Unveiling the Clinical Path of Microinvasive Breast Cancer: A Comparative Study With Tis-T1 Breast Cancer.

PURPOSE: The prognosis of microinvasive breast cancer (MIBC) is controversial, with a high reported rate of local recurrence (LR). This study aimed to evaluate the characteristics, treatments, and prognosis of patients with MIBC compared to those with carcinoma in situ (CIS) or early invasive cancer. METHODS: Patients who diagnosed with CIS or stage I breast cancer were retrospectively enrolled. Using the Kaplan-Meier method, local recurrence-free survival (LRFS), systemic recurrence-free survival (SRFS), and cancer-specific survival (CSS) were compared according to T stage. The prognostic factors associated with LRFS were identified using the Cox proportional hazards model. RESULTS: According to T stage, 517 (21.6%), 200 (8.4%), 207 (8.7%), 363 (15.2%), and 1101 (46.1%) patients had Tis, T1mi, T1a, T1b, and T1c tumors, respectively. The proportion of human epidermal growth factor receptor 2-positive tumors was significantly higher in patients with MIBC (p < 0.0001). The administered adjuvant treatments also showed differences according to T stage (p < 0.0001). During the 73-month median follow-up period, patients with MIBC showed significantly worse LRFS than those with T1a or T1c tumors (p = 0.002). There was no significant difference in SRFS and CSS. In the Cox regression analysis, tumor multiplicity (p = 0.017), Ki-67 (p = 0.025), cancer subtype (p = 0.034), adjuvant endocrine therapy (p = 0.003), and adjuvant radiation therapy (p < 0.0001) were significant prognostic factors associated with LRFS. CONCLUSION: The risk of LR was higher in patients with MIBC than in those with small invasive breast cancer. Therefore, if indicated, adjuvant endocrine and radiation therapies should be administered to prevent undertreatment in patients with MIBC.

Meta-analysis on axillary lymph node metastasis rate in ductal carcinoma in situ with microinvasion.

OBJECTIVE: To address the question of axillary lymph node staging in ductal carcinoma in situ with microinvasion (DCIS-MI), we retrospectively evaluated axillary lymph nodes metastasis (ALNM) rate in a cohort of postsurgical DCIS-MI patients. By analyzing these data, we aimed to generate clinically relevant insights to inform treatment decision-making for this patient population. METHODS: A systematic search was conducted on PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang Database, Wipe, and China Biomedical Literature Database to identify relevant publications in any language. All the analyses were performed using Stata 16.0 software. RESULTS: Among the 28 studies involving 8279 patients, the pooled analysis revealed an ALNM rate of 8% (95% CI, 7% to 10%) in patients with DCIS-MI. Furthermore, the rates of axillary lymph node macrometastasis, micrometastasis, and ITC in patients with DCIS-MI were 2% (95% CI, 2% to 3%), 3% (95% CI, 2% to 4%), and 2% (95% CI, 1% to 3%), respectively. Moreover, 13 studies investigated the non-sentinel lymph node (Non-SLN) metastasis rate, encompassing a total of 1236 DCIS-MI cases. The pooled analysis identified a Non-SLN metastasis rate of 33% (95% CI, 14% to 55%) in patients with DCIS-MI. CONCLUSION: The SLNB for patients with DCIS-MI is justifiable and could provide a novel therapeutic basis for systemic treatment decisions.

Evaluation of the Efficacy of Postoperative Adjuvant Therapy for HER2-Positive Ductal Carcinoma in Situ with Microinvasion.

A retrospective study on 90 eligible HER2+ ductal carcinoma in situ with microinvasion (DCIS-MI) patients was performed with a median follow-up time of 57 months. The baseline was consistent between the 4-cycle and 6-cycle chemotherapy groups. There were more patients with multiple foci of micrometastasis in the target therapy group in the two groups with or without target therapy (p < 0.01). Postoperative chemotherapy with a 4-cycle regimen can achieve the expected therapeutic effect in patients with HER2+ DCIS-MI, but the role of target therapy in HER2+ DCIS-MI patients has not been confirmed.

Microinvasion in hepatocellular carcinoma: predictive factor and application for definition of clinical target volume for radiotherapy.

