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1.
Sci Bull (Beijing) ; 69(11): 1748-1756, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38702279

RESUMEN

An intraoperative diagnosis is critical for precise cancer surgery. However, traditional intraoperative assessments based on hematoxylin and eosin (H&E) histology, such as frozen section, are time-, resource-, and labor-intensive, and involve specimen-consuming concerns. Here, we report a near-real-time automated cancer diagnosis workflow for breast cancer that combines dynamic full-field optical coherence tomography (D-FFOCT), a label-free optical imaging method, and deep learning for bedside tumor diagnosis during surgery. To classify the benign and malignant breast tissues, we conducted a prospective cohort trial. In the modeling group (n = 182), D-FFOCT images were captured from April 26 to June 20, 2018, encompassing 48 benign lesions, 114 invasive ductal carcinoma (IDC), 10 invasive lobular carcinoma, 4 ductal carcinoma in situ (DCIS), and 6 rare tumors. Deep learning model was built up and fine-tuned in 10,357 D-FFOCT patches. Subsequently, from June 22 to August 17, 2018, independent tests (n = 42) were conducted on 10 benign lesions, 29 IDC, 1 DCIS, and 2 rare tumors. The model yielded excellent performance, with an accuracy of 97.62%, sensitivity of 96.88% and specificity of 100%; only one IDC was misclassified. Meanwhile, the acquisition of the D-FFOCT images was non-destructive and did not require any tissue preparation or staining procedures. In the simulated intraoperative margin evaluation procedure, the time required for our novel workflow (approximately 3 min) was significantly shorter than that required for traditional procedures (approximately 30 min). These findings indicate that the combination of D-FFOCT and deep learning algorithms can streamline intraoperative cancer diagnosis independently of traditional pathology laboratory procedures.


Asunto(s)
Neoplasias de la Mama , Aprendizaje Profundo , Tomografía de Coherencia Óptica , Humanos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Tomografía de Coherencia Óptica/métodos , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/cirugía , Carcinoma Ductal de Mama/patología , Anciano , Adulto , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Periodo Intraoperatorio
2.
Breast Cancer Res ; 26(1): 82, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38790005

RESUMEN

BACKGROUND: Patients with a Breast Imaging Reporting and Data System (BI-RADS) 4 mammogram are currently recommended for biopsy. However, 70-80% of the biopsies are negative/benign. In this study, we developed a deep learning classification algorithm on mammogram images to classify BI-RADS 4 suspicious lesions aiming to reduce unnecessary breast biopsies. MATERIALS AND METHODS: This retrospective study included 847 patients with a BI-RADS 4 breast lesion that underwent biopsy at a single institution and included 200 invasive breast cancers, 200 ductal carcinoma in-situ (DCIS), 198 pure atypias, 194 benign, and 55 atypias upstaged to malignancy after excisional biopsy. We employed convolutional neural networks to perform 4 binary classification tasks: (I) benign vs. all atypia + invasive + DCIS, aiming to identify the benign cases for whom biopsy may be avoided; (II) benign + pure atypia vs. atypia-upstaged + invasive + DCIS, aiming to reduce excision of atypia that is not upgraded to cancer at surgery; (III) benign vs. each of the other 3 classes individually (atypia, DCIS, invasive), aiming for a precise diagnosis; and (IV) pure atypia vs. atypia-upstaged, aiming to reduce unnecessary excisional biopsies on atypia patients. RESULTS: A 95% sensitivity for the "higher stage disease" class was ensured for all tasks. The specificity value was 33% in Task I, and 25% in Task II, respectively. In Task III, the respective specificity value was 30% (vs. atypia), 30% (vs. DCIS), and 46% (vs. invasive tumor). In Task IV, the specificity was 35%. The AUC values for the 4 tasks were 0.72, 0.67, 0.70/0.73/0.72, and 0.67, respectively. CONCLUSION: Deep learning of digital mammograms containing BI-RADS 4 findings can identify lesions that may not need breast biopsy, leading to potential reduction of unnecessary procedures and the attendant costs and stress.


Asunto(s)
Neoplasias de la Mama , Aprendizaje Profundo , Mamografía , Humanos , Femenino , Mamografía/métodos , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico , Persona de Mediana Edad , Estudios Retrospectivos , Biopsia , Anciano , Adulto , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/diagnóstico , Procedimientos Innecesarios/estadística & datos numéricos , Mama/patología , Mama/diagnóstico por imagen
3.
Eur J Radiol ; 176: 111511, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38776805

