Search Results (162)

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article

Mammary Paget disease (MPD) is a rare cutaneous malignancy associated with underlying ductal carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC). Clinically, it appears as eczematous changes in the nipple and areola complex (NAC), which may include itching, redness, crusting, and ulceration; these symptoms can sometimes mimic benign dermatologic conditions such as nipple eczema, making early diagnosis challenging. A 56-year-old woman presented with persistent erythema and scaling of the left nipple, which did not respond to conventional dermatologic treatments: a high degree of suspicion prompted further investigation. Reflectance confocal microscopy (RCM) revealed atypical, enlarged epidermal cells with irregular boundaries, while line-field confocal–optical coherence tomography (LC-OCT) demonstrated thickening of the epidermis, hypo-reflective vacuous spaces and abnormally large round cells (Paget cells). These non-invasive imaging findings were consistent with an aggressive case of Paget disease despite the absence of clear mammographic evidence of underlying carcinoma: in fact, several biopsies were needed, and at the end, massive surgery was necessary. Non-invasive imaging techniques, such as dermoscopy, RCM, and LC-OCT, offer a valuable diagnostic tool in detecting Paget disease, especially in early stages and atypical forms. Full article

Purpose: This study aimed to develop a predictive nomogram integrating AI-based BI-RADS lexicons and lesion-to-nipple distance (LND) ultrasound features to differentiate mass-type ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) visible on ultrasound. Methods: The final study cohort consisted of 170 women with 175 pathologically confirmed malignant breast lesions, including 26 cases of DCIS and 149 cases of IDC. LND and AI-based features from the S-Detect system (BI-RADS lexicons) were analyzed. Rare features were consolidated into broader categories to enhance model stability. Data were split into training (70%) and validation (30%) sets. Logistic regression identified key predictors for an LND nomogram. Model performance was evaluated using receiver operating characteristic (ROC) curves, 1000 bootstrap resamples, and calibration curves to assess discrimination and calibration. Results: Multivariate logistic regression identified smaller lesion size, irregular shape, LND ≤ 3 cm, and non-hypoechoic echogenicity as independent predictors of DCIS. These variables were integrated into the LND nomogram, which demonstrated strong discriminative performance (AUC = 0.851 training; AUC = 0.842 validation). Calibration was excellent, with non-significant Hosmer-Lemeshow tests (p = 0.127 training, p = 0.972 validation) and low mean absolute errors (MAE = 0.016 and 0.034, respectively), supporting the model’s accuracy and reliability. Conclusions: The AI-based comprehensive nomogram demonstrates strong reliability in distinguishing mass-type DCIS from IDC, offering a practical tool to enhance non-invasive breast cancer diagnosis and inform preoperative planning. Full article

Background/Objectives: Thirty to fifty percent of ductal carcinoma in situ (DCIS) cases are high-grade and at risk of progressing to invasive carcinoma. The most important treatment-related risk factor for recurrence is the presence of residual DCIS. The aim of our study was to evaluate the relationship between size and imaging features on preoperative mammography and magnetic resonance imaging (MRI) and histopathological size and nuclear grade in patients with pure DCIS. Methods: Between 2015 and 2023, 90 patients who underwent surgery for DCIS, had no microinvasive/invasive component, and underwent a preoperative mammography and MRI were included in this study. Results: DCIS was detected in 91.1% of patients using mammography and 95.5% using MRI. Microcalcifications (MCs) were most common in mammography (85.4%). Thin pleomorphic and thin linear branching MCs were detected in 42% of high-grade DCIS, while amorphous (42%) MCs were most common in low-grade DCIS. In low-grade DCIS cases, a grouped distribution of MCs was observed most commonly (69%). There was a statistically significant difference between DCIS groups in terms of MC morphology and distribution (p = 0.043, p = 0.005, respectively). Diffusion restriction on MRI was associated with high-grade DCIS (p = 0.043). The tumor size was greater than the pathological size and correlated poorly with mammography and moderately with MRI. Conclusions: Compared to mammography, MRI is more effective in detecting and estimating the size of DCIS. Both methods overestimate tumor size compared to histopathological size. The nuclear grade is associated with a poor prognosis and local recurrence in DCIS. Full article

