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Breast Pathology Lecture - 2013

Breast Pathology Lecture - 2013



Updated Breast Pathology Lecture to medical students.

Updated Breast Pathology Lecture to medical students.



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    Breast Pathology Lecture - 2013 Breast Pathology Lecture - 2013 Presentation Transcript

    • Knowledge is a burden, If it robs you of innocence, If it makes you feel you are special, If it gives you an idea you are wise, If it is not integrated into life, If it does not bring you joy, If it does not set you free. Sri Sri Ravi Shankar, Humanitarian and founder of the Art of Living Foundation, India.
    • CPC 4.5 – 42y Woman, sore R. breast. Mrs JM is a 45y old woman, primary school teacher, living in Weipa.             “odd change in my left breast when I was showering last week” Duration. Noticed it 8 days ago What? “My left breast feels a bit thicker – points to upper outer quad* Pain No, Nipple discharge: No, Trauma to breast: No Menstrual cycle: regular, Mastalgia: not usually LMP: about 4/52 ago; K due now. Age of menarche: 13 years*, Parity: none* (failed IVF / infertility*) Appetite, Weight : stable* was on COCP* ages 17yrs – 30 yrs. Cervical smear: Never* Menarche aged 13yrs* Has never had mammogram/breast USS* ‘I check regularly’ *
    • CPC 4.5- Examination Key .. ? Fibrocystic o R breast NAD, L breast firm thickening ? upper Tumor outer axillary tail ?; no discrete mass ? no skin Cancer tethering ? / changes; no nipple inversion ?; no areola changes ?, no axillary or supracla. LN. No Cancer Paget’s nipple discharge(blood/pus) ? Cancer  What Differentials: Papilloma  Benign proliferations, Breast malignancy Duct ectasia  What further investigations?  Mammogram, FNAB, CT Scan, PET Scan, Biopsy + immunochemistry (HER2) ? Labs: ER PR HER2 BRC
    • CPC 4.5- Examination      Mammogram – solid* non mobile* irregular* mass lying at the 10 o’clock position of the L breast. Mass has prominent radiating spicules*; 2 x small calcifications* within the mass. Overall mass 1x 1.5x 1cm. US guided FNAB: High grade infiltrating ductal carcinoma ? CT scan: no sign metastatic disease in liver or lung Bone scan: no sign of metastases. Immunochemistry : ER: ++ PR: neg HER2: +++.. ? ? ? (? Sub types, Luminal B)
    • CPC 4.5 – 42y Woman, sore R. breast. 2013 Term 4 CPC 5 Title: Breast Cancer System: Breast Aim: Clinical, Pathology & population study of patients breast disease 1. Demonstrate competency in history taking & the clinical examination of patients with breast disease. 2. Describe the first line investigation and management of patients with breast disease or symptoms. Learning outcomes The student will be 3. Describe the Pathophysiology of breast disease (benign and malignant) able to 4. Outline the basic sciences relating to function of the breasts. 5. Describe the Epidemiology and aetiology of breast disease in Australia and world wide. 6. Illustrate the advantages and disadvantages of the breast screening program in Australia
    • CPC 4.5- Core Learning Issues Pathology Major CLI: • • • • • • Pathology of Breast – overview, classification & common dis.. Breast Lumps - Differential diagnosis. Trauma, infections & Inflam. – Mastitis, fat necrosis, abscess. Hyperplasia – Fibrocystic disease Tumours – Benign – Fibroadenoma, giant fibroadenoma. Breast cancer – etiology, pathogenesis, morphology & complications, Laboratory diagnosis, including markers. Pathology Minor CLI: • • • • Duct ectasia, Breast Cysts. Paget’s disease. Gynecomastia & male breast disorders.
    • Case studies:        22year female, noticed small mobile round lump in her right breast, lower inner quadrant. 39year female, multiple small lumps, irregular, firm, tender more during mid cycle. 41year female, two left axillary LN, no pain, no breast mass. mild loss of weight. 34year female, diffuse firm left breast. FNAC reports abnormal cells. No LN. 39year female, painful lump, chronic pus discharge from nipple. 71year old female. Rough, red scaling pruritic patch on left nipple and areola. 26y nurse, right breast lump 5m, firm irregular, 6cm firm, fixed lump. • Fibroadenoma • Fibrocystic dis • Ca breast. • DCIS • Duct ectasia • Paget’s dis • BRCA Ca.