BACKGROUND: To investigate the correlation between microinvasion and various features of hepatocellular carcinoma (HCC), and to clarify the microinvasion distance from visible HCC lesions to subclinical lesions, so as to provide clinical basis for the expandable boundary of clinical target volume (CTV) from gross tumor volume (GTV) in the radiotherapy of HCC. METHODS: HCC patients underwent hepatectomy of liver cancer in our hospital between July 2019 and November 2021 were enrolled. Data on various features and tumor microinvasion distance were collected. The distribution characteristics of microinvasion distance were analyzed to investigate its potential correlation with various features. Tumor size compared between radiographic and pathologic samples was analyzed to clarify the application of pathologic microinvasion to identify subclinical lesions of radiographic imaging. RESULTS: The average microinvasion distance was 0.6 mm, with 95% patients exhibiting microinvasion distance less than 3.0 mm, and the maximum microinvasion distance was 4.0 mm. A significant correlation was found between microinvasion and liver cirrhosis (P = 0.036), serum albumin level (P = 0.049). Multivariate logistic regression analysis revealed that HCC patients with cirrhosis had a significantly lower risk of microinvasion (OR = 0.09, 95%CI = 0.02 ~ 0.50, P = 0.006). Tumor size was overestimated by 1.6 mm (95%CI=-12.8 ~ 16.0 mm) on radiographic size compared to pathologic size, with a mean %Δsize of 2.96% (95%CI=-0.57%~6.50%). The %Δsize ranged from - 29.03% to 34.78%. CONCLUSIONS: CTV expanding by 5.4 mm from radiographic GTV could include all pathologic microinvasive lesions in the radiotherapy of HCC. Liver cirrhosis was correlated with microinvasion and were independent predictive factor of microinvasion in HCC.

Clinical and Imaging Characteristics of Contrast-enhanced Mammography and MRI to Distinguish Microinvasive Carcinoma from Ductal Carcinoma In situ.

RATIONALE AND OBJECTIVES: The prognosis of ductal carcinoma in situ with microinvasion (DCISM) is more similar to that of small invasive ductal carcinoma (IDC) than to pure ductal carcinoma in situ (DCIS). It is particularly important to accurately distinguish between DCISM and DCIS. The present study aims to compare the clinical and imaging characteristics of contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) between DCISM and pure DCIS, and to identify predictive factors of microinvasive carcinoma, which may contribute to a comprehensive understanding of DCISM in clinical diagnosis and support surveillance strategies, such as surgery, radiation, and other treatment decisions. MATERIALS AND METHODS: Forty-seven female patients diagnosed with DCIS were included in the study from May 2019 to August 2023. Patients were further divided into two groups based on pathological diagnosis: DCIS and DCISM. Clinical and imaging characteristics of these two groups were analyzed statistically. The independent clinical risk factors were selected using multivariate logistic regression and used to establish the logistic model [Logit(P)]. The diagnostic performance of independent predictors was assessed and compared using receiver operating characteristic (ROC) analysis and DeLong's test. RESULTS: In CEM, the maximum cross-sectional area (CSAmax), the percentage signal difference between the enhancing lesion and background in the craniocaudal and mediolateral oblique projection (%RSCC, and %RSMLO) were found to be significantly higher for DCISM compared to DCIS (p = 0.001; p < 0.001; p = 0.008). Additionally, there were noticeable statistical differences in the patterns of enhancement morphological distribution (EMD) and internal enhancement pattern (IEP) between DCIS and DCISM (p = 0.047; p = 0.008). In MRI, only CSAmax (p = 0.012) and IEP (p = 0.020) showed significant statistical differences. The multivariate regression analysis suggested that CSAmax (in CEM or MR) and %RSCC were independent predictors of DCISM (all p < 0.05). The area under the curve (AUC) of CSAmax (CEM), %RSCC (CEM), Logit(P) (CEM), and CSAmax (MR) were 0.764, 0.795, 0.842, and 0.739, respectively. There were no significant differences in DeLong's test for these values (all p > 0.10). DCISM was significantly associated with high nuclear grade, comedo type, high axillary lymph node (ALN) metastasis, and high Ki-67 positivity compared to DCIS (all p < 0.05). CONCLUSION: The tumor size (CSAmax), enhancement index (%RS), and internal enhancement pattern (IEP) were highly indicative of DCISM. DCISM tends to express more aggressive pathological features, such as high nuclear grade, comedo-type necrosis, ALN metastasis, and Ki-67 overexpression. As with MRI, CEM has the capability to help predict when DCISM is accompanying DCIS.