Breast cancer invasion and subsequent metastasis to distant tissues occur when cancer cells lose cell–cell contact, develop a migrating phenotype, and invade the basement membrane (BM) and the extracellular matrix (ECM) to penetrate blood and lymphatic vessels. The identification of the mechanisms which induce the development from a ductal carcinoma in situ (DCIS) to a minimally invasive breast carcinoma (MIBC) is an emerging area of research in understanding tumor invasion and metastatic potential. To investigate the progression from DCIS to MIBC, we analyzed peritumoral collagen architecture using correlative scanning electron microscopy (SEM) on histological sections from human biopsies. In DCIS, the peritumoral collagen organizes into concentric lamellae (‘circular fibers’) parallel to the ducts. Within each lamella, type I collagen fibrils align in parallel, while neighboring lamellae show orthogonal fiber orientation. The concentric lamellar arrangement of collagen may physically constrain cancer cell migration, explaining the lack of visible tumor cell invasion into the peritumoral ECM in DCIS. A lamellar dissociation or the development of small inter fiber gaps allowed isolated breast cancer cell invasion and exosomes infiltration in the DCIS microenvironment. The radially arranged fibers observed in the peri-tumoral microenvironment of MIBC biopsies develop from a bending of the circular fibers of DCIS and drive a collective cancer cell invasion associated with an intense immune cell infiltrate. Type I collagen fibrils represent the peri-tumoral nano-environment which can play a mechanical role in regulating the development from DCIS to MIBC. Collectively, it is plausible to suggest that the ECM effectors implicated in breast cancer progression released by the interplay between cancer, stromal, and/or immune cells, and degrading inter fiber/fibril hydrophilic ECM components of the peritumoral ECM, may serve as key players in promoting the dissociation of the concentric collagen lamellae. Full article

Background/Objectives: Accurately correlating mammographic findings with corresponding histopathologic features is considered one of the essential aspects of mammographic evaluation, guiding the next steps in cancer management and preventing overdiagnosis. The objective of this study was to evaluate patterns of mammographic microcalcifications and their association with histopathological findings related to various breast tumors. Methods: 110 out of 3603 women had microcalcification of BIRADS 3 or higher and were subjected to stereotactic/ultrasound (USG) guided biopsies, and hook-wire localization excision procedures. Ultrasound and mammography images were reviewed by experienced radiologists using the standard American College of Radiology Breast-Imaging Reporting and Data System (ACR BI-RADS). Results: Our study showed that features with a high positive predictive value (PPV) of breast malignancy were heterogeneous (75%), fine linear/branching pleomorphic microcalcifications (66.7%), linear (100%), and segmental distributions (57.1%). Features that showed a higher risk of association with ductal carcinoma in situ (DCIS) were fine linear/branching pleomorphic (odds ratio (OR): 3.952), heterogeneous microcalcifications (OR: 3.818), segmental (OR: 5.533), linear (OR: 3.696), and regional (OR: 2.929) distributions. Furthermore, the features with higher risks associated with invasive carcinoma had heterogeneous (OR: 2.022), fine linear/branching pleomorphic (OR: 1.187) microcalcifications, linear (OR: 6.2), and regional (OR: 2.543) distributions. The features of associated masses in mammograms that showed a high PPV of malignancy had high density (75%), microlobulation (100%), and spiculated margins (75%). Conclusions: We concluded that specific patterns and distributions of microcalcifications were indeed associated with a higher risk of malignancy. Those with fine linear or branching pleomorphic and segmental distribution were at a higher risk of DCIS, whereas those with heterogeneous morphology with a linear distribution were at a higher risk of invasive carcinoma. Full article

Ductal carcinoma in situ (DCIS) is the most common form of non-invasive breast cancer and a recognized precursor to invasive ductal carcinoma (IDC). Although DCIS itself is confined to the milk duct and not immediately life-threatening, its potential for progression to invasive disease necessitates careful clinical management. The increased detection of DCIS due to advancements in imaging and widespread screening programs has raised critical questions regarding its classification, prognosis, and optimal treatment strategies. While most cases exhibit indolent behavior, others harbor molecular characteristics that drive malignant transformation. A key challenge lies in distinguishing low-risk DCIS, which may never progress, from aggressive cases requiring intervention. Tumor microenvironment dynamics, immune cell infiltration, and molecular alterations, including hormone receptor (HR) status, human epidermal growth factor 2 (HER2) expression, and genetic mutations, play crucial roles in determining disease trajectory. This review explores the biological and molecular mechanisms underlying DCIS progression, with an emphasis on myoepithelial cells, tumor-infiltrating lymphocytes, and microenvironmental factors. By integrating recent findings, this article aims to refine risk stratification approaches and guide future strategies for personalized DCIS management. Improved prognostic biomarkers and targeted therapeutic interventions could help optimize treatment decisions, balancing the need for effective cancer prevention while minimizing overtreatment in low-risk patients. Full article