RESUMEN

INTRODUCTION: In the last two decades there has been a paradigm shift with breast conserving surgery (BCS) being applied to larger and more extensive breast malignancies. The aim of this study is to examine the success of BCS being performed in patients with extensive breast malignancies requiring at least 3 wires for localization, and to assess possible risk factors for failure. MATERIALS AND METHODS: We performed a retrospective single center review of 232 patients who underwent BCS between 2010 and 2020 requiring at least 3 wires for localization, thus comprising the multi-wire group (MWG). The cohort included a control group of 232 single-wire BCS patients (SWG) chronologically matched with the MWG. Patients with either invasive malignancy or ductal carcinoma in situ (DCIS) were included in the study. Clinical, radiological, and pathological data was collected. Proportions of positive surgical margins, re-lumpectomies and conversion to mastectomy were calculated. Survival analysis for locoregional and distant recurrence was performed. RESULTS: Women in the MWG were younger (mean age 57 vs. 63.1, P < 0.001), had larger tumor size (mean size 5.1 cm vs. 1.3 cm, p < 0.001), a higher prevalence of calcifications on mammograms (72 % vs. 17 %, P < 0.001), a higher proportion of positive lymph nodes (75 % vs. 45 %, P = 0.019), and an elevated incidence of a ductal carcinoma in situ (DCIS) component (72 % vs. 38 %, P < 0.001). Positive surgical margins were higher in the MWG (13 % vs 7 %, P = 0.03), which lead to higher proportions of re-lumpectomies or conversion to mastectomies (7 % vs 4 %, P = 0.17). On multivariate analysis of the entire cohort, patients with positive margins were more likely to have a DCIS component (77 % vs 53 %, P = 0.001), an infiltrating lobular carcinoma (ILC) component (15 % vs 9 %, P = 0.013), and positive ER hormonal status (94 % vs 85 %, p = 0.05). The number of wires was not an independent predictor of positive margins. On long-term analysis, the locoregional disease-free survival was similar between the SWG and MWG (P = 0.1). However, the MWG showed higher rates of distant metastasis (12 % vs 4 %, P = 0.006). CONCLUSIONS: BCS requiring 3 or more wires is associated with a slightly higher proportion of positive margins. The increased risk of positive margins appears to be related to the type of tumor (DCIS component, ILC component and ER status) rather than to the number of wires. The number of wires does not significantly impact locoregional disease-free survival.


Asunto(s)
Neoplasias de la Mama , Márgenes de Escisión , Mastectomía Segmentaria , Recurrencia Local de Neoplasia , Humanos , Femenino , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Anciano , Adulto , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología
4.
Cancer Imaging ; 24(1): 48, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38576031

RESUMEN

BACKGROUND: Ductal Carcinoma In Situ (DCIS) can progress to invasive breast cancer, but most DCIS lesions never will. Therefore, four clinical trials (COMET, LORIS, LORETTA, AND LORD) test whether active surveillance for women with low-risk Ductal carcinoma In Situ is safe (E. S. Hwang et al., BMJ Open, 9: e026797, 2019, A. Francis et al., Eur J Cancer. 51: 2296-2303, 2015, Chizuko Kanbayashi et al. The international collaboration of active surveillance trials for low-risk DCIS (LORIS, LORD, COMET, LORETTA),  L. E. Elshof et al., Eur J Cancer, 51, 1497-510, 2015). Low-risk is defined as grade I or II DCIS. Because DCIS grade is a major eligibility criteria in these trials, it would be very helpful to assess DCIS grade on mammography, informed by grade assessed on DCIS histopathology in pre-surgery biopsies, since surgery will not be performed on a significant number of patients participating in these trials. OBJECTIVE: To assess the performance and clinical utility of a convolutional neural network (CNN) in discriminating high-risk (grade III) DCIS and/or Invasive Breast Cancer (IBC) from low-risk (grade I/II) DCIS based on mammographic features. We explored whether the CNN could be used as a decision support tool, from excluding high-risk patients for active surveillance. METHODS: In this single centre retrospective study, 464 patients diagnosed with DCIS based on pre-surgery biopsy between 2000 and 2014 were included. The collection of mammography images was partitioned on a patient-level into two subsets, one for training containing 80% of cases (371 cases, 681 images) and 20% (93 cases, 173 images) for testing. A deep learning model based on the U-Net CNN was trained and validated on 681 two-dimensional mammograms. Classification performance was assessed with the Area Under the Curve (AUC) receiver operating characteristic and predictive values on the test set for predicting high risk DCIS-and high-risk DCIS and/ or IBC from low-risk DCIS. RESULTS: When classifying DCIS as high-risk, the deep learning network achieved a Positive Predictive Value (PPV) of 0.40, Negative Predictive Value (NPV) of 0.91 and an AUC of 0.72 on the test dataset. For distinguishing high-risk and/or upstaged DCIS (occult invasive breast cancer) from low-risk DCIS a PPV of 0.80, a NPV of 0.84 and an AUC of 0.76 were achieved. CONCLUSION: For both scenarios (DCIS grade I/II vs. III, DCIS grade I/II vs. III and/or IBC) AUCs were high, 0.72 and 0.76, respectively, concluding that our convolutional neural network can discriminate low-grade from high-grade DCIS.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Aprendizaje Profundo , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología , Estudios Retrospectivos , Participación del Paciente , Espera Vigilante , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Mamografía , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía
5.
J Cancer Res Ther ; 20(2): 665-668, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38687938

