow radiologists to discriminate 2 types of breast tumours which are challenging to identify with precision and accuracy, and subsequently to make more informed decisions about surgical plans.

[Borderlines and malignant phyllodes tumors of the breast: From the anatomopathological challenge to the standard of care]. / Tumeurs phyllodes borderlines et malignes du sein : du défi anatomopathologique à l'élaboration d'un standard de prise en charge.

Phyllodes tumors, borderline (BPT) and malignant (MPT), represent a rare group of fibroepithelial breast tumors. Due to their rarity, their treatment remains poorly codified. The precise incidence of these tumors remains unknown. TPMs represent half of breast sarcomas and 1 % of breast tumors. Their treatment at the localized stage is based on surgery, that can be conservative surgery or a mastectomy. The impact of oncoplastic techniques and immediate breast reconstruction is not documented. The excision margins of the BPT and MPT must be free, a wider margin can provide a benefit in local recurrence but in also overall survival in the case of TPM. The optimal width of the excision margin is not known. In the event of positive margins, a second surgery could make up the result of an insufficient first surgery. Chemotherapy does not seem to provide any benefit on recurrence-free survival, but the available data are particularly weak. The data on adjuvant radiotherapy are more important. This allows better local control in the event of breast-conserving surgery. The benefit of post-mastectomy radiotherapy is less documented but can be considered in cases of poor prognostic factors. The management of TPM at the metastatic stage is based on the use of chemotherapy (anthracyclines, Ifosfamide) and local treatment of metastases in cases of oligometastatic disease. Due to the rarity of these tumors, it is essential that their management be discussed within a network of qualified professionals (NETSARC+).

Hippo pathway effectors YAP, TAZ and TEAD are associated with EMT master regulators ZEB, Snail and with aggressive phenotype in phyllodes breast tumors.

BACKGROUND: Phyllodes tumors (PTs) of the breast are uncommon fibroepithelial neoplasms that tend to recur locally and may have metastatic potential. Their pathogenesis is poorly understood. Hippo signaling pathway plays an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. Hippo signaling dysfunction has been implicated in cancer. Recent evidence suggests that there is cross-talk between the Hippo signaling key proteins YAP/TAZ and the epithelial-mesenchymal transition (EMT) master regulators Snail and ZEB. In this study we aimed to investigate the expression of Hippo signaling pathway components and EMT regulators in PTs, in relation to tumor grade. METHODS: Expression of Hippo signaling effector proteins YAP, TAZ and their DNA binding partner TEAD was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 86 human phyllodes breast tumors (45 benign, 21 borderline, 20 malignant), in comparison with tumor grade and with the expression of EMT-related transcription factors ZEB and Snail. RESULTS: Nuclear immunopositivity for YAP, TAZ and TEAD was detected in both stromal and epithelial cells in PTs and was significantly higher in high grade tumors. Interestingly, there was a significant correlation between the expression of YAP, TAZ, TEAD and the expression of ZEB and SNAIL. CONCLUSIONS: Our results originally implicate Hippo signaling pathway in PTs pathogenesis and suggest that an interaction between Hippo signaling key components and EMT regulators may promote the malignant features of PTs.

The variable histogenesis and biology of selected bland fibroblastic lesions of the breast - pitfalls in the differential diagnostics and optimal therapeutic approach (three case reports).

Presented are three casuistics of seemingly identical breast lesions which even by adopting advanced laboratory techniques may represent diagnostic challenge. Microscopic features of some bland spindle cell lesions of different histogenesis (epithelial or mesenchymal) are misleading and a potential source of unaware errors, which might affect optimal therapeutic strategy. In the setting of three diverse entities (low-grade spindle cell metaplastic carcinoma, desmoid fibromatosis and phyllodes tumor) is documented both demanding diagnostic algorithm and revealing molecular landscape on one side as well as evolving predictive/prognostic parameters on the other one. Close interdisciplinary cooperation is inevitable for accurate interpretation/understanding of revealed diagnostic facts which is required for adjustment of competent rational and individualized therapy.

Malignant phyllodes: 10 year review of management through a sarcoma service.

