Phyllodes tumors (PTs) are rare fibroepithelial breast tumors, albeit clinically significant. This study was implemented to investigate the immunohistochemical (IHC) expression of cyclin D1 in PT subtypes and in metaplastic spindle cell carcinoma. Fifty-three resected cases of PT subtypes were analyzed. IHC analysis assessed the percentage of positive stromal tumor cells and the intensity of cyclin D1 staining. The score was classified as either negative, low, or high positive. Statistical analysis was implemented to evaluate the outcomes. Significant variations in scores were observed among various subtypes of PT, with cyclin D1 exhibiting positive nuclear expression in the stromal component of borderline and malignant tumors ( P =0.001). Malignant PTs also showed significantly different cyclin D1 expression compared with triple-negative metaplastic spindle cell carcinoma ( P =0.028). Tumor recurrence was significantly associated with high cyclin D1 expression ( P =0.013). Receiver Operating Characteristic (ROC) curve analysis demonstrated moderate discriminatory ability, with an area under the curve (AUC) of 0.701 (95% CI: 0.535-0.856, P =0.023). Univariate analysis confirmed high cyclin D1 expression as a predictor of recurrence ( P =0.035). In conclusion, cyclin D1 overexpression provides insights into tumor progression and prognosis in PTs. Notably, positive cyclin D1 expression in metastatic malignant PT could be a diagnostic challenge, if not carefully considered within clinical context. Furthermore, the significant difference in cyclin D1 expression between malignant PT and triple-negative metaplastic spindle cell carcinoma highlights its potential utility in distinguishing between them.

Breast phyllodes tumors (PT) are classified as benign, borderline, or malignant, primarily based on histological features, but lack reliable biomarkers for grading. Our aim is to find a protein marker to improve the accuracy of PT grading. We analyzed formalin-fixed paraffin-embedded (FFPE) samples of fibroadenoma (FA) and PT using quantitative proteomics to screen the protein marker S100A8, confirmed its role in PT grading via immunohistochemistry, and examined its correlation with clinicopathological features. Quantitative proteomics studies showed that the differential proteins between FA and PT primarily involve calcium ion binding, including S100A8, FKBP10, MMP9, SPARC, and MMP14. Meanwhile, the proteomic studies showed a statistically significant increase in the expression of S100A8 in malignant PT compared with benign PT. Immunohistochemical validation showed that S100A8 was predominantly expressed in the nucleus and cytoplasm of stromal cells in malignant PT. The expression level of S100A8 in stromal cells demonstrated a positive correlation with PT categories (p<.001), as well as with Ki67 expression (p<.001). To the best of our knowledge, this study is the first to demonstrate the integration of S100A8 and Ki67 expression in stromal cells with histological characteristics aids in grading PT.

To assess whether adjuvant radiotherapy (RT) confers a survival benefit in patients with malignant phyllodes tumors of the breast (MPTB). We conducted a retrospective cohort study of 1899 adult MPTB patients in the SEER database. Patients were categorized as having received RT (341) and not having received RT (1558). Baseline demographic data, tumor grade, AJCC stage, surgery approach, chemotherapy, and local lymphatic biopsy were extracted. Breast cancer-specific survival (BCSS) and overall survival (OS) of MPTB patients before and after propensity score matching (PSM) were compared using Kaplan-Meyer analysis. Predictors of RT were studied using multifactorial logistic regression. Multivariate Cox proportional risk regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for outcome-related factors. Subgroup analyses explored effect modification by grade, stage, and surgery. Multifactorial logistic regression showed that year of diagnosis, tumor grade, surgical approach and adjuvant chemotherapy were significant predictors of RT. Kaplan-Meier analysis showed that BCSS and OS were worse in the RT group before PSM (both p < 0.001), and there was no significant difference between the two groups after PSM (both p > 0.05). In a multifactorial Cox model, RT was not associated with BCSS (HR 0.975; 95% CI 0.699-1.36; p = 0.881) and OS (HR 0.867; 95% CI 0.662-1.135; p = 0.299) in MPTB patients. Classification of MPTB patients by tumor grade, AJCC.T, AJCC.N, and surgical approach did not identify subgroups that would benefit from long-term survival outcomes (BCSS or OS) from RT (all p > 0.05). In this large retrospective cohort of MPTB patients, adjuvant RT was not associated with improved long-term survival-even among those with high-risk features. Prospective studies are needed to further clarify its therapeutic value.

