A Nationwide Study of GATA2 Deficiency in Norway—the Majority of Patients Have Undergone Allo-HSCT

Purpose GATA2 deficiency is a rare primary immunodeficiency that has become increasingly recognized due to improved molecular diagnostics and clinical awareness. The only cure for GATA2 deficiency is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The inconsistency of genotype–phenotype correlations makes the decision regarding “who and when” to transplant challenging. Despite considerable morbidity and mortality, the reported proportion of patients with GATA2 deficiency that has undergone allo-HSCT is low (~ 35%). The purpose of this study was to explore if detailed clinical, genetic, and bone marrow characteristics could predict end-point outcome, i.e., death and allo-HSCT. Methods All medical genetics departments in Norway were contacted to identify GATA2 deficient individuals. Clinical information, genetic variants, treatment, and outcome were subsequently retrieved from the patients’ medical records. Results Between 2013 and 2020, we identified 10 index cases or probands, four additional symptomatic patients, and no asymptomatic patients with germline GATA2 variants. These patients had a diverse clinical phenotype dominated by cytopenia (13/14), myeloid neoplasia (10/14), warts (8/14), and hearing loss (7/14). No valid genotype–phenotype correlations were found in our data set, and the phenotypes varied also within families. We found that 11/14 patients (79%), with known GATA2 deficiency, had already undergone allo-HSCT. In addition, one patient is awaiting allo-HSCT. The indications to perform allo-HSCT were myeloid neoplasia, disseminated viral infection, severe obliterating bronchiolitis, and/or HPV-associated in situ carcinoma. Two patients died, 8 months and 7 years after allo-HSCT, respectively. Conclusion Our main conclusion is that the majority of patients with symptomatic GATA2 deficiency will need allo-HSCT, and a close surveillance of these patients is important to find the “optimal window” for allo-HSCT. We advocate a more offensive approach to allo-HSCT than previously described.

Role of Ag NORs in Improve Diagnosis of Breast Cancer with Different grades and Subtypes’ among Sudanese women

This study aimed to evaluate the role of Ag NORs in improves diagnosis of Breast cancer with different subtypes’ among Sudanese Patients. This study include tissue sections of breast cancer diagnosed women, they were 30, ductal and lobular invasive carcinoma were 10 for each, while ductal and lobular in-situ carcinoma were 5 each. Found correlation between subtypes of breast cancer and Ag NOR , Invasive ductal carcinoma had more NOR while the lobular carcinoma in situ was less one , Stage III most frequency than the other stage. Silver staining were performed and Ag-NOR were detected in ductal and lobular invasive carcinoma more than ductal and lobular in-situ carcinoma, grade III has more frequency of Ag-NOR than other stages, and no correlation found between Ag-NOR and age group

Papillary Neoplasm of Breast-Changing Trends in Diagnosis and Management

Papillary neoplasm of breast comprises of seven separate heterogeneous entities ranging from benign, atypical and malignancy including non-invasive and invasive carcinoma. Papillary carcinoma (PC) is seen more commonly in older postmenopausal women with favorable prognosis. PC breast typically presents with bloody nipple discharge and an abnormal mass with radiologic features of intraductal mass. Encapsulated PC and solid PC is to be treated as in situ carcinoma, but distinction of invasive PC from non invasive carcinoma is critical both at microscopic and molecular level. So, surgical excision should be the choice of definitive diagnostic technique in papillary neoplasm instead of core needle biopsy. Furthermore, treatment guidelines for invasive PC also have been framed, but incidence of recurrence and death attributable to various subtypes of carcinoma remained same. So, this is important topic to be addressed to understand the need for further management and outcome of the disease.

Assessment of Deep Learning Algorithms to Predict Histopathological Diagnosis of Breast Cancer: First Moroccan Prospective Study on a Private Dataset

Objective: Breast cancer is a critical public health issue and a leading cause of cancer-related deaths among women worldwide. Its early diagnosis and detection can effectively help in increasing the chances of survival rate. The aim of this work is to develop a computational approach based on deep convolutional neural networks for an efficient classification of breast cancer histopathological images by using our own created dataset. Two models of deep neural network architectures were used combined to gradient boosted trees classifier. Images were classified in three classes, normal tissue-benign lesions, in situ carcinoma and invasive carcinoma. Results: Both Resnet50 and Xception models achieved comparable results, with a small advantage to Xception extracted features. The proposed classification allowed us to obtain high degree of precision, a good generalization performance and avoided an eventual overfitting scenario due to the limited size of the data. In addition, we reported high sensitivity for detection of carcinoma cases, which is important for diagnostic pathology workflow in order to assist pathologists for diagnosing breast cancer with precision.

EGFR Overexpression and Sequence Analysis of KRAS, BRAF, and EGFR Mutation Hot Spots in Canine Intestinal Adenocarcinoma

Epidermal growth factor receptor (EGFR) is overexpressed in many human colorectal cancers and anti-EGFR agents are employed as immunotherapies. However, KRAS, EGFR, and BRAF gene mutations can influence the activity of the anti-EGFR agents. We evaluated EGFR expression at protein and mRNA levels in canine intestinal adenocarcinomas using immunohistochemistry (IHC) and RNA in situ hybridization (RNA-ISH). We also investigated the mutation status of EGFR, KRAS, and BRAF to aid the development of anti-EGFR agents for canine intestinal adenocarcinoma. EGFR expression was highest in adenocarcinoma, followed by intramucosal neoplasia (adenoma and in situ carcinoma), and nonneoplastic canine intestinal tissue, at both protein ( P = .000) and mRNA ( P = .005) levels. The EGFR, KRAS, and BRAF genes showed wild-type sequences at the mutation hot spots in all 13 specimens. Thus, EGFR might serve as a promising diagnostic marker in canine intestinal adenocarcinoma, and further studies would be needed to develop EGFR-targeted anticancer therapies.

