Breast Pathology Flashcards
Clinical anatomy of the breast: main units, categories of disease based on region affected
Terminal ductal-lobular units
- origin of most malignant lesions
- 2 cell layers of inner epithelial and outer myoepithelial cells (structure lost in CA)
- most lesions affect inner epithelial layer
Other anatomy: large ducts (duct ectasia, papilloma, Paget), intralobular stroma (fibroadenoma, phyllodes tumour), interlobular stroma (lipoma, haemangioma, fat necrosis, angiosarcoma)
Diagnosis of Breast Disease
Triple Assessment
- clinical
- radiological –> MMG (look for speculated margin, distortion of adjacent tissue, calcification), USG (internal structures e.g. necrotic debris, cystic; vascularity - peripheral more metabolically active in tumours), MRI occasionally (dynamic contrast enhancement - tumour has higher blood flow and leaky vessels leading to faster uptake of contrast and faster washout - Type I-III: steady, plateau or washout)
- pathological (FNAC, core needle or excisional biopsy)
MMG for early detection of asymptomatic and non-palpable carcinoma before metastasis
Note: MRI may be oversensitive in metabolically active conditions e.g. inflammation
MMG not good in young women due to dense breasts
Differential Diagnoses of Breast lump, Mastalgia and Nipple discharge
Breast lump (usually already 2-3 cm large)
- fibrocystic changes
- fibroadenoma
- CA breast
Mastalgia
- cyclical: fibrocystic changes
- non-cyclical: fibroadenoma, sclerosing adenosis, trauma, ruptured cyst, acute mastitis
- extra-mammary
Nipple discharge
- milky = lactation
- serous = early pregnancy
- yellow serous = fibrocystic change
- purulent = acute mastitis
- green = ductal ectasia
- bright blood = large duct intraductal papilloma (single orifice), fibrocystic change (haemorrhagic), CA breast
Fibrocystic changes: epidemiology (2), risk of CA, pathophysiology (2), pathology (5)
Most common breast mass in women of reproductive age
Most common cause of breast pain
Non-proliferative disease with no increased risk of CA
Pathophysiology:
- exaggeration or distortion of cyclic breast changes related to menstrual cycle
- not related to use of OCP or HRT
Pathology:
- cysts, apocrine metaplasia , fibrosis, adenosis, calcifications
- cysts: filled with serous fluid or blood (blue dome cyst of bloodgood), lined by single layer of metaplasic apocrine cells (abundant oncocytic cytoplasm full of mitochondria - pink and granular)
- fibrosis: rupture of cysts leads to secretion of material into stroma –> trigger chronic inflammation, lymphocytic infiltrations and fibrosis
- calcification: of apocrine secretions in glandular lumen or stroma –> Ca phosphate seen on MMG, Ca oxalate not visible
- adenosis: glandular proliferation
Inflammatory Diseases of the Breast - Acute : pathophysiology (2), symptoms (3), complications (2), treatment (1)
Acute mastitis
- uncommon, always consider inflammatory CA
- due to post-partum nursing: damage to epithelium during breast-feeding –> risk of secondary infection through ascending infection by skin commensals esp S aureus
- can also be caused by inspissation of secretion in blocked ducts leading to dilation and infection
- redness, swelling and tenderness
- form lactational abscesses and tissue necrosis if untreated
- treat with antibiotics
Chronic inflammation of the Breast
Duct ectasia
- common in menopause
- duct dilatation with secretion (greenish brown nipple discharge)
- secretion inspissated, dried and then inflamed –> lymphocytes and plasma cells
- skin and nipple retraction (like cancer) but NO MALIGNANT RISK
Traumatic fat necrosis
- trauma cause disruption of fat leading to lipid leakage and hence acute inflammation around necrotic fat cells
- lymphocytic infiltrate and histiocytes with ingested fat cells (foam cells)
- MIMICS CA clinically and histologically – irregular firm lesion due to fibrosis and calcification of fats; painless; skin retraction
Idiopathic granulomatous mastitis
- rare, at reproductive age
- possible autoimmune cause, NOT TB RELATED
- prominent granuloma formation and giant cells
- not to be mistaken as TB since tx is entirely different - anti-TB vs steroids
Breast augmentation
- PAAG: direct injection into breast tissue causing inflammation (lymphocytes and fibrosis)
- Silicone: rupture of implant bag (foreign body type giant cells)
Epithelial Hyperplasia: cancer risk, treatment, pathology
Usual hyperplasia
- no increased cancer risk (1.5x?)
