Q4 LONG ANSWER 10M ★ High-yield

Classify breast lesions. Describe the risk factors, classification, morphology and prognostic factors of breast carcinoma.

Pathology · 2nd Professional — Para-Clinical

Approach to a Breast Lump

Category	Lesions
Inflammatory	Acute mastitis and breast abscess (lactational, Staphylococcus aureus); fat necrosis after trauma; duct ectasia; granulomatous mastitis; tuberculous mastitis, which is important in India
Fibrocystic change	Non-proliferative (cysts, apocrine metaplasia, fibrosis); proliferative without atypia (epithelial hyperplasia, sclerosing adenosis, papilloma); proliferative with atypia (atypical ductal or lobular hyperplasia)
Benign tumours	Fibroadenoma (the commonest benign tumour, in young women); intraductal papilloma; phyllodes tumour
Malignant	Carcinoma in situ (ductal and lobular); invasive carcinoma; Paget disease of the nipple; rarely sarcoma and lymphoma

Relative risk of subsequent carcinoma — non-proliferative: NO increase; proliferative without atypia: about 1.5 to 2 fold; atypical hyperplasia: 4 to 5 fold; carcinoma in situ: 8 to 10 fold. This gradient is the reason the categories exist
Triple assessment is the standard approach — clinical examination, imaging (mammography over 40, ultrasound in younger women), and pathology (core biopsy, or fine needle aspiration cytology)

Risk Factors for Breast Carcinoma

Category	Factors
Genetic	BRCA1 (chromosome 17; also ovarian carcinoma; often triple-negative tumours) and BRCA2 (chromosome 13; also male breast cancer); p53 in Li–Fraumeni; family history in a first-degree relative
Hormonal — prolonged oestrogen exposure	Early menarche, late menopause, nulliparity, first pregnancy after 30, absence of breastfeeding, hormone replacement therapy, obesity after the menopause
Proliferative breast disease	Atypical hyperplasia; previous carcinoma in the other breast
Environmental	Radiation to the chest, especially in adolescence; alcohol; Western diet
Other	Increasing age; female sex; dense breast tissue

Classification and Morphology

Type	Share	Features
Ductal carcinoma IN situ	15–30% of detected cancers	Malignant cells confined within ducts by an intact basement membrane; COMEDO type shows central necrosis with microcalcification, which is how mammography detects it. PAGET disease of the nipple is ductal carcinoma in situ extending along ducts into the nipple skin, giving an eczematous crusted lesion
Lobular carcinoma in situ	About 1–6%	A marker of risk to both breasts rather than a direct precursor; E-cadherin negative; usually an incidental finding
Invasive ductal carcinoma (no special type)	70–80% — much the commonest	Hard, gritty, irregular grey-white mass that cuts with a grating sensation; abundant desmoplastic stroma ("scirrhous"); cords and nests of malignant cells
Invasive lobular carcinoma	About 10%	Discohesive cells in single file "INDIAN file" strands and concentric "targetoid" rings; E-cadherin negative; often bilateral and multifocal, and harder to see on mammography
Special types	The remainder	Medullary (soft, well-circumscribed, lymphocytic infiltrate, better prognosis, BRCA1-associated), mucinous/colloid (elderly, good prognosis), tubular (excellent prognosis), papillary
Inflammatory carcinoma	Under 5%	Not a histological type but a clinical presentation — dermal lymphatic invasion causes a red, hot, swollen breast with peau D’orange; poor prognosis

CLINICAL PEARL

Loss of E-cadherin explains the whole lobular phenotype, exactly as it does in diffuse gastric carcinoma. Without the molecule that binds epithelial cells together, the cells cannot form masses — so they infiltrate singly, in Indian file, produce little desmoplastic reaction, form no discrete lump, and are poorly seen on mammography. The same molecular defect accounts for the histology, the clinical presentation and the radiological difficulty.

Clinical Features and Spread

A painless, hard, irregular, fixed lump; the upper outer quadrant is involved in about 50%
Skin changes — dimpling or puckering from traction on the suspensory ligaments of Cooper; peau D’orange from lymphatic obstruction; ulceration; nipple retraction or discharge
Lymphatic spread — chiefly to axillary nodes (about 75% of drainage), and to internal mammary nodes from medial tumours; nodal status is the single most important prognostic factor
Haematogenous spread — lung, bone (osteolytic, especially vertebrae through the vertebral venous plexus), liver, brain and adrenal; late recurrence after many years is characteristic
Male breast carcinoma is rare but presents late and behaves worse stage for stage, because of the small volume of tissue and early skin and chest wall involvement

Benign Breast Disease in Detail

Lesion	Features	Cancer risk
Fibrocystic change — non-proliferative	Cysts with blue dome appearance, apocrine metaplasia, fibrosis; lumpy painful breasts varying with the cycle	None
Sclerosing adenosis	Proliferation of acini with stromal fibrosis; may mimic carcinoma clinically, radiologically and histologically, but the myoepithelial layer is preserved	Mildly increased
Intraductal papilloma	The commonest cause of bloody nipple discharge; a small papillary growth in a large duct	Mildly increased
Fat necrosis	Follows trauma or surgery; a hard, irregular, sometimes tethered mass with skin dimpling and calcification that closely mimics carcinoma; foamy macrophages and giant cells around necrotic fat	None — but biopsy is needed to prove it
Duct ectasia	Dilated subareolar ducts with inspissated secretion; thick cheesy discharge and nipple retraction in older women	None
Atypical hyperplasia	Ductal or lobular; some but not all features of carcinoma in situ	4 to 5 fold increase — the highest of the benign lesions
Gynaecomastia	Male breast enlargement from a raised oestrogen:androgen ratio — puberty, cirrhosis, Klinefelter syndrome, drugs (spironolactone, digoxin, cimetidine), testicular tumours	Not premalignant in itself

Prognostic Factors and Applied Aspects

Factor	Significance
Lymph node status	The strongest single factor
Tumour size	Independent predictor
Histological grade	Nottingham (Bloom–Richardson) — tubule formation, nuclear pleomorphism, mitotic count
Oestrogen and progesterone receptors	Positive tumours have a better prognosis and respond to endocrine therapy (tamoxifen, aromatase inhibitors)
HER2 status	Amplified in about 20%; worse prognosis but responds to trastuzumab
Triple-negative	ER, PR and HER2 all negative; younger women, BRCA1-associated; no targeted therapy available, so chemotherapy alone; worst prognosis
Lymphovascular invasion	Adverse

Receptor status must be determined on every tumour, since it determines treatment as much as prognosis — this is the clearest example in oncology of pathology directing therapy
Sentinel lymph node biopsy identifies the first draining node; if it is negative, full axillary clearance and its lymphoedema can be avoided
Screening mammography reduces mortality in women over 50; in India coverage is low and clinical breast examination and awareness are the realistic mainstays, since most present with advanced palpable disease
Breast cancer is now the commonest cancer in Indian women, having overtaken cervical cancer, and presents about a decade earlier than in the West
BRCA testing is offered where family history warrants; carriers are offered intensive surveillance, risk-reducing surgery and PARP inhibitors if cancer develops
Any breast lump in a woman over 30 requires triple assessment, and a lump that persists after a menstrual cycle must never be dismissed as "fibrocystic"
Bloody nipple discharge is most often an intraductal papilloma but must be investigated to exclude carcinoma
Lymphoedema of the arm after axillary clearance and radiotherapy is a major cause of long-term morbidity, which is why sentinel node biopsy matters so much

All questions in Endocrine, Bone & Breast Pathology

Every Pathology chapter →