    • Self assessment: Clinical features of benign, malignant & reactive…  Breast cancer screening guidelines.  Hyperplasia / tumour features.  Familial vs Non familial breast Ca features.  Screening Mammogram – policy, procedure & interpretation.  Fibrocystic disease, fibroadenoma & cancer.  Breast cancer common types & features (gross, microscopy, complications etc.)  Duct carcinoma, lobular carcinoma, other types.  BRCA testing in familial breast ca. 
    • “Strength does not come from winning, Struggles & Hardship develop strength. - - Arnold Schwarzenegger Bodybuilder, Actor & Leader.
    • Pathology of Breast Dr. Venkatesh M. Shashidhar Associate Prof. & Head of Pathology
    • CPC- 44 – Core learning Issues  Major CLI:      Pathology of breast diseases – over view Congenital, Inflammatory & Neoplastic disorders. Breast Lumps – Hyperplasia – Fibrocystic disease. Benign neoplasms: Fibroadenoma, Duct papilloma & Breast cancer – Ductal Carcinoma & DCIS. Minor CLI:      Cong: Hypertrophy, atrophy, accessory, supernumerary.. Mastitis (acute/chronic), Breast trauma, fat necrosis. Phyllodes tumor, other carcinoma (Lobular etc) Duct ectasia. Paget’s disease.
    • Introduction: Anatomy Modified sweat glands. Lobes and lobules of gland in fat tissue stroma. Ducts emerge from acini of glands Smaller ducts join to form lactiferous ducts Lactiferous ducts merge just beneath the nipple to form a lactiferous sinus. Then individually open on nipple
    • Anatomy T4 level
    • Breast Physiology: Male Female
    • Normal Breast – glands & stroma Dense stroma Loose stroma Acinus
    • Normal Breast – glands & stroma Loose stroma Acinus Dense stroma
    • Breast – Acini (SEM)
    • Age changes in breast: Puberty Fibrous  Adult (Lactating) Fibro-Fatty  Menopause Fat
    • Disorders of Breast:  Congenital    Inflammatory      Acute: lactational* / Chronic Mastitis Trauma – Traumatic Fat necrosis Duct ectasia – chronic, discharge, sinus, Galactocele Proliferative Conditions    Aplasia : turners / Juvenile hypertrophy Accessory/ectopic breasts – along milk line Fibrocystic disease – common cause of lumps Cysts, Adenosis, Metaplasia & mixed. Neoplastic   Benign – Fibroadenoma, duct papilloma Malignant – Ductal Carcinoma & DCIS – several types.
    • Disorders of Breast:
    • Gynecomastia:        Breast enlargement in men. Estrogen excess – Klinefelter’s, Hyperthyroidism, pitu itary & adrenal tumors, testicular failure, hormonal. Liver failure, cirrhosis Lung, Testicular Cancer diethylstilbestrol therapy for prostatic carcinoma. Drugs (Spironolactone, H2 antagonists, Neuroactive agents). Microscopy – only duct & stromal hyperplasia. (no acini)
    • Acute Mastitis:  Acute Mastitis:   Non Lactational (central, periductal, rare) Lactational (periphery, common)      First few weeks after delivery. Crack in the nipple – entry point. Staph. aureus, Strep. pyogenes. Localized inflammation, Swelling erythema & pus. Chronic Mastitis:    Granulomatous (TB, Fungal, Silicone etc.) Traumatic fat necrosis: Chronic granuloma, foam macrophages, radial scar – dd Ca. Diabetic mastopathy: DM1, rubbery lymphocytic.
    • Duct Ectasia: Mimics Ca.     >50y, multiparous. Periareolar mass with white, cheesy nipple discharge. Duct obstruction/destruction, inflammation, dilation, fibrosis with fat globules & foamy macrophages in lumen. Recurrent abscess / fistula. Scarring with nipple inversion may mimic Ca.
