Surgical management of a giant fibroadenoma during lactation.

Fibroadenomas are the most common breast lesion in women of reproductive age. During pregnancy and lactation, fibroadenomas can undergo rapid growth in response to hormonal stimulus. These changes may prompt further investigation and/or intervention due to the risk of an underlying phyllodes tumour. We present a case of a female patient who underwent surgical excision of a giant fibroepithelial lesion at 4 months post partum while continuing to breastfeed. The lesion was successfully excised while maintaining lactation. A postoperative milk fistula resolved with non-operative management. There is limited literature on the surgical management of breast lesions in lactating women. This case illuminates the surgical management of breast lesions in an often well informed group of patients who may choose to have surgery while lactating in spite of the increased risk of complications. This case also highlights the need for a holistic approach to maintain the overall health of mother and child.

Detailed DNA methylation characterisation of phyllodes tumours identifies a signature of malignancy and distinguishes phyllodes from metaplastic breast carcinoma.

Phyllodes tumours (PTs) are rare fibroepithelial lesions of the breast that are classified as benign, borderline, or malignant. As little is known about the molecular underpinnings of PTs, current diagnosis relies on histological examination. However, accurate classification is often difficult, particularly for distinguishing borderline from malignant PTs. Furthermore, PTs can be misdiagnosed as other tumour types with shared histological features, such as fibroadenoma and metaplastic breast cancers. As DNA methylation is a recognised hallmark of many cancers, we hypothesised that DNA methylation could provide novel biomarkers for diagnosis and tumour stratification in PTs, whilst also allowing insight into the molecular aetiology of this otherwise understudied tumour. We generated whole-genome methylation data using the Illumina EPIC microarray in a novel PT cohort (n = 33) and curated methylation microarray data from published datasets including PTs and other potentially histopathologically similar tumours (total n = 817 samples). Analyses revealed that PTs have a unique methylome compared to normal breast tissue and to potentially histopathologically similar tumours (metaplastic breast cancer, fibroadenoma and sarcomas), with PT-specific methylation changes enriched in gene sets involved in KRAS signalling and epithelial-mesenchymal transition. Next, we identified 53 differentially methylated regions (DMRs) (false discovery rate < 0.05) that specifically delineated malignant from non-malignant PTs. The top DMR in both discovery and validation cohorts was hypermethylation at the HSD17B8 CpG island promoter. Matched PT single-cell expression data showed that HSD17B8 had minimal expression in fibroblast (putative tumour) cells. Finally, we created a methylation classifier to distinguish PTs from metaplastic breast cancer samples, where we revealed a likely misdiagnosis for two TCGA metaplastic breast cancer samples. In conclusion, DNA methylation alterations are associated with PT histopathology and hold the potential to improve our understanding of PT molecular aetiology, diagnostics, and risk stratification. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Are both distinct epithelial and stromal cells molecular analysis from phyllodes tumors versus fibroadenoma components affected in breast fibroepithelial progression?

PURPOSE: To determine molecular events involved in the tumorigenesis of phyllodes tumors (PT) and the role of each stromal (SC) and epithelial (EC) cell. METHODS: Frozen breast samples enriched with epithelial and stromal cells from three fibroadenomas and 14 PT were retrieved and laser microdissected. Sanger and polymerase chain reaction-based sequencing of exon 2 MED12 and TERT promoter hotspot mutations were performed; 44K microarray platform was used to analyze gene expression. RESULTS: All three fibroadenomas (FAs) presented mutations in MED12, but not in TERT, whose mutation was observed in five of the 14 PTs. EC and SC of each affected tumor displayed identical alterations. Of the total differentially expressed genes (DEG) (EC = 1,543 and SC = 850), 984 were EC-eDEGs and 291 were SC-eDEGs. We found a high similarity of diseases and functions enriched by both cell types, but dissimilarity in the number of enriched canonical pathways. Three signaling canonical pathways overlapping with EC and SC were predicted to be activated in one cell type and inactivated in the other, while no overlap in eDEGs was assigned to them. We also identified 13 EC-eDEGs and five SC-eDEGs enriched networks, in which the SC-eDEGs were able to segregate FA from PT samples. CONCLUSIONS: Identical TERT mutations from both SC and ES origins might affect the PTs tumorigenesis. Gene expression differences suggest coordinated molecular processes between these components with determinant differences acquired by SC, able to fully distinguish PTs from FAs lesions.

Breast development and disorders in children and adolescents.

Breast masses are infrequently encountered in pediatric and adolescent populations. Most breast masses in children are benign entities arising from embryological defects which can be managed once breast development is complete. Diagnostic and management dilemmas arise when fibroepithelial lesions of the breast are seen in clinical practice. Differentiation between a fibroadenoma and a phyllodes tumor is important to guide management. Breast cancer in children under 18 years of age is extremely rare and invasive diagnostic testing and aggressive management is only recommended when clinical suspicion of malignancy is very high. Patient and caregiver counseling plays an important role in the management of these diseases. While adult-onset breast diseases have been studied very closely, there is a dearth of literature on pediatric breast anomalies. This review aims to provide a scoping overview of the available literature on benign, fibroepithelial, and malignant lesions of the breast in pediatric and adolescent populations to help guide physicians and surgeons with decision-making regarding the diagnosis and management of pediatric breast diseases.

Precise diagnosis of breast phyllodes tumors using Raman spectroscopy: Biochemical fingerprint, tumor metabolism and possible mechanism.

BACKGROUND: Breast fibroadenomas and phyllodes tumors are both fibroepithelial tumors with comparable histological characteristics. However, rapid and precise differential diagnosis is a tough point in clinical pathology. Given the tendency of phyllodes tumors to recur, the difficulty in differential diagnosis with fibroadenomas leads to the difficulty in optimal management for these patients. METHOD: In this study, we used Raman spectroscopy to differentiate phyllodes tumors from breast fibroadenomas based on the biochemical and metabolic composition and develop a classification model. The model was validated by 5-fold cross-validation in the training set and tested in an independent test set. The potential metabolic differences between the two types of tumors observed in Raman spectroscopy were confirmed by targeted metabolomic analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: A total of 204 patients with formalin-fixed paraffin-embedded (FFPE) tissue samples, including 100 fibroadenomas and 104 phyllodes tumors were recruited from April 2014 to August 2021. All patients were randomly divided into the training cohort (n = 153) and the test cohort (n = 51). The Raman classification model could differentiate phyllodes tumor versus fibroadenoma with cross-validation accuracy, sensitivity, precision, and area under curve (AUC) of 85.58 % ± 1.77 %, 83.82 % ± 1.01 %, 87.65 % ± 4.22 %, and 93.18 % ± 1.98 %, respectively. When tested in the independent test set, it performed well with the test accuracy, sensitivity, specificity, and AUC of 83.50 %, 86.54 %, 80.39 %, and 90.71 %. Furthermore, the AUC was significantly higher for the Raman model than that for ultrasound (P = 0.0017) and frozen section diagnosis (P < 0.0001). When it came to much more difficult diagnosis between fibroadenoma and benign or small-size phyllodes tumor for pathological examination, the Raman model was capable of differentiating with AUC up to 97.45 % and 95.61 %, respectively. On the other hand, targeted metabolomic analysis, based on fresh-frozen tissue samples, confirmed the differential metabolites (including thymine, dihydrothymine, trans-4-hydroxy-l-proline, etc.) identified from Raman spectra between phyllodes tumor and fibroadenoma. SIGNIFICANCE AND NOVELTY: In this study, we obtained the molecular information map of breast phyllodes tumors provided by Raman spectroscopy for the first time. We identified a novel Raman fingerprint signature with the potential to precisely characterize and distinguish phyllodes tumors from fibroadenoma as a quick and accurate diagnostic tool. Raman spectroscopy is expected to further guide the precise diagnosis and optimal treatment of breast fibroepithelial tumors in the future.

A rapidly growing fibroadenoma in a pregnant woman: A case report.