RESUMEN

AIMS: The aims of this study were to investigate the ultrasound features of non-mass-type ductal carcinoma in situ (DCIS) of the breast and conduct a pathological analysis. MATERIAL AND METHODS: Ultrasound images of 32 cases of non-mass-type DCIS of the breast, collected between September 2014 and June 2016, were analyzed. The characteristics of the lesions, including border, internal echogenicity, local glandular hyperplasia, micro-calcification, and intra-tumoral blood flow resistance index (RI), were analyzed, and a concurrent pathological analysis was conducted. RESULTS: Obvious local glandular hyperplasia was commonly observed in the 32 cases of non-mass-type DCIS of the breast. The internal echogenicity varied in intensity, exhibiting a "leopard pattern" or "zebra pattern." Color Doppler imaging revealed abundant blood flow signals within the lesion with an RI of >0.7. Isolated duct dilatation and micro-calcifications were occasionally observed within the lesions. High-grade DCIS was the predominant pathological type of non-mass-type DCIS. CONCLUSIONS: Non-mass-type DCIS of the breast often presents with obvious local glandular hyperplasia and varying internal echogenicity. High-grade DCIS is the frequent pathological type. Color Doppler imaging and RI measurement can assist in diagnosing non-mass-type DCIS of the breast.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Persona de Mediana Edad , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/diagnóstico , Anciano , Adulto , Hiperplasia/patología , Hiperplasia/diagnóstico por imagen , Ultrasonografía Mamaria/métodos , Mama/patología , Mama/diagnóstico por imagen , Ultrasonografía Doppler en Color/métodos , Clasificación del Tumor
6.
Eur J Radiol ; 175: 111415, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38471320

RESUMEN

OBJECTIVE: To investigate the independent risk variables associated with the potential invasiveness of ductal carcinoma in situ (DCIS) on multi-parametric ultrasonography, and further construct a nomogram for risk assessment. METHODS: Consecutive patients from January 2017 to December 2022 who were suspected of having ductal carcinoma in situ (DCIS) based on magnetic resonance imaging or mammography were prospectively enrolled. Histopathological findings after surgical resection served as the gold standard. Grayscale ultrasound, Doppler ultrasound, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) examinations were preoperative performed. Binary logistic regression was used for multifactorial analysis to identify independent risk factors from multi-parametric ultrasonography. The correlation between independent risk factors and pathological prognostic markers was analyzed. The predictive efficacy of DCIS associated with invasiveness was assessed by logistic analysis, and a nomogram was established. RESULTS: A total of 250 DCIS lesions were enrolled from 249 patients, comprising 85 pure DCIS and 165 DCIS with invasion (DCIS-IDC), of which 41 exhibited micro-invasion. The multivariate analysis identified independent risk factors for DCIS with invasion on multi-parametric ultrasonography, including image size (>2cm), Doppler ultrasound RI (≥0.72), SWE's Emax (≥66.4 kPa), hyper-enhancement, centripetal enhancement, increased surrounding vessel, and no contrast agent retention on CEUS. These factors correlated with histological grade, Ki-67, and human epidermal growth factor receptor 2 (HER2) (P < 0.1). The multi-parametric ultrasound approach demonstrated good predictive performance (sensitivity 89.7 %, specificity 73.8 %, AUC 0.903), surpassing single US modality or combinations with SWE or CEUS modalities. Utilizing these factors, a predictive nomogram achieved a respectable performance (AUC of 0.889) for predicting DCIS with invasion. Additionally, a separate nomogram for predicting DCIS with micro-invasion, incorporating independent risk factors such as RI (≥0.72), SWE's Emax (≥65.2 kPa), and centripetal enhancement, demonstrated an AUC of 0.867. CONCLUSION: Multi-parametric ultrasonography demonstrates good discriminatory ability in predicting both DCIS with invasion and micro-invasion through the analysis of lesion morphology, stiffness, neovascular architecture, and perfusion. The use of a nomogram based on ultrasonographic images offers an intuitive and effective method for assessing the risk of invasion in DCIS. Although the nomogram is not currently considered a clinically applicable diagnostic tool due to its AUC being below the threshold of 0.9, further research and development are anticipated to yield positive outcomes and enhance its viability for clinical utilization.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Diagnóstico por Imagen de Elasticidad , Invasividad Neoplásica , Nomogramas , Ultrasonografía Mamaria , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Invasividad Neoplásica/diagnóstico por imagen , Ultrasonografía Mamaria/métodos , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología , Anciano , Diagnóstico por Imagen de Elasticidad/métodos , Adulto , Estudios Prospectivos , Medios de Contraste , Factores de Riesgo , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Medición de Riesgo
7.
Breast Cancer Res ; 26(1): 27, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347651

RESUMEN

BACKGROUND: A malignancy might be found at surgery in cases of atypical ductal hyperplasia (ADH) diagnosed via US-guided core needle biopsy (CNB). The objective of this study was to investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in predicting ADH diagnosed by US-guided CNB that was upgraded to malignancy after surgery. METHODS: In this retrospective study, 110 CNB-diagnosed ADH lesions in 109 consecutive women who underwent US, CEUS, and surgery between June 2018 and June 2023 were included. CEUS was incorporated into US BI-RADS and yielded a CEUS-adjusted BI-RADS. The diagnostic performance of US BI-RADS and CEUS-adjusted BI-RADS for ADH were analyzed and compared. RESULTS: The mean age of the 109 women was 49.7 years ± 11.6 (SD). The upgrade rate of ADH at CNB was 48.2% (53 of 110). The sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for identification of malignant upgrading were 96.2%, 66.7%,72.9%, and 95.0%, respectively, based on BI-RADS category 4B threshold. The two false-negative cases were low-grade ductal carcinoma in situ. Compared with the US, CEUS-adjusted BI-RADS had better specificity for lesions smaller than 2 cm (76.7% vs. 96.7%, P = 0.031). After CEUS, 16 (10 malignant and 6 nonmalignant) of the 45 original US BI-RADS category 4A lesions were up-classified to BI-RADS 4B, and 3 (1 malignant and 2 nonmalignant) of the 41 original US BI-RADS category 4B lesions were down-classified to BI-RADS 4A. CONCLUSIONS: CEUS is helpful in predicting malignant upgrading of ADH, especially for lesions smaller than 2 cm and those classified as BI-RADS 4A and 4B on ultrasound.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Femenino , Humanos , Persona de Mediana Edad , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Ultrasonografía Mamaria , Estudios Retrospectivos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Biopsia con Aguja Gruesa
8.
Acta Radiol ; 65(6): 565-574, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38196268