BACKGROUND: Phyllodes tumours of the breast are rare, and their treatment is still subject to discussion. They are classified as benign, borderline, or malignant based on histopathological characteristics of the stroma. This study demonstrates 10 years' experience in diagnosis and management of malignant phyllodes. METHODS: All patients referred for discussion at our sarcoma multidisciplinary team meeting from 2003 to 2013 with a diagnosis of malignant phyllodes were identified. Patient demographics, biopsy details, excision extent, final pathology, reconstruction, adjuvant treatment, recurrence and overall survival were assessed. RESULTS: Thirty patients were identified over the 10 year period. Eight (26.7 %) had their diagnosis upgraded to malignant phyllodes on completion excision, compared to initial biopsy. Nine (30 %) had breast surgery elsewhere as definitive treatment before referral to our service. Four of these (44.4 %) required more extensive excision and three developed metastases (33.3 %) and died. Twenty-one patients had primary surgery through our service and three (14.3 %) died from disease. Overall, 13 patients had radical mastectomy, 92.3 % with adequate margins (>1 cm histologically) and no local recurrence, 9 simple mastectomy 22.2 % with adequate margins and 1 local recurrence and 8 wide local excision with 37.5 % adequate margins and 1 local recurrence. CONCLUSION: For malignant phyllodes patients, the best chance to reduce recurrence and improve survival is adequate excision and radical mastectomy should be considered. For borderline lesions, consideration should be given for referral to a specialist centre and we recommend delayed reconstruction, because of the chance of histological upgrade to malignancy.

Margin Width and Local Recurrence in Patients with Phyllodes Tumors of the Breast.

BACKGROUND: Optimal surgical margin width for patients with phyllodes tumors (PTs) of the breast remains debated. The aim of this study was to assess the influence of margin width on long-term local recurrence risk. PATIENTS AND METHODS: This was a single-institution retrospective review of patients with confirmed PT treated from 2008-2015. Margins were defined as positive (ink on tumor), narrow (no tumor at inked margin but < 10mm), or widely free (>/= 10mm). LR rates were estimated by the Kaplan-Meier method. RESULTS: Among 117 female patients, histology included 55 (47%) benign, 29 (25%) borderline, and 33 (28%) malignant PT. Final margins were positive in 16 (14%), narrow in 32 (27%), widely free in 64 (55%), and unknown in 5 (4%) patients. Compared with margins > 10 mm, patients with positive and narrow margins had a higher LR risk [HR 10.57 (95% CI 2.48-45.02) and HR 5.66 (95% CI 1.19-26.99), respectively]. Among benign PTs, the 10-year LR-free rates were 100%, 94%, and 66% for widely negative, narrow, and positive margins, respectively (p = 0.056). For borderline/malignant PT, the 10-year LR-free rates were 93% and 57% for widely negative and narrow margins, respectively (p = 0.02), with no difference in LR between narrow and positive margin groups (p = 1.00). CONCLUSIONS: For benign PTs, a margin of no ink on tumor appears sufficient to optimize local control. In patients with borderline or malignant PTs, achieving a wide surgical margin may remain important as narrower margins were associated with LR rates comparable to those with positive margins.

Pneumothorax as a rare presentation in a case of phyllodes tumor of breast with cavitating lung metastasis.

ABSTRACT: The lung is the most common site of metastases in the case of phyllodes tumor of the breast followed by bone. However, pneumothorax as a presenting complaint in a patient of bilateral cavitating lung metastases from malignant phyllodes tumor of the breast has never been reported to our knowledge. We herein report a case of a 34-year-old female presenting with sudden onset of chest pain in already existing lung metastases who on imaging showed the development of bilateral pneumothorax. We should, therefore, be on the lookout for the potential development of spontaneous pneumothorax in such cases.

Nipple-sparing mastectomy and immediate breast reconstruction by prepectoral implant for the management of giant phyllodes tumors: A case series.

Phyllodes tumor is an uncommon breast neoplasm that is present in variable sizes. Giant phyllodes are those larger than 10 cm in diameter. Clinically, giant phyllodes tumors present as a visible, rapidly growing mass distorting the breast contour. Such tumors with large size and rapid growth rate suggest a phyllode diagnosis of fibroadenoma. Planning a standard treatment strategy for these tumors is quite challenging. While adequate surgical excision with tumor-free resection margins is the standard of care for most giant phyllodes cases, borderline and malignant giant phyllodes tumors might require wider resections given their high recurrence rates. Some authors described total mastectomy as the treatment option for giant borderline and malignant phyllodes to obtain wide, clear margins. Between March 2022 and September 2023, our surgical oncology department presented and operated on three cases of giant phyllodes. They underwent a nipple-sparing mastectomy and immediate breast reconstruction using pre-pectoral silicone implants. We think that with such a procedure, we can benefit from the wide, safe margins of mastectomy that have been proven to decrease local recurrence rates while considering the aesthetic outcome.

Relapsing malignant phyllodes tumour presenting as isolated acrometastases.

Malignant phyllodes tumours (PTs) are aggressive neoplasms with high rates of local recurrence and distant metastasis. With no known effective chemotherapy and no approved targeted therapy in the setting of metastatic disease, prognosis is limited with an often-relapsing course of disease. We report a case of a woman in her late 30s with a diagnosis of recurrent metastatic malignant PT who was found to have acrometastases of the malignant PT to the right distal index and small digits. We emphasise the potential for atypical patterns of metastases in patients with malignant PT and the need to recognise acrometastasis as an unusual but morbid manifestation of disease. Given the high growth rate of malignant PTs, the lack of systemic treatment options, and the ensuing distress for patients, prompt diagnosis and early intervention is crucial.

