Breast Pathology. Terminal Duct Lobular Unit (TDLU) 1/20/15. Normal breast anatomy. Site and disease associakon
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1 Breast Pathology Normal breast anatomy Modified skin appendage terminal duct lobular unit (TDLU) 2 cell types line TDLU Breast stroma - 2 types Mark Fons, DO mfons@iuhealth.org Terminal Duct Lobular Unit (TDLU) Site and disease associakon Post-pubertal female breast TDLU >>male or pre-pubertal female Young women Radiodense, Predominance fibrous interlobular stroma Menstrual Cycle Pregnancy Branched ducts Larger lobules Postpartum/Lactation Senescence: Colostrum (high protein) à Milk (higher Lobular atrophy and Fatty replacement fat and calories) over 10 days. Increased radiolucency Maternal antibodies (IgA) 1
2 Milk Line Remnants Axillary fold to perineum Supranumery nipples Disorders of Development Clinical presentakon of Breast disease Accessory Axillary Breast Tissue Congenital Nipple Inversion (disknguish from acquired inversion cancer) Common Causes of Mass Lesions by Age Group Age Group Most Common Lesion Fibroadenoma Fibrocystic change > cancer >50 Cancer till proven otherwise Pregnant/Lactating Lactating adenoma > cyst> mastitis > cancer Diagnos:c Modali:es: Evalua:on of Breast Masses Self examinakon Radiologic Imaging Mammography Ultrasound MRI Tissue diagnosis Core needle biopsy Excision Mammogram Screening y: annual/ biannual >50 y: annual 1st degree relakve : 10 y prior Ultrasound Suspicious Findings: Density or MicrocalcificaKons Younger women usually clinically benign lesion 2
3 MRI Core Needle Biopsy Pre- operakve evaluakon of malignant disease. Eval tumor response to radiakon therapy or chemotherapy Core needle biopsy Excision - Lumpectomy Benign Breast - Inflammatory Acute maskks Periductal MasKKs Mammary duct ectasia Fat necrosis Incidence: LactaKon Clinical: Erythema, Pain, Fever Causes: Staph. aureus > Streptococci Therapy: AnKbioKcs, expression of milk Acute Mas::s DDx Inflam carcinoma 3
4 Acute Mas::s Periductal Mas::s (Subareolar abcess) Clinical: Pain, erythema, subareolar mass Cause: 90% smokers Mammary duct ectasia (plasma cell mas::s) Mammary duct ectasia (plasma cell mas::s) Incidence: y, mulkparous Clinical: Mass- like Thick secrekons, Lymphadenopathy Fat necrosis Fat Necrosis Defini:on: Nodular dead adipose Incidence: Prior trauma/ surgery Clinical: Painless palpable mass 4
5 "Benign" Breast Hematoxylon Stromal lesions/tumors Fibroadenoma Phylloides tumor Low- grade High grade Epithelial lesions Nonprolifera:ve Breast Changes (Fibrocys:c) Prolifera:ve Breast disease without atypia Prolifera:ve Breast disease with atypia Nonproliferat ive No atypia with atypia Risks for Breast cancer Disease Risk Ratio Fibroadenoma Fibrosis Cysts Apocrine metaplasia Papilloma Sclerosing adenosis Usual ductal hyperplasia Atypical Ductal Hyperplasia (ADH) Atypical Lobular Hyperplasia (ALH) No increased risk 1.5-2x 4-5x Ductal Carcinoma In-Situ (DCIS) Lobular Carcinoma In-Situ (LCIS) 8-10x Fibroadenoma Incidence: Clinical: 3rd decade Well- circumscribed Most common tumor Mobile young adults Mostly painless Fibroadenoma Phylloides tumor Incidence y, LaKn 3-4x incidence Clinical Rapid growth Other info <1% of breast tumors 15% l 5