RESUMEN

BACKGROUND: Ductal carcinoma in situ (DCIS) is often reclassified as invasive cancer in the final pathology report of the surgical specimen. It is of significant clinical relevance to acknowledge the possibility of underestimating invasive disease when utilizing preoperative biopsies for a DCIS diagnosis. In cases where such histologic upgrades occur, it is imperative to consider them in the preoperative planning process, including the potential inclusion of sentinel lymph node biopsy due to the risk of axillary lymph node metastasis. PURPOSE: To assess the capability of breast multiparametric magnetic resonance imaging (MP-MRI) in differentiating between pure DCIS and microinvasive carcinoma (MIC). MATERIAL AND METHODS: Between January 2018 and November 2022, this retrospective study enrolled patients with biopsy-proven DCIS who had undergone preoperative breast MP-MRI. We assessed various MP-MRI features, including size, morphology, margins, internal enhancement pattern, extent of disease, presence of peritumoral edema, time-intensity curve value, diffusion restriction, and ADC value. Subsequently, a logistic regression analysis was conducted to explore the association of these features with the pathological outcome. RESULTS: Of 129 patients with biopsy-proven DCIS, 36 had foci of micro-infiltration on surgical specimens and eight were diagnosed with invasive ductal carcinoma (IDC). The presence of micro-infiltration foci was significantly associated with several MP-MRI features, including tumor size (P <0.001), clustered ring enhancement (P <0.001), segmental distribution (P <0.001), diffusion restriction (P = 0.005), and ADC values <1.3 × 10-3 mm2/s (P = 0.004). CONCLUSION: Breast MP-MRI has the potential to predict the presence of micro-infiltration foci in biopsy-proven DCIS and may serve as a valuable tool for guiding therapeutic planning.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Imágenes de Resonancia Magnética Multiparamétrica , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Persona de Mediana Edad , Estudios Retrospectivos , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología , Anciano , Adulto , Diagnóstico Diferencial , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Invasividad Neoplásica , Mama/diagnóstico por imagen , Mama/patología , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/patología , Anciano de 80 o más Años
9.
Comput Methods Programs Biomed ; 245: 108039, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38266556

RESUMEN

BACKGROUND: The risk of ductal carcinoma in situ (DCIS) identified by biopsy often increases during surgery. Therefore, confirming the DCIS grade preoperatively is necessary for clinical decision-making. PURPOSE: To train a three-classification deep learning (DL) model based on ultrasound (US), combining clinical data, mammography (MG), US, and core needle biopsy (CNB) pathology to predict low-grade DCIS, intermediate-to-high-grade DCIS, and upstaged DCIS. MATERIALS AND METHODS: Data of 733 patients with 754 DCIS cases confirmed by biopsy were retrospectively collected from May 2013 to June 2022 (N1), and other data (N2) were confirmed by biopsy as low-grade DCIS. The lesions were randomly divided into training (n=471), validation (n=142), and test (n = 141) sets to establish the DCIS-Net. Information on the DCIS-Net, clinical (age and sign), US (size, calcifications, type, breast imaging reporting and data system [BI-RADS]), MG (microcalcifications, BI-RADS), and CNB pathology (nuclear grade, architectural features, and immunohistochemistry) were collected. Logistic regression and random forest analyses were conducted to develop Multimodal DCIS-Net to calculate the specificity, sensitivity, accuracy, receiver operating characteristic curve, and area under the curve (AUC). RESULTS: In the test set of N1, the accuracy and AUC of the multimodal DCIS-Net were 0.752-0.766 and 0.859-0.907 in the three-classification task, respectively. The accuracy and AUC for discriminating DCIS from upstaged DCIS were 0.751-0.780 and 0.829-0.861, respectively. In the test set of N2, the accuracy and AUC of discriminating low-grade DCIS from upstaged low-grade DCIS were 0.769-0.987 and 0.818-0.939, respectively. DL was ranked from one to five in the importance of features in the multimodal-DCIS-Net. CONCLUSION: By developing the DCIS-Net and integrating it with multimodal information, diagnosing low-grade DCIS, intermediate-to high-grade DCIS, and upstaged DCIS is possible. It can also be used to distinguish DCIS from upstaged DCIS and low-grade DCIS from upstaged low-grade DCIS, which could pave the way for the DCIS clinical workflow.