Genetic profiling of mammary periductal stromal tumors with histologic correlation highlights high-grade and low-grade groups and similarities to phyllodes tumors.

ObjectivesTo develop and validate an automated diagnostic framework that combines deep learning and radiomics models for the segmentation and classification of benign and malignant parotid gland tumors on magnetic resonance imaging (MRI).MethodsIn total, 493 patients with pathologically confirmed parotid tumors (396 benign and 97 malignant) were included. Patients were stratified by MRI scanner type into a training cohort (n = 288), an internal validation cohort (n = 123), and an external testing cohort (n = 82). An automated tumor segmentation model based on the nnU-NetV2 architecture was developed and evaluated using the Dice similarity coefficient (DSC) and Intersection over Union (IoU). Based on the automatically segmented regions, a radiomics-based classifier and a ResNet18-based deep learning model were independently constructed to differentiate malignant from benign tumors. A combined diagnostic model was further developed by integrating deep learning outputs, radiomics features, and clinical-radiological features. Model performance was assessed using the area under the receiver operating characteristic curve (AUC).ResultsThe automated segmentation model achieved a Dice similarity coefficient (DSC) of 0.93 and an Intersection over Union (IoU) of 0.88 in the training cohort, 0.91 and 0.84 in the validation cohort, and 0.84 and 0.76 in the testing cohort, respectively. The ResNet18-based DL model achieved AUCs of 0.90, 0.84, and 0.77, respectively, compared to the radiomics model’s AUCs of 0.79, 0.72, and 0.71. The combined model demonstrated superior performance, with AUCs of 0.92 in the validation cohort and 0.90 in the testing cohort, outperforming the clinical-radiological model, which achieved AUCs of 0.69 and 0.82 (p < 0.001 in validation, p = 0.042 in testing).ConclusionsThis automated MRI-based framework, combining deep learning and radiomics approaches, enables accurate segmentation and reliable classification of parotid gland tumors. It offers a promising noninvasive tool to assist in clinical decision-making.Clinical trial numberNot applicable.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40644-025-00982-x.

To evaluate facial nerve reconstruction's impact on quality of life (QoL) and clinical outcomes in radical parotid malignancy surgery. Patients were stratified into the Preservation Group, Reconstruction Group, and Disconnection Group, retrospectively analyzed objective measures (from medical records and operative reports) and subjective measures (using the Sunnybrook Facial Grading System [SFGS] and Facial Clinimetric Evaluation [FaCE] scale) across the three patient groups. No significant differences in recurrence or mortality were observed between Reconstruction and Disconnection groups (p > 0.05). Facial nerve reconstruction significantly improves outcomes in patients with high-risk parotid malignancies (p < 0.05), despite higher-risk profiles in the reconstruction cohort. This improvement remained stable over time, showing no significant decline (p > 0.05). Venous nerve conduit trap yielded superior facial nerve function and QoL versus end-to-end repair (p < 0.05). Facial nerve reconstruction effectively improves outcomes in parotid malignancy surgery. Venous nerve conduit trap application is better than end-to-end repair.