Perineural invasion (PNI) is a well-recognized histopathologic feature in multiple malignancies; however, its significance in breast cancer remains relatively underexplored. This review provides a synopsis of the current knowledge on PNI in breast cancer, discussing its histopathologic features, molecular mechanisms, diagnostic challenges, and clinical relevance. PNI is most frequently observed in high-grade invasive ductal carcinoma (IDC), particularly in triple-negative and HER2-positive subtypes. It is also seen in special histological subtypes such as mixed, metaplastic, and invasive micropapillary carcinomas. Mechanistically, PNI involves tumor–neural interactions, including neurotrophic factor signaling and epithelial–mesenchymal transition, contributing to tumor progression and potential locoregional recurrence (LRR). While PNI is linked to adverse prognosis in other tumors, its independent role remains unclear in breast cancer due to limited large-scale studies. Therefore, further investigation into its prognostic significance and potential therapeutic implications is needed. Future research should focus on refining diagnostic criteria and assessing targeted therapies to mitigate PNI-associated progression. This review summarizes the current knowledge on perineural invasion (PNI) in breast cancer, addressing its histological features, molecular mechanisms, diagnostic challenges, and clinical implications. Full article

Cancerization of lobules (COL) is defined as the involvement of lobular acini by ductal carcinoma in situ (DCIS). Whether it represents a morphological variation in DCIS or a secondary extension of DCIS into lobules is debatable. The relation between COL and the probability of invasion is conflicting among different studies. We assessed if COL is a predictor of adverse pathological outcomes in mastectomy specimens. We reviewed the clinicopathological data of patients who underwent partial or total mastectomy for DCIS during a 3-year period (January 2015 until December 2017). Pathological parameters and follow-up data were collected. Whole-tissue hematoxylin and eosin (H&E) slides were reviewed and re-evaluated for COL. Cases with COL were stained immunohistochemically for E-cadherin and p120 to confirm the ductal phenotype of the neoplasms. In total, 171 mastectomies were identified including 65 specimens with pure DCIS and 106 specimens with DCIS with invasive carcinoma. COL was identified in 73 specimens. COL was significantly associated with adverse pathological outcomes including higher DCIS nuclear grade (p-value = 0.006), central (expansive “comedo”) necrosis (p-value = 0.008), presence of DCIS within or less than 2 mm from the surgical resection margin(s) (p-value = 0.004), higher percentage of blocks/slides with DCIS (p-value < 0.001), and extensive intraductal component (EIC) (applicable in cases with invasion) (p-value < 0.001). Invasion was seen in approximately two-thirds of the cases regardless of the presence of COL, with no statistical significance. Ninety-eight patients achieved 60 months of follow-up, of which only one patient developed local DCIS recurrence and had COL and EIC. Four other patients developed metastatic disease related to the invasive component. While other studies have previously hypothesized that COL may be associated with a worse pathological outcome at mastectomy, our results show that it may indeed be a measure of a higher disease burden representing EIC; however, it is not associated with an increased risk of detecting invasive carcinoma. Full article

Background/Objectives: Elevated expression of human epididymis protein 4 (HE4) has been observed in breast cancer and is associated with cancer progression; however, its role in ductal carcinoma in situ (DCIS) remains unclear. This study aimed to evaluate HE4 levels in serum and tissue from patients with DCIS and their correlation with clinicopathological features. Methods: Preoperative serum HE4 levels were measured in 59 DCIS patients. HE4 mRNA and protein expression in DCIS and adjacent normal tissues were assessed using RNAscope in situ hybridization and immunohistochemistry, respectively. An additional independent tissue microarray of 41 DCIS cases was also analyzed for HE4 expression in tumor tissue only. Furthermore, the BreastMark database was applied to assess the prognostic significance of HE4 expression in a larger cohort of breast cancer. Results: Serum HE4 levels (mean ± SD: 39.4 ± 11.9 pmol/L) were within the normal range and showed no significant correlation with clinicopathological parameters except menopausal status. HE4 expression was significantly higher in DCIS tissues compared to adjacent normal tissues, with a positive correlation between mRNA and protein levels (r = 0.771, p < 0.001). High HE4 mRNA and protein expression was associated with ER positivity, HER2 negativity, low stromal tumor-infiltrating lymphocyte density, and HR+/HER2− subtypes, but was not predictive of DCIS recurrence. In breast cancer patients, high HE4 expression was significantly correlated with improved survival outcomes. Conclusions: Although serum HE4 is not elevated in DCIS, high HE4 expression in tissue is associated with favorable clinicopathological features. These findings highlight the need for further investigation into the potential prognostic role of HE4. Full article

