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Cat scratch disease rarely presents as a breast or axillary mass mimicking carcinoma both clinically and radiologically. Diagnosing breast/axillary cat scratch disease is challenging due to its rarity and nonspecific findings. Here, we reported 2 patients with breast cat scratch disease and reviewed 14 patients with cat scratch disease involving breast/axilla from the past 30 years. It mainly affects women (median age: 48), consistently presenting as axillary lymphadenopathy, and demonstrates ipsilateral breast mass in half of patients (50%, 8/16). The breast mass was most commonly located in the upper outer quadrant (88%, 7/8), indicating the possibility of disease extension from axillary adenopathy. Around half of patients (56%, 9/16) reported cat exposure. Histologically, most patients (93%, 14/15) presented as necrotizing granulomas, with characteristic stellate-shaped necrosis in 5 patients. Although pathologic differential diagnoses between cat scratch disease and cancer are straightforward, distinguishing cat scratch disease from other granulomatous mastitis poses diagnostic challenges. Silver stains should be included in the diagnostic workup panel when highly suspecting cat scratch disease clinically. However, they were only able to highlight the causative microorganism in 54% (7/18) patients, and the gram stain was negative in all 12 tested patients. In contrast, polymerase chain reaction (PCR) for the causative microorganism was consistently positive in all 3 tested patients, while serologic test confirmed diagnosis in 85% (11/13) patients; 1 patient with negative serology showed a positive PCR result. Therefore, upfront PCR tests with or without serologic study should be considered to confirm the diagnosis of cat scratch disease in a timely manner., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

BACKGROUND Amyloidosis results in fibrillar sheets of beta-pleated amorphous congophilic protein deposition in the extracellular space. Breast amyloidosis is a rare entity, with the first case reported in 1973 and only 2 major case series published since. These deposits can have local or systemic manifestations and typically present unilaterally, although bilateral involvement has been described. Some reported cases of amyloidosis have been linked to breast cancer. CASE REPORT The patient was a 60-year-old woman who presented to the breast surgery clinic for evaluation after image-guided biopsy of a right breast lesion. Core needle biopsy under stereotactic guidance demonstrated pathology consistent with nodular deposition of amyloid, associated with calcifications. Microscopic examination revealed extracellular deposition of acellular eosinophilic material in fat, stoma, and blood vessels. Congo red special stain was positive. Amyloid with Congo red special stain showed apple green birefringence under polarized light. Surgical excision under needle localization was performed, with the final surgical pathology report confirming amyloid deposits. CONCLUSIONS Breast amyloidosis can have calcium affinity, create a foreign body-like reaction with giant cell infiltration, and distribute through periductal, perivascular, or intralobar patterns. Some factors that can contribute to an increased risk or are associated with breast amyloidosis are predisposing clinical conditions, including autoimmune disease, various breast cancers, and B-cell lymphomas. Amyloidosis of the breast should be treated either as primary or secondary, based on etiology. Further studies need to be conducted on whether there are specific genetic markers that predispose populations to the development of amyloidosis of the breast.

Objective: To investigate the clinicopathological features and differential diagnosis of breast angiomatosis. Methods: Six cases of breast angiomatosis diagnosed at the Department of Pathology, the Seventh Medical Center, People's Liberation Army General Hospital and the Department of Pathology, Dongzhimen Hospital, Beijing University of Chinese Medicine from January 2011 to December 2023 were evaluated and reviewed. Results: All patients were female with an average age of 46 years at presentation, ranging from 25 to 62 years. The most common clinical presentation was a palpable unilateral breast mass with diameter ranging from 7 to 14 cm, and the average size was 11 cm. Histologically, all cases were composed of variably-sized ectatic, thin-walled blood vessels with minimal to no apparent smooth muscle, lined by flat normochromic endothelium without atypia, and diffusely infiltrating the breast stroma. Where present, the lesional vessels infiltrated between and around terminal duct lobular units but not into individual intralobular stroma. Immunohistochemical staining for CD31, CD34, Factor Ⅷ, Fli-1 and D2-40 revealed positive expression in vascular and/or lymphatic endothelial cells. Additionally, the Ki-67 proliferation index was found to be less than 1%. Conclusions: Angiomatosis of the breast is a rare benign vascular lesion. Distinguishing it from low-grade angiosarcoma requires careful consideration of the growth pattern, atypical features, and Ki-67 proliferation index.

Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplastic entities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed., (© 2024 John Wiley & Sons Ltd.)

A female patient with a history of ductal carcinoma in situ in the left breast, status-post bilateral mastectomy with deep inferior epigastric perforator artery flap reconstructive surgery, presented with a right breast asymmetry concerning for fat necrosis. Histological analysis revealed the presence of benign glands and associated stroma within fibroadipose tissue, confirmed as endometriosis by immunohistochemical analysis. Further investigation revealed that the patient had a previous diagnosis of endometriosis associated with a cesarean section scar that likely seeded the ectopic endometrial glands into a tertiary site by utilizing abdominal tissue that may have harbored endometriosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The inverted nipple is a condition that affects approximately 10% of women and can have negative cosmetic and psychological implications. Surgical correction is a common approach to address this concern; however, this method can lead to complications, such as nipple necrosis. As comprehensive guidelines are currently lacking for postoperative nipple necrosis management, this study reports our experience in the management of postoperative nipple necrosis following initial attempt at surgical management., Methods: A retrospective chart review was conducted and included female patients who experienced postoperative nipple necrosis after inverted nipple correction between 2018 and 2021. Cases of recurrent nipple retraction following partial necrosis and cases of complete nipple necrosis were evaluated. Recurrent nipple retraction was managed using various inverted nipple correction techniques, while complete necrosis required a modified C-V flap for nipple reconstruction., Results: A total of 25 patients with a total of 42 affected nipples were included. Thirteen cases (26 nipples) experienced recurrent nipple retraction following partial necrosis, while 12 cases (16 nipples) exhibited complete necrosis. No significant predictive variables for these complications were found. Notably, all patients achieved successful healing following single-stage surgical repair. At 6 months postoperation, the treated nipples exhibited satisfactory healing and appearance and an absence of infection or papillary necrosis. Seven reconstructed nipples showed a mean loss of projection (2.7 ± 0.98) compared with only 2 nipples in the inverted nipple correction group., Conclusions: Distinguishing between recurrent nipple retraction after partial necrosis and complete nipple necrosis is crucial and should be taken into consideration when managing patients following inverted nipple correction., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Although Hispanic White (HW) females have a lower incidence of breast cancer than non-Hispanic White (NHW) females, breast cancer risk is unclear for HW females after benign breast disease (BBD)., Methods: We compared BBD characteristics and subsequent breast cancer risk among HW and NHW females in New Mexico using a population-based collection of benign breast biopsies (1996-2007). BBD was categorized as nonproliferative disease (NPD), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). Breast cancer risk was assessed as absolute risk (AR) using cumulative incidence and RR by comparing the number of breast cancer events in BBDs to non-BBD., Results: This study included 3,684 HW and 6,587 NHW females with BBD. HW females had similar proportions of NPD (58.6% vs. 54.3%), PDWA (21.4% vs. 23.5%), and AH (3.6% vs. 3.3%) as NHW females. Breast cancer risk among all females with BBD was higher than population-based expected rates (RR, 1.87) and was similar for HW and NHW subgroups (RR = 1.99 vs. 1.84). As expected, breast cancer risk increased with increasing BBD severity, both overall [RR, 1.81 (NPD), 1.85 (PDWA), and 3.10 (AH)] and in the HW and NHW subgroups. Adjusted AR of breast cancer at 5 years also increased with the severity of BBD (HW vs. NHW; NPD: 1.4% vs. 2.1%; PDWA: 1.5% vs. 2.7%; AH: 6% vs. 4.8%)., Conclusions: We found similar breast cancer RRs and ARs in HW and NHW. Risk counseling should ensure that HW females receive breast cancer clinical management warranted by their similar absolute risks., Impact: The present population-based provides evidence for the clinical management of HW females with BBD for the prevention of breast cancer., (©2024 American Association for Cancer Research.)