Asunto(s)
Neoplasias de la Mama , Calcinosis , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Patología Quirúrgica , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Estudios Retrospectivos , Mamografía , Neoplasias de la Mama/diagnóstico por imagen
10.
AJR Am J Roentgenol ; 222(3): e2330503, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38090808

RESUMEN

Ductal carcinoma in situ (DCIS) is a nonobligate precursor to invasive cancer that classically presents as asymptomatic calcifications on screening mammography. The increase in DCIS diagnoses with organized screening programs has raised concerns about overdiagnosis, while a patientcentric push for more personalized care has increased awareness about DCIS overtreatment. The standard of care for most new DCIS diagnoses is surgical excision, but nonsurgical management via active monitoring is gaining attention, and multiple clinical trials are ongoing. Imaging, along with demographic and pathologic information, is a critical component of active monitoring efforts. Commonly used imaging modalities including mammography, ultrasound, and MRI, as well as newer modalities such as contrast-enhanced mammography and dedicated breast PET, can provide prognostic information to risk stratify patients for DCIS active monitoring eligibility. Furthermore, radiologists will be responsible for closely surveilling patients on active monitoring and identifying if invasive progression occurs. Active monitoring is a paradigm shift for DCIS care, but the success or failure will rely heavily on the interpretations and guidance of radiologists.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/terapia , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Mamografía/métodos , Detección Precoz del Cáncer , Mama/patología , Carcinoma Ductal de Mama/patología
11.
Breast ; 73: 103616, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38064928

RESUMEN

BACKGROUND: Involved resection margins after breast conserving surgery (BCS) often require a re-operation with increased patient anxiety and risk of impaired cosmesis. We investigated the number of re-operations due to involved resection margins after BCS comparing digital breast tomosynthesis(DBT) with X-ray for intraoperative margin evaluation. Furthermore, we assessed the diagnostic accuracy of these methods to predict histopathological margin status. Finally, we evaluated risk factors for re-operation. METHODS: In this randomized, non-blinded study, 250 invasive breast cancer patients were randomized (1:1), whereof 241 were analyzed intraoperatively with either DBT (intervention, n = 119) or X-ray (standard, n = 122). Pearson's chi-squared test, Fisher's exact test, t-test, logistic and ordinal regression analysis was used as appropriate. RESULTS: No difference was found in the number of re-operations between the DBT and X-ray group (16.8 % vs 19.7 %, p = 0.57), or in diagnostic accuracy to predict histopathological margin status (77.5 %, CI: 68.6-84.9 %) and (67.3 %, CI: 57.7-75.9 %), respectively. We evaluated 5 potential risk factors for re-operation: Ductal carcinoma in situ (DCIS) outside tumor, OR = 9.4 (CI: 4.3-20.6, p < 0.001); high mammographic breast density, OR = 6.1 (CI: 1.0-38.1, p = 0.047); non-evaluable margins on imaging, OR = 3.8 (CI: 1.3-10.8, p = 0.016); neoadjuvant chemotherapy, OR = 3.0 (CI: 1.0-8.8, p = 0.048); and T2 tumor-size, OR = 2.6 (CI: 1.0-6.4, p = 0.045). CONCLUSIONS: No difference was found in the number of re-operations or in diagnostic accuracy to predict histopathological margin status between DBT and X-ray groups. DCIS outside the tumor showed the highest risk of re-operation. Intraoperative methods with improved visualization of DCIS are needed to obtain tumor free margins in BCS.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Rayos X , Márgenes de Escisión , Mamografía/métodos , Mastectomía Segmentaria , Carcinoma Ductal de Mama/patología , Estudios Retrospectivos
12.
Clin Breast Cancer ; 24(1): 45-52, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37821332

RESUMEN

BACKGROUND: Supplemental screening with breast MRI is recommended annually for patients who have greater than 20% lifetime risk for breast cancer. While there is robust data regarding features of mammographic screen-detected breast cancers, there is limited data regarding MRI-screen-detected cancers. PATIENTS AND METHODS: Screening breast MRIs performed between August 1, 2016 and July 30, 2022 identified 50 screen-detected breast cancers in 47 patients. Clinical and imaging features of all eligible cancers were recorded. RESULTS: During the study period, 50 MRI-screen detected cancers were identified in 47 patients. The majority of MRI-screen detected cancers (32/50, 64%) were invasive. Pathology revealed ductal carcinoma in situ (DCIS) in 36% (18/50), invasive ductal carcinoma (IDC) in 52% (26/50), invasive lobular carcinoma in 10% (5/50), and angiosarcoma in 2% (1/50). The majority of patients (43/47, 91%) were stage 0 or 1 at diagnosis and there were no breast cancer-related deaths during the follow-up periods. Cancers presented as masses in 50% (25/50), nonmass enhancement in 48% (25/50), and a focus in 2% (1/50). DCIS was more likely to present as nonmass enhancement (94.4%, 17/18), whereas invasive cancers were more likely to present as masses (75%, 24/32) (P < .001). All cancers that were stage 2 at diagnosis were detected either on a baseline exam or more than 4 years since the prior MRI exam. CONCLUSION: MRI screen-detected breast cancers were most often invasive cancers. Cancers detected by MRI screening had an excellent prognosis in our study population. Invasive cancers most commonly presented as a mass.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/epidemiología , Mama/patología , Mamografía , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos
13.
Ann Surg Oncol ; 31(4): 2224-2230, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38117388