Background/Objectives: Management of the clinically negative neck in malignant parotid tumors remains controversial. We aimed to identify clinicopathologic predictors of nodal involvement and to evaluate whether elective neck dissection (END) improves disease-free survival (DFS) versus observation in cN0 patients. Methods: We performed a retrospective cohort study of adults undergoing surgery for malignant parotid tumors at a single tertiary center (2013–2023) with ≥24 months of follow-up. Collected variables included demographics, tumor T category and histologic grade (AJCC 8th), parotidectomy type, neck management [END vs. therapeutic neck dissection (TND) vs. observation], lymph node yield, and outcomes. Associations were tested with Fisher’s exact tests; disease-free survival (DFS) was analyzed using Kaplan–Meier curves, log-rank tests and an exploratory multivariable Cox proportional hazards model. Results: Seventy-four patients were included (mean age 54.3 years; 12.2% preoperative facial nerve impairment). Parotidectomy was partial (41.9%), total (31.1%), radical (21.6%), or extended (5.4%). Neck dissection was performed in 40.5% (END 23.0%; TND 17.6%). Overall pathologic nodal positivity (pN+) was 18.9%. T3–T4 tumors had greater odds of nodal metastasis than T1–T2 (OR 10.58; p < 0.05). Among cN0 patients, occult metastasis was 17.6%; notably, all high-grade cN0 tumors that underwent END were pN+. Intraparotid nodal metastases occurred in 28.6% and always co-occurred with cervical metastases. DFS did not differ significantly between cN0 patients managed with END versus observation (log-rank p > 0.05). Patients with pN0 had superior DFS versus pN+ (p < 0.05). Lymph node yield groupings (0–17 vs. 18–40 vs. >40) were not associated with recurrences. In the exploratory multivariable Cox model, high/intermediate-grade and T3-T4 tumors and nodal positivity were associated with reduced DFS. Conclusions: Higher T category and high/intermediate grade strongly predict nodal involvement, and pN+ status portends worse DFS. Although END did not show a DFS advantage over observation in cN0 patients, the 17.6% occult metastasis rate—especially in high-grade disease—and the linkage between intraparotid and cervical metastases support a risk-adapted END strategy and intraoperative assessment of intraparotid nodes to guide neck management.

Malignant phyllodes tumors account for 0.18% of all malignant breast tumors, and of these, tumors with heterologous differentiation of osteosarcoma and chondrosarcoma are rare, accounting for 1.3% of all phyllodes tumors. We report a case of malignant phylloid tumor with atypical heterologous osteochondroid component, which arrived at our Pathological Anatomy Unit. Keywords : Osteochondroid differentiation, malignant phylloid, breast cancer, thoracic oncology.

BackgroundDiffusion weighted imaging (DWI) has been used to evaluate parotid gland tumors. Warthin’s tumors (WTs) have very high diffusion-derived vessel ‘density’ (DDVD) and low ADC, while pleomorphic adenomas (PAs) have moderately high DDVD and very high apparent diffusion coefficient (ADC). These two most common benign tumors (BTs) can be largely separated by a combination of ADC and DDVD. However, most of the MTs (malignant tumors) had moderately high DDVD and low ADC, the differentiation between BT and MT remains challenging. Slow diffusion coefficient (SDC) is a novel metric being proposed to measure in vivo tissue slow diffusion. In its basic form, SDC is derived from a high b-value DWI image and a higher b-value DWI image. This study tested the application of SDC to evaluate parotid gland tumors.MethodsTwenty-four PAs, 16 WTs, and 14 MTs had DWI at 3T. ADC was calculated with b = 0 and 800 s/mm2 images. SDC was calculated with b = 600 and 800 s/mm2 images. DDVD was calculated with b = 0 and 20 mm2/s images. The ratio of a tumor diffusion metric measure to a contra-lateral tumor-free parotid gland tissue diffusion metric measure was obtained, resulting in ADCr, SDCr, and DDVDr. Pearson test was used for correlation analysis. A receiver operating characteristic curve analysis and the area under the ROC curve (AUROC) were used to assess the diagnostic performance.ResultsParotid gland tumors had a higher SDC than normal parotid gland tissue with SDCr > 1. SDCr was on average PAs (median: 3.075) > MTs (2.755) > WTs (2.250). Separation of BT against MT by ADCr alone, by a combination of ADCr and SDCr, and by a combination of ADCr, SDCr, and DDVDr had AUROC of 0.7393, 0.8018, 0.8054, respectively. The probability of a tumor being MT is given by: ln(p/1-p) = 0.7006*SDCr-3.198*ADCr + 1.417; or ln(p/1-p)=-0.2225*DDVDr-3.41ADCr + 0.7603*SDCr + 2.103. SDCr was positively correlated with ADCr with a Pearson r of 0.624, while SDCr was not apparently correlated with DDVDr.ConclusionThis study tested the principle of applying four b-values DWI to generate three diffusion metrics, namely, ADC, SDC, and DDVD, to evaluate parotid gland tumors. A combination of these three diffusion metrics may offer clinically useful separation of MT from BT.Clinical trial numberNot applicable.

