Paper II
Question
A 50-year-old nulliparous female presents with a hard lesion of the right breast that she had noticed 2 weeks ago. Clinical examination reveals puckering of the overlying skin and retraction of the nipple along with a 3 cm hard mass in the upper outer quadrant of the right breast. 3 hard masses are palpable in the right axilla. On questioning the patient reveals a weight loss of 7kg in the last 2 months. Mammogram reveals a 3.4 cm mass with irregular spiculated margins and increased density compared to the surrounding breast tissue. (
- (a) What is your diagnosis. Justify it ( 4 mark(s)
- (b) What is the gross and histology of this lesion ( 4 mark(s)
- (c) List the major prognostic and predictive markers ( 4 mark(s)
- (d) Discuss the mode of spread of this disease 3 mark(s)
Answer
(a) Diagnosis and justification
- Invasive (infiltrating) ductal carcinoma of the breast, no special type (NST), with axillary lymph node metastasis
- Justification: A hard, irregular breast mass with skin puckering (from involvement of Cooper’s ligaments) and nipple retraction (from involvement of subareolar ducts) are classic clinical signs of an invasive, desmoplastic (fibrotic) breast carcinoma; the mammographic finding of a spiculated, irregular, dense mass is highly characteristic of malignancy (as opposed to the smooth, well-circumscribed appearance of benign lesions like fibroadenoma); palpable hard axillary lymph nodes indicate regional metastatic spread; and unintentional weight loss suggests systemic/advanced disease
(b) Gross and histology
Gross
- Firm to hard, grey-white, irregular, stellate/spiculated mass with poorly defined margins infiltrating into surrounding breast tissue and fat, producing a gritty sensation on cutting (“crab-like” invasive pattern, giving the tumour its name — carcinoma, from the Greek for “crab”)
- Chalky white/yellow streaks may be seen (necrosis, elastosis)
Histology
- Infiltrating cords, nests, and glands of malignant epithelial cells invading through the basement membrane into the surrounding stroma
- Marked desmoplastic (fibrous) stromal response surrounding the tumour cells (accounts for the hard/firm gross consistency and skin/nipple retraction)
- Tumour cells show nuclear pleomorphism, hyperchromasia, and variable mitotic activity, with the grade based on tubule formation, nuclear pleomorphism, and mitotic count (Nottingham/Bloom-Richardson grading system)
(c) Major prognostic and predictive markers
- Tumour size and histological grade
- Axillary lymph node status (single most important prognostic factor)
- Hormone receptor status: Oestrogen receptor (ER) and Progesterone receptor (PR) — predictive of response to hormonal therapy (tamoxifen, aromatase inhibitors)
- HER2/neu (ERBB2) status: Overexpression predicts response to trastuzumab (anti-HER2 therapy) and is associated with more aggressive behaviour if untreated
- Ki-67 proliferation index: Higher index correlates with more aggressive tumour behaviour
- Lymphovascular invasion
(d) Mode of spread
- Local invasion: Direct extension into surrounding breast tissue, skin, chest wall
- Lymphatic spread: To axillary lymph nodes (most common, as seen in this patient), internal mammary nodes, supraclavicular nodes
- Haematogenous spread: To distant organs — bone (most common site), lungs, liver, brain