BACKGROUND: Fibroadenomas are the most common benign breast lesions in women. They present as a unilateral mass and can rapidly enlarge in size through hormonal changes. Fibroadenomas could be classified as small or giant, and as simple or complex. They are classified as 'giant' when the size exceeds 5 cm and/or weight 500 gram; and as 'complex' if one of the following characteristics is present: cysts with a size >3 mm, epithelial calcifications, sclerosing adenosis and papillary apocrine metaplasia. Giant fibroadenomas can cause compression of surrounding breast tissue or breast asymmetry, requiring surgical excision in order to preserve a normal breast shape. CASE: A 26-year-old pregnant woman was referred with a palpable mass of her right breast. The mass rapidly increased in size to a diameter of 13 cm during the second trimester of her pregnancy. A tru-cut biopsy confirmed a fibroadenoma. The rapid growth and compression of normal breast tissues indicated a lumpectomy during her pregnancy. The mass was easily excised without any consequences for the pregnancy. Pathological examination showed a complex giant fibroadenoma. CONCLUSION: A unique case of a pregnant woman with rapid progression of a fibroadenoma that met the criteria of a complex and giant fibroadenoma, was presented. This case emphasizes the importance of timely surgical intervention, even during pregnancy, to prevent permanent breast tissue damage.

Incidental DCIS within a fibroadenoma.

A female in her early 20s was referred to the breast-endocrine surgeons with a self-detected tender left breast lump on the background of a family history of breast cancer. A physical examination revealed a rubbery and mobile mass in the left upper breast. Ultrasound demonstrated a solid hypoechoic mass with a likely differential diagnosis of fibroadenoma, with a subsequent core needle biopsy (CNB) confirming a fibroadenoma. Given the size and tenderness of the lump, an excisional biopsy was performed. Histology revealed a fibroadenoma with components of low-grade ductal carcinoma in situ, contained within the fibroadenoma and excised with clear margins.Following surgical excision, a multidisciplinary review determined that no further local therapy was required and recommended a genetics referral. This case was interesting as it raised important questions, including what the best surveillance strategies are for female patients with breast cancer within fibroadenoma and determining the risk and probability of missing epithelial atypia via CNB.

Efficacy and safety of vacuum-assisted excision (VAE) of fibroadenomas: experience in a tertiary centre.

PURPOSE: To evaluate the technical success and efficacy rates of US-guided percutaneous vacuum-assisted excision (VAE) of breast fibroadenomas, also assessing procedural complications and long-term patient satisfaction rates. MATERIALS AND METHODS: The institutional database of a tertiary breast cancer referral centre was retrospectively reviewed to retrieve all women with fibroadenomas who underwent US-guided VAE between May 2011 and September 2019. We subsequently included in this study all fibroadenomas with a maximum diameter of 3 cm at US and an available histological confirmation obtained by core-needle biopsy before VAE. Immediately after VAE, technical success (defined as the correct VAE execution) and the occurrence of procedural complications were evaluated. Imaging follow-up (US ± mammography) after 6, 12, 24 and 36 months was performed to evaluate technical efficacy (defined as the absence of fibroadenoma recurrence at 6-month follow-up). Long-term patient satisfaction was evaluated with telephonic interviews in October 2022. RESULTS: We retrospectively included 108 women (median age 46 years) with 110 fibroadenomas diagnosed at core-needle biopsy with a median lesion size at US of 12 mm. Technical success was obtained in 110/110 VAEs (100%). Minor procedural complications (haematomas) occurred in 7/110 VAEs (6%), whereas 8/110 patients had a fibroadenoma recurrence at 6-month follow-up, resulting in a 93% technical efficacy (102/110 VAEs). All patients available for telephonic follow-up (104/104, 100%) reported high satisfaction with VAE results. CONCLUSION: US-guided VAE is a safe and effective procedure for the excision of fibroadenomas, representing a viable alternative to surgery, with a low complication rate and high patient satisfaction.

Cytomorphological patterns of breast lesions among women with palpable breast lumps attending select teaching and referral hospitals in Kenya: a descriptive cross-sectional study.

Introduction: breast lumps account for a greater number of lesions in women attending surgical clinics in the developing world. Breast cancer which mostly presents as a breast lump is the leading cancer in Kenya, with an incidence of 12.5%. The study aims to describe the patterns of breast lesions in women presenting with palpable breast lumps in two major referral hospitals in Kenya. Methods: seven hundred and sixty-eight study participants with palpable lumps underwent fine needle aspiration cytology (FNAC). Sociodemographic data were captured using structured questionnaires. The FNAC materials were evaluated using the International Academy of Cytology Yokohama System (IACYS) and the lesions were classified into five-tier categories. Frequencies and percentages were used to summarize qualitative variables. Results: of 768 smears, 84.8% (n=651) were adequate for evaluation while 15.2% (n=117) were inadequate. Neoplastic lesions comprised 84.5% (n=550) and non-neoplastic 15.5% (n=101). Benign lesions accounted for 83.6% of the lesions followed by breast carcinoma (10.4%). Ductal carcinoma comprised 98.5% of cancerous lesions. The age group most affected with ductal carcinoma and suspicious lesions was 20-34 years (37.3% and 55.6% respectively). Fibroadenoma formed the bulk of the benign lesions identified (44.1%). Suspicious of malignancy was 4.1% (n=27). The age group with the most lesions (47.5%) was 20-34 years. Conclusion: a wide spectrum of breast lesions was established. Such include inflammatory, atypical, benign, suspicious of malignancy, and malignant lesions. Fibroadenoma was a common lesion diagnosed. The age group most affected by malignant lesions was 16-49 years, necessitating enhanced screening of women with breast lumps in our setups.

Differentiation between Phyllodes Tumors and Fibroadenomas through Breast Ultrasound: Deep-Learning Model Outperforms Ultrasound Physicians.

The preoperative differentiation of breast phyllodes tumors (PTs) from fibroadenomas (FAs) plays a critical role in identifying an appropriate surgical treatment. Although several imaging modalities are available, reliable differentiation between PT and FA remains a great challenge for radiologists in clinical work. Artificial intelligence (AI)-assisted diagnosis has shown promise in distinguishing PT from FA. However, a very small sample size was adopted in previous studies. In this work, we retrospectively enrolled 656 breast tumors (372 FAs and 284 PTs) with 1945 ultrasound images in total. Two experienced ultrasound physicians independently evaluated the ultrasound images. Meanwhile, three deep-learning models (i.e., ResNet, VGG, and GoogLeNet) were applied to classify FAs and PTs. The robustness of the models was evaluated by fivefold cross validation. The performance of each model was assessed by using the receiver operating characteristic (ROC) curve. The area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were also calculated. Among the three models, the ResNet model yielded the highest AUC value, of 0.91, with an accuracy value of 95.3%, a sensitivity value of 96.2%, and a specificity value of 94.7% in the testing data set. In contrast, the two physicians yielded an average AUC value of 0.69, an accuracy value of 70.7%, a sensitivity value of 54.4%, and a specificity value of 53.2%. Our findings indicate that the diagnostic performance of deep learning is better than that of physicians in the distinction of PTs from FAs. This further suggests that AI is a valuable tool for aiding clinical diagnosis, thereby advancing precision therapy.

Giant juvenile fibroadenomas with and without prominent pseudoangiomatous stromal hyperplasia (PASH)-like change: clinicopathological and molecular characteristics.

AIMS: Juvenile fibroadenomas (JFA) are biphasic fibroepithelial lesions (FEL) usually occurring in adolescent female patients. Giant (G) JFA, like other FEL, may exhibit prominent pseudoangiomatous stromal hyperplasia (PASH)-like change. We sought to determine clinicopathological and molecular characteristics of GJFA with and without PASH. METHODS AND RESULTS: Archives were searched for cases of GJFA (1985-2020). All were stained for androgen receptor (AR), beta-catenin, CD34 and progesterone receptor (PR). Cases were sequenced using a custom 16-gene panel - MED12 (exons 1 and 2), TERT promoter (-124C>T and -146Ctable>T), SETD2, KMT2D, RARA (exons 5-9), FLNA, NF1, PIK3CA (exons 10, 11 and 21), EGFR, RB1, BCOR, TP53, PTEN, ERBB4, IGF1R and MAP3K1. Twenty-seven GJFA from 21 female patients aged 10.1-25.2 years were identified. Size ranged from 5.2 to 21 cm. Two patients had multiple, bilateral and later recurrent GJFA. Thirteen (48%) cases showed prominent PASH-like stroma. All were positive for stromal CD34, negative for AR and beta-catenin and one case showed focal PR expression. Sequencing showed MAP3K1 and SETD2 mutations in 17 samples, with KMT2D, TP53 and BCOR aberrations in 10 (45%), 10 (45%) and seven (32%) cases, respectively. Tumours with a PASH-like pattern had higher prevalence of SETD2 (P = 0.004) and TP53 (P = 0.029) mutations, while those without PASH had more RB1 mutations (P = 0.043). MED12 mutation was identified in one case. TERT promoter mutation was observed in four (18%), including two recurrences. CONCLUSIONS: Gene mutations along more advanced phases of the proposed FEL pathogenetic pathway in GJFA are unusual, and suggest a mechanism for more aggressive growth in these tumours.

Gene Expression Profiling of Fibroepithelial Lesions of the Breast.

Fibroepithelial lesions of the breast (FELs) are a heterogeneous group of neoplasms exhibiting a histologic spectrum ranging from fibroadenomas (FAs) to malignant phyllodes tumors (PTs). Despite published histologic criteria for their classification, it is common for such lesions to exhibit overlapping features, leading to subjective interpretation and interobserver disagreements in histologic diagnosis. Therefore, there is a need for a more objective diagnostic modality to aid in the accurate classification of these lesions and to guide appropriate clinical management. In this study, the expression of 750 tumor-related genes was measured in a cohort of 34 FELs (5 FAs, 9 cellular FAs, 9 benign PTs, 7 borderline PTs, and 4 malignant PTs). Differentially expressed gene analysis, gene set analysis, pathway analysis, and cell type analysis were performed. Genes involved in matrix remodeling and metastasis (e.g., MMP9, SPP1, COL11A1), angiogenesis (VEGFA, ITGAV, NFIL3, FDFR1, CCND2), hypoxia (ENO1, HK1, CYBB, HK2), metabolic stress (e.g., UBE2C, CDKN2A, FBP1), cell proliferation (e.g., CENPF, CCNB1), and the PI3K-Akt pathway (e.g., ITGB3, NRAS) were highly expressed in malignant PTs and less expressed in borderline PTs, benign PTs, cellular FAs, and FAs. The overall gene expression profiles of benign PTs, cellular FAs, and FAs were very similar. Although a slight difference was observed between borderline and benign PTs, a higher degree of difference was observed between borderline and malignant PTs. Additionally, the macrophage cell abundance scores and CCL5 were significantly higher in malignant PTs compared with all other groups. Our results suggest that the gene-expression-profiling-based approach could lead to further stratification of FELs and may provide clinically useful biological and pathophysiological information to improve the existing histologic diagnostic algorithm.

Idiopathic fibroadenoma in an elderly man.

A fibroadenoma within the male breast remains a rarely diagnosed entity. Though it was once believed that a fibroadenoma could not exist within a male breast, this has now been demonstrated as incorrect by several reported cases. Most have been in individuals with gynecomastia. There are only a handful of reported cases of men with a diagnosed fibroadenoma in the absence of gynecomastia. We describe a man in his 80s with a left breast fibroadenoma and no features of gynecomastia or hormonal alterations. Based on our findings, we suggest that for men of all ages presenting with a breast lesion, a fibroadenoma remains a possible diagnosis.

Focused ultrasound ablation surgery for multiple breast fibroadenomas: pathological and follow-up results.