Artifacts and foreign bodies can mimic microcalcifications. We report a series of 17 postsurgical women in whom mammograms showed fine linear radiodensities at the surgical bed. Vacuum-assisted biopsy histopathology of one of the lesions showed foreign bodies of different sizes with macrophage reaction. After discussion with the surgeons, we ascertained that a particular type of gauze was used that had fragmented, and we reproduced the mammographic appearance in a chicken breast. Furthermore, we showed the same pathology was reproduced in mice implanted with the gauze threads. It is important to be aware of this entity to avoid unnecessary examinations and even biopsy. The presence of foreign body linear gauze fragments at the surgical site can pose challenges in the mammographic follow-up of these patients., (© Society of Breast Imaging 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

With the growing utilization and expanding role of breast MRI, breast imaging radiologists may encounter an increasing number of incidental findings beyond the breast and axilla. Breast MRI encompasses a large area of anatomic coverage extending from the lower neck to the upper abdomen. While most incidental findings on breast MRI are benign, identifying metastatic disease can have a substantial impact on staging, prognosis, and treatment. Breast imaging radiologists should be familiar with common sites, MRI features, and breast cancer subtypes associated with metastatic disease to assist in differentiating malignant from benign findings. Furthermore, detection of malignancies of nonbreast origin as well as nonmalignant, but clinically relevant, incidental findings can significantly impact clinical management and patient outcomes. Breast imaging radiologists should consistently follow a comprehensive search pattern and employ techniques to improve the detection of these important incidental findings., (© Society of Breast Imaging 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Breast tuberculosis (TB) is a rare extra-pulmonary presentation of tuberculosis. In the western world, this accounts for less than 0.1% of breast conditions (all breast conditions, not limited to TB or extra-pulmonary TB), but can be up to 3-4% in regions endemic for TB such as in Africa and Asia., Case Presentation: We report a case of a 54-year- old human immunodeficiency virus (HIV)-positive lady who presented with six months history of multiple masses on the left breast which were initially suspected to be cancer of the breast. However, histology report of the mass confirmed TB of the breast., Conclusions: Presentation of TB can be non-specific and atypical in patients with HIV infection, especially when it presents in extra-pulmonary forms., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Iyonu J Onaghinor, Izuchukwu B Achusi, Olumuyiwa E Ariyo.)

Background: Fibroadenoma (FA) is documented as the most common benign breast disease typically presenting as a lump. A wide variety of other diseases including breast cancer can similarly present as lumps hence the need for further differentiation. Ultrasonography plays a vital role in the evaluation and treatment of breast lumps with histological analysis as the gold standard., Objective: This study compared the physical and sonographic features of the breast in women with FA and women with breast lumps due to other diseases., Materials and Methods: This is a single-centre comparative study. Clinical and sonographic breast evaluations of the recruited patients with lumps were done and reported using the American College of Radiology Breast Imaging Reporting and Data System score. The lumps were biopsied, and histological diagnosis was documented. Clinical and imaging features of the breasts of women with FA were then compared with those of women with lumps from other breast diseases, and collated data were analysed using SPSS Statistical version 23.0., Results: Data from 118 subjects (59 in each group) were used for this study. There was a significant difference in the physical and sonographic appearance of FA concerning the patient's age, parity, change in lesion size, perilesional architecture, echogenicity, borders, capsule and background breast density. No FA was found in women with less dense breasts., Conclusion: The sonographic features of breasts showed some differences from the corresponding features of FA and other breast lesions. This has the potential to increase the efficiency of pre-operative diagnosis of FA and could be further applied in developing diagnostic criteria for FA in our environment., (Copyright © 2024 Copyright: © 2024 Nigerian Postgraduate Medical Journal.)

Papillary endothelial hyperplasia (PEH) or Masson's tumor is a rare benign vascular tumor that usually appears in the soft tissues of the head and neck, trunk and extremities, being extremely rare in the breast. Its diagnosis can be a challenge, especially in the follow-up of patients with previous disease of breast carcinoma. We present the case of a 65-year-old patient, with a history of bilateral breast cancer and reconstruction with implants, who presented a Masson's tumor during follow-up. An ultrasound scan was performed, showing a well-circumscribed mass in the left breast, located in the posterior contour of the implant. Subsequently, magnetic resonance imaging (MR) depicted an enhancing tumor, without infiltration of adjacent structures. Finally, the definitive anatomopathological diagnosis was obtained after surgical excision., (Copyright © 2023 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To assess the role of contrast-enhanced mammography (CEM) in predicting the malignancy of breast calcifications., Material and Methods: We retrospectively evaluated patients with suspicious calcifications (BIRADS 4) who underwent CEM and stereotactic vacuum-assisted biopsy (VAB) at our institution. We assessed the sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) of CEM in predicting malignancy of microcalcifications with a 95% confidence interval; we performed an overall analysis and a subgroup analysis stratified into group A-low risk (BIRADS 4a) and group B-medium/high risk (BIRADS 4b-4c). We then evaluated the correlation between enhancement and tumour proliferation index (Ki-67) for all malignant lesions., Results: Data from 182 patients with 184 lesions were collected. Overall the SE of CEM in predicting the malignancy of microcalcifications was 0.70, SP was 0.85, the PPV was 0.82, the NPV was 0.76 and AUC was 0.78. SE in group A was 0.89, SP was 0.89, PPV was 0.57, NPV was 0.98 and AUC was 0.75. SE in group B was 0.68, SP was 0.80, PPV was 0.87, NPV was 0.57 and AUC was 0.75. Among malignant microcalcifications that showed enhancement (N = 52), 61.5% had Ki-67 ≥ 20% and 38.5% had low Ki-67 values. Among the lesions that did not show enhancement (N = 22), 90.9% had Ki-67 < 20% and 9.1% showed high Ki-67 values 20%., Conclusions: The absence of enhancement can be used as an indicative parameter for the absence of disease in cases of low-suspicious microcalcifications, but not in intermediate-high suspicious ones for which biopsy remains mandatory and can be used to distinguish indolent lesions from more aggressive neoplasms, with consequent reduction of overdiagnosis and overtreatment., (© 2024. Italian Society of Medical Radiology.)

Breast microcalcifications are observed in 80% of mammograms, and a notable proportion can lead to invasive tumors. However, diagnosing microcalcifications is a highly complicated and error-prone process due to their diverse sizes, shapes, and subtle variations. In this study, we propose a radiomic signature that effectively differentiates between healthy tissue, benign microcalcifications, and malignant microcalcifications. Radiomic features were extracted from a proprietary dataset, composed of 380 healthy tissue, 136 benign, and 242 malignant microcalcifications ROIs. Subsequently, two distinct signatures were selected to differentiate between healthy tissue and microcalcifications (detection task) and between benign and malignant microcalcifications (classification task). Machine learning models, namely Support Vector Machine, Random Forest, and XGBoost, were employed as classifiers. The shared signature selected for both tasks was then used to train a multi-class model capable of simultaneously classifying healthy, benign, and malignant ROIs. A significant overlap was discovered between the detection and classification signatures. The performance of the models was highly promising, with XGBoost exhibiting an AUC-ROC of 0.830, 0.856, and 0.876 for healthy, benign, and malignant microcalcifications classification, respectively. The intrinsic interpretability of radiomic features, and the use of the Mean Score Decrease method for model introspection, enabled models' clinical validation. In fact, the most important features, namely GLCM Contrast, FO Minimum and FO Entropy, were compared and found important in other studies on breast cancer., (© 2024. The Author(s).)