Bacterial surface lipoproteins mediate epithelial microinvasion by Streptococcus pneumoniae.

Streptococcus pneumoniae, a common colonizer of the upper respiratory tract, invades nasopharyngeal epithelial cells without causing disease in healthy participants of controlled human infection studies. We hypothesized that surface expression of pneumococcal lipoproteins, recognized by the innate immune receptor TLR2, mediates epithelial microinvasion. Mutation of lgt in serotype 4 (TIGR4) and serotype 6B (BHN418) pneumococcal strains abolishes the ability of the mutants to activate TLR2 signaling. Loss of lgt also led to the concomitant decrease in interferon signaling triggered by the bacterium. However, only BHN418 lgt::cm but not TIGR4 lgt::cm was significantly attenuated in epithelial adherence and microinvasion compared to their respective wild-type strains. To test the hypothesis that differential lipoprotein repertoires in TIGR4 and BHN418 lead to the intraspecies variation in epithelial microinvasion, we employed a motif-based genome analysis and identified an additional 525 a.a. lipoprotein (pneumococcal accessory lipoprotein A; palA) encoded by BHN418 that is absent in TIGR4. The gene encoding palA sits within a putative genetic island present in ~10% of global pneumococcal isolates. While palA was enriched in the carriage and otitis media pneumococcal strains, neither mutation nor overexpression of the gene encoding this lipoprotein significantly changed microinvasion patterns. In conclusion, mutation of lgt attenuates epithelial inflammatory responses during pneumococcal-epithelial interactions, with intraspecies variation in the effect on microinvasion. Differential lipoprotein repertoires encoded by the different strains do not explain these differences in microinvasion. Rather, we postulate that post-translational modifications of lipoproteins may account for the differences in microinvasion.IMPORTANCEStreptococcus pneumoniae (pneumococcus) is an important mucosal pathogen, estimated to cause over 500,000 deaths annually. Nasopharyngeal colonization is considered a necessary prerequisite for disease, yet many people are transiently and asymptomatically colonized by pneumococci without becoming unwell. It is therefore important to better understand how the colonization process is controlled at the epithelial surface. Controlled human infection studies revealed the presence of pneumococci within the epithelium of healthy volunteers (microinvasion). In this study, we focused on the regulation of epithelial microinvasion by pneumococcal lipoproteins. We found that pneumococcal lipoproteins induce epithelial inflammation but that differing lipoprotein repertoires do not significantly impact the magnitude of microinvasion. Targeting mucosal innate immunity and epithelial microinvasion alongside the induction of an adaptive immune response may be effective in preventing pneumococcal colonization and disease.

Intratesticular Mullerian Serous Borderline Tumor With Microinvasion: A Rare Tumor and Review of the Literature.

Ovarian-type (ie, Mullerian) epithelial tumors occurring in the testicular and paratesticular regions are exceptionally rare, with only a handful reported worldwide. Serous tumors are the most frequently encountered subtype among these rare tumors. The pathogenesis of these tumors within the testicular and paratesticular regions remains a subject of intrigue and debate, with various hypotheses attempting to explain their presence in the paratestis region, where most tumors occur. However, our understanding of the pathogenesis of intratesticular tumors is limited. To date, 11 known examples of intratesticular serous Mullerian tumors have been reported globally. In this report, we present an extraordinary tumor, an intratesticular Mullerian serous borderline tumor with foci of microinvasion, in a 38-year-old male patient. This tumor exhibits histological features similar to their ovarian counterparts and is confirmed through an immunohistochemical panel. Our report underscores the extreme rarity of these tumors, emphasizes the importance of heightened awareness among clinicians and pathologists, and provides valuable insights into their complex development and histogenesis. This contribution aims to enhance diagnostic precision and optimize therapeutic strategies for similar tumors.

