Paper II
Question
A 49-year-old lady presented with a lump in the upper outer quadrant of the left breast. It was about 3cm, firm and immobile. A mammogram done showed stippled calcifications. She underwent FNAC followed by lumpectomy. Gross examination of the specimen showed a 3x2 cm, firm, greyish mass with irregular margins
- (a) What is the most likely diagnosis 2 mark(s)
- (b) Explain the risk factors and histopathologic features of this condition 8 mark(s)
- (c) What are the prognostic and predictive factors of this condition 5 mark(s)
Answer
(a) Most likely diagnosis: Invasive breast carcinoma (invasive ductal carcinoma, no special type) — a firm, irregular-margined mass with mammographic stippled (“fine, pleomorphic”) calcifications in a postmenopausal-age woman is highly suspicious for malignancy.
(b) Risk factors and histopathologic features:
Risk factors:
- Increasing age
- Prolonged estrogen exposure — early menarche, late menopause, nulliparity or late first pregnancy, obesity (postmenopausal), exogenous hormone therapy
- Family history and genetic mutations (BRCA1/BRCA2, TP53 — Li-Fraumeni)
- Personal history of breast cancer or proliferative breast disease with atypia
- Radiation exposure to chest
- Alcohol consumption
Histopathologic features:
- Infiltrating cords, nests, and glands of malignant epithelial cells invading a desmoplastic (fibrous) stroma — producing the firm, gritty, irregular gross mass.
- Cellular pleomorphism, nuclear atypia, increased mitotic activity (graded via the Nottingham/modified Bloom-Richardson system, scoring tubule formation, nuclear pleomorphism, mitotic rate).
- Stippled/pleomorphic microcalcifications correspond histologically to calcification within necrotic tumour debris (comedo-type necrosis) or secretions.
- Lymphovascular invasion may be present.
- Immunohistochemistry typically performed for ER, PR, and HER2/neu status.
(c) Prognostic and predictive factors:
- Tumour size and axillary lymph node status (most important prognostic factors)
- Histologic grade and type
- Lymphovascular invasion
- TNM stage
- ER/PR status (predictive of hormonal therapy response; also prognostic — positivity favourable)
- HER2/neu status (predictive of anti-HER2 targeted therapy; overexpression associated with more aggressive behaviour if untreated)
- Ki-67 proliferation index
- Molecular subtype (Luminal A/B, HER2-enriched, triple-negative/basal-like) — triple-negative carries the worst prognosis