OBJECTIVE: To investigate the histopathological findings and follow-up outcome of focused ultrasound ablation surgery (FUAS) treatment of multiple fibroadenomas (FA). METHODS: A total of 20 patients with 101 multiple FAs were enrolled. After one session FUAS ablation, 21 lesions (≥15.0 mm) were surgically removed within one week for histopathological analysis, including 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, H&E staining, nicotinamide adenine dinucleotide (NADH) -flavretin enzyme staining, Transmission electron microscope (TEM) and scanning electron microscope (SEM). The remaining 80 lesions were followed up at 3, 6 and 12 months after treatment. RESULTS: All ablation procedures were performed successfully. Pathologic findings showed that irreversible damage of FA was confirmed. TTC, H&E and NADH staining and TEM/SEM demonstrated tumor cell death and tumor structural destruction at the gross, cellular, and subcellular levels, respectively. The median shrinkage rate at 12 months post-FUAS was 66.4 (43.6, 89.5) %. CONCLUSION: Histopathological analysis for FAs after FUAS treatment proved that FUAS could effectively induce irreversible coagulative necrosis of FA, and the tumor volume would gradually shrink in follow-up. FUAS was safe and effective to treat multiple FAs with good cosmesis.Key pointsThis study was the first study of detailed histopathological analysis for FAs after FUAS treatment.FUAS can effectively induce irreversible coagulative necrosis of fibroadenoma cells.FUAS ablation of multiple fibroadenomas is safe and effective.

Refining the classification of breast phyllodes tumours.

Phyllodes tumours of the breast are uncommon fibroepithelial neoplasms that pose recurrent classification challenges, in large part due to the multiple histological parameters of stromal hypercellularity and atypia, stromal mitotic count, stromal overgrowth and tumour borders, that are used for grading. While the World Health Organization (WHO) Classification of Breast Tumours provides recommendations on diagnostic features, defining criteria are not always applied in routine practice. Lack of concordance among pathologists in typing and grading further underscores the classification difficulties, especially in the borderline category. Although there has been significant molecular information on phyllodes tumours in recent years which has been diagnostically helpful, it has not been translated into daily clinical practice. In order to refine the classification of phyllodes tumours into one that is simple yet comprehensive, reproducible and prognostically precise, a multipronged approach is needed that leverages on global contributions of the International Fibroepithelial Consortium, support by the International Collaboration on Cancer Classification and Research (IC3 R) in amalgamating evidence translation, and guidance from the International Collaboration on Cancer Reporting (ICCR) for standardised reporting. It is hoped that the evidence generated can be used towards refining the classification of phyllodes tumours for the future.

The largest and heaviest giant juvenile fibroadenoma of the breast in the Chinese population: A case report.

RATIONALE: Fibroadenoma is the most common benign tumor of the breast, but giant juvenile fibroadenoma exceeding 20 cm is much rare. This report presents the largest and heaviest giant juvenile fibroadenoma in an 18-year-old Chinese girl. DIAGNOSIS AND INTERVENTIONS: An 18-year-old adolescent girl with a 2-year history of a large left breast mass with progressive expansion over 11 months. A 28 × 21 cm soft swelling occupied the entire outer quadrants of the left breast. The huge mass sagged below the belly button, resulting in high asymmetry of the shoulders. Contralateral breast examination results were normal except for hypopigmentary detected on the nipple-areola complex. Under general anesthesia, the lump was completely excised along the outer envelope of the tumor, while reserving excessive resection of the skin. The patient's postoperative recovery was uneventful, and the surgical wound healed well. OUTCOMES: A radial incision operation was finally performed to remove the huge mass and to preserve the normal breast tissue and the nipple-areolar complex, not only considering the aesthetics but also preserving the ability to lactate. LESSONS: Currently, there is a lack of clear guidelines regarding the diagnostic and treatment modalities for a giant juvenile fibroadenoma. The principle of surgical choice is to balance aesthetics and function preservation.

[Pathological features and clinicopathological significance of TERT promoter mutation in breast fibroepithelial tumors without definite diagnosis].

