The tumor microenvironment (TME) in breast cancer comprises local factors, cancer cells, immune cells and stromal cells of the local and distant tissues. The interaction between cancer cells and their microenvironment plays important roles in tumor proliferation, propagation and response to therapies. There is increasing research in exploring and manipulating the non-cancerous components of the TME for breast cancer treatment. As the TME is now increasingly recognized as a treatment target, its pathologic assessment has become a critical component of breast cancer management. The latest WHO classification of tumors of the breast listed stromal response pattern/fibrotic focus as a prognostic factor and includes recommendations on the assessment of tumor infiltrating lymphocytes and PD-1/PD-L1 expression, with therapeutic implications. This review dissects the TME of breast cancer, describes pathologic assessment relevant for prognostication and treatment decision, and details therapeutic options that interacts with and/or exploits the TME in breast cancer.

BACKGROUND:The aim of the International Academy of Cytology Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy Cytopathology is to improve cytology practice. This study assessed cytologic diagnoses made with the system and its efficacy when it was applied by pathologists with different levels of experience. METHODS: In all, 1080 cases of breast fine-needle aspiration biopsy (FNAB) over a period of 16 years were reviewed and reclassified with the system. The category distribution and the diagnostic performance were compared with the original diagnoses. The concordance rates for diagnoses from pathologists with different levels of experience were also determined. RESULTS: The distribution of cytologic diagnoses made with the system was as follows: 11.7% were insufficient, 56.6% were benign, 20.1% were atypical, 6.1% were suspicious for malignancy, and 5.6% were malignant. The rates for the insufficient and atypical categories were lower than the original diagnosis rates (13.1% and 23.8%, respectively). Overall, 120 cases (11.1%) were recategorized. Among those recategorized as benign, suspicious, or malignant with follow-up data, 96.7% were correctly reclassified. A significant improvement in diagnostic performance was found with the system (P < .001). Such improvement was also seen in problematic breast lesions, including fibroepithelial lesions, papillary lesions, and low-grade carcinomas. Pathologists with intermediate experience showed a higher concordance with an expert pathologist in the diagnoses than those with short experience (κ, 0.838 vs 0.634). CONCLUSIONS:The system effectively categorized the diagnoses, and the diagnostic performance of FNAB reporting was improved. The structured reporting also enhanced the reproducibility of reporting by pathologists with intermediate experience and, to some extent, those with short experience.

Epidermolysis bullosa (EB) is a heterogeneous group of congenital blistering diseases that are usually present in the neonatal period. They are characterized by blister formation in response to rubbing or frictional trauma. EB is classified into three major categories, each with many subtypes based on the precise location at which separation or blistering occurs, namely epidermolysis bullosa simplex (EBS), junctional epidermolysis bullosa (JEB), and dystrophic epidermolysis bullosa (DEB). We describe the causes and ages of death of three cases of EB in Hong Kong. A 24-year-old male with EBD diagnosed in the neonatal period lived a withdrawn life after completing secondary school and died of metastaic squamous cell carcinoma. Two neonates of consanguineous Pakistani parents, one with JEB and the other with EB-Pyloric Atresia variant, died of sepsis in infancy. We performed an extensive literature review of the causes and ages of death of these diseases. EB is a heterogeneous inherited blistering skin disease associated with significant morbidity and mortality. EBS is occasionally associated with death at early ages with sepsis. Patients with JEB usually died of sepsis at young age. DEB patients often survive to adulthood and die of cardiopulmonary and renal complications. Squamous cell carcinoma and metastases are unique in DEB.