Improving the diagnosis of ductal carcinoma in situ with microinvasion without immunohistochemistry: An innovative method with H&E-stained and multiphoton microscopy images.

Ductal carcinoma in situ with microinvasion (DCISM) is a challenging subtype of breast cancer with controversial invasiveness and prognosis. Accurate diagnosis of DCISM from ductal carcinoma in situ (DCIS) is crucial for optimal treatment and improved clinical outcomes. However, there are often some suspicious small cancer nests in DCIS, and it is difficult to diagnose the presence of intact myoepithelium by conventional hematoxylin and eosin (H&E) stained images. Although a variety of biomarkers are available for immunohistochemical (IHC) staining of myoepithelial cells, no single biomarker is consistently sensitive to all tumor lesions. Here, we introduced a new diagnostic method that provides rapid and accurate diagnosis of DCISM using multiphoton microscopy (MPM). Suspicious foci in H&E-stained images were labeled as regions of interest (ROIs), and the nuclei within these ROIs were segmented using a deep learning model. MPM was used to capture images of the ROIs in H&E-stained sections. The intensity of two-photon excitation fluorescence (TPEF) in the myoepithelium was significantly different from that in tumor parenchyma and tumor stroma. Through the use of MPM, the myoepithelium and basement membrane can be easily observed via TPEF and second-harmonic generation (SHG), respectively. By fusing the nuclei in H&E-stained images with MPM images, DCISM can be differentiated from suspicious small cancer clusters in DCIS. The proposed method demonstrated good consistency with the cytokeratin 5/6 (CK5/6) myoepithelial staining method (kappa coefficient = 0.818).

Could breast multiparametric MRI discriminate between pure ductal carcinoma in situ and microinvasive carcinoma?

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.

Frequency of post-treatment disease after excisional procedure in stage IA1 squamous cervical carcinoma - a case series.

Early stages of cervical cancer in young women need conservative treatments. Electrosurgical therapies (LLETZ, LEEP, SWETZ, NETZ) have been recommended for these women. However, there are recommendations to perform a second excision when the specimen margins are not free of disease. This can lead to some important complications. This article aims to verify the frequency of residual invasive or microinvasive disease after the excisional procedure in women with IA1CC. Data on women with IA1CC diagnosed between 1990 and 2022, were retrieved from medical records. Post-treatment disease was detected during a second surgical procedure or postoperative follow-up. Among the 69 included women, three (4.3 percent; CI95 percent 0-9.2) had residual microinvasive lesions, while none showed invasive disease during a second procedure or follow-up. Only the age of 37 years or more was significantly related to the presence of preinvasive or microinvasive residual lesions. Nearly 80 percent of the women who underwent a second procedure showed no residual lesions. The absence of invasive disease in a second procedure or during the follow-up of these women and the large proportion of women with no residual lesion questions the need for a new surgical procedure even when the surgical margins of the initial specimen are involved.

KRT15 in early breast cancer screening and correlation with HER2 positivity, pathological grade and N stage.

Objective: This study was designed to explore KRT15 dysregulation and its correlation with clinical characteristics among ductal carcinoma in situ (DCIS), DCIS with microinvasion (DCIS-MI) and invasive breast cancer (IBC) patients. Methods: KRT15 from lesion samples of 50 DCIS patients, 48 DCIS-MI patients and 50 IBC patients was detected by immunohistochemistry. Results: KRT15 discriminated IBC patients from DCIS patients (area under the curve [AUC] = 0.895; 95% CI = 0.836-0.954) and DCIS-MI patients (AUC = 0.707; 95% CI = 0.606-0.808). In DCIS patients, KRT15 was negatively correlated with pathological grade (p = 0.015). In DCIS-MI patients, KRT15 was positively related to estrogen receptor positivity but negatively associated with Ki-67 (both p < 0.05). In IBC patients, KRT15 was negatively linked to HER2 positivity, histological grade, N stage and tumor node metastasis stage (all p < 0.05). Conclusion: KRT15 assessment may help with early breast cancer screening.