Objective: To investigate the pathological features and the clinicopathological significance of TERT detection in those tumors that were difficult to diagnosis. Methods: A total of 93 cases of fibroepithelial tumors without definite diagnosis were collected from the Affiliated Hospital of Qigndao University between 2013 and 2021. The clinical details such as patients' age and tumor size were collected. All slides were re-reviewed and the pathologic parameters, including stromal cellularity, stromal cell atypia, stromal cell mitoses, and stromal overgrowth were re-interpreted. Sanger sequencing was used to detect TERT promoter status, and immunohistochemistry was performed to detect TERT protein expression. The relationship between TERT promoter mutation as well as protein expression levels and the clinicopathological parameters were also analyzed. Results: The patients' ages ranged from 30 to 71 years (mean of 46 years); the tumor size ranged from 1.2 to 8.0 cm (mean 3.8 cm). These tumors showed the following morphologic features: leafy structures in the background of fibroadenoma, or moderately to severely abundant stromal cells. The interpretations of tumor border status were ambiguous in some cases. The incidence of TERT promoter mutation was high in patients of age≥50 years, tumor size≥4 cm, and stromal overgrowth at ×4 or ×10 objective, and these clinicopathologic features were in favor of diagnosis of phyllodes tumors. TERT protein expression levels was not associated with the above clinicopathologic parameters and its promoter mutation status. Conclusions: The diagnostic difficulty for the breast fibroepithelial tumors is due to the difficulty in recognition of the leafy structures or in those cases with abundant stromal cells. A comprehensive evaluation combined with morphologic characteristics and molecular parameters such as TERT promoter may be helpful for the correct diagnosis and better evaluating recurrence risk.

Periductal Stromal Tumor of the Breast with a TERT Promoter Mutation: First Case Report with Comprehensive Molecular Analysis.

The molecular pathogenesis of breast fibroepithelial tumors continues to be elucidated. Recently, highly recurrent MED12 mutations arising in exon 2 at codon 44 were discovered in fibroadenomas and phyllodes tumors. In addition, a high prevalence of TERT promoter mutations in two hotspots (124 and 126 bp upstream from the translation start site) was discovered in up to 65% of phyllodes tumors. Breast periductal stromal tumors are a potentially distinct category of fibroepithelial lesions that are exceptionally rare with controversial classification and pathogenesis. Herein, we report the first comprehensive molecular genetic workup of a breast periductal stromal tumor that harbored a TERT promoter -124C > T mutation, supporting a relation to phyllodes tumors.

Differential Diagnosis of DCIS and Fibroadenoma Based on Ultrasound Images: a Difference-Based Self-Supervised Approach.

Differentiation of ductal carcinoma in situ (DCIS, a precancerous lesion of the breast) from fibroadenoma (FA) using ultrasonography is significant for the early prevention of malignant breast tumors. Radiomics-based artificial intelligence (AI) can provide additional diagnostic information but usually requires extensive labeling efforts by clinicians with specialized knowledge. This study aims to investigate the feasibility of differentially diagnosing DCIS and FA using ultrasound radiomics-based AI techniques and further explore a novel approach that can reduce labeling efforts without sacrificing diagnostic performance. We included 461 DCIS and 651 FA patients, of whom 139 DCIS and 181 FA patients constituted a prospective test cohort. First, various feature engineering-based machine learning (FEML) and deep learning (DL) approaches were developed. Then, we designed a difference-based self-supervised (DSS) learning approach that only required FA samples to participate in training. The DSS approach consists of three steps: (1) pretraining a Bootstrap Your Own Latent (BYOL) model using FA images, (2) reconstructing images using the encoder and decoder of the pretrained model, and (3) distinguishing DCIS from FA based on the differences between the original and reconstructed images. The experimental results showed that the trained FEML and DL models achieved the highest AUC of 0.7935 (95% confidence interval, 0.7900-0.7969) on the prospective test cohort, indicating that the developed models are effective for assisting in differentiating DCIS from FA based on ultrasound images. Furthermore, the DSS model achieved an AUC of 0.8172 (95% confidence interval, 0.8124-0.8219), indicating that our model outperforms the conventional radiomics-based AI models and is more competitive.

Fibroepithelial Lesions of the Breast: Update on Molecular Profile With Focus on Pediatric Population.

CONTEXT.­: This review article derives from the breast pathology lecture at the Eighth Princeton Integrated Pathology Symposium (PIPS VIII). OBJECTIVE.­: To provide a literature review and update on fibroepithelial lesions of the breast with molecular findings and findings regarding the pediatric population. DATA SOURCES.­: The sources include extensive literature review, personal research, and experience. CONCLUSIONS.­: Given significant differences in prognosis and management of fibroepithelial lesions, we aim to provide readers with pertinent definitions, pathomorphology, molecular findings, and management for each diagnosis, with insights on the pediatric population.