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WHO classification of breast tumours 2019 Dr Puay Hoon Tan Singapore General Hospital Singapore Email: [email protected] Hong Kong Division of the International Academy of Pathology (IAP) 30th Anniversary Scientific Congress Published, November 2019 Online version https://tumourclassification.iarc.who.int/ 2 WHO Classification of Tumours - ONLINE Now available at: tumourclassification.iarc.who.int Instant access to the following books: 5th edition 4th edition Digestive Tumours Eye Tumours Breast Tumours Skin Tumours Soft Tissue and Bone Endocrine Tumours Head and Neck Tumours Central Nervous System - update Special subscription rate of 100 Euros This new, easy to use resource provides: ▪ Interactive database ▪ Access to whole slide images ▪ Ability to search for information through all the books ▪ Easy access to reference information ▪ Quick access to many, soon to be all, of the books in the series WHO Classification of Tumours ~ ‘Blue Books’ • Essential tool for standardising diagnostic practice. • Allows translation of cancer research into clinical utility. • Diagnostic criteria and standards are underpinned by evidence evaluated and debated by experts in the field. • About 200 authors and editors participate in each book. Foreword, Dr Ian Cree, Breast blue book 2019 WHO Classification of Tumours ~ ‘Blue Books’ ▪ Localisation • Tumour types common to ▪ Clinical features multiple systems are ▪ Epidemiology described together ~ ▪ Aetiology haematolymphoid, ▪ Pathogenesis mesenchymal tumours, ▪ Macroscopic appearance genetic tumour syndromes. ▪ Histopathology • Benign to malignant lesions. ▪ Cytology ▪ Diagnostic molecular • Systematic approach with pathology tumours described in a ▪ Essential and desirable uniform manner. diagnostic criteria • Standardised modular ▪ Staging arrangement. ▪ Prognosis & prediction Foreword, Dr Ian Cree, Breast blue book 2019 WHO Classification of Breast Tumours 2019 • 2nd volume of the WHO 5th series of tumour classifications • Led by Dr Ian Cree, Head WHO Classification of Tumours Group, IARC • Standing Editorial Board • Expert Editorial Board • Includes surgeon, radiologist • Contributors ~ 154 • Website ~ https://tumourclassification.iarc.who.int Countries No. of Contributors Australia 9 Austria 2 Belgium 6 Brazil 4 Canada 6 China 6 France 3 Germany 5 Hungary 2 Italy 5 Japan 14 Lebanon 1 Netherlands 8 Portugal 2 Qatar 1 Republic of Korea 1 Singapore 5 Spain 3 Switzerland 2 United Kingdom 14 USA 55 Total: 154 Houston Texas USA WHO breast tumour classification 2019 ~ table of contents I ▪ Introduction to tumours of the breast ▪ Epithelial tumours of the breast • Benign epithelial proliferations and precursors • Usual ductal hyperplasia • Columnar cell lesions including flat epithelial atypia • Atypical ductal hyperplasia • Adenosis and benign sclerosing lesions • Sclerosing adenosis • Apocrine adenosis and adenoma • Microglandular adenosis • Radial scar/complex sclerosing lesion • Adenomas • Tubular adenoma • Lactating adenoma • Ductal adenoma • Epithelial-myoepithelial tumours • Pleomorphic adenoma • Adenomyoepithelioma • Malignant adenomyoepithelioma WHO breast tumour classification 2019 ~ table of contents II ▪ Epithelial tumours of the breast (continued) • Papillary neoplasms • Intraductal papilloma • Papillary ductal carcinoma in situ • Encapsulated papillary carcinoma • Solid papillary carcinoma (in situ and invasive) • Invasive papillary carcinoma ▪ Invasive breast carcinoma NST • Non-invasive lobular neoplasia ▪ Microinvasive carcinoma • Atypical lobular hyperplasia ▪ Invasive lobular carcinoma ▪ Tubular carcinoma • Lobular carcinoma in situ ▪ Cribriform carcinoma • Ductal carcinoma in situ ▪ Mucinous carcinoma • Invasive breast carcinoma ▪ Mucinous cystadenocarcinoma ▪ Invasive micropapillary carcinoma ▪ Carcinoma with apocrine differentiation ▪ Metaplastic carcinoma WHO breast tumour classification 2019 ~ table of contents III ▪ Epithelial tumours of the breast (continued) • Rare and salivary gland-type tumours ▪ Acinic cell carcinoma ▪ Adenoid cystic carcinoma ▪ Secretory carcinoma ▪ Mucoepidermoid carcinoma ▪ Polymorphous adenocarcinoma ▪ Tall cell carcinoma with reversed polarity • Neuroendocrine neoplasms ▪ Neuroendocrine tumour ▪ Neuroendocrine carcinoma WHO breast tumour classification 2019 ~ table of contents IV ▪ Fibroepithelial tumours and hamartomas of the breast • Hamartoma • Fibroadenoma • Phyllodes tumour ▪ Tumours of the nipple • Syringomatous tumour • Nipple adenoma • Paget disease of the breast WHO breast tumour classification 2019 ~ table of contents V Mesenchymal tumours of the breast ▪ Vascular tumours ▪ Peripheral nerve sheath tumours • Haemangioma • Schwannoma • Angiomatosis • Neurofibroma • Atypical vascular lesions • Granular cell