RESUMEN

OBJECTIVE: The aim of this study was to determine surgical and clinical outcomes of lobular neoplasia (LN) diagnosed by magnetic resonance imaging (MRI) biopsy, including upgrade to malignancy, and to assess for characteristics associated with upgrade. METHOD: A single-institution retrospective study, between 2013 and 2022, of patients with histopathological findings of LN via MRI-guided biopsy was performed using an institutional database and review of the electronic medical records. Decision for excision or surveillance was made by a multidisciplinary team per institutional practice. Patient demographics and imaging characteristics were summarized using descriptive analyses. Upgrade was defined as upgrade to cancer on surgical pathology for patients treated with excision or the development of cancer at the biopsy site during surveillance. The Wilcoxon rank-sum test and Fisher's exact test were used to compare features of the upgraded cohort with the remainder of the group. RESULTS: Ninety-four MRI biopsies diagnosing LN were included. Median age was 57 years (range 37-78 years). Forty-six lesions underwent excision while 48 lesions were surveilled. The upgrade rate was 7.4% (7/94). Upgrades in the excised cohort consisted of pleomorphic lobular carcinoma in situ (LCIS; n = 1), ductal carcinoma in situ (DCIS; n = 3) and invasive lobular carcinoma (ILC; n = 2), while one interval development of DCIS was observed at the site of biopsy in the surveillance cohort. No MRI or patient variables were associated with upgrade. CONCLUSIONS: In this contemporary cohort of MRI-detected LNs, the upgrade rate was low. Omission of surgery for MRI-detected LNs in carefully selected patients may be considered in a shared decision-making capacity between the patient and the treatment team. Larger cohorts are needed to determine factors predictive of upgrade risk.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Carcinoma Lobular , Lesiones Precancerosas , Humanos , Adulto , Persona de Mediana Edad , Anciano , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Estudios Retrospectivos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Lesiones Precancerosas/patología , Biopsia Guiada por Imagen , Imagen por Resonancia Magnética , Carcinoma Lobular/diagnóstico por imagen , Carcinoma Lobular/cirugía , Biopsia con Aguja Gruesa , Hiperplasia
14.
Medicine (Baltimore) ; 102(50): e36173, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38115362

RESUMEN

RATIONALE: Breast cancer represents a prevalent malignancy that primarily impacts women, with pronounced consequences on their overarching health. The major therapeutic approach, encompassing surgical procedures, can often culminate in mastectomy, potentially inciting psychological turmoil and disorders. PATIENT CONCERNS: A patient was admitted to our facility on May 5, 2023, precipitated by the discovery of bilateral breast masses during a routine physical examination conducted 3 days before admission. DIAGNOSIS: The breasts were symmetric, with the right nipple inverted and a palpable mass in the upper outer quadrant of the right breast, measuring approximately 5 cm × 4 cm. The mass was firm with indistinct borders, relatively regular morphology, poor mobility, and no tenderness. Outpatient color Doppler ultrasound revealed heterogeneous echogenicity in the right breast, classified as Breast Imaging Reporting and Data System (BI-RADS) category 0, along with multiple ductal dilatations. The left breast exhibited a hypoechoic area (BI-RADS 3), indicative of proliferative changes. Radiographic mammography confirmed diffuse changes in the right breast (BI-RADS 0) and proliferative signs in the left breast (BI-RADS 2). Biopsy results reveal significant atypical ductal hyperplasia consistent with intermediate-grade ductal carcinoma in situ. This patient was diagnosed as ductal carcinoma in situ of the right breast (cTisN0M0 and Stage 0), accompanied by a left breast mass. INTERVENTIONS: On May 15, 2023, the patient was readmitted for further surgical intervention. Following relevant auxiliary examinations, the patient underwent nipple-areola complex-sparing radical mastectomy for the right breast, sentinel lymph node biopsy in the right axillary area, prosthesis-based breast reconstruction for the right breast, and microrotatotomy of the left breast mass on the left side on May 17. OUTCOMES: The patient made a successful recovery under scrupulous perioperative supervision and was discharged 7 days post-surgery. LESSONS: The axillary approach for endoscopic mammary gland excision and immediate implant reconstruction permits patients to preserve the esthetics of the female form while undergoing conventional medical treatment. This methodology considerably enhances the psychophysical health of the patients, thereby marking it as an advantageous practice worthy of broad dissemination in the medical community.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Mamoplastia , Femenino , Humanos , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Pezones/cirugía , Pezones/patología , Mastectomía/métodos , Estudios de Seguimiento , Mamoplastia/métodos , Biopsia del Ganglio Linfático Centinela , Atención Perioperativa , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/cirugía , Carcinoma Ductal de Mama/patología , Estudios Retrospectivos
15.
Korean J Radiol ; 24(12): 1190-1199, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38016679

RESUMEN

OBJECTIVE: This study aimed to investigate the feasibility of ultrafast magnetic resonance imaging (MRI) and radiomic features derived from breast MRI for predicting the upstaging of ductal carcinoma in situ (DCIS) diagnosed using percutaneous needle biopsy. MATERIALS AND METHODS: Between August 2018 and June 2020, 95 patients with 98 DCIS lesions who underwent preoperative breast MRI, including an ultrafast sequence, and subsequent surgery were included. Four ultrafast MRI parameters were analyzed: time-to-enhancement, maximum slope (MS), area under the curve for 60 s after enhancement, and time-to-peak enhancement. One hundred and seven radiomic features were extracted for the whole tumor on the first post-contrast T1WI and T2WI using PyRadiomics. Clinicopathological characteristics, ultrafast MRI findings, and radiomic features were compared between the pure DCIS and DCIS with invasion groups. Prediction models, incorporating clinicopathological, ultrafast MRI, and radiomic features, were developed. Receiver operating characteristic curve analysis and area under the curve (AUC) were used to evaluate model performance in distinguishing between the two groups using leave-one-out cross-validation. RESULTS: Thirty-six of the 98 lesions (36.7%) were confirmed to have invasive components after surgery. Compared to the pure DCIS group, the DCIS with invasion group had a higher nuclear grade (P < 0.001), larger mean lesion size (P = 0.038), larger mean MS (P = 0.002), and different radiomic-related characteristics, including a more extensive tumor volume; higher maximum gray-level intensity; coarser, more complex, and heterogeneous texture; and a greater concentration of high gray-level intensity. No significant differences in AUCs were found between the model incorporating nuclear grade and lesion size (0.687) and the models integrating additional ultrafast MRI and radiomic features (0.680-0.732). CONCLUSION: High nuclear grade, larger lesion size, larger MS, and multiple radiomic features were associated with DCIS upstaging. However, the addition of MS and radiomic features to the prediction model did not significantly improve the prediction performance.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Imagen por Resonancia Magnética/métodos , Biopsia con Aguja , Curva ROC , Neoplasias de la Mama/diagnóstico por imagen , Estudios Retrospectivos
16.
BMC Med Imaging ; 23(1): 118, 2023 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-37679713

RESUMEN

PURPOSE: To predict ductal carcinoma in situ with microinvasion (DCISMI) based on clinicopathologic, conventional breast magnetic resonance imaging (MRI), and dynamic contrast enhanced MRI (DCE-MRI) radiomics signatures in women with biopsy-confirmed ductal carcinoma in situ (DCIS). METHODS: Eighty-six women with eighty-seven biopsy-proven DCIS who underwent preoperative MRI and underwent surgery were retrospectively identified. Clinicopathologic, conventional MRI, DCE-MRI radiomics, combine (based on conventional MRI and DCE-MRI radiomics), traditional (based on clinicopathologic and conventional MRI) and mixed (based on clinicopathologic, conventional MRI and DCE-MRI radiomics) models were constructed by logistic regression (LR) with a 3-fold cross-validation, all evaluated using receiver operating characteristic (ROC) curve analysis. A clinical radiomics nomogram was then built by incorporating the Radiomics score, significant clinicopathologic and conventional MRI features of mixed model. RESULTS: The area under the curves (AUCs) of clinicopathologic, conventional MRI, DCE-MRI radiomics, traditional, combine, and mixed model were 0.76 (95% confidence interval [CI] 0.59-0.94), 0.77 (95%CI 0.59-0.95), 0.74 (95%CI 0.55-0.93), 0.87 (95%CI 0.73-1), 0.8 (95%CI 0.63-0.96), and 0.93 (95%CI 0.84-1) in the validation cohort, respectively. The clinical radiomics nomogram based on mixed model showed higher AUCs than both clinicopathologic and DCE-MRI radiomics models in training/test (all P < 0.05) set and showed the greatest overall net benefit for upstaging according to decision curve analysis (DCA). CONCLUSION: A nomogram constructed by combining clinicopathologic, conventional MRI features and DCE-MRI radiomics signatures may be useful in predicting DCISMI from DICS preoperatively.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Femenino , Humanos , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Nomogramas , Estudios Retrospectivos , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Biopsia
17.
J Pathol ; 261(2): 125-138, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37555360

RESUMEN

Due to limited biopsy samples, ~20% of DCIS lesions confirmed by biopsy are upgraded to invasive ductal carcinoma (IDC) upon surgical resection. Avoiding underestimation of IDC when diagnosing DCIS has become an urgent challenge in an era discouraging overtreatment of DCIS. In this study, the metabolic profiles of 284 fresh frozen breast samples, including tumor tissues and adjacent benign tissues (ABTs) and distant surrounding tissues (DSTs), were analyzed using desorption electrospray ionization-mass spectrometry (DESI-MS) imaging. Metabolomics analysis using DESI-MS data revealed significant differences in metabolite levels, including small-molecule antioxidants, long-chain polyunsaturated fatty acids (PUFAs) and phospholipids between pure DCIS and IDC. However, the metabolic profile in DCIS with invasive carcinoma components clearly shifts to be closer to adjacent IDC components. For instance, DCIS with invasive carcinoma components showed lower levels of antioxidants and higher levels of free fatty acids compared to pure DCIS. Furthermore, the accumulation of long-chain PUFAs and the phosphatidylinositols (PIs) containing PUFA residues may also be associated with the progression of DCIS. These distinctive metabolic characteristics may offer valuable indications for investigating the malignant potential of DCIS. By combining DESI-MS data with machine learning (ML) methods, various breast lesions were discriminated. Importantly, the pure DCIS components were successfully distinguished from the DCIS components in samples with invasion in postoperative specimens by a Lasso prediction model, achieving an AUC value of 0.851. In addition, pixel-level prediction based on DESI-MS data enabled automatic visualization of tissue properties across whole tissue sections. Summarily, DESI-MS imaging on histopathological sections can provide abundant metabolic information about breast lesions. By analyzing the spatial metabolic characteristics in tissue sections, this technology has the potential to facilitate accurate diagnosis and individualized treatment of DCIS by inferring the presence of IDC components surrounding DCIS lesions. © 2023 The Pathological Society of Great Britain and Ireland.


Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/patología , Antioxidantes , Espectrometría de Masas , Neoplasias de la Mama/diagnóstico por imagen
18.
Breast Cancer Res ; 25(1): 80, 2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37403150

RESUMEN

BACKGROUND: Some breast carcinomas detected at screening, especially ductal carcinoma in situ, may have limited potential for progression to symptomatic disease. To determine non-progression is a challenge, but if all screening-detected breast tumors eventually reach a clinical stage, the cumulative incidence at a reasonably high age would be similar for women with or without screening, conditional on the women being alive. METHODS: Using high-quality population data with 24 years of follow-up from the gradually introduced BreastScreen Norway program, we studied whether all breast carcinomas detected at mammography screening 50-69 years of age would progress to clinical symptoms within 85 years of age. First, we estimated the incidence rates of breast carcinomas by age in scenarios with or without screening, based on an extended age-period-cohort incidence model. Next, we estimated the frequency of non-progressive tumors among screening-detected cases, by calculating the difference in the cumulative rate of breast carcinomas between the screening and non-screening scenarios at 85 years of age. RESULTS: Among women who attended BreastScreen Norway from the age of 50 to 69 years, we estimated that 1.1% of the participants were diagnosed with a breast carcinoma without the potential to progress to symptomatic disease by 85 years of age. This proportion of potentially non-progressive tumors corresponded to 15.7% [95% CI 3.3, 27.1] of breast carcinomas detected at screening. CONCLUSIONS: Our findings suggest that nearly one in six breast carcinomas detected at screening may be non-progressive.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Femenino , Humanos , Anciano de 80 o más Años , Persona de Mediana Edad , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/epidemiología , Mamografía , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/epidemiología , Tamizaje Masivo , Detección Precoz del Cáncer
19.
J Med Imaging Radiat Oncol ; 67(6): 647-652, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37454369

RESUMEN

Non-calcified ductal carcinoma in situ (NCDCIS) presents as a heterogeneous entity on various imaging modalities, most frequently presenting symptomatically as a palpable lump. The combination of multiple modalities and knowledge of its potential radiological appearances are important in minimising misdiagnosis. Compared to conventional 2D mammography, both sonography and digital breast tomosynthesis show higher diagnostic accuracy in the detection of NCDCIS. Newer modalities of contrast-enhanced digital mammography and MRI have limited data at present, but early results indicate greater sensitivity for the detection of lesions that may be occult on ultrasound or mammography. Here, we present an illustrative study highlighting the varied appearances of NCDCIS on several imaging modalities including a brief review of the literature.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Mamografía/métodos , Ultrasonografía , Imagen por Resonancia Magnética/métodos , Neoplasias de la Mama/diagnóstico por imagen
20.
Clin Breast Cancer ; 23(6): 649-657, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37328333

RESUMEN

BACKGROUND: When needle core biopsy (NCB) of the breast yields atypical ductal hyperplasia (ADH), excision is typically recommended. The natural history of ADH undergoing active surveillance (AS) is not well described. We investigate the rates of upgrade to malignancy of excised ADH and the rates of radiographic progression under AS. MATERIALS AND METHODS: We retrospectively reviewed records of 220 cases of ADH on NCB. Of patients who had surgery within 6 months of NCB, we examined the malignancy upgrade rate. In the AS cohort, we examined rates of radiographic progression on interval imaging. RESULTS: The malignancy upgrade rate among patients who underwent immediate excision (n = 185) was 15.7%: 14.1% (n = 26) ductal carcinoma in situ (DCIS) and 1.6% (n = 3) invasive ductal carcinoma (IDC). Upgrade to malignancy was less common in lesions <4 mm in size (0%) or with focal ADH (5%), and more common among lesions presenting with a radiographic mass (26%). Among the 35 patients who underwent AS, median follow-up was 20 months. Two lesions progressed on imaging (incidence 3.8% at 2 years). One patient without radiographic progression was found to have IDC at delayed surgery. The remaining lesions remained stable (46%), decreased in size (11%), or resolved (37%). CONCLUSIONS: Our findings suggest that AS is a safe approach to managing ADH on NCB for most patients. This could spare many patients with ADH from unnecessary surgery. Given that AS is being investigated for low-risk DCIS in multiple international prospective trials, these results suggest that AS should also be investigated for ADH.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Humanos , Femenino , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/patología , Estudios Retrospectivos , Estudios Prospectivos , Espera Vigilante , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Mama/diagnóstico por imagen , Mama/cirugía , Mama/patología , Biopsia con Aguja Gruesa , Hiperplasia/diagnóstico por imagen , Hiperplasia/cirugía , Hiperplasia/patología
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