Benign breast disease (BBD) is a heterogenous group of lesions often classified as nonproliferative or proliferative, with the latter group further categorized based on the presence of atypia. Although nonproliferative lesions are more common, the risk of breast cancer is elevated in women with proliferative lesions. Historically, the majority of proliferative lesions were excised due to concern for future and/or concomitant breast cancer at the site of the index lesion. However, contemporary data suggest that the risk of cancer associated with various proliferative lesions may be lower than previously thought, and management of BBD has become more nuanced. In this review, we will focus on recent updates in the management of a select group of benign and high-risk lesions., Competing Interests: Disclosure Chelsea Marin: none. Jessica C. Gooch: none. Anna Weiss: Advisory Board member for Myriad Genetics, Inc. and Merck & Co., Inc., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Mammography has become an invaluable tool for diagnosing breast lesions and detecting early breast cancer in women of 35 years and above., Aims: To correlate the mammography Breast Imaging Reporting and Data System (BI-RADS) categories with the histology in breast lesions and to determine the predictive values, sensitivity, specificity and accuracy of mammography., Patients and Method: This was a one- year prospective study carried out from March 2015 to February 2016. Consecutive female patients of 35 years and above with breast lesions at the University of Benin Teaching Hospital, Benin-City were recruited. Patients with fungating breast lesions and those who declined recruitment were excluded. All patients had mammography and core biopsy of the breast lesion which was examined histologically., Results: A total of 101 patients were studied. Five patients had bilateral breast lesions making a total of 106 biopsies that were performed. The mean age of patients with benign breast disease was 47.0 ± 4.9 years while those with malignant breast disease was 49.9 ± 8.5 years; P-value was 0.080 which was not statistically significant. Fibrocystic disease 6 (5.6%) was the most common benign disease while invasive ductal carcinoma was the most common malignant breast disease 84(79.2%). BI-RADS 5 correlated mostly with malignant breast disease (97.0%); P value < 0.001 and was statistically significant., Conclusion: This study showed that mammography is useful in the diagnosis of breast lesions in women who are 35 years and older. Patients with BI-RADS category 3, 4 and 5 had an increasing correlation with malignant breast disease., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Diabetic mastopathy is a rare and benign pathology affecting young individuals with type 1 diabetes or autoimmune diseases. It clinically resembles breast cancer, necessitating a histological examination for a definitive diagnosis. These cases underscore the diagnostic challenges and the importance of histological examination. This report details two cases of diabetic mastopathy at Mohammed VI Hospital in Marrakech. The first case involved a 35-year-old with type 1 diabetes and mastodynia, revealing a 4 x 3 cm nodule in the left breast. Biopsies confirmed fibrous breast tissue with lymphocytic infiltrates, characteristic of diabetic mastopathy, with no recurrence during follow-up. The second case featured a 38-year-old with trisomy 21 and type 1 diabetes presenting with a right breast abscess. Drainage revealed lymphocytic infiltrates, confirming diabetic mastopathy. Though diagnostically challenging, diabetic mastopathy lacks a direct link to breast cancer. Long-term cancer risks in affected patients mirror the general population., Competing Interests: The authors declare no competing interests., (Copyright: Karam Harou et al.)

Technique: From January 1, 2018, to December 31, 2021, we localized the breast microcalcification of 40 patients before the surgical excision. We measured the distance between the nipple and the center of the calcification on the CC view and the ML view, respectively. The operation proceeded around the intersection between two lines, slightly larger than the diameter of the microcalcification. We also analyze the pathological findings., Results: All 40 patients successfully detected calcification by mammograms preoperatively using the method mentioned above. 38 patients have the microcalcification removal within the one-time operation, while the other two underwent an extended lumpectomy. 20 of 40 calcifications (50 %) were malignant and 12(30 %) were precancerous lesions. In the group of women older than 45 years old, the percentages of malignant and atypical hyperplasias are 56.25 % (18/32) and 31.25 % (10/32) respectively., Conclusion: Our non-invasive method of preoperative localization is safe and cost-effective. Furthermore, initial observations suggest that there may be a link between age and malignant microcalcification., Competing Interests: Conflict of interest statement There is no potential conflict of interest between the authors in this manuscript., (Copyright © 2024 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Abstract: Mammary hamartoma are rare neoplasms of the breast. Myoid mammary hamartoma are a subtype comprising of prominent smooth muscle component along with normal breast tissue components including fibrous, adipose, and glandular tissue. We report the case of a 38-year-old lady who presented with a large 21 × 15 cm, firm, mobile lump in right breast, clinically mimicking as phyllodes tumor. The lesion was reported as BIRADS 4a on mammography. Fine needle aspiration cytology suggested benign breast disease. Wide local excision was performed. The excised lump was solid, gray-white with fatty yellowish areas. Histological features were of myoid mammary hamartoma. To the best of our knowledge, this is the largest myoid hamartoma reported till date. Fine needle aspiration, needle biopsy, and immunohistochemistry are of limited value as diagnostic modalities in these lesions. Complete surgical excision, proper identification, and follow-up is essential, as these lesions, more commonly those which are incompletely excised, can recur., (Copyright © 2023 Copyright: © 2023 Journal of Cancer Research and Therapeutics.)

The nipple-areolar complex (NAC), a unique anatomic structure of the breast, encompasses the terminal intramammary ducts and skin appendages. Several benign and malignant diseases can arise within the NAC. As several conditions have overlapping symptoms and imaging findings, understanding the distinctive nipple anatomy, as well as the clinical and imaging features of each NAC disease process, is essential. A multimodality imaging approach is optimal in the presence or absence of clinical symptoms. The authors review the ductal anatomy and anomalies, including congenital abnormalities and nipple retraction. They then discuss the causes of nipple discharge and highlight best practices for the imaging workup of pathologic nipple discharge, a common condition that can pose a diagnostic challenge and may be the presenting symptom of breast cancer. The imaging modalities used to evaluate and differentiate benign conditions (eg, dermatologic conditions, epidermal inclusion cyst, mammary ductal ectasia, periductal mastitis, and nonpuerperal abscess), benign tumors (eg, papilloma, nipple adenoma, and syringomatous tumor of the nipple), and malignant conditions (eg, breast cancer and Paget disease of the breast) are reviewed. Breast MRI is the current preferred imaging modality used to evaluate for NAC involvement by breast cancer and select suitable candidates for nipple-sparing mastectomy. Different biopsy techniques (US -guided biopsy and stereotactic biopsy) for sampling NAC masses and calcifications are described. This multimodality imaging approach ensures an accurate diagnosis, enabling optimal clinical management and patient outcomes. © RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Lymphocytic lobulitis (LL) is characterized by prominent lymphocytic infiltrates centered on lobules. Sclerosing lymphocytic lobulitis (SCLL) associated with diabetes mellitus (DM) or autoimmune disease (AI) was the first type to be described. Subsequently, non-sclerosing LL (NSCLL) was reported as an incidental finding in prophylactic mastectomies due to high risk germline mutations or a family history of breast cancer. The two types of LL were distinguished by stromal features and a predominant population of B-cells in the former and T-cells in the latter. In this study, 8 cases of NSCLL detected clinically or by screening were compared to 44 cases of SCLL. One case of NSCLL presented as a palpable mass, 2 as masses on screening, and 5 as MRI enhancement. In contrast, 80% of SCLL cases presented as palpable masses. Half the cases of NSCLL were associated with a BRCA1 or 2 mutation compared to 1 case of SCLL (2%). Three additional cases of NSCLL were associated with a strong family and/or personal history of breast cancer. Almost half (52%) of SCLL cases were associated with DM or AI, but only 25% of NSCLL. Immunoperoxidase studies confirmed a predominance of T-cells in NSCLL and B-cells in SCLL associated with DM or AI. It is important for pathologists to be aware of this new observation that NSCLL can be detected as a palpable mass or an imaging finding in diagnostic biopsies, as its presence can be indicative of a significant risk for breast cancer., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. Acknowledgement Assistance with preparation of the figures was provided by Mary E. Lester (marylesterdesign.com)., (Copyright © 2024. Published by Elsevier Inc.)