Background: The use of dynamic magnetic resonance imaging (MRI) for the evaluation, detection, and characterization of ductal carcinoma in situ (DCIS) has been increasing; however, its application in this context remains controversial and uncertain. Materials: A retrospective study including women with pure DCIS, confirmed between January 2012 and December 2022 using ultrasound-guided core-needle biopsy (CNB) or stereotaxy-guided vacuum-assisted biopsy (VAB), was conducted. Mammography, ultrasound (US), and MRI of DCIS lesions were evaluated according to histological grade. The size of the DCIS, as assessed by mammography, US, MRI, and final surgical histopathology, was compared using Lin’s concordance correlation and Bland–Altman plots. Results: A total of 144 women (mean age 55.5 ± 10.3 years) with histopathological diagnoses of pure DCIS and no evidence of infiltration in the percutaneous biopsy were included in the study. Microcalcifications were the most prevalent feature observed in mammography (82.63%). Round/punctate morphology was more common in low-grade lesions, while fine pleomorphic morphology was more frequent in medium- and high-grade lesions. Lesions manifesting as microcalcifications only on mammography were significantly associated with intermediate and high-nuclear grade DCIS (p = 0.005). The most common MRI manifestation of DCIS was non-mass enhancement (86.11%). A total of 141 lesions showed enhancement with MRI (sensibility 97.92%). There were no significant differences (p = 0.29) between negative and positive enhancement with MRI and the histological grade of the lesions. There were no significant differences (p = 0.49) between the type of enhancement curve with MRI and the histological grade. Preoperative MRI detected additional malignancies (multifocal, multicentric, or bilateral) in 35 patients (24.31%). Conclusions: DCIS demonstrated enhancement with MRI regardless of histological grade but overestimated the size of the lesions in low-nuclear-grade DCIS. Preoperative MRI identified additional malignancies (multifocal, multicentric, and bilateral lesions) in 24 patients (16.67%), which were confirmed by histopathological examination. These malignancies were either undetected or not visible with mammography and ultrasound. However, MRI also overestimated the size of the DCIS, leading to three unnecessary mastectomies in our study. Full article

Mammography is an essential tool in breast screening, often revealing lesions that appear as microcalcifications with or without an associated mass. Decisions about biopsy requirements are guided by the BI-RADS system, aiming to confirm the histopathology of suspicious lesions while avoiding unnecessary procedures. A vacuum-assisted breast biopsy (VABB) is a minimally invasive procedure for diagnosing breast abnormalities. Precise lesion targeting is ensured under stereotactic guidance, reducing the need for repeated procedures. Compared to traditional core needle biopsy (CNB) and fine-needle aspiration cytology (FNAC), it differs in using vacuum assistance to gather more tissue volume, increasing diagnostic accuracy and reducing the likelihood of histological underestimation. This is particularly crucial in cases where microcalcifications are the primary finding, as they are often the earliest signs of ductal carcinoma in situ (DCIS). Managing such findings requires precise diagnostic tools to differentiate benign from malignant lesions without subjecting patients to unnecessary surgical interventions. Building on several years of experience in our department, we have assembled a selection of ten interesting cases encountered in our clinical practice. Each case is documented with paired mammographic images and their corresponding image of histopathological findings, offering a comprehensive view of the diagnostic journey. These cases were selected for their educational value, highlighting the integration of imaging modalities, histopathological evaluation, and clinical decision-making. All cases underwent an extensive diagnostic workup at our facility. This compilation aims to provide valuable insights for both clinicians and researchers, offering a deeper understanding of advanced diagnostic techniques and their role in improving patient outcomes. Full article

Background: Ductal carcinoma in situ (DCIS) is a precursor of invasive breast cancer and its early diagnosis and treatment are essential to prevent progression and recurrences. Risk stratification guidelines, such as the Van Nuys Prognostic Index (VNPI) and those by the National Comprehensive Cancer Network (NCCN), help guide appropriate treatment. This study compares VNPI recommendations for DCIS patients treated at Hospital do Servidor Público Estadual de São Paulo (HSPE) with NCCN guidelines, focusing on treatment conducted and recurrence rates. Methods: This retrospective, cross-sectional study reviewed medical records of 145 patients treated for DCIS at HSPE between January 1996 and June 2022, with a mean follow-up of 60.3 months. Results: Based on VNPI, 38.8% were low risk, 53.2% intermediate risk, and 7.8% high risk. NCCN guidelines classified only 12.9% as low risk and 87.1% as high risk. Treatment included breast-conserving surgery (BCS) with radiotherapy (43.1%), BCS alone (38.8%), and mastectomy (18.1%). There were 18 recurrences (15.5%): 5.2% as DCIS and 10.3% as invasive cancer. Of these recurrences, 5.6% occurred in patients who, according to NCCN, would have received BCS with radiotherapy or mastectomy. Conclusion: By integrating the VNPI with NCCN treatment guidelines, the NCCN’s recommendations could potentially reduce local recurrence rates by 5.6%. However, further studies are necessary to evaluate the long-term impact of these guidelines on overall survival outcomes. Full article