Paraneoplastic syndromes, though uncommon, present systemic effects secondary to primary malignancies or metastases. We presented a case of a 25-year-old nullipara with a left breast malignant phyllodes. Pre-operative investigations revealed hypercalcaemia. Her staging computed tomography scan did not demonstrate any enlarged parathyroid gland. Her serum intact parathyroid hormone level was not raised. After correction with saline hydration, she underwent a left mastectomy, axillary dissection and a supercharged bipedicle TRAM flap. The following day, due to flap congestion, she underwent flap exploration but unfortunately, the flap necrosed. She required temporary coverage with a split-skin graft to allow her post operative sepsis to resolve. She underwent a delayed extended latissimus dorsi myocutaneous pedicled flap for chest wall closure. The cause of hypercalcemia was attributed to be a paraneoplastic syndrome which has not been reported previously in a malignant phyllodes tumor. The hypercalcaemia is postulated to have caused the thrombosis leading to flap failure.

Background: Demographic patterns of parotid gland tumors (PGTs) vary across regions and over time, which is important for clinical practice. We aimed to characterize the epidemiology of PGTs in seven regions from northeastern and north-central Bulgaria, focusing on patient demographics, laterality, benign–malignant distribution, histologic subtypes and temporal incidence. Methods: A retrospective descriptive study was conducted at a single university maxillofacial surgery clinic in Bulgaria. Cases were reviewed over a 10-year period (1 January 2015–31 December 2024). Age, sex, histology, and benign/malignant status were recorded. Group differences were assessed with t-tests and χ² tests. Annual crude benign, malignant and total parotid tumor incidence rates of per 100,000 population were calculated (2015–2024). Results: Benign tumors constituted 86.4% (312/361) and malignant 13.6% (49/361). Patients with benign tumors were significantly younger than those with malignancy (56.5 ± 14.2 vs 65.4 ± 14.3 years; t = −4.1; p &lt; 0.001). The proportion of malignancy increased with age (χ² = 22.965; p &lt; 0.001). Among benign neoplasms, Warthin’s tumor (WT) was most frequent (44.9%), followed by pleomorphic adenoma (PA) (34.3%); WT predominated in men and PA in women (p &lt; 0.001). In children, PA was the only benign entity identified. Among malignancies, salivary duct carcinoma and adenoid cystic carcinoma were most common (18.4% each), with mucoepidermoid carcinoma close behind (16.3%); when pooled, malignant tumors showed no significant associations with sex or age. Crude annual incidence rates for benign PGTs rose from 1.50 (2015) to 3.48 per 100 000 in 2023, (p=0.002). Malignant rates varied without a clear trend, (p=0.25) and total PGT incidence increased significantly from 1.79 (2015) to 3.80 per 100 000 in 2023, (p=0.001). Conclusions: In this single-center study, most PGTs were benign (86.4%); benign cases presented younger, and the likelihood of malignancy increased with age. WT predominated, especially in men, whereas PA was more common in women and was the only diagnosed pediatric tumor; malignancies were mainly salivary duct carcinoma and adenoid cystic carcinoma (with mucoepidermoid carcinoma being also common) with no sex/age associations, and crude incidence rose over time for benign and total tumors but not for malignant entities.