- no treatment required
- proliferating epithelium expanding duct lumen
- irregular peripheral lumens
- nuclear streaming, non-clonal cells
Atypical hyperplasia
- atypical ductal or lobular hyperplasia (+LCIS)
- not pre-malignant lesion but increases cancer risk (4x) and may be associated with low grade CA
- requires evaluation and excision
- ADH: cribriform pattern (lots of central and peripheral lumens); monoclonal uniform cells (rounded); Roman bridge (cells lined radially away from lumen, form sharply marginated spaces)
- ALH: solid distension of lobular spaces with no lumen
Sclerosing adenosis
- benign epithelial and myoepithelial proliferation in small ducts; very small (>1cm = complex sclerosing lesion - recall histology features x3)
- increased risk of CA
- MIMICS CA (hard irregular mass fixed to underlying tissue)
- enlarged, complex glands distorted by densely fibrotic stroma which compresses ducts to create appearance of infiltrating solid cords (as in CA)
Benign Tumours of the Breast
Very common
Fibroadenoma
- most common breast tumour in women <50
- RF: cyclosporine A
- “breast mice” - lumps not fixed to skin or underlying structure
- pathology: multi-lobular proliferation of stroma (and epithelial cells); loose expanded fibromyxoid stroma distorting epithelial cells into slit like structures
- firm nodule, uniform tan colour and some soft yellow specks
- well circumscribed, low cellularity
- “popcorn calcification” - may be seen as irregular large calcification on MMG
- never malignant, may not need excision
Phyllodes tumour
- bulky tumour with proliferation of stromal cells which outgrows epithelial cells to form bulbous nodules covered by epithelial cells
- leaf-like pattern
- high grade tumours may have scanty or absent epithelial cells forming a sarcomatous appearance
Intraductal Papilloma
- most common cause of blood nipple discharge in women <50
- pathology: solitary papillary growth (delicate branching growth with fibrovascular cores) of sub-areolar large duct, causing obstruction
- present as bloody nipple discharge (single orifice), sub-areolar nodule (<1cm)
- benign but may be complicated by other epithelial lesions that increase CA risk e.g. small focus of ADH
- treatment: microdochectomy (excision to decrease risk of CA)
Epithelial Hyperplasia and Benign tumours risk of malignancy
Non-malignant:
Usual Hyperplasia, Fibroadenoma, Phyllodes
Increased risk of malignancy:
Atypical hyperplasia, Sclerosing adenosis, Intraductal papilloma with other epithelial lesions, Phyllodes
Breast calcifications: 2 types, 2 mechanisms, Benign vs Malignant Morphology, Distribution and Timing
Ca phosphate and oxalate
Secretory vs Necrotic
Secretory = accumulation of excess secretions with sequestration and calcium deposits due to high Ca concentration
- in benign (e.g. fibrocystic change) and low grade malignant tumours –> can’t differentiate by MMG
Necrotic = tumour outgrows its blood supply leading to coagulative necrosis, change in pH and calcification
- in malignant tumours
Morphology:
- Benign - small, smooth contour, annular/ circular, tram track vascular calcifications, tea-cup sediment calcification (fibrocystic changes)
- Malignant - irregular, branching rod (necrotic calcification at central core of column of malignant cells in ductal system)
Distribution:
- benign - diffuse, bilateral
- malignant - segmental, wedge shaped
Time:
- benign - no change over time
- suspicious - interval changes over a short time