Mammary intraductal macrophages (foam cells) in humans are the most commonly encountered cells in spontaneous breast nipple discharge, nipple aspirate fluid, and ductal lavage, yet their origin remains unproven. These cells, in both humans and murine model systems, increase in pregnancy, pseudopregnancy, and other conditions like proliferative fibrocystic disease and intraductal neoplasia, ductal carcinoma in situ (DCIS), where there is intraductal ectasia and obstruction. Previous immunocytochemical studies with macrophage (CD68, lysozyme), epithelial (cytokeratin, estrogen receptor), and myoepithelial (smooth muscle actin, CALLA, maspin) markers have indicated that intraductal foam cells are of macrophage lineage. These foam cells engage in phagocytosis of both endogenous and exogenous substances present within the ducts and are not proliferative. Although it has been suggested that foam cells could derive from tissue-specific and niche-specific precursors or circulating monocytes, to date no experimental nor clinical studies have provided direct proof of their origin. In this study, we provide evidence in both human and murine bone marrow transplant studies that intraductal foam cells are bone marrow-derived. We first studied a registry of sex-mismatched bone marrow transplant recipients who later in life had undergone breast biopsies for either proliferative fibrocystic disease, DCIS, or gynecomastia, and studied these biopsies by XY chromosome fluorescence in situ hybridization (FISH) and informative microsatellite polymorphic markers. The intraductal foam cells were of bone marrow donor-origin. Then, in the experimental bone marrow transplant murine studies, donor marrow from female ROSA26 containing the lacZ reporter were transplanted into either irradiated female recipient transgenic mice carrying the highly penetrant MMTV-pymT or FVB/N background mice, where induced pluripotent stem (iPS) cells derived from tail vein fibroblasts of FVB/N-Tg(MMTV-PyVT)634Mul/J mice were subsequently injected into their mammary fat pads. In all of the transplanted recipient mice, the intraductal foam cells expressed the β-galactosidase (lacZ) reporter and also co-expressed markers of myeloid–macrophage lineage. The number of donor-derived intraductal foam cells increased in pseudopregnancy 5-fold and in intraductal neoplasia 10-fold. Although macrophages of different origins and lineages are undoubtedly present within both the murine and human breasts, those macrophages that qualify as phagocytic intraductal foam cells are bone marrow-derived. Full article

Background/Objectives: Ductal carcinoma in situ (DCIS) is the most common non-invasive form of breast cancer. It is not clear to what extent DCIS is a part of the hereditary breast/ovarian cancer syndrome caused by BRCA1/2 mutations. Therefore, we investigated the association of BRCA1/2 mutations in patients with DCIS and assessed their impact on survival. Methods: We studied 564 Polish women with DCIS for six alleles in BRCA1 (c.181T>G, c.5266dupC, c.4035delA, c.3700_3704del5, c.68_69del and c.5251C>T) and four in BRCA2 (c.658_659del, c.3847_3848del, c.5946del and c.7913_7917del). To investigate the association of BRCA1/2 founder mutations with DCIS risk, we tested 4702 controls as a reference. To analyze survival, mutation carriers were followed for an average of 110 months. Results: A BRCA1 mutation was present in seven (1.24%) cases and in twenty-two (0.47%) controls (OR = 3.27, 95%CI 1.36 to 7.87, p = 0.01). A BRCA2 mutation was present in eight (1.42%) cases versus six (0.13%) controls (OR = 11.3, 95%CI 3.9 to 32.6, p < 0.0001). Three of the fifteen cases with BRCA1/2 mutations developed invasive ipsilateral or contralateral breast cancer, on average 6 years from the diagnosis of DCIS. There were no deaths reported among the 15 mutation carriers with DCIS. Conclusions: DCIS is a part of the hereditary breast/ovarian cancer syndrome caused by BRCA1/2 mutations. Women with DCIS should receive genetic counseling and testing for BRCA1/2 mutations. BRCA1/2 mutations may predispose women to a better DCIS prognosis, but further studies are needed. Full article