    • Lump in Breast: Diagnosis & Features Clinical presentation <25 years 25-35 years 35-55 years >55 years Mobile lump (single) Fibroadenoma Fibroadenoma Fibroadenoma Phyllodes tumour Phyllodes tumour ill-defined lump/s or lumpy areas – cyclic pain. Uncommon Fibrocystic change Uncommon Firm lump tethering (fixed) Uncommon Fibrocystic change Sclerosing adenosis Carcinoma* Carcinoma Carcinoma Fat necrosis Nipple discharge Clear/pus Uncommon Uncommon Duct ectasia Duct ectasia Bloody Uncommon Uncommon Duct papilloma Duct papilloma In situ carcinoma Paget's disease In situ carcinoma Paget's disease Nipple adenoma Nipple adenoma Nipple ulceration, eczema Nipple adenoma Nipple adenoma
    • Fibrocystic Disease/change:      Pathology: Harmone induced acinar hyperplasia. Oestrogens* Clinical: Commonest (40%) cause of lumps in 20-40y. Irregular induration/ lumps. Cyclic pain/discomfort. Gross: Grey white scar tissue with cysts. Micro: Fibrosis, cysts, hyperplastic glands. Pathogenesis: Hyperplasia of glands and stroma  DCIS  Carcinoma.
    • Fibrocystic Disease
    • FibroCystic Disease: types Non prol. / low grade Prol. / High grade A. Simple Fibrocystic change. B. Lobular hyperplaisa without atypica (adenosis) C,D - Ductal hyperplasia without atypia (E. with atypia - cribriform) F. Lobular hyperplasia.
    • FCD: Cysts, Fibrosis & Proliferation
    • FCD + Ductal Hyperplasia* Hyperplasia may progress to DCIS (Duct Carcinoma In-Situ). Progress to duct carcinoma.
    • FCD: Ep. Hyperpl. - Sclerosing Adenosis* Small duct proliferation. Clinical & biopsy mimics carcinoma.
    • Fibrocystic Disease-Blue dome cyst When single large cyst - blue
    • Education must instill the fundamental human values; it must broaden the vision to include the entire world and all mankind. Education must equip man to live happily. -- Satya Sai Baba
    • Breast Neoplasms:  Benign: (round, smooth, soft, mobile)  Fibroadenoma  Duct Papilloma  Others – rare.  Malignant: (irregular, rough, hard, fixed)  Ductal carcinoma – classic.  Lobular carcinoma  Others - rare Fibrocystic Disease (Not a neoplasm)
    • Fibroadenoma Types Solitary Few (< 5 / breast ) Multiple (> 5 / breast ) Giant (> 4 / 5 cms) & Juvenile Low grade Benign Natural history Majority remain small & static 50% involute spontaneously No future risk of malignancy High grade
    • Fibroadenoma Pathology: Benign tumor of acini tissue (gland & stroma) Clinical: Well demarcated, mobile, round/nod (mouse) Gross: Capsulated, firm grey, nodular tumour, cysts+/-. Micro: Compressed slit like ducts/glands in cellular stroma.
    • Mammogram - Benign
    • Fibroadenoma Note: well demarcated, capsulated, nodular tumour
    • Fibroadenoma
    • Fibroadenoma In P P In P C = capsule; In = intracanicular pattern; P = pericanicular pattern
    • Fibroadenoma Summary:  Small discrete mobile.  Stromal neoplasm with reactive glands.  No malignant potential.  Regress / calcify in menopause.  Increase in pregnancy.
    • Giant Fibroadenoma     Pathology: Benign(young) to malignant(adult) tumor of acinii. Clinical: young (Low grade) /adult (high grade)*, unilateral macromastia, recurrent, metastasis 15%. Gross: Large 10-15cm . Giant. With linear “leaf-like” clefts and slits – Giant/Juvenile in young - Phyllodes tumor in adult. Micro: Both stroma & glands are hypercellular & pleomorphic. glands show branching..
    • Fibroadenoma Flat slit glands, fibrous stroma, Benign. – Giant Fibroadenoma Branching leaf like glands, Cellular stroma Benign 85%  malignant 15%.
