Pathology

Oxford American handbook of oncology. Second Edition. Oxford University Press (2015)


Approximately 50% of breast cancer cases arise in the upper outer quadrant. The most common pathology is ductal carcinoma (Table 28.1).

Ductal carcinoma in situ

Ninety percent of breast carcinomas arise in the ducts of the breast. It begins as atypical proliferation of ductal epithelium that eventually fills and plugs the ducts with neoplastic cells. As long as the tumor remains within the confines of the ductal basement membrane, it is classified as ductal carcinoma in situ (DCIS).

Localized DCIS is not palpable but is often visible on mammography as an area of microcalcification.

Not all DCIS will inevitably progress, but the probability of development of invasive cancer is estimated at 30%–50%.

Lobular carcinoma in situ

These preinvasive lesions carry a risk not only of ipsilateral invasive lobular carcinoma but also of contralateral breast cancer. Typically, they are neither palpable nor contain microcalcification.

Invasive ductal carcinoma

This accounts for 75% of breast cancers. Tumor invades through breast tissue into the lymphatics and vascular spaces, to gain access to the regional nodes (axillary and, less often, internal mammary) and the systemic circulation. Systemic spread can involve almost any organ, but most commonly bone, other lymph nodes, lung or pleura, liver, skin, and CNS.

The histological grade (I–III) of the tumor predicts tumor behavior and is assessed from three features:

  • Tubule formation
  • Nuclear pleomorphism
  • Mitotic frequency

Estrogen and progesterone receptor status is commonly assessed by immunohistochemistry. Hormone receptor positivity confers a more favorable prognosis and allows for treatment with endocrine therapies such as tamoxifen and aromatase inhibitors.

HER2 amplification or overexpression occurs in approximately 18%– 20% of breast cancer and is associated with a more aggressive phenotype. This subtype of breast cancer can be treated with anti-HER2 agents such as trastuzumab, lapatinib, pertuzumab, and trastuzumab emtansine (T-DM.).

Basal-like or triple-negative breast cancer has no hormone receptor or HER2 expression, is more common in patients with African ancestry, and has a poor prognosis.

Special types of ductal carcinoma

A number of pathological variants are identified with relatively good prognosis, namely medullary carcinoma, tubular carcinoma, and mucinous carcinoma.

Paget’s disease of the breast presents clinically with scaly, often erythematous, involvement of the nipple and is defined pathologically by the presence of intraepithelial malignant adenocarcinoma cells within the nipple-areolar complex. The vast majority (estimated at 97%) of patients who present with Paget’s disease are diagnosed with underlying invasive or in situ breast cancer.

Invasive lobular carcinoma

Lobular carcinomas account for 5%–10% of breast cancers. About 20% of patients develop contralateral breast cancer.

Unusual patterns of spread are recognized, including propensity for spread to the peritoneum, gastrointestinal tract, orbit, meninges, ovaries, and uterus.

Table 28.1. Histological types of breast malignancy

  • Invasive ductal carcinoma
  • No special type
  • Combined with other type
  • Medullary carcinoma
  • Mucinous carcinoma
  • Paget’s disease
  • Invasive lobular carcinoma
  • Mixed lobular and ductal carcinoma
  • Sarcoma (various)
  • Lymphoma
  • Metastases (e.g., breast cancer, small cell lung cancer)
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