6 Phylloides tumor Pseudoangiomatous stromal hyperplasia (PASH) Clinical: Benign, incidental, nodule- like Pseudoangiomatous stromal hyperplasia (PASH) PASH Inset:Angiosarcoma Non-proliferative Breast Changes (Fibrocystic Changes) Most common breast lesion Premenopausal Pain from swelling Ked to menstrual cycle Nipple discharge Lumpy bumpy No cancer risk Radiology Non-proliferative Breast Changes (Fibrocystic Changes) multiple ill-defined densities usually bilaterally, no calcifications Apocrine Metaplasia with microcalcifications 6
7 Nonproliferat ive No atypia with atypia Risks for Breast cancer Disease Risk Ratio Fibroadenoma Fibrosis Cysts Apocrine metaplasia Papilloma Sclerosing adenosis Usual ductal hyperplasia Atypical Ductal Hyperplasia (ADH) Atypical Lobular Hyperplasia (ALH) No increased risk 1.5-2x 4-5x Ductal Carcinoma In-Situ (DCIS) Lobular Carcinoma In-Situ (LCIS) 8-10x Clinical: Prolif Breast Disease W/O Atypia Intraductal papilloma Bloody, nipple discharge Radiology: densikes, calcificakons Intraductal Papilloma PBD Without Atypia: Sclerosing Adenosis PBD Without Atypia: Usual ductal hyperplasia Nonproliferat ive No atypia Risks for Breast cancer Disease Risk Ratio Fibroadenoma Fibrosis Cysts Apocrine metaplasia Papilloma Sclerosing adenosis Usual ductal hyperplasia No increased risk 1.5-2x with atypia Atypical Ductal Hyperplasia (ADH) Atypical Lobular Hyperplasia (ALH) 4-5x Ductal Carcinoma In-Situ (DCIS) Lobular Carcinoma In-Situ (LCIS) 8-10x 7
8 Prolifera:ve Breast Disease with Atypia ADH: Ofen associated with ductal carcinoma in- situ ALH Atypical ductal hyperplasia - ADH Malignant Breast Tumors Carcinoma (95%) In- situ Invasive 75%, ductal adenocarcinomas GeneKc subclassificakons Other histologic subtypes Diagnosis of Neoplasms Benign/Malignant? Histologic Classification Grading Staging Prognostic markers Genetics subtype 8
9 Hereditary Breast Carcinoma Gene Locus Assoc cancers Function Comment BRCA1 17q21 Breast Ovarian Male breast BRCA2 13q12 Same as above Same Tumor suppressor, dsdna repair 50% hereditary cancers. 2% of breast cancers Usually basal-like (Triple neg). More common: medullary and poorly differentiated carcinoma Majority have both breast and ovarian carcinoma 32% hereditary breast cancers 1% of breast cancers 14% both breast and ovarian carcinoma Male breast cancer Familial cancer syndromes Tumor suppressors p53 17p13 Li-Fraumeni syndrome As above and + cell cycle + apoptosis Most common mutation in sporadic cancer Carcinoma progression Nonproliferat ive No atypia with atypia Risks for Breast cancer Disease Risk Ratio Fibroadenoma Fibrosis Cysts Apocrine metaplasia Papilloma Sclerosing adenosis Usual ductal hyperplasia Atypical Ductal Hyperplasia (ADH) Atypical Lobular Hyperplasia (ALH) No increased risk 1.5-2x 4-5x Ductal Carcinoma In-Situ (DCIS) Lobular Carcinoma In-Situ (LCIS) 8-10x Ductal Carcinoma in Situ (DCIS) Radiology: Linear/branching calcificakons Screening, increased dx 5% - 30% Therapy: Hormone, RadiaKon, Surgery 9
10 DCIS DCIS Comedo- type P63 IHC Cribriform DCIS Solid DCIS (Noncomedo) Papillary and Micropapillary DCIS (Noncomedo) Paget s disease of the breast/nipple (DCIS) DCIS- Paget s Disease Microscopic Findings 10
11 Lobular Carcinoma In Situ (LCIS) LCIS Invasive ductal carcinoma NOS,NST (Not otherwise specified or No Special Type) Invasive ductal carcinoma NOS Incidence: 75% >50 y LifeKme risk is 1 in 8 Clinical: Palpable mass RetracKon of the nipple Prognosis 85%, 5 year survival Radiology: Mass with irregular borders, calcificakons Prognos:c Factors in Breast Cancer Stage (TNM) Size, lymph node involvement, distant metastasis Grade 3 queskons: Making ducts?, ugly nuclei?, mitoses? Histological type ductal, lobular, mucinous, metaplaskc others Hormone receptors TherapeuKc/prognosKc (theranoskc) markers Invasive ductal carcinoma NOS Microscopic Findings: Grade 1 Grade 2 Grade 3 11