An MRI-Based Radiomics Nomogram to Distinguish Ductal Carcinoma In Situ with Microinvasion From Ductal Carcinoma In Situ of Breast Cancer.

RATIONALE AND OBJECTIVES: Accurate preoperative differentiation between ductal carcinoma in situ with microinvasion (DCISM) and ductal carcinoma in situ (DCIS) could facilitate treatment optimization and individualized risk assessment. The present study aims to build and validate a radiomics nomogram based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) that could distinguish DCISM from pure DCIS breast cancer. MATERIALS AND METHODS: MR images of 140 patients obtained between March 2019 and November 2022 at our institution were included. Patients were randomly divided into a training (n = 97) and a test set (n = 43). Patients in both sets were further split into DCIS and DCISM subgroups. The independent clinical risk factors were selected by multivariate logistic regression to establish the clinical model. The optimal radiomics features were chosen by the least absolute shrinkage and selection operator, and a radiomics signature was built. The nomogram model was constructed by integrating the radiomics signature and independent risk factors. The discrimination efficacy of our nomogram was assessed by using calibration and decision curves. RESULTS: Six features were selected to construct the radiomics signature for distinguishing DCISM from DCIS. The radiomics signature and nomogram model exhibited better calibration and validation performance in the training (AUC 0.815, 0.911, 95% confidence interval [CI], 0.703-0.926, 0.848-0.974) and test (AUC 0.830, 0.882, 95% CI, 0.672-0.989, 0.764-0.999) sets than in the clinical factor model (AUC 0.672, 0.717, 95% CI, 0.544-0.801, 0.527-0.907). The decision curve also demonstrated that the nomogram model exhibited good clinical utility. CONCLUSION: The proposed noninvasive MRI-based radiomics nomogram model showed good performance in distinguishing DCISM from DCIS.

Ductal Carcinoma In Situ (DCIS) and Microinvasive DCIS: Role of Surgery in Early Diagnosis of Breast Cancer.

Advances in treatments, screening, and awareness have led to continually decreasing breast cancer-related mortality rates in the past decades. This achievement is coupled with early breast cancer diagnosis. Ductal carcinoma in situ (DCIS) and microinvasive breast cancer have increasingly been diagnosed in the context of mammographic screening. Clinical management of DCIS is heterogenous, and the clinical significance of microinvasion in DCIS remains elusive, although microinvasive DCIS (DCIS-Mi) is distinct from "pure" DCIS. Upfront surgery has a fundamental role in the overall treatment of these breast diseases. The growing number of screen-detected DCIS diagnoses with clinicopathological features of low risk for local recurrence (LR) allows more conservative surgical options, followed by personalised adjuvant radiotherapy plans. Furthermore, studies are underway to evaluate the validity of surgery omission in selected low-risk categories. Nevertheless, the management, the priority of axillary surgical staging, and the prognosis of DCIS-Mi remain the subject of debate, demonstrating how the paucity of data still necessitates adequate studies to provide conclusive guidelines. The current scientific scenario for DCIS and DCIS-Mi surgical approach consists of highly controversial and diversified sources, which this narrative review will delineate and clarify.

Histopathological parameters reported in microinvasive oral squamous cell carcinoma: a systematic review

Background: Microinvasive oral squamous cell carcinoma (OSCCmi) is an incipient stage of oral cancer. Through this systematic review, we aim to assess patterns of histopathological outcomes reported in OSCCmi cases. Material and methods: An online search in major databases was performed without period restriction, and 2,024 publications in English, Spanish and Portuguese were obtained. After screening and eligibility, 4 studies were selected. The risk of bias was assessed using Joanna Briggs Institute Critical Appraisal Checklist. A descriptive synthesis was conducted. Results: All 4 publications included were retrospective, reporting a total of 116 OSCCmi patients, with a male predominance (1.6:1) and a mean age of 55.9 years. The main parameters considered for microinvasion were tumor thickness (TT) (range 4-10mm) and depth of invasion (DOI) (range 0,02-5mm). Definition, cut-off values, and assessment of microscopic features were not standardized. Other relevant measures such as perineural or lymphovascular invasion and pattern of invasive front were barely described, and cytological/architectural characteristics were not discussed. Conclusions: TT and DOI are currently the primary histopathological criteria used to define OSCCmi. Nonetheless, the outcomes of this systematic review showed the absence of standardized quantitative parameters to render the diagnosis of microinvasive OSCC. Therefore, additional studies aiming to standardize histopathological features to diagnose OSCCmi are paramount. (AU)

Clinicopathological characteristics, treatments, and prognosis of breast ductal carcinoma in situ with microinvasion: A narrative review.