Malignant Breast Tumours: epidemiology, genetics (3), risk factors
1 in 12-16 women (lifetime risk)
Most common malignancy/ cause of mortality in young women
Genetics: 5-10% attributable to inherited AD genes in germline
- BRCA1/2 –> DNA repair gene, BRCA1 associated with triple negative breast cancer, BRCA2 associated with ER+ve or male cancer; variable penetrance; potential treatment: platinum based chemo, PARP inhibitors (inhibit alternate DNA repair)
- TP53 –> Li Fraumeni Syndrome
- PTEN (negative regulator for PI3K-AKT) –> Cowden Syndrome
Risk factors:
- 1st degree relative with early onset CA (50% increase in risk)
- age (risk increase until 65)
- lack of exercise, poor diet
- ethnicity and geographical influence
- increased oestrogen exposure
- early menarche and late menopause, nulliparity, >30 years old when having first child, no breastfeeding, obesity post-menopause (in ER +ve tumours), atypical hyperplasia, carcinoma of contralateral breast or endometrium
Ductal carcinoma in situ: pathology (3), presentation (2), investigations (2), diagnosis, CA risk, treatment (3)
Malignant cells not yet penetrated the basement membrane (no metastasis)
Arise from terminal ducts giving rise to lobules
Pathology:
- distorts lobules into duct-like spaces
- low grade (ER+ve) – non-comedo: various histological patterns including papillary, micropapillary, solid, cribriform; monotonous nuclei; secretory calcification
- high grade (HER2+ve/ TNBC) – comedo: central necrosis (outgrow blood supply) with dystrophic calcification; marked pleomorphism, hyperchromatic
- LG DCIS is distinguished from ADH by size (2mm cutoff)
Presentation:
- asymptomatic
- non-palpable mass (usually identify through screening)
Investigations:
- MMG –> microcalcifications (HG DCIS with rod-like cast of ductal system)
- sentinel LN for HG
Diagnosis: core biopsy
CA risk
- precursor to invasive DUCTAL carcinoma of the SAME breast (1%/year)
- overall increase CA risk 8-10x
Treatment
- lumpectomy +/- RT
- total mastectomy if diffuse breast involvement
- adjuvant therapy (tamoxifen if ER+ve) for preventing recurrence
- > 97% survival
Lobular carcinoma in situ: pathology, presentation, investigations, diagnosis, CA risk, treatment
Malignant cells not yet penetrated the basement membrane (no metastasis)
Also arises from terminal ducts giving rise to lobules
More severe and extensive version of atypical lobular hyperplasia (not staged as CIS)
Pathology:
- low grade – solid groups of uniform cells distending lobules (may have cytoplasmic vacuoles); bland round nuclei
- loose arrangement of cells due to loss of E-cadherin (16q)
Presentation;
- asymptomatic
- non-palpable
Investigations: MMG NAD
Diagnosis: core biopsy
CA risk:
- precursor and marker of BILATERAL invasive carcinoma (DUCTAL/LOBULAR)
- 1%/year
- overall increase CA risk 8-10x
Treatment
- lifelong close surveillance
- prophylactic bilateral total mastectomy
- adjuvant: tamoxifen
Paget Disease of Nipple
A form of CIS
Eczematous changes and crusting exudate of the nipple due to infiltration of nipple epidermis by malignant cells extending up lactiferous ducts
Pathology;
- spreading of malignant cells along dermal-epidermal region with large clusters at the deep epidermis
- single intraepithelial cells may be found at superficial dermis
Associated with underlying carcinoma e.g. HG DCIS or IDC
Invasive Carcinoma (3)
Many historical variants and subtypes
Metastasise to bone, viscera, brain
Treat by local excision and LN sample/excision