Malignant phyllodes tumors (MPTs) are rare fibroepithelial breast tumors with no standard treatment for metastatic or recurrent cases. Comprehensive genomic profiling (CGP) has been conducted for MPT; however, its association with treatment remains unclear. A retrospective study was conducted on patients with advanced or recurrent MPTs treated with chemotherapy between 2013 and 2022 at two hospitals, analyzing clinical data, CGP, treatment outcomes, and survival. Five patients with metastatic MPTs who had received chemotherapy were identified. The median age was 55years (range, 50-66), and all patients were female. As first-line treatment, four patients received doxorubicin plus ifosfamide (AI) combination therapy, while one received doxorubicin monotherapy. Among those treated with AI therapy, the best responses were partial response in three patients and stable disease in one. The median progression-free survival (PFS) for patients treated with AI therapy was 5.3months. Of the five patients two proceeded to second-line therapy, and one patient received up to fourth-line treatment. Next-generation sequencing-based CGP testing was performed in four cases. One patient with an FGFR1-N546K-mutated MPT achieved a relatively long PFS of 6.8months with pazopanib therapy, a multi-kinase inhibitor targeting FGFR1 among other kinases, as fourth-line therapy. AI therapy is useful for advanced or recurrent MPTs. The observed clinical benefit of pazopanib in a patient with FGFR1 N546K-mutated MPT suggests that FGFR1 kinase domain mutations may be a relevant factor in responsiveness of FGFR1-targeted therapy. Further data accumulation is warranted.

Giant malignant phyllodes tumor with ulceration: A case report and brief review of the literature

Postoperative radiation therapy in localized breast malignant phyllodes tumors: RPA-derived risk model identifies high-benefit subgroups with local control improvement

Background and Objectives: Breast lesions of uncertain malignant potential identified on biopsy, known as “B3 lesions,” constitute a significant portion of diagnoses in numerous published studies. These lesions are associated with a variable risk of coinciding malignant tumors, and current guidelines recommend complete excision, which can occasionally lead to an upgrade in the resection specimen. However, alternative, less invasive treatment strategies, such as clinical follow-up, may be considered. In this study, we retrospectively analyzed diagnostic biopsies from our institution to determine the upgrade rate of each B3 lesion subgroup to breast malignancy following complete excision. Materials and Methods: All breast biopsies conducted at our institution from 1 January 2018 to 30 November 2022 and classified as B3 lesions were included in this study. The lesions were categorized into groups and subgroups based on their growth pattern and histopathological features. To determine the upgrade rate to ductal carcinoma in situ (DCIS) or invasive breast cancer (IBC) for each B3 lesion subgroup, we assessed the histological concordance between the biopsy and the resection specimen. Results: During the study period, 10,531 biopsies were performed, of which 1045 (9.93%) were classified as B3 lesions. Among these, 795 (76.08%) were subsequently resected, either through surgical procedures (98.32%) or using the Vacuum-Assisted Excision technique (1.68%). Histological examination revealed that 89 (11.19%) of the resected B3 lesions were upgraded to breast malignancy, with 59 cases (7.42%) progressing to DCIS, 22 cases (2.76%) to IBC, and 8 cases (1.01%) to borderline or malignant phyllodes tumor. The upgrade rate varied among histopathological subgroups, being lowest in complex sclerosing lesions without atypia (4.95%, 95% CI: 2.5–8.7%) and highest in intraductal papillomas with atypia (58.82%; 95% CI: 32.9–81.6%). Conclusions: Statistically significant differences were observed between B3 lesion subgroups, with a higher risk of upgrade in lesions exhibiting atypia. As our understanding of B3 lesions evolves, there is potential to implement therapeutic strategies tailored to the specific risk associated with each subgroup. This approach could allow for less invasive management options, such as clinical or radiological follow-up, thereby sparing patients from unnecessary invasive procedures when appropriate.