The "breast within a breast" sign is used to describe the appearance of a breast hamartoma, also known as a fibroadenolipoma. A breast hamartoma is a benign mass made up of the same tissues that are found in a normal breast, giving the appearance of a breast within a breast on mammography. The "breast within a breast" sign is pathognomonic for a breast hamartoma and can help confidently diagnose these masses as benign without the need for further imaging or biopsy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To explore the capability and clinical significance of chest thin-section computed tomography (CT) for localization of mammographically detected clustered microcalcifications., Methods: A total of 69 patients with 71 mammographically detected clustered microcalcifications received surgical biopsy under the guidance of mammography (MG), CT was used to localize calcifications combined with MG if calcifications can be seen on CT. Intraoperative mammography of the specimens were performed in all cases for identification of the resected microcalcifications. The clinical, imaging and pathological information of these patients were analyzed., Results: A total of 42 (59.15%) cases of calcifications were localized by CT + MG, 29 (40.85%) cases were guided only by the mammography. All suspicious calcifications on the mammography were successfully removed. Pathological results showed 42 cases were cancer, 23 cases were benign, and 6 cases were atypical hyperplasia. The mean age in the CT + MG group was older than that of the MG group (54.12 vs. 49.27 years; P = 0.014). The maximum diameter of clusters of microcalcifications on mammography in the CT + MG group was larger than that of the MG group [(cranio-caudal view, 1.52 vs. 0.61 mm, P = 0.000; mediolateral oblique (MLO) view, 1.53 vs. 0.62 mm, P = 0.000)]. The gray value ratio (calcified area / paraglandular; MLO, P = 0.004) and the gray value difference (calcified area - paraglandular; MLO, P = 0.005) in the CT + MG group was higher than that of the MG group. Multivariate analysis showed that the max diameter of clusters of microcalcifications (MLO view) was a significant predictive factor of localization by CT in total patients (P = 0.001)., Conclusions: About half of the mammographically detected clustered microcalcifications could be localized by thin-section CT. Maximum diameter of clusters of microcalcifications (MLO view) was a predictor of visibility of calcifications by CT. Chest thin-section CT may be useful for localization of calcifications in some patients, especially for calcifications that are only visible in one view on the mammography., (© 2024. The Author(s).)

Importance: Benign breast disease (BBD) comprises approximately 75% of breast biopsy diagnoses. Surgical biopsy specimens diagnosed as nonproliferative (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH) are associated with increasing breast cancer (BC) risk; however, knowledge is limited on risk associated with percutaneously diagnosed BBD., Objectives: To estimate BC risk associated with BBD in the percutaneous biopsy era irrespective of surgical biopsy., Design, Setting, and Participants: In this retrospective cohort study, BBD biopsy specimens collected from January 1, 2002, to December 31, 2013, from patients with BBD at Mayo Clinic in Rochester, Minnesota, were reviewed by 2 pathologists masked to outcomes. Women were followed up from 6 months after biopsy until censoring, BC diagnosis, or December 31, 2021., Exposure: Benign breast disease classification and multiplicity by pathology panel review., Main Outcomes: The main outcome was diagnosis of BC overall and stratified as ductal carcinoma in situ (DCIS) or invasive BC. Risk for presence vs absence of BBD lesions was assessed by Cox proportional hazards regression. Risk in patients with BBD compared with female breast cancer incidence rates from the Iowa Surveillance, Epidemiology, and End Results (SEER) program were estimated., Results: Among 4819 female participants, median age was 51 years (IQR, 43-62 years). Median follow-up was 10.9 years (IQR, 7.7-14.2 years) for control individuals without BC vs 6.6 years (IQR, 3.7-10.1 years) for patients with BC. Risk was higher in the cohort with BBD than in SEER data: BC overall (standard incidence ratio [SIR], 1.95; 95% CI, 1.76-2.17), invasive BC (SIR, 1.56; 95% CI, 1.37-1.78), and DCIS (SIR, 3.10; 95% CI, 2.54-3.77). The SIRs increased with increasing BBD severity (1.42 [95% CI, 1.19-1.71] for NP, 2.19 [95% CI, 1.88-2.54] for PDWA, and 3.91 [95% CI, 2.97-5.14] for AH), comparable to surgical cohorts with BBD. Risk also increased with increasing lesion multiplicity (SIR: 2.40 [95% CI, 2.06-2.79] for ≥3 foci of NP, 3.72 [95% CI, 2.31-5.99] for ≥3 foci of PDWA, and 5.29 [95% CI, 3.37-8.29] for ≥3 foci of AH). Ten-year BC cumulative incidence was 4.3% for NP, 6.6% for PDWA, and 14.6% for AH vs an expected population cumulative incidence of 2.9%., Conclusions and Relevance: In this contemporary cohort study of women diagnosed with BBD in the percutaneous biopsy era, overall risk of BC was increased vs the general population (DCIS and invasive cancer combined), similar to that in historical BBD cohorts. Development and validation of pathologic classifications including both BBD severity and multiplicity may enable improved BC risk stratification.

BACKGROUND. Biopsy site markers (BSMs) placed during image-guided core needle biopsy (CNB) are typically targeted for surgical excision, along with the breast imaging abnormality. Retained BSMs raise concern of incomplete resection of the breast abnormality. OBJECTIVE. The purpose of our study was to assess the frequency of residual malignancy in patients with retained BSMs identified on the initial mammography performed after breast lesion surgical excision. METHODS. This retrospective study included 30 patients (median age, 59 years) who underwent surgical resection between August 2015 and April 2022 of a borderline, high-risk, or malignant breast lesion after CNB and technically adequate preoperative image-guided localization, in whom the initial postoperative mammography report described a retained nonmigrated BSM. EMR data were extracted. The index pathology from CNB and initial surgical resection was classified as malignant or nonmalignant. The presence of residual malignancy after initial surgical resection required pathologic confirmation from subsequent tissue sampling; the absence of residual malignancy required 2 years of benign imaging follow-up. RESULTS. Thirteen specimen radiographs were interpreted intraoperatively by a surgeon with later radiologist interpretation, and 17 underwent real-time radiologist interpretation. Eighteen patients had malignant index pathology from the initially resected lesion. The frequency of residual malignancy on subsequent follow-up after initial surgical resection was higher in patients with malignant than nonmalignant index pathology (39% [7/18] vs 0% [0/12], respectively; p = .02). Among patients with malignant index pathology, the frequency of residual malignancy was higher in those without, than with, malignancy in the initial surgical specimen (80% [4/5] vs 23% [3/13]; p = .047). Also in these patients, the frequency of a positive interpretation of the initial postoperative mammography (BI-RADS category 4 or 6) was not significantly different between those with and without residual malignancy (57% [4/7] vs 55% [6/11]; p > .99). CONCLUSION. Patients with retained BSMs associated with malignant index lesions are at substantial risk of having residual malignancy. Initial postoperative mammography is not sufficient for excluding residual malignancy. CLINICAL IMPACT. Retained BSMs associated with index malignancy should be considered suspicious for residual malignancy. In this scenario, timely additional tissue sampling targeting the retained BSM is warranted, given the greater-than-2% chance of malignancy. Active surveillance is a reasonable management strategy in patients with retained BSMs from nonmalignant index lesions.