Complex fibroadenoma with focal ossification- an enigmatic finding in a less common tumor

Breast lumps have diverse causes including benign as well as malignant lesions. Fibroadenoma (FA) is a common cause of breast lump. Complex fibroadenomas, a particular subtype, pose diagnostic dilemmas due to confusing the radiological findings and hold higher incidence of transformation to malignancy. A 49 year old female presented with a painless lump in right breast for 2 years which appeared calcified on radiology. Excision biopsy was performed which grossly revealed an encapsulated grey-white firm to hard with cystic areas. Microscopically the sections showed a well encapsulated fibroepithelial tumor showing areas of sclerosing adenosis, hyalinization, cysts lined by cuboidal cells with eosinophilic secretions, areas of calcification and ossification. No evidence of lobular hyperplasia or in-situ carcinoma was seen. Patient was advised follow up. This case represents the unusual occurrence of complex fibroadenoma in a middle-aged female showing with ossification.

Classification of Hematoxylin and Eosin-Stained Breast Cancer Histology Microscopy Images Using Transfer Learning with EfficientNets

Breast cancer is a fatal disease and is a leading cause of death in women worldwide. The process of diagnosis based on biopsy tissue is nontrivial, time-consuming, and prone to human error, and there may be conflict about the final diagnosis due to interobserver variability. Computer-aided diagnosis systems have been designed and implemented to combat these issues. These systems contribute significantly to increasing the efficiency and accuracy and reducing the cost of diagnosis. Moreover, these systems must perform better so that their determined diagnosis can be more reliable. This research investigates the application of the EfficientNet architecture for the classification of hematoxylin and eosin-stained breast cancer histology images provided by the ICIAR2018 dataset. Specifically, seven EfficientNets were fine-tuned and evaluated on their ability to classify images into four classes: normal, benign, in situ carcinoma, and invasive carcinoma. Moreover, two standard stain normalization techniques, Reinhard and Macenko, were observed to measure the impact of stain normalization on performance. The outcome of this approach reveals that the EfficientNet-B2 model yielded an accuracy and sensitivity of 98.33% using Reinhard stain normalization method on the training images and an accuracy and sensitivity of 96.67% using the Macenko stain normalization method. These satisfactory results indicate that transferring generic features from natural images to medical images through fine-tuning on EfficientNets can achieve satisfactory results.

Not All Cases of Mammary Paget’s Disease are Cytokeratin-7 Positive: A Challenging Diagnosis!

Mammary Paget’s disease accounts for 1% to 3% of all breast tumors and manifests as a chronic eczematous lesion of the areolar skin. It can occur without any underlying neoplasia or can be present in association with an underlying invasive and/or in situ carcinoma of the breast. The present report describes a challenging nipple punch biopsy showing an infiltration of the lower third to two-thirds of the epidermis by large, ovoid, neoplastic cells. The morphology was consistent with mammary Paget's disease, although immunohistochemistry for cytokeratin-7 (CK7) was repeatedly negative. This resulted in an initial misdiagnosis and, subsequently, a delay in the patient's follow-up. Additional immunohistochemistry for GATA binding protein 3 (GATA3) and human epidermal growth factor receptor 2 (HER2), as well as a second opinion of a breast pathologist, resulted in the diagnosis of mammary Paget's disease. The aim of this article is to raise awareness among pathologists and prevent them from misdiagnosing CK7-negative Paget disease of the breast.

Upgrade rates and outcomes of screen-detected atypical intraductal epithelial proliferation (AIDEP) diagnosed on core needle biopsy

INTRODUCTION: Atypical intraductal epithelial proliferation (AIDEP) is a breast lesion categorised as “indeterminate” if identified on core needle biopsy (CNB). The rate at which these lesions are upgraded following diagnostic excision varies in the literature. Women diagnosed with AIDEP are thought to be at increased risk of breast cancer. Our aim was to identify the rate of upgrade to invasive or in situ carcinoma in a group of patients diagnosed with AIDEP on screening mammography and to quantify their risk of subsequent breast cancer. METHODS: We conducted a retrospective review of a prospectively maintained database containing all patients diagnosed with AIDEP on CNB between 2005 and 2012 in an Irish breast screening centre. Basic demographic data was collected along with details of the original CNB result, rate of upgrade to carcinoma and details of any subsequent cancer diagnoses. RESULTS: In total 113 patients were diagnosed with AIDEP on CNB during the study period. The upgrade rate on diagnostic excision was 28.3% (n = 32). 6.2% (n = 7) were upgraded to invasive cancer and 22.1% (n = 25) to DCIS. 81 patients were not upgraded on diagnostic excision and were offered 5 years of annual mammographic surveillance. 9.88% (8/81) of these patients went on to receive a subsequent diagnosis of malignancy. The mean time to diagnosis of these subsequent cancers was 65.41 months (range 20.18–145.21). CONCLUSION: Our data showing an upgrade rate of 28% to carcinoma reflects recently published data and we believe it supports the continued practice of excising AIDEP to exclude co-existing carcinoma.