Background: Ductal carcinoma in situ with microinvasion (DCIS-MI) is defined as ductal carcinoma in situ (DCIS) with a microscopic invasive focus ≤1 mm in the longest diameter. The current literature is controversial concerning the clinical prognostic features and management of DCIS-MI. This narrative review described recently reported literature regarding the characteristics, treatment, and prognosis of it. Methods: Searching PubMed for relevant articles covering the period of 1982 to 2021 using the following terms by MeSH and free-word: breast cancer, microinvasion, DCIS, DCIS-MI, and invasive ductal carcinoma (IDC). Results: DCIS-MI tends to express more aggressive pathological features such as necrosis, HER2+, ER- or PR-, and high nuclear grade. The overall prognosis of DCIS-MI is typically good, however, some indicators such as young age, HR-, HER2+ and multimicroinvasive lesions, were associated with worse prognoses. And there are also conflicting results on the differences between the prognoses of DCIS-MI and DCIS or T1a-IDC. Postoperative chemotherapy and anti-HER2 therapy still have uncertain benefits and are more likely to be used to treat high-risk patients who are HR- orHER2+ to improve the prognosis. Conclusion: DCIS-MI has more aggressive pathological features, which may suggest its biological behavior is worse than that of DCIS and similar to early IDC. Although the overall prognosis of DCIS-MI is good, when making decisions about adjuvant therapy clinicians need to give priority to the hormone receptor status, HER2 expression and axillary lymph node status of patients, because these may affect the prognosis and treatment response.

More microinvasive foci in larger tumours of breast ductal carcinoma in situ.

Introduction: Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers. Methods: The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci. Results: Higher numbers of Mi foci were found in larger tumours (P = 0.031). Conclusion: Greater extent of DCIS is associated with multifocal Mi.

Prognostic significance of microinvasion with ductal carcinoma in situ of the breast: a meta-analysis.

PURPOSE: Ductal carcinoma in situ (DCIS) associated with invasive carcinoma ≤ 1 mm in size is defined as DCIS with microinvasion (DCIS/microinvasion) rather than as invasive breast carcinoma. The number of patients with microinvasion accounts for < 1% of all breast cancer in published studies. As the numbers are limited, the prognostic significance of DCIS/microinvasion has not been clearly elucidated. This meta-analysis aimed to investigate the survival differences between patients with DCIS/microinvasion and those with pure DCIS. METHODS: A meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was performed. We searched three electronic databases (MEDLINE, Cochrane Library, and EMBASE) and included observational studies published in English that contained survival details of patients with either DCIS or DCIS/microinvasion. RESULTS: This study identified 26 studies that described the clinicopathological characteristics of patients in both the DCIS and DCIS/microinvasion groups. Survival differences were evaluated in 10 of 26 studies. Disease-free survival and loco-regional recurrence-free survival were significantly shorter in patients with DCIS/microinvasion than in those with DCIS (Hazard ratio, 1.52; 95% confidence interval, 1.11-2.08; p = 0.01 and hazard ratio, 2.53; 95% confidence interval, 1.45-4.41; p = 0.001, respectively). Both overall survival and distant metastasis-free survival tended to be shorter in patients with DCIS/microinvasion than in patients with DCIS (Hazard ratio, 1.63; 95% CI, 0.63-4.23; p = 0.31 and hazard ratio, 1.85; 95% confidence interval, 0.74-4.66; p = 0.19, respectively) but the difference was not statistically significant. CONCLUSION: Our meta-analysis suggests that DCIS/microinvasion may display more aggressive biological and clinical behavior than pure DCIS, highlighting the potential need for closer follow-up and consideration of adjuvant treatment strategies in DCIS patients with microinvasive disease.

