OncoLink

Histologic Classification of Breast Cancer

Li Liu, MD
OncoLink
Last Modified: November 1, 2001

The basic component of the breast is the "mammary gland". Each mammary gland is made of multiple lobules connected to ducts and surrounding tissue which includes blood vessels.

Malignant tumors may arise from any of the above structures. Ductal carcinomas are the most common ones, followed by lobular carcinomas, and malignancies arising from other connective tissues. The following is a list of breast cancer histologic classifications from American Joint Committee on Cancer (AJCC).

Carcinoma, NOS (not otherwise specified)

Ductal
  • Intraductal (in situ)
  • Invasive with predominant intraductal component
  • Invasive, NOS
  • Comedo
  • Inflammatory
  • Medullary with lymphocytic infiltrate
  • Mