Breast Pathology Workup
On this page
Direct answer
A breast lump earns the label of carcinoma only after triple assessment — clinical examination, imaging and pathological confirmation — converges, with image-guided core needle biopsy as the pathological arm. Ductal carcinoma in situ distends duct spaces with monomorphic tumour cells, sometimes with comedo-type central necrosis and its mammographic correlate of microcalcification, while lobular neoplasia is defined by loss of E-cadherin, small dyscohesive cells filing the lobule. Reporting then quantifies what therapy needs: Nottingham (Elston-Ellis) grade from tubule formation, nuclear pleomorphism and mitoses; oestrogen and progesterone receptor status; and human epidermal growth factor receptor 2 by immunohistochemistry, with equivocal scores reflexed to in-situ hybridisation. Micrometastasis is defined as a deposit greater than 0.2 mm and up to 2 mm in a lymph node.
What you must remember
- DCIS patterns: comedo (high grade, necrosis, calcifications) versus low-grade cribriform, micropapillary and solid architectures; nuclear grade trumps architecture for prognosis.
- E-cadherin rule: lost in lobular carcinoma (dyscohesive, single-file, Indian-file infiltration, signet-ring forms) and retained in ductal lesions; the stain that settles every ambiguous intraepithelial proliferation.
- Benign mimics to know: fibroadenoma (intracanalicular and pericanalicular stromal growth), phyllodes tumour with leaf-like fronds and stromal overgrowth, radial scar, and sclerosing adenosis — the classic false-positive for malignancy on gross and imaging.
- Proliferative borderline: atypical ductal hyperplasia shares cytology with low-grade DCIS but is limited to under 2 mm or two duct spaces; flat epithelial atypia is the deceptively bland end of the spectrum.
- Receptor reporting: oestrogen receptor by Allred score; HER2 scored 0, 1+, 2+ (equivocal, reflex to fluorescence in-situ hybridisation) and 3+ (positive) per ASCO-CAP rules on properly fixed tissue.
- Nottingham arithmetic: tubule formation 1-3, pleomorphism 1-3, mitotic count 1-3; totals 3-5 grade 1, 6-7 grade 2, 8-9 grade 3.
- Special types: tubular and mucinous carry excellent prognosis; inflammatory carcinoma is dermal lymphatic embolism, not an infection, and medullary carcinoma sits in the triple-negative group.
Walking a screen-detected lesion through the laboratory
A 54-year-old has clustered pleomorphic microcalcifications on mammography; ultrasound shows no mass. Stereotactic core biopsies target the calcifications and specimen radiography confirms they were sampled. Histology shows low-grade DCIS with comedo necrosis filling duct spaces; E-cadherin is retained, excluding lobular neoplasia; no invasion is identified. Receptor studies on the in-situ component guide endocrine prevention later. Wire-guided wide local excision follows, with margin and calcification assessment on specimen radiographs, and radiotherapy completes breast conservation for this lesion. Had the core shown only atypical ductal hyperplasia, the excision would still be mandatory — a third of such upgrades hide invasive carcinoma. Every step of this chain exists because breast-conserving surgery lives and dies by margins, receptors and grade, all of which are pathology products.
Where candidates slip
Three slips dominate. Inflammatory carcinoma is described as an "infected cancer"; it is tumour embolising dermal lymphatics, causing the erythematous, oedematous peau d'orange breast, and biopsy shows skin lymphatics plugged by tumour, often with no palpable mass. Phyllodes tumour is equated with fibroadenoma; stromal cellularity, overgrowth, atypia and mitotic activity separate them, and a phyllodes can recur or metastasise. And HER2 2+ is read as positive; it is equivocal — only in-situ hybridisation amplification data permit trastuzumab, which is why the reflex pathway is examined so often.
Frequently asked questions
What does loss of E-cadherin indicate in a breast lesion?
Lobular phenotype — dyscohesive cells filling lobules and infiltrating in single files — distinguishing lobular carcinoma in situ and invasive lobular carcinoma from ductal lesions.
Which histological feature defines comedo DCIS?
High-grade malignant cells filling duct spaces with central areas of necrosis, corresponding mammographically to pleomorphic microcalcifications.
What happens to a HER2 immunohistochemistry score of 2+?
It is equivocal and reflexed to in-situ hybridisation for HER2 amplification; only amplification, or a 3+ score, justifies anti-HER2 therapy.
What three components make up the Nottingham grade?
Tubule formation, nuclear pleomorphism and mitotic count, each scored 1-3 and summed to grades 1-3.
How is micrometastasis defined in an axillary node?
A tumour deposit greater than 0.2 mm and up to 2 mm; deposits of 0.2 mm or less are isolated tumour cells.
Why is sclerosing adenosis a classic false-positive?
Distorted, entrapped glands in a sclerotic stroma mimic invasive carcinoma on imaging and frozen section, but the myoepithelial layer is preserved.