The Impact of Adjuvant Chemotherapy on the Long-Term Prognosis of Breast Malignant Phyllodes Tumors: A Propensity Score-Matched Study.

BACKGROUND: Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. PATIENTS AND METHODS: Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence-free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. RESULTS: We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). CONCLUSIONS: According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.

Malignant phyllodes tumor with EGFR variant III mutation: A rare case report with immunohistochemical and genomic studies.

A female in her 60's presented with a left-sided breast mass. A core needle biopsy specimen showed diffuse proliferation of a round cell tumor, which was positive for vimentin, NKX2.2, BCOR, and focal CD99 on immunohistochemistry (IHC). No fusion genes of the Ewing family sarcomas were detected. With a tentative diagnosis of primary breast sarcoma (PBS), total mastectomy was performed after chemotherapy. The resected tissues showed proliferation of round or spindle-shaped tumor cells with a high nuclear-to-cytoplasmic ratio, exhibiting solid and fascicular arrangements but no epithelial component or organoid pattern. While IHC indicated no particular histological diagnosis, genomic examination revealed gene alterations in MED12 p.G44D, MLL2 (KMT2D) p.T1496fs*27, and EGFR variant III (vIII). Moreover, a retrospective IHC study showed overexpression of EGFRvIII. A malignant phyllodes tumor (PT) with extensive sarcomatous overgrowth was indicated as an integrative diagnosis. This is a rare case of a malignant PT harboring EGFRvIII. The present case provides an importance of accurate diagnosis and genomic analysis of rare breast tumors, as malignant PT and PBS are different in its treatment strategy and prognosis.

Clinical presentation and radiologic imaging findings of phyllodes tumors: benign and borderline/malignant phyllodes tumors.

Background: Phyllodes tumor is a rare fibroepithelial neoplasm of the breast, which is classified histologically as benign, borderline, or malignant. Accurate preoperative diagnosis allows the correct surgical planning and reoperation avoidance. Objective: To describe the clinical presentation and radiologic features of phyllodes tumors and differentiate between benign and non-benign (borderline and malignant) groups. Methods: A retrospective study of 57 patients with a diagnosis of phyllodes tumor who had preoperative imaging (mammography, ultrasound, or CT chest) and histological confirmation. The data was collected from 1 June 2011 to 30 September 2021. The imaging features of the phyllodes tumors were described according to the 5th edition of the ACR BI-RADS lexicon. For comparing between two groups, the student t-test, Wilcoxon rank sum test, Chi-square test, and Fisher's exact test were used for statistical analyses. The logistic regression analysis was calculated for non-benign phyllodes tumor prediction. Results: From 57 patients, the pathologic results were benign for 43 cases and non-benign phyllodes tumors for 14 cases. There was no differentiation of mammographic and CT features between benign and non-benign groups. Non-benign phyllodes tumors had the statistical significance of menopausal status, entire breast involvement, tumor size larger than 10 cm, and heterogeneous echo on univariable analysis. After multivariable analysis, menopausal status (odd ratios=13.79, p=0.04) and presence of vessels in the rim (odd ratios=16.51, p=0.019) or absent vascularity (odd ratios=8.45, p=0.047) on doppler ultrasound were significantly increased possibility of non-benign phyllodes tumor. Conclusions: Menopausal status and presence of vessels in the rim or absent vascularity on Doppler ultrasound were important predictors for the diagnosis of non-benign phyllodes tumor.

Predicting Prognosis of Phyllodes Tumors Using a Mammography- and Magnetic Resonance Imaging-Based Radiomics Model: A Preliminary Study.

PURPOSE: To investigate whether a radiomics model based on mammography (MG) and magnetic resonance imaging (MRI) can be used to predict disease-free survival (DFS) after phyllodes tumor (PT) surgery. METHOD: About 131 PT patients who underwent MG and MRI before surgery between January 2010 and December 2020 were retrospectively enrolled, including 15 patients with recurrence and metastasis and 116 without recurrence. 884 and 3138 radiomic features were extracted from MG and MR images, respectively. Then, multiple radiomics models were established to predict the recurrence risk of the patients by applying a support vector machine classifier. The area under the ROC curve (AUC) was calculated to evaluate model performance. After dividing the patients into high- and low-risk groups based on the predicted radiomics scores, survival analysis was conducted to compare differences between the groups. RESULTS: In total, 3 MG-related and 5 MRI-related radiomic models were established; the prediction performance of the T1WI feature fusion model was the best, with an AUC value of 0.93. After combining the features of MG and MRI, the AUC increased to 0.95. Furthermore, the MG, MRI and all-image radiomic models had statistically significant differences in survival between the high- and low-risk groups (P < .001). All-image radiomics model showed higher survival performance than the MG and MRI radiomics models alone. CONCLUSIONS: Radiomics features based on preoperative MG and MR images can predict DFS after PT surgery, and the prediction score of the image radiomics model can be used as a potential indicator of recurrence risk.

Validation Study of the Newly Proposed Refined Diagnostic Criteria for Malignant Phyllodes Tumor With 136 Borderline and Malignant Phyllodes Tumor Cases.

The World Health Organization (WHO) diagnostic criteria for malignant phyllodes tumor (MPT) may miss a significant number of MPTs with metastatic potential. New refined diagnostic criteria (Refined Criteria) for MPT were recently proposed. The aim of this study is to validate the Refined Criteria. This validation study included 136 borderline (borderline phyllodes tumor [BoPT]) and MPT cases that were not included in the initial study. We evaluated tumor classifications based on both the Refined Criteria and the WHO criteria. The Refined Criteria defines MPT when these criteria are met (1) stromal overgrowth with ≥ 1 feature(s) of marked stromal cellularity, marked stromal cytologic atypia, or ≥10 mitoses per 10 high-power fields (10 mitoses/10 HPFs) or (2) marked stromal cellularity with ≥1 feature(s) of marked stromal cytologic atypia, ≥10 mitoses/10 HPFs or permeative border. The WHO criteria require all 5 morphologic features (stromal overgrowth, permeative border, marked stromal cellularity, marked stromal cytologic atypia, and ≥10 mitoses/10 HPFs) for an MPT diagnosis. Using the Refined Criteria, none of the 61 BoPTs developed metastasis and 40.0% of the 75 MPTs developed metastases; local recurrence was seen in 11.5% BoPTs and 25.3% MPTs. Using the WHO criteria, 9.6% of the 94 BoPTs developed metastases and 50.0% of the 42 MPTs developed metastases; 14.9% of the BoPTs had local recurrence and 28.6% of the MPTs had local recurrence. Nine (30.0%) of the 30 tumors that developed distant metastases were diagnosed as BoPTs by the WHO criteria. When we combined the 75 MPTs from this validation cohort with the 65 MPT cases from the published data using the Refined Criteria, 50 (35.7%) of the 140 MPTs developed metastases, whereas 8 cases with metastases were <5 cm. In the univariate analysis with log-rank test, stromal overgrowth, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses/10 HPFs, presence of heterologous components other than liposarcomatous component, and presence of stromal necrosis were significantly associated with the risk of metastasis (all with P < 0.05). In multivariate analysis with Cox proportional hazard regression, stromal overgrowth and marked stromal cellularity were significantly associated with metastasis (both with P < 0.001). The Refined Criteria are superior to the WHO criteria in predicting the clinical outcomes of BoPTs and MPTs. Using the Refined Criteria, 35.7% of 140 patients with MPT developed metastases, whereas none (0%) of the patients with BoPT developed metastases. Patients with MPT have a high metastatic rate; these patients may benefit from systemic chemotherapy or targeted therapies. In contrast, patients with BoPT may be managed with complete local excision alone without chemotherapy.

De-escalating indications for excision when breast core needle biopsy returns fibroepithelial lesion-not further characterized.

PURPOSE: Surgical excision is often performed to exclude phyllodes tumor (PT) when Core Needle Biopsy (CNB) of the breast returns fibroepithelial lesion-not further characterized (FEL-NFC). If imaging or CNB pathology features can be identified that predict a very low probability of borderline/malignant PT, thousands of women could be spared the expense and morbidity of surgical excisions. METHODS: This retrospective cohort study includes 180 FEL-NFC from 164 patients who underwent surgical excisional biopsy. RESULTS: The upgrade rate from FEL-NFC to benign PT was 15%, and to borderline/malignant PT 7%. Imaging features predicting upgrade to borderline/malignant PT included greater size (p = 0.0002) and heterogeneous echo pattern on sonography (p = 0.117). Histologic features of CNB predicting upgrade to borderline/malignant PT included "pathologist favors PT" (p = 0.012), mitoses (p = 0.014), stromal overgrowth (p = 0.006), increased cellularity (p = 0.0001) and leaf-like architecture (p = 0.077). A three-component score including size > 4.5 cm (Size), heterogeneous echo pattern on sonography (Heterogeneity), and stromal overgrowth on CNB (Overgrowth) maximized the product of sensitivity x specificity for the prediction of borderline/malignant PT. When the SHO score was 0 (72% of FEL-NFC) the probability of borderline/malignant PT on excision was only 1%. CONCLUSION: The combination of size ≤ 4.5 cm, homogeneous echo pattern, and absence of stromal overgrowth is highly predictive of a benign excision potentially sparing most patients diagnosed with FEL-NFC the expense and morbidity of a surgical excision.