    • Intraductal papilloma     Clinical: Middle age, Bloody discharge, sub areolar lump. Duct wall Gross: Solitary, Intra-ductal papillary Proliferation. Micro/Path: Benign papillary proliferation of lactiferous duct epithelium. Stalk & papillae Prognosis: recurrent, but no risk of malignancy. (rare)
    • Education has two important characteristics. One is learning of a subject & skill. The other is the personality to apply this knowledge to the benefit of community. --Baba One without the other is either useless or dangerous…. ! Knowledge, Skill & Attitude * JCU graduate attributes..
    • Breast Carcinoma – Aus. stat.  The most common cancer among Australian women (also in aboriginals). (20%)  UK 1 in 10 women, 1 in 8 in US, 1 in 9 Aus.  One in nine women before the age of 85.  28% of all cancer diagnoses in 2006.  Increased from 5,289 in 1982 to 12,614 in 2006  Commonest cause of death in young < 55y  Rare before age 30. (30-50 genetic, >50 sporadic)  Much less incidence in Asia, Japan.  Majority of cancers arise in the ducts.  Survival is improving with therapy. (96% 5y – 2006)
    • Etiology of Breast Carcinoma: • HER2/NEU • RAS & MYC • BRC A1, A2. Environment Hormone • Family history – First degree relative. • Premenopausal & bilateral. • Early menarche/Late menopause. • • • • Genetics • Estrogen therapy. • Alcohol, Smoking. • High fat diet, Obesity. Overexposure to oestrogens and underexposure to progesterone No definite relationship to oral contraceptives Some tumours contain hormone receptors and respond to hormone manipulation No good evidence for viral involvement
    • Pathogenesis of Breast Cancer. Duct Ca. in-Situ DCIS Hyperplasia  Dysplasia  DCIS  Carcinoma Fibrocystic change  Cancer
    • Pathogenesis:
    • Ductal Carcinoma in Situ (DCIS)  Dysplastic cells filling ducts with Ca+, no invasion. Pre-cancer state.  Increasing incidence of DCIS due to mammographic screening. (diffuse irregular firm/lumpy areas)  Spreads throughout ductal system to produce extensive lesions.  Many types: solid cribriform, papillary, and micropapilary, comedo type or mixed pattern. (dysplasia: low – high grade)  Progress to invasive carcinoma.
    • Ductal Carcinoma in Situ, DCIS
    • DCIS – Comedo type (high grade) DCIS Central necrosis (comedo)
    • Myoepithelial Cells in DCIS (imunoperoxidase stain note intact BM & ME cells) DCIS All ducts, ductules and acini are separated from the interlobular and intralobular connective tissue (stroma) by a basement membrane & Myoepithelial cells.
    • DCIS- High grade
    • Ca Breast: Histological Types Histologic Type Freq. (UK) InfiltratingDuct Ca 63.6 (75) Lobular Carcinoma 5.9 (10) InfiltratingDuctal & Lobular Ca 1.6 Medullary Carcinoma 2.8 (3) Mucinous (colloid) Carcinoma 2.1 (3) Comedocarcinoma 1.4 Carcinoma-In-Situ 5%
    • Prognostic / Genetic Classification: (new) 1. Luminal A – 50% of NST. ER+, HER2 –ve. Low grade, slow L growing, post menopausal, respond to harmone therapy. – Better prognosis. 2. Luminal B – 20% of NST. ER+, HER2/neu +ve. (triple positive ca.) high grade, respond to chemo. 3. Basal like – (Triple neg) 15% of NST. ER-, HER2/neu – H ve, BRCA1+, young. Poor prog. 4. HER2 positive – 10% ER- HER2 +, high grade, poor prognosis, early brain mets. (Trastuzumab) HER - Human Epidermal Growth factor Receptor  Growth. ER - Estrogen receptor  function. ER is good & HER is bad…!