Abstract: Tuberculosis (TB) remains a significant global health concern and kills millions of people every year. While TB can affect any organ in the body, breast TB is relatively uncommon. This study presents a comprehensive review of literature spanning 23 years, with a focus on cases of breast TB in Iran. Among the 96 cases found, the majority (89.6%) fell within the age range of 20-60, with a striking prevalence among women (98.9%). Common symptoms included pain and palpable mass, each presenting in approximately 60.4% of cases. Notably, only a quarter of patients had a confirmed history of exposure to a known TB case. Left breast involvement was more prevalent (58.3%), with ipsilateral lymph node enlargement observed in 40.6% of cases. Given the clinical presentation of breast TB, which often leads to misdiagnosis, a significant proportion of cases (68.7%) were diagnosed through excisional biopsy. Following a standard 6-month regimen of anti-TB drugs, relapse occurred in only 4.2% of cases. This study highlights the need for heightened awareness and vigilance in diagnosing breast TB, especially in regions with a high burden. Although breast TB poses diagnostic challenges, with prompt identification and treatment, the prognosis is generally favorable, with a low incidence of relapse., (Copyright © 2024 Copyright: © 2024 International Journal of Mycobacteriology.)

Objective. MamoRef is an mammography device that uses near-infrared light, designed to provide clinically relevant information for the screening of diseases of the breast. Using low power continuous wave lasers and a high sensitivity CCD (Charge-coupled device) that captures a diffusely reflected image of the tissue, MamoRef results in a versatile diagnostic tool that aims to fulfill a complementary role in the diagnosis of breast cancer providing information about the relative hemoglobin concentrations as well as oxygen saturation. Approach. We present the design and development of an initial prototype of MamoRef. To ensure its effectiveness, we conducted validation tests on both the theoretical basis of the reconstruction algorithm and the hardware design. Furthermore, we initiated a clinical feasibility study involving patients diagnosed with breast disease, thus evaluating the practical application and potential benefits of MamoRef in a real-world setting. Main results. Our study demonstrates the effectiveness of the reconstruction algorithm in recovering relative concentration differences among various chromophores, as confirmed by Monte Carlo simulations. These simulations show that the recovered data correlates well with the ground truth, with SSIMs of 0.8 or more. Additionally, the phantom experiments validate the hardware implementation. The initial clinical findings exhibit highly promising outcomes regarding MamoRef's ability to differentiate between lesions. Significance. MamoRef aims to be an advancement in the field of breast pathology screening and diagnostics, providing complementary information to standard diagnostic techniques. One of its main advantages is the ability of determining oxy/deoxyhemoglobin concentrations and oxygen saturation; this constitutes valuable complementary information to standard diagnostic techniques. Besides, MamoRef is a portable and relatively inexpensive device, intended to be not only used in specific medical imaging facilities. Finally, its use does not require external compression of the breast. The findings of this study underscore the potential of MamoRef in fulfilling this crucial role., (Creative Commons Attribution license.)

Background and Objective: Computer-aided detection (CADe) of microcalcification clusters (MCs) in digital breast tomosynthesis (DBT) is crucial in the early diagnosis of breast cancer. Although convolutional neural network (CNN)-based detection models have achieved excellent performance in medical lesion detection, they are subject to some limitations in MC detection: 1) Most existing models employ the feature pyramid network (FPN) for multi-scale object detection; however, the rough feature sharing between adjacent layers in the FPN may limit the detection ability for small and low-contrast MCs; and 2) the MCs region only accounts for a small part of the annotation box, so the features extracted indiscriminately within the whole box may easily be affected by the background. In this paper, we develop a novel CNN-based CADe method to alleviate the impacts of the above limitations for the accurate and rapid detection of MCs in DBT., Methods: The proposed method has two parts: a novel context attention pyramid network (CAPNet) for intra-layer MC detection in two-dimensional (2D) slices and a three-dimensional (3D) aggregation procedure for aggregating 2D intra-layer MCs into a 3D result according to their connectivity in 3D space. The proposed CAPNet is based on an anchor-free and one-stage detection architecture and contains a context feature selection fusion (CFSF) module and a microcalcification response (MCR) branch. The CFSF module can efficiently enrich shallow layers' features by the complementary selection of local context features, aiming to reduce the missed detection of small and low-contrast MCs. The MCR branch is a one-layer branch parallel to the classification branch, which can alleviate the influence of the background region within the annotation box on feature extraction and enhance the ability of the model to distinguish MCs from normal breast tissue., Results: We performed a comparison experiment on an in-house clinical dataset with 648 DBT volumes, and the proposed method achieved impressive performance with a sensitivity of 91.56 % at 1 false positive per DBT volume (FPs/volume) and 93.51 % at 2 FPs/volume, outperforming other representative detection models., Conclusions: The experimental results indicate that the proposed method is effective in the detection of MCs in DBT. This method can provide objective, accurate, and quick diagnostic suggestions for radiologists, presenting potential clinical value for early breast cancer screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Milk of calcium (MOC) is a term used for sedimented calcifications within small cysts (Milk of Calcium - an overview|ScienceDirect Topics, n.d.). MOC in the breast is a benign entity and present in 4-6% of women that undergo diagnostic mammography (Park et al., 2008). 2 Calcium particles within cysts produce 'teacup'-shaped calcifications on true lateral views, and smudged calcifications on craniocaudal (CC) views (Veloso Gomes et al., n.d.). 3 On the CC projection, the calcifications will have a cloudlike or smudgy appearance like tea leaves in the bottom of a teacup (Milk of Calcium - an overview|ScienceDirect Topics, n.d.). Because this is a characteristic benign finding, there is no need for the patient to undergo a biopsy., Competing Interests: Declaration of competing interest We have no competing interests or conflicts of interest to disclose. We received no financial support for the research, funding, or publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Both the uterus and breasts have sex hormone dependence, yet there are few studies on the association between breast disease and uterine fibroids (UFs). The purpose of this study was to investigate the incidence of benign breast disease (BBD), carcinoma in situ (CIS), and breast cancer (BC) in women treated for UFs compared to women who were not treated for UFs. This retrospective cohort study used national health insurance data from January 1st, 2011, to December 31st, 2020. We selected women between 20 and 50 years old who (1) were treated for UFs (UF group) or (2) visited medical institutions for personal health screening tests without UFs (control group). We analyzed independent variables such as age, socioeconomic status (SES), region, Charlson comorbidity index (CCI), delivery status, menopausal status, menopausal hormone therapy (MHT), endometriosis, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia based on the first date of uterine myomectomy in the UF group and the first visiting date for health screening in the non-UF group. There were 190,583 and 439,940 participants in the UF and control groups, respectively. Compared with those of the control group, the RRs of BBD, CIS, and BC were increased in the UF group. The hazard ratios (HRs) of BBD, CIS, and BC in the UF group were 1.335 (95% confidence interval (CI) 1.299-1.372), 1.796 (95% CI 1.542-2.092), and 1.3 (95% CI 1.198-1.41), respectively. When we analyzed the risk of BC according to age at inclusion, UFs group had the increased risk of BCs in all age groups in comparison with control group. Women with low SES (HR 0.514, 95% CI 0.36-0.734) and living in rural areas (HR 0.889, 95% CI 0.822-0.962) had a lower risk of BC. Our study showed that women with UFs had a higher risk of BBD, CIS, and BC than those without UFs. This result suggests that women with UFs should be more conscious of BC than those without UFs. Therefore, doctors should consider recommending regular breast self-exams, mammography, or ultrasound for the early detection of BC in women with UFs., (© 2023. Springer Nature Limited.)