12 TherapeuKc markers: Hormones Her2/neu Estrogen receptor (ER) Progesterone receptor (PR) Predict response to tamoxifine Chromosome 17q21; synonym: hegfr, ERbB- 2 Signaling pathways ackvated by HER2 receptor 30% breast cancer, Her2 amplified Hercep:n (Trastuzumab) ankbody inackvates HER2 protein Her2/neu - methods GeneKc profile Molecular/ genekc subtypes Type ER Her2 Cells Other Basal-like - - Her Luminal A + - Genes similar to ovarian serous carcinoma. 20% Triple negative Many BRCA1 Medullary and Metaplastic Poorly differentiated 10% Herceptin responsive, aggressive, poor differentiated, brain mets Genes similar to lumen cells 50% in this group, ductal/lobular Tamoxifen responsive Luminal B + + Genes similar to lumen cells 20% Triple positive Standard chemotx Cells of origin for the intrinsic subtypes of breast cancer Expression panerns: luminal, mesenchymal /claudin- low, and basal- like. Gradients of expression (not 'on' or 'off ). Molecular cancer groups correlate prognosis and therapy response. 12
13 Invasive Lobular Carcinoma Medullary Carcinoma Ofen BRCA1 gene + All triple negakve Basal- type Bener prognosis than ductal Mucinous (Colloid) Carcinoma Excellent prognosis Tubular Carcinoma Excellent prognosis Comma shaped groups, low nuclear grade Metaplas:c Carcinoma More aggressive than invasive ductal NOS Triple negakve Basal- type Myxoid areas, mesenchymal elements Papillary carcinoma of breast Micro Papillary structures with vascular cores 13
14 Inflammatory Carcinoma Clinical diagnosis: Not histological subtype, skin with underlying carcinoma Bad prognosis Tumor plugging lympha:cs DDx: acute mas::s Angiosarcoma 3 seyngs Spontaneous Post radiakon :<0.5% risk post- radiakon treatment Stewart- Treves syndrome: Chronic lymphedema from lymph node disseckon Bad prognosis Male Breast - Gynecomas:a Clinical Breast enlargement Palpable subareolar mass Syndromes Klinefelter XXY Systemic disease (High estrogen) Cirrhosis Drugs Anabolic steroids Carcinoma Rare: 0.1% (vs 1 in 8 women) Associated with BRCA2 mutakons late stage Treatment Surgery Lumpectomy (conservakve) Mastectomy Lymph node disseckon, SenKnel Lymph nodes RadiaKon Systemic treatment Chemotherapy Hormonal therapy Neoadjuvant :Presurgical RadiaKon and Chemotherapy Treatment of high risk pakent (BRCA posikve) Bilateral prophylackc mastectomy (50-90% risk) Oopherectomy is opkonal (40% risk Ovarian cancer) ChemoprevenKon (Tamoxifen) Side effects Venous thromboembolism Increased risk endometrial cancer Cataracts 14
15 Axillary node disseckon Axillary lymph node status: important prognoskc factor Axillary lymph node disseckon Stage breast cancer Prevent regional recurrence of the disease. Risk of Lymphedema, risk of Stewart- Treves syndrome (angiosarcoma) SenKnel node biopsy (SLNB) 1- RadioacKve materail +/- blue dye injected near tumor. 2- Injected material is located visually and/or with Geiger 3- SenKnel node (first lymph node to take up the material) is removed and checked for cancer cells. Sufficient for staging breast cancer without signs of axillary metastasis.? 15
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