    • Breast Ca-Clinical Lymphnode mets. Skin Puckering Nipple retraction
    • Breast Carcinoma      Irregular, hard, grit ty Painless nodule. Tethering/puckerin gfixation Nipple retraction Oedema Lymphnodes
    • Infiltrating Duct Carcinoma: Breast Ca. (NOS or Classic or typical “Schirrhous carcinoma”) Note: Fibrotic tumor, radiating fibrous scar around resulting in nipple retraction & skin pulling (puckering)
    • Mammogram - Ca
    • Breast Carcinoma Inflammatory / medullary    Inflamed, bulging without nipple/skin retraction. Uncommon. High grade / medullary type (HER2 & BCRA1)
    • Breast Carcinoma - Schirrous
    • Infiltrating Duct Carcinoma: small hard
    • Typical Invasive Ductal Carcinoma / Duct Ca (NOS) Ca-tubules collagen stroma
    • DCIS component within Duct Ca (NOS) DCIS
    • Infiltrating Duct Carcinoma
    • Breast Ca. Lymphedema Pathogenesis of Peu-de Orange in High grade Ca. Tumor in lymph Vessel Tumour emboli within lymphatic vessels  obstruction  Lymphedema (also radiation induced lymphangitis can cause peu-de orange)
    • Medullary type (high grade): * note lymphocytes, no collagen/scar Expansile tum Ca. cells Lymphocytes
    • Lobular Carcinoma:       Multifocal, Bilateral. Small cells, uniform, no tubules. Target like growth around normal tubules. ‘Indian file (single cell lines) between collagen bundles. No tubule formation. Lobular Ca-in-situ(LCIS) E-cadherin –ve (unlike IDC) ER/PR neg, HER2/neu pos.
    • Spread of Breast Carcinoma:
    • Pagets Disease  Spread of Breast cancer cells to skin (areola) & resulting in Eczematous reaction. Ca. Cell Ca. Cells
    • Diagnosis: History First….!       Mammorgraphy Fine Needle Aspiration Biopsy Core/Needle Biopsy Excision Biopsy Ultrasound Special molecular tests on Biopsy:   Immunoperoxidase – HER2, ER & PR. Molecular techniques – Gene detection (BRCA). Triple Assessment  Clinical, Imaging & Biopsy
    • Breast clinic: incidence
    • Breast clinic: incidence
    • Mammorgram • Low radiation (0.1rad) • Light compression by plates to stabilize and spread its interior structures. • Detect Fibrosis & Calcifications <100 µm • Reveals a lump 1-2y before BSE. • Women >40y should have yearly* mammogram. • More for those at risk or symptoms.
    • Mammogram : Normal – 18y Normal 40y Carcinoma Dusty Ca+ Malignant Cancer
    • Breast Ca. screening: new research  Cochrane Summaries:  Research involving 600,000 women, results showed “for every 2000 women screened    one will avoid dying of breast cancer 10 healthy women will be treated unnecessarily. >200 experience distress due to false positive findings.
    • Breast Cytology - FNAB Benign Malignant
    • Tumor Markers in Breast Ca. ER: Estrogen Receptors. PR: Progesterone Receptors. HER2/neu: Human Epidermal growth factor Receptor 2 E-Cadherin: Cell adhesion protein. BRCA: Breast Carcinoma Antigen.
    • Immunoperoxidase stain: (ER, PR, HER, BCL, p53, E-Cad), Neg 1+ 2+ 3+
    • Nuclear ER positivity - 3+
    • Gene expressions portraits of breast carcinomas. (micro array) Identify new breast cancer subtypes (“luminal A,” “HER2/neu positive,” & “basallike”).
    • HER2 (Human Epidermal growth factor Receptor 2)  The HER2 proto-oncogene encodes a cell surface receptor that is over expressed in approximately 25%30% of breast cancers. (normally 2 copies).  HER2 positive breast cancers grow quickly and spread more than others. (poor prognosis)  HER2 testing (Immunohistochemistry/FISH) results are critical to ensuring that patients who may benefit from the anti-HER2 antibody therapy.  Trastuzumab (Herceptin®) is the first monoclonal antibody that targets the extra cellular domain of the HER2 protein, and inhibits growth of breast cancer cells that over express this protein.
    • BRCA1        (FISH Technique) 52% of genetic type (2% overall) Young age. Risk of Ca – 40-90% High grade, necrosis, inflam (.. Medullary) Triple –ve (ER,PR, HER2) F/H of ovarian, prostate, pancre as ca. Chromosome 17q        BRCA2 32% of genetic type (1% overall) Not specific. Risk of Ca 30-90% Low grade, NOS type. Scaring (..Schirrous) ER positive. F/H of male breast ca (ovary, prostate also) Chromosome 13q.