Objectives: In the women with compressed thin thickness (≦ 3 cm), mammographic guiding vacuum-assist breast biopsy (MG-VABB) is a technical challenge. We herein report their performance of MG-VABB on suspicious microcalcification by modern mammography., Methods: We retrospectively reviewed the consecutive MG-VABB in our hospital from February 2019 to January 2021. All the patients received biopsy because of suspicious microcalcifications discovered by mammography and had at least one-year post-biopsy follow-up., Results: We reviewed 745 consecutive patients revealing 195 with compressed thin breasts ≦ 3 cm (mean age: 50.12 ± 7.0; breast thickness: 24.99 mm range 11.6-30 mm). Of the 191 patients received biopsy, the microcalcification retrieval rate was 97.9%. Using the half-open notch biopsy or horizontal needle approach, the biopsies were technically achieved in 30.4% and 9.4% of patients respectively. Regarding to the gold standard of surgicohistology, the cancer sensitivities was 88.46% and the atypia upgrade rate was 16.67%. There was no statistical difference of the procedure time between stereotactic guided and tomosynthesis guided., Conclusions: The modern MG-VABB has technically improve the performance of biopsy to the patients with compressed thin breasts (≦ 3 cm), revealing approximate results to those breasts > 3 cm. The diagnosis helps the management of suspicious microcalcifications discovered by mammography., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: The noise in digital breast tomosynthesis (DBT) includes x-ray quantum noise and detector readout noise. The total radiation dose of a DBT scan is kept at about the level of a digital mammogram but the detector noise is increased due to acquisition of multiple projections. The high noise can degrade the detectability of subtle lesions, specifically microcalcifications (MCs)., Purpose: We previously developed a deep-learning-based denoiser to improve the image quality of DBT. In the current study, we conducted an observer performance study with breast radiologists to investigate the feasibility of using deep-learning-based denoising to improve the detection of MCs in DBT., Methods: We have a modular breast phantom set containing seven 1-cm-thick heterogeneous 50% adipose/50% fibroglandular slabs custom-made by CIRS, Inc. (Norfolk, VA). We made six 5-cm-thick breast phantoms embedded with 144 simulated MC clusters of four nominal speck sizes (0.125-0.150, 0.150-0.180, 0.180-0.212, 0.212-0.250 mm) at random locations. The phantoms were imaged with a GE Pristina DBT system using the automatic standard (STD) mode. The phantoms were also imaged with the STD+ mode that increased the average glandular dose by 54% to be used as a reference condition for comparison of radiologists' reading. Our previously trained and validated denoiser was deployed to the STD images to obtain a denoised DBT set (dnSTD). Seven breast radiologists participated as readers to detect the MCs in the DBT volumes of the six phantoms under the three conditions (STD, STD+, dnSTD), totaling 18 DBT volumes. Each radiologist read all the 18 DBT volumes sequentially, which were arranged in a different order for each reader in a counter-balanced manner to minimize any potential reading order effects. They marked the location of each detected MC cluster and provided a conspicuity rating and their confidence level for the perceived cluster. The visual grading characteristics (VGC) analysis was used to compare the conspicuity ratings and the confidence levels of the radiologists for the detection of MCs., Results: The average sensitivities over all MC speck sizes were 65.3%, 73.2%, and 72.3%, respectively, for the radiologists reading the STD, dnSTD, and STD+ volumes. The sensitivity for dnSTD was significantly higher than that for STD (p < 0.005, two-tailed Wilcoxon signed rank test) and comparable to that for STD+. The average false positive rates were 3.9 ± 4.6, 2.8 ± 3.7, and 2.7 ± 3.9 marks per DBT volume, respectively, for reading the STD, dnSTD, and STD+ images but the difference between dnSTD and STD or STD+ did not reach statistical significance. The overall conspicuity ratings and confidence levels by VGC analysis for dnSTD were significantly higher than those for both STD and STD+ (p ≤ 0.001). The critical alpha value for significance was adjusted to be 0.025 with Bonferroni correction., Conclusions: This observer study using breast phantom images showed that deep-learning-based denoising has the potential to improve the detection of MCs in noisy DBT images and increase radiologists' confidence in differentiating noise from MCs without increasing radiation dose. Further studies are needed to evaluate the generalizability of these results to the wide range of DBTs from human subjects and patient populations in clinical settings., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

A female in her early 20s was referred to the breast-endocrine surgeons with a self-detected tender left breast lump on the background of a family history of breast cancer. A physical examination revealed a rubbery and mobile mass in the left upper breast. Ultrasound demonstrated a solid hypoechoic mass with a likely differential diagnosis of fibroadenoma, with a subsequent core needle biopsy (CNB) confirming a fibroadenoma. Given the size and tenderness of the lump, an excisional biopsy was performed. Histology revealed a fibroadenoma with components of low-grade ductal carcinoma in situ, contained within the fibroadenoma and excised with clear margins.Following surgical excision, a multidisciplinary review determined that no further local therapy was required and recommended a genetics referral. This case was interesting as it raised important questions, including what the best surveillance strategies are for female patients with breast cancer within fibroadenoma and determining the risk and probability of missing epithelial atypia via CNB., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Juvenile fibroadenomas (JFA) are biphasic fibroepithelial lesions (FEL) usually occurring in adolescent female patients. Giant (G) JFA, like other FEL, may exhibit prominent pseudoangiomatous stromal hyperplasia (PASH)-like change. We sought to determine clinicopathological and molecular characteristics of GJFA with and without PASH., Methods and Results: Archives were searched for cases of GJFA (1985-2020). All were stained for androgen receptor (AR), beta-catenin, CD34 and progesterone receptor (PR). Cases were sequenced using a custom 16-gene panel - MED12 (exons 1 and 2), TERT promoter (-124C>T and -146Ctable>T), SETD2, KMT2D, RARA (exons 5-9), FLNA, NF1, PIK3CA (exons 10, 11 and 21), EGFR, RB1, BCOR, TP53, PTEN, ERBB4, IGF1R and MAP3K1. Twenty-seven GJFA from 21 female patients aged 10.1-25.2 years were identified. Size ranged from 5.2 to 21 cm. Two patients had multiple, bilateral and later recurrent GJFA. Thirteen (48%) cases showed prominent PASH-like stroma. All were positive for stromal CD34, negative for AR and beta-catenin and one case showed focal PR expression. Sequencing showed MAP3K1 and SETD2 mutations in 17 samples, with KMT2D, TP53 and BCOR aberrations in 10 (45%), 10 (45%) and seven (32%) cases, respectively. Tumours with a PASH-like pattern had higher prevalence of SETD2 (P = 0.004) and TP53 (P = 0.029) mutations, while those without PASH had more RB1 mutations (P = 0.043). MED12 mutation was identified in one case. TERT promoter mutation was observed in four (18%), including two recurrences., Conclusions: Gene mutations along more advanced phases of the proposed FEL pathogenetic pathway in GJFA are unusual, and suggest a mechanism for more aggressive growth in these tumours., (© 2023 John Wiley & Sons Ltd.)