More microinvasive foci in larger tumours of breast ductal carcinoma in situ

INTRODUCTION@#Microinvasion (Mi) is often thought to be an interim stage between ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. This study aimed to investigate the potential influence of Mi on survival and assess its correlations with clinicopathological parameters, prognosis and molecular markers.@*METHODS@#The number of Mi foci in a cohort of 66 DCIS-Mi cases was assessed from haematoxylin and eosin-stained sections. Disease-free survival, clinicopathological parameters and biomarker expression were correlated with the number of Mi foci.@*RESULTS@#Higher numbers of Mi foci were found in larger tumours (P = 0.031).@*CONCLUSION@#Greater extent of DCIS is associated with multifocal Mi.

Application of deep learning to identify ductal carcinoma in situ and microinvasion of the breast using ultrasound imaging.

Background: The treatment and prognosis of breast ductal carcinoma in situ (DCIS) with and without microinvasion (MIC) are different. Ultrasound imaging shows that DCIS is a heterogeneous breast tumor with diverse manifestations. DCIS means that the cancer cells are confined in the duct without penetrating the basement membrane, MIC means that the cancer cells penetrate the basement membrane and the maximum diameter of any largest invasive lesion is less than or equal to 1 mm. This study was designed to evaluate how deep learning can be used to identify DCIS with MIC on ultrasound images. Methods: The clinical and ultrasound data of 467 consecutive inpatients diagnosed with DCIS (213 with MIC) in West China Hospital of Sichuan University were collected from January 2013 to April 2019 and randomly apportioned to training and internal validation sets. An external validation set comprised data from Sichuan Provincial People's Hospital with 101 patients (33 with MIC) collected between January 2017 and December 2019. There were 2,492 original images; 66% of these were used to establish a model, and the remaining 34% were used to evaluate the model. Three experienced breast ultrasound clinicians analyzed the ultrasound images to establish a logistic regression model. Finally, the logistic regression model and five deep learning models (ResNet-50, ResNet-101, DenseNet-161, DenseNet-169, and Inception-v3) were compared and evaluated to assess their diagnostic efficiency when identifying MIC based on ultrasound image data. Results: The characteristics of high nuclear grade (P<0.001), necrosis (P=0.006), estrogen receptor negative (ER-; P=0.003), progesterone receptor negative (PR-; P=0.001), human epidermal growth factor receptor 2 positive (HER2+; P=0.034), lymphatic metastasis (P=0.008), and calcification (P<0.001) all showed significant correlations with MIC. The Inception-v3 model achieved the best performance (P<0.05) in MIC identification. The area under the receiver operating curve (AUC) of the Inception-v3 model was 0.803 [95% confidence interval (CI): 0.709 to 0.878], with a classification accuracy of 0.766, a sensitivity of 0.767, and a specificity of 0.765. Conclusions: Deep learning can be used to identify MIC of breast DCIS from ultrasound images. Models based on Inception-v3 can provide automated detection of DCIS with MIC from ultrasound images.

Multiple Metastases of the Liver and Lung After Breast-Conserving Surgery for Ductal Carcinoma In Situ Without Microinvasion of the Breast: A Case Report and Literature Review.

Background: Ductal carcinoma in situ (DCIS) is a non-invasive disease that rarely causes distant metastasis. It is extremely rare for patients diagnosed with DCIS without microinvasion to develop distant metastasis in the absence of ipsilateral or contralateral breast recurrence. This is the first case report of multiple liver and lung metastases from DCIS after breast-conserving surgery and radiotherapy. Case Presentation: A 45-year-old woman who was diagnosed with DCIS and received breast-conserving surgery, radiotherapy, and sequential endocrine therapy developed multiple metastases in the liver and lung despite not having bilateral breast recurrence at the 62-month follow-up. Comprehensive advanced breast cancer therapy was administered but did not prevent the progression of metastatic foci in the liver. Conclusions: This case shows the poor potential outcome in DCIS. Further research should be conducted on metastasis in DCIS; reexamination and monitoring are indispensable for patients diagnosed with DCIS.