tumour ▪ • Postradiation angiosarcoma Smooth muscle tumours • of the breast Leiomyoma • Leiomyosarcoma • Primary angiosarcoma of the ▪ Adipocytic tumours breast • Lipoma ▪ Fibroblastic and • Angiolipoma myofibroblastic tumours • Liposarcoma • Nodular fasciitis ▪ Other mesenchymal tumours and • Myofibroblastoma tumour-like conditions • Pseudoangiomatous stromal • Desmoid fibromatosis hyperplasia • Inflammatory myofibroblastic tumour WHO breast tumour classification 2019 ~ table of contents VI ▪ Haematolymphoid tumours of the breast • Lymphoma • Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) • Follicular lymphoma • Diffuse large B-cell lymphoma • Burkitt lymphoma • Breast implant-associated anaplastic large cell lymphoma ▪ Tumours of the male breast • Gynaecomastia • Carcinoma in situ • Invasive carcinoma ▪ Metastases to the breast WHO breast tumour classification 2019 ~ table of contents VII ▪ Genetic tumour syndromes of the breast • BRCA1/2-associated hereditary breast and ovarian cancer syndrome • Cowden syndrome • Ataxia-telangiectasia • Li-Fraumeni syndrome, TP53-associated • Li-Fraumeni syndrome, CHEK2-associated • CDH1-associated breast cancer • PALB2-associated cancers • Peutz-Jeghers syndrome • Neurofibromatosis type 1 • Polygenic component of breast cancer susceptibility Scope ▪ Invasive carcinoma • Mitotic count per mm2 • Carcinoma with medullary features • Invasive carcinoma NST with basal-like and medullary features • Stromal response & tumour microenvironment • Rare cancers re-allocated ▪ Neuroendocrine tumours ▪ Fibroepithelial tumours ▪ New entities Invasive carcinoma Microscope field diameter and corresponding field area for mitotic count scores Mitotic count • Conversion of mitotic count from the traditional denominator of 10 high-power fields to a defined area expressed in mm2. • This serves to standardize the true area over which mitoses are enumerated, because different microscopes have high-power fields of different sizes. • Also helpful for reporting using digital systems. • Facilitates future AI models of mitotic counting. Mitotic count • Challenges in conversion! • x mitoses/10hpf ≠ x mitoses/mm2. • If the microscope field diameter (HPF) is 0.5mm ~ • If the microscope field diameter (HPF) is 0.6mm ~ Field diameter Field area Area of 10 HPF Mitotic count Mitotic count of HPF (mm) (mm2) (mm2) /10HPF /mm2 0.5 0.196 1.96 7 3.57 0.6 0.283 2.83 10 3.53 “Medullary carcinoma” ▪ Well circumscribed tumour. ▪ Histologic criteria: • Syncytial growth pattern (> 75%). • Absence of glandular structures. • Diffuse lymphoplasmacytic infiltrate, moderate to marked. • Nuclear pleomorphism, moderate to marked. • Complete histological circumscription. (syncytial growth pattern plus 2 or 3 other criteria: atypical medullary carcinoma) Poor interobserver reproducibility Carcinoma with medullary features ~ WHO 2019 approach ▪ 2012 ~ medullary carcinoma, atypical medullary carcinoma and invasive carcinoma no special type (NST) with medullary features were grouped together under ‘carcinomas with medullary features’, in recognition of their common characteristics of an immune enriched microenvironment, basal-like expression and occasional association with BRCA1 mutations. ▪ 2019 ~ these tumours are subsumed as a combined morphologic subset under ‘invasive carcinoma NST with medullary pattern’, regarding them as part of the spectrum of TIL-rich breast cancers with basal-like molecular profiles. Invasive carcinoma NST with medullary pattern Invasive carcinoma NST with medullary pattern Stromal microenvironment ~ response patterns ▪ Cellular fibroblastic proliferation. ▪ Scant connective tissue. ▪ Marked hyalinization. ▪ Foci of elastosis. ▪ Fibrotic focus ~ • Area of exaggerated reactive stromal formation larger than 1mm within the tumour with or without coagulative necrosis • More aggressive behaviour ▪ Tumour infiltrating lymphocytes (TILs). ▪ Immune infiltrate in tumours – mononuclear lymphoid cells infiltrating the tumour and its stroma, reflecting the host immune response against tumour cells. ▪ High numberTumour of TILsinfiltrating associated with improved lymphocytesoutcome. ~ ▪ High number of TILs associated with better response to neoadjuvant therapy in triple negative and HER2 positive breast cancer. Scoring of TILs in invasive breast cancer • Use H&E sections, with evaluation at 200x (20x ocular, 10x eyepiece) or 400x (40x ocular, 10x eyepiece) microscope magnification. • Score TILs in the stroma between areas of carcinoma. • All mononuclear cells (lymphocytes and plasma cells) are scored. • Stromal TILs scored as a % of stromal areas alone. • Peri-tumoural follicular aggregates and tertiary lymphoid structures should not be included in the assessment. • If TILs are heterogeneously
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