Breast masses are infrequently encountered in pediatric and adolescent populations. Most breast masses in children are benign entities arising from embryological defects which can be managed once breast development is complete. Diagnostic and management dilemmas arise when fibroepithelial lesions of the breast are seen in clinical practice. Differentiation between a fibroadenoma and a phyllodes tumor is important to guide management. Breast cancer in children under 18 years of age is extremely rare and invasive diagnostic testing and aggressive management is only recommended when clinical suspicion of malignancy is very high. Patient and caregiver counseling plays an important role in the management of these diseases. While adult-onset breast diseases have been studied very closely, there is a dearth of literature on pediatric breast anomalies. This review aims to provide a scoping overview of the available literature on benign, fibroepithelial, and malignant lesions of the breast in pediatric and adolescent populations to help guide physicians and surgeons with decision-making regarding the diagnosis and management of pediatric breast diseases., Competing Interests: Declaration of Competing Interest The authors have no conflicts or fundings to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: A tumour-bed boost delivered after whole-breast radiotherapy increases local cancer-control rates but requires more patient visits and can increase breast hardness. IMPORT HIGH tested simultaneous integrated boost against sequential boost with the aim of reducing treatment duration while maintaining excellent local control and similar or reduced toxicity., Methods: IMPORT HIGH is a phase 3, non-inferiority, open-label, randomised controlled trial that recruited women after breast-conserving surgery for pT1-3pN0-3aM0 invasive carcinoma from radiotherapy and referral centres in the UK. Patients were randomly allocated to receive one of three treatments in a 1:1:1 ratio, with computer-generated random permuted blocks used to stratify patients by centre. The control group received 40 Gy in 15 fractions to the whole breast and 16 Gy in 8 fractions sequential photon tumour-bed boost. Test group 1 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 48 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. Test group 2 received 36 Gy in 15 fractions to the whole breast, 40 Gy in 15 fractions to the partial breast, and 53 Gy in 15 fractions concomitant photon boost to the tumour-bed volume. The boost clinical target volume was the clip-defined tumour bed. Patients and clinicians were not masked to treatment allocation. The primary endpoint was ipsilateral breast tumour relapse (IBTR) analysed by intention to treat; assuming 5% 5-year incidence with the control group, non-inferiority was predefined as 3% or less absolute excess in the test groups (upper limit of two-sided 95% CI). Adverse events were assessed by clinicians, patients, and photographs. This trial is registered with the ISRCTN registry, ISRCTN47437448, and is closed to new participants., Findings: Between March 4, 2009, and Sept 16, 2015, 2617 patients were recruited. 871 individuals were assigned to the control group, 874 to test group 1, and 872 to test group 2. Median boost clinical target volume was 13 cm 3 (IQR 7 to 22). At a median follow-up of 74 months there were 76 IBTR events (20 for the control group, 21 for test group 1, and 35 for test group 2). 5-year IBTR incidence was 1·9% (95% CI 1·2 to 3·1) for the control group, 2·0% (1·2 to 3·2) for test group 1, and 3·2% (2·2 to 4·7) for test group 2. The estimated absolute differences versus the control group were 0·1% (-0·8 to 1·7) for test group 1 and 1·4% (0·03 to 3·8) for test group 2. The upper confidence limit for test group 1 versus the control group indicated non-inferiority for 48 Gy. Cumulative 5-year incidence of clinician-reported moderate or marked breast induration was 11·5% for the control group, 10·6% for test group 1 (p=0·40 vs control group), and 15·5% for test group 2 (p=0·015 vs control group)., Interpretation: In all groups 5-year IBTR incidence was lower than the 5% originally expected regardless of boost sequencing. Dose-escalation is not advantageous. 5-year moderate or marked adverse event rates were low using small boost volumes. Simultaneous integrated boost in IMPORT HIGH was safe and reduced patient visits., Funding: Cancer Research UK., Competing Interests: Declaration of interests JMB, EMD, ME, CLG, JSH, PH, MAS, JCT, and YT report grants from Cancer Research UK during the conduct of the study. SVL reports PhD funding from Cancer Research UK. JMB reports grants and non-financial support from AstraZeneca, Clovis Oncology, Eli Lilly, Janssen-Cilag, Merck Sharp & Dohme, Novartis (previously GlaxoSmithKline), Pfizer, Puma Biotechnology, and Roche outside the submitted work. CEC reports grants from National Institute for Health Research Efficacy and Mechanism Evaluation, RADNET, the Lancet Breast Cancer Commission, and Addenbrooke's Charitable Trust outside the submitted work. CEC also reports membership of five external independent monitoring committees and is Chair of the Lancet Breast Cancer Commission. AMK is President of the European Society of Radiation Oncology. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Breast cancer is the world's most prevalent form of cancer. The survival rates have increased in the last years mainly due to factors such as screening programs for early detection, new insights on the disease mechanisms as well as personalised treatments. Microcalcifications are the only first detectable sign of breast cancer and diagnosis timing is strongly related to the chances of survival. Nevertheless microcalcifications detection and classification as benign or malignant lesions is still a challenging clinical task and their malignancy can only be proven after a biopsy procedure. We propose DeepMiCa, a fully automated and visually explainable deep-learning based pipeline for the analysis of raw mammograms with microcalcifications. Our aim is to propose a reliable decision support system able to guide the diagnosis and help the clinicians to better inspect borderline difficult cases., Methods: DeepMiCa is composed by three main steps: (1) Preprocessing of the raw scans (2) Automatic patch-based Semantic Segmentation using a UNet based network with a custom loss function appositely designed to deal with extremely small lesions (3) Classification of the detected lesions with a deep transfer-learning approach. Finally, state-of-the-art explainable AI methods are used to produce maps for a visual interpretation of the classification results. Each step of DeepMiCa is designed to address the main limitations of the previous proposed works resulting in a novel automated and accurate pipeline easily customisable to meet radiologists' needs., Results: The proposed segmentation and classification algorithms achieve an area under the ROC curve of 0.95 and 0.89 respectively. Compared to previously proposed works, this method does not require high performance computational resources and provides a visual explanation of the final classification results., Conclusion: To conclude, we designed a novel fully automated pipeline for detection and classification of breast microcalcifications. We believe that the proposed system has the potential to provide a second opinion in the diagnosis process giving the clinicians the opportunity to quickly visualise and inspect relevant imaging characteristics. In the clinical practice the proposed decision support system could help reduce the rate of misclassified lesions and consequently the number of unnecessary biopsies., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Microcalcifications play an important role in cancer detection. They are evaluated by their radiological and histological characteristics but it is challenging to find a link between their morphology, their composition and the nature of a specific type of breast lesion. Whilst there are some mammographic features that are either typically benign or typically malignant often the appearances are indeterminate. Here, we explore a large range of vibrational spectroscopic and multiphoton imaging techniques in order to gain more information about the composition of the microcalcifications. For the first time, we validated the presence of carbonate ions in the microcalcifications by O-PTIR and Raman spectroscopy at the same time, the same location and the same high resolution (0.5 μm). Furthermore, the use of multiphoton imaging allowed us to create stimulated Raman histology (SRH) images which mimic histological images with all chemical information. In conclusion, we established a protocol for efficiently analysing the microcalcifications by iteratively refining the area of interest.

Abstract: Nonsteroidal anti-inflammatory agents (NSAID) are associated with modest inconsistent reductions in breast cancer risk in population-based cohorts, whereas two focused studies of patients with benign breast disease (BBD) have found lower risk with NSAID use. Given that BBD includes fibroinflammatory lesions linked to elevated breast cancer risk, we assessed whether NSAID use was associated with lower breast cancer risk among patients with BBD.Participants were postmenopausal women in the Cancer Prevention Study-II (CPS-II), a prospective study of cancer incidence and mortality, who completed follow-up surveys in 1997 with follow-up through June 30, 2015. History of BBD, NSAID use, and covariate data were updated biennially. This analysis included 23,615 patients with BBD and 36,751 patients with non-BBD, including 3,896 incident breast cancers over an average of 12.72 years of follow-up among participants. NSAID use, overall and by formulation, recency, duration, and pills per month was analyzed versus breast cancer risk overall and by BBD status using multivariable-adjusted Cox models; BBD status and NSAID use were modeled as time-dependent exposures.Patients with BBD who reported using NSAIDs experienced lower breast cancer risk (HR, 0.87; 95% CI, 0.78-0.97), with similar effects for estrogen receptor (ER)-positive breast cancers [HR, 0.85; 95% confidence interval (CI), 0.74-0.97] and ER-negative breast cancers (HR, 0.87; 95% CI, 0.59-1.29); among women without BBD, NSAID use was unrelated to risk (HR, 1.02; 95% CI, 0.92-1.13; Pinteraction = 0.04). Associations stratified by age, obesity, menopausal hormone use, and cardiovascular disease were similar.Among patients with BBD, NSAID use appears linked to lower breast cancer risk. Further studies to assess the value of NSAID use among patients with BBD are warranted., Prevention Relevance: We examined whether NSAID use, a modifiable exposure, is associated with breast cancer risk in postmenopausal women from the Cancer Prevention Study-II with self-reported benign breast disease, an often inflammatory condition associated with higher rates of breast cancer., (©2023 American Association for Cancer Research.)