    • Progression of Breast Ca: (new)
    • Common Ca. Breast: NST / NOS / Schirrhous Ca / Infiltrating duct Ca. Mammogram: Stellate Lesion on Mammogram Gross: Hard irregular - Schirrhous Micro: Pleomorphic cells forming tubules in dense fibrous stroma.
    • Summary:  Anatomy & Physiology.  Congenital, Inflammatory & Neoplastic dis.  Fat Necrosis, Abscess, Duct ectasia.  Proliferative Disorders:   Fibrocystic Disease – hormonal, benign. Neoplastic Disorders    Benign – Fibroadenoma, papilloma Malignant – Invasive Duct Carcinoma, Lobular Carcinoma, DCIS – Ductal carcinoma in-situ.
    • Sign or symptom Pathological basis LUMP DIFFUSE Fibrosis, epithelial hyperplasia and cysts in fibrocystic change DISCRETE Neoplasm or solitary cyst MOBILE Benign neoplasm (usually fibroadenoma) TETHERED Invasive neoplasm (carcinoma) SKIN FEATURES OEDEMA (PEAU D'ORANGE) Impaired lymphatic drainage due to carcinoma PUCKERING AND TETHERING Invasion of skin by carcinoma ERYTHEMA Increased blood flow due to inflammation or tumour NIPPLE DISCHARGE Milky-pregnancy or prolactinoma White/green-duct ectasia Bloody-duct papilloma or carcinoma (rare) RETRACTION Tethering by invasive carcinoma ERYTHEMA AND SCALING Paget's disease of nipple (cancer) or eczema BREAST PAIN CYCLICAL Benign breast changes – fibrocystic change ON PALPATION Inflammatory lesion (e.g. mastitis) MICROCALCIFICATION invasive carcinoma (also in cysts, benign changes, DCIS) BONE PAIN OR FRACTURE Possibly due to metastatic breast carcinoma or associated with hypercalcemia
    • Confusion Distinction and explanation Fibroadenoma & Fibroadenosis Fibroadenoma is a localized circumscribed benign neoplasm comprising epithelial cells and specialised fibrous tissue. Fibroadenosis is an obsolete name for fibrocystic change, a diffuse hyperplastic lesion. Fibroadenoma & phyllodes tumour both comprise neoplastic epithelial and fibrous tissue components. However, in phyllodes tumours the fibrous tissue component is more cellular and abundant, and the lesion has less well defined margins; borderline and malignant variants occur. Ductal epithelial hyperplasia & ductalcarcinoma in situ Ductal epithelial hyperplasia is a benign proliferation of duct epithelium, whereas ductal carcinoma in situ has undergone neoplastic transformation, although it is not yet invasive. These lesions can have morphological similarities. A proportion share genetic alterations. Radial scar & complex sclerosing lesion Radial scars and complex sclerosing lesions differ only in size: the latter are >10 mm diameter. Both mimic carcinomas radiologically and histologically, but they are benign non-neoplastic lesions. Medullary carcinoma of the breast & of the thyroid The term medullary refers only to the soft consistency (resembling the medulla of the brain). There is no other relationship between these lesions. Paget's disease of the nipple & of bone Both lesions were described by Sir James Paget (1814-1899). There is no other relationship between these lesions.
    • Benign          Young <35y Multiple Painful No bleeding Soft, cystic, rubbery Regular, nodular Mobile No lymphnodes No weight loss. vs Malignant          Old >35y Single Painless Bleeding Hard gritty Irregular Fixed Lymphnodes Weight loss
    • What is this?  • • • • What is PET Scan? What contrast is used? What does it show? What are its Indications ? • • • • Positron Emission Tomography. Radiolabelled glucose by IV. High metabolic rate cells (cancer cells) 3D view of cancer spread over body.
    • Infections 2. NonLactational infections : Central  Usually due to Periductal mastitis  Affects younger women. Often smokers in the West  May present as : inflammation +/mass, abscess, mammary duct fistula  Aerobic + anaerobic organisms may be involved Treatment :  Antibiotics (E.G. Co amoxyclav etc) before pus formation  Abscess : Repeated aspiration / mini incision with topical anaesthetic cream ( I& D under GA occasionally)  MDF : Excision fistula + Total duct excision