Breast Cancer - Basic Pathology

Pathological Subtypes

'Breast Cancer' typically refers to adenocarcinoma arising from the glandular tissue of the mammary glands. The most common subtype is ductal carcinoma of no special type. Other tumours include other carcinomas of the gland, various sarcomas, skin cancers of the breast tissue and some benign lesions.

Adenocarcinoma of the Breast

Ductal Carcinoma of No Special Type

This category makes up about 80% of invasive carcinomas of the breast. There are several grades of ductal carcinoma. Well differentiated tumours typically show tubule formation and have a low mitotic count. Higher grade tumours lose these features, have an increase in mitotic rate and show nuclear pleomorphism.

Lobular Carcinoma

These account for 10% of invasive carcinomas. They may present as a mass or infiltrate diffusely - the classical term is 'Indian file' referring to single cells arranged in a line. Another common feature is the absence of e-cadherin, a cell anchoring molecule, which may explain their unique behaviour. They do not occur with greater frequency in the contralateral breast.

Tubular / Cribriform Carcinoma

Tubular carcinoma is notable for an excellent prognosis. Cribriform carcinoma is a subtype, and refers to the lace-like pattern seen on histology. Tubular carcinoma is always well differentiated with extensive tubule formation (hence the name). They make up about 6% of invasive carcinomas.

Mucinous Carcinoma

Mucinous carcinomas produce large amounts of extracellular mucin. This gives them the macroscopic features of sliminess and microscopic features of large, clear mucous lakes. They are rare, accounting for about 2% of invasive carcinomas of the breast.

Medullary Carcinoma

Medullary carcinomas are the opposite of tubular carcinoma but are fortunately even rarer. They have different macroscopic features (typically soft as opposed to hard ductal carcinomas) and are poorly differentiated on microscopy. Despite these features they have a better prognosis than ductal carcinoma of no special type.

Metaplastic Carcinomas

These are a diverse group of carcinomas which arise from the ducts. They include squamous cell carcinoma, small cell carcinoma or spindle cell carcinomas. They may arise from the myoepithelial layer of cells in the ducts. They generally have a poor prognosis.

Pre-Malignant Tumours of the Breast

Premalignant tumours are more frequently detected in modern times due to screening mammography.

Ductal Carcinoma in situ

The more common form of carcinoma in situ (80% of cases), these are frequently seen on mammography due to their classical calcification pattern. They typically have a variety of histological apperance, although necrosis and high nuclear grade are thought to convey poorer prognosis. Ductal carcinoma in situ may transform into invasive cancer at the rate of 1% per year.

Lobular Carcinoma in situ

Like invasive lobular carcinoma, LCIS also has loss of e-cadherin and results in a typically apperance of poorly adhering cells on microscopy. LCIS is not visible on imaging and is an incidental finding in nearly all cases (often in association with invasive lobular carcinoma).

Non-epithelial tumours

Fibroadenoma

This is a benign condition with abnormal growth of a rounded nodule. It typically affects young women. On microscopy, there is proliferation of the intralobular stroma and epithelium.

Phyloddes tumour

Phyloddes is Greek for 'leaf-like'
A more aggressive but still frequently benign tumour of the intralobular stroma. Unlike fibroadenoma, it has a higher mitotic rate, infiltrative borders and has an irregular shape. They typically recur locally and do not metastasise.

Sarcomas

Sarcomas may arise from the interlobular stroma (between the lobules of the mammary glands). They are similar to sarcomas in other parts of the body, although angiosarcoma is more frequent following radiotherapy.

Natural History and Patterns of Spread

Adenocarcinoma

Adenocarcinomas typically grow locally before metastasising. If the primary breast lesion is palpable, there is a 50% risk of regional lymphatic involvement. Distant metastasis in the absence of lymph node involvement is rare, but may occur in cases of self neglect or in women with large or dense breasts. Screening may detect tumours before they are palpable, reducing the likelihood of axillary node invovlement. Metastasis typically occurs to the lung, bones and the brain. The most commonly involved regional nodes are in the axilla.

Metaplastic carcinomas

Metaplastic carcinomas frequently metastasise earlier than standard adenocarcinoma and have a poorer prognosis.

Pre-invasive lesions

DCIS is usually detected mammographically. It may transform into invasive carcinoma at the rate of 1% per year. Surgical resection with radiotherapy is curative in nearly all cases.

Non-epithelial tumours

Fibroadenoma is a benign condition that typically presents in the 20s - 30s. They are sensitive to the female sex hormones and may change in size with the menstrual cycle.
Phyloddes tumours are frequently low grade but may recur locally after excision. High grade lesions may metastasise to nodes or viscera.
Sarcomas typically spread haemotogenously. This varies according to the histological grade and subtype.


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