Microcalcifications, primarily biogenic apatite, occur in cancerous and benign breast pathologies and are key mammographic indicators. Outside the clinic, numerous microcalcification compositional metrics (e.g., carbonate and metal content) are linked to malignancy, yet microcalcification formation is dependent on microenvironmental conditions, which are notoriously heterogeneous in breast cancer. We interrogate multiscale heterogeneity in 93 calcifications from 21 breast cancer patients using an omics-inspired approach: For each microcalcification, we define a "biomineralogical signature" combining metrics derived from Raman microscopy and energy-dispersive spectroscopy. We observe that (i) calcifications cluster into physiologically relevant groups reflecting tissue type and local malignancy; (ii) carbonate content exhibits substantial intratumor heterogeneity; (iii) trace metals including zinc, iron, and aluminum are enhanced in malignant-localized calcifications; and (iv) the lipid-to-protein ratio within calcifications is lower in patients with poor composite outcome, suggesting that there is potential clinical value in expanding research on calcification diagnostic metrics to include "mineral-entrapped" organic matrix.

BACKGROUND. Studies have shown improved targeting and sampling of noncalcified lesions (asymmetries, masses, and architectural distortion) with digital breast tomosynthesis (DBT)-guided biopsy in comparison with digital mammography (DM)-guided stereotactic biopsy. Literature that compares the two techniques specifically for sampling calcifications has been scarce. OBJECTIVE. The purpose of this study was to compare the performance and outcomes of DM- and DBT-guided biopsy of suspicious calcifications. METHODS. This retrospective study included 1310 patients (mean age, 58 ± 12 [SD] years) who underwent a total of 1354 9-gauge vacuum-assisted core biopsies of suspicious calcifications performed at a single institution from May 22, 2017, to December 31, 2021. The decision to use a DM-guided or DBT-guided technique was made at the discretion of the radiologist performing the biopsy. Procedure time, the number of exposures during the procedure, and the histopathologic outcomes were recorded. The two techniques were compared using a two-sample t test for continuous variables and a chi-square test for categoric variables. Additional tests were performed using generalized estimating equations to control for the effect of the individual radiologist performing the biopsy. RESULTS. A total of 348 (26%) biopsies used DM guidance, and 1006 (74%) used DBT guidance. The mean procedure time was significantly lower for DBT-guided biopsy (14.9 ± 8.0 [SD] minutes) than for DM-guided biopsy (24.7 ± 14.3 minutes) ( p < .001). The mean number of exposures was significantly lower for DBT-guided biopsy (4.1 ± 1.0 [SD] exposures) than for DM-guided biopsy (9.1 ± 3.3 exposures) ( p < .001). The differences in procedure time and number of exposures remained significant (both p < .001) when controlling for the effect of the radiologist performing the biopsy. There were no significant differences (all p > .05) between DM-guided and DBT-guided biopsy in terms of the malignancy rate on initial biopsy (20% vs 19%), the rate of high-risk lesion upgrading (14% vs 22%), or the final malignancy rate (23% vs 22%). CONCLUSION. DBT-guided biopsy of suspicious calcifications can be performed with shorter procedure time and fewer exposures compared with DM-guided biopsy, without a significant difference in rates of malignancy or high-risk lesion upgrading. CLINICAL IMPACT. The use of a DBT-guided, rather than a DM-guided, biopsy technique for suspicious calcifications can potentially reduce patient discomfort and radiation exposure without affecting clinical outcomes.

Background: Intraductal papillary carcinoma (IDPC) is a rare but fatal disease. Preoperative ultrasound diagnosis of IDPC remains challenging and meaningful. The aim of the study was to determine an effective ultrasound model to predict intraductal papillary carcinoma (IDPC) in patients with partially cystic breast lesions on ultrasound., Methods: We reviewed female patients with breast nodules who underwent biopsy or surgery between 2004 and 2019, and pathological results were used as the reference standard. We finally included 21 IDPC patients with partially cystic lesions on preoperative ultrasound matched to 40 patients with intraductal papilloma. The association of ultrasound features with IDPC was analysed., Results: Posterior echo enhancement (P < 0.001), tumour size (P = 0.002), irregular shape (P = 0.003), wide base (P = 0.003), solid-mainly component (P = 0.013), rich Doppler flow (P < 0.001) and multiple lesions (P = 0.044) were associated with IDPC by univariate analysis. Based on univariate analysis, variables were included in the regression analysis to obtain independent factors. The regression analysis showed that microcalcification, multiple lesions, posterior echo enhancement, wide base of solid components and rich colour Doppler flow were predictors for IDPC (P < 0.001). The collective model of the independent factors (microcalcification, multiple lesions, posterior echo enhancement, wide base of solid components and rich colour Doppler flow) could predict IDPC with an area under the curve (AUC) of 0.99 (95% CI 0.95-1.00). The collective model had a better net benefit demonstrated by the decision curve., Conclusion: Ultrasonic features may be an applicable model for predicting IDPC with partially cystic breast lesions on ultrasound and has a better potential to facilitate decision-making preoperatively., (© 2023. The Author(s).)

Breast masses in children and adolescents are uncommon, and the spectrum of pediatric breast masses is predominantly benign and different from that in adults. Knowledge of the clinical presentation and imaging features of the various stages of normal development and mass-forming lesions in the pediatric breast can guide a tailored imaging approach and help the radiologist make a definitive diagnosis. Breast development begins during fetal gestation along the embryologic milk lines and continues through puberty as the breast matures through the Tanner stages of development. Normal and developmental variants and benign neoplastic and nonneoplastic lesions in the pediatric breast are common causes of concern. Malignant breast masses in children are rare and are more often due to metastasis than primary breast cancer. When clinically warranted, US is the mainstay for imaging the pediatric breast and requires careful correlation of sonographic findings with patient age and history. Breast MRI can be used to further characterize lesions and evaluate the extent of disease. Biopsy should be considered only for suspicious findings and must be weighed against the risk of iatrogenic injury to the developing breast. Given that the majority of mass-forming lesions in the pediatric breast are benign, the diagnostic and management approach should emphasize "first do no harm." Knowledge of the imaging appearance of normal breast development and the spectrum of benign and malignant pediatric breast masses is necessary to make the correct diagnosis. © RSNA, 2022.

Development of a neoplasm in an ectopic breast is uncommon, while the development of phyllodes tumor in an ectopic breast in the axilla is even rarer. We report a rare case of a 51-year-old female who presented with a complain of swelling and pain in the right axilla with no associated complaints in other organs. Magnetic resonance imaging suggested a possibility of metastatic lymphadenopathy. Complete excision of the right axillary mass was performed and sent for histopathological examination which was examined thoroughly and sections were given. On microscopic examination, stromal proliferation in a leaf-like pattern with mild stromal atypia and focal permeation of borders were seen, and a diagnosis of Ectopic borderline phyllodes tumor in axilla was made, which is extremely rare and needs to be differentiated from its close differentials like fibroadenoma and periductal stromal sarcoma.