Abstract Background Parotid gland tumors constitute the majority of salivary gland neoplasms, with a predominance of benign lesions. Malignant counterparts, although less common, necessitate more aggressive treatment strategies. Differentiating between benign and malignant tumors based on clinical findings alone is challenging. Magnetic Resonance Imaging (MRI), particularly when combined with diffusion-weighted imaging and apparent diffusion coefficient (ADC) analysis, provides valuable insights into lesion characteristics. Histogram analysis of ADC maps may enhance diagnostic precision by capturing the distribution of diffusion values within tumors. We aimed to assess the diagnostic accuracy of the MRI and ADC histogram analysis and the inter-observer agreement in differentiating benign and malignant parotid gland masses. Results This cross-sectional retrospective study involved 100 patients who underwent MRI examination and had histopathologically proven parotid tumors. Conventional and diffusion-weighted MRI sequences were analyzed by two radiologists. ADC values and histogram metrics were compared between benign and malignant lesions, and inter-observer agreement was evaluated. Among 100 patients (57% males), 59% had benign and 41% had malignant parotid tumors. Most lesions were unilateral (80%) and located in the superior lobe (57%). Malignancy was associated with solid composition (P = 0.027), hypointense T2 (P = 0.011), ill-defined margins (P = 0.010), high diffusion (P &lt; 0.001), lymphadenopathy (P = 0.001), skin infiltration (P = 0.023), and vascular invasion (P = 0.006). MRI feature assessment showed excellent agreement between observers, with κ values ranging from 0.820 to 1.000 (P &lt; 0.001), confirming high reliability in interpreting composition, signals, margins, enhancement, and diffusion. Malignant lesions had significantly lower ADC values (median = 0.9 vs 1.4–1.5; P &lt; 0.001) and higher skewness (P = 0.008). Lesions’ ADC values showed near-perfect inter-observer agreement (ICC = 0.959, P &lt; 0.001). Using ADC &lt; 1.15 × 10⁻3 mm2/s, observer 1 achieved 80.6% accuracy (AUC = 0.847, P &lt; 0.001), and observer 2 reached 78.6% accuracy (AUC = 0.857, P &lt; 0.001), with high sensitivity and specificity in both. Mean ADC had the best performance (AUC = 0.793, accuracy = 74.3%, P &lt; 0.001). Minimum ADC showed 64.3% accuracy (AUC = 0.720), and Maximum ADC had the highest sensitivity (80.5%) but lower accuracy (67.2%, AUC = 0.712, P &lt; 0.001). Conclusions MRI combined with ADC histogram analysis demonstrates high diagnostic performance and excellent inter-observer agreement in differentiating benign and malignant parotid gland tumors. This approach can enhance preoperative assessment and guide clinical decision-making.

Background: The majority of parotid gland tumors are benign, while malignant forms are uncommon, affecting fewer than 1 in 100,000 individuals. The main challenge resides in the histopathological complexity and the clinical overlap between benign and malignant parotid tumors, which frequently results in misdiagnosis. Aim: The objective of this research was to evaluate the clinical and histopathological characteristics of parotid gland tumors at a Romanian healthcare center. Materials and methods: A five-year retrospective study was conducted, with the inclusion criterion being the presence of complete clinical, pathological, and surgical records. Results: Of 156 patients included in the study, 67.3% were found to have benign lesions (male/female ratio 1.14:1), and there was a slight male predominance (53.3%). Partial parotidectomy was the most common surgical intervention for benign parotid tumors (59.6%), whereas total parotidectomy was predominantly indicated for malignant tumors, with facial nerve sacrifice occurring in 20% of cases to ensure complete tumor excision. Patients with benign tumors were found to be younger. Malignant tumors were commonly diagnosed at stage III (36.4%), indicative of more advanced disease at the time of diagnosis. Clinical diagnosis showed a high specificity of 96.9%, indicating high accuracy in malignancy suspicion, yet the sensitivity of 56% indicates that a significant number of malignancies were not detected during the initial evaluation. Tumor size was found to be influenced by gender and correlated with surgical methods, suggesting that patient characteristics and tumor biology may impact surgical strategy. Conclusions: This retrospective study highlights differences in gender, tumor size, and surgical approach between benign and malignant parotid gland tumors, offering valuable contributions in terms of diagnostic accuracy and treatment patterns despite a limited number of malignant cases.

Long term outcomes of breast primary sarcomas and malignant phyllodes tumors: 20 years observational analysis of the BEAM∗ study group. (∗the breast European association for mesenchymal tumors).

Proposing New Criteria for Classification of Benign Fibroepithelial Lesions Based on Clinicopathologic Evaluations of 507 Cases with Clinical Outcome.

Magnetic resonance neurography: Preoperative assessment of facial nerve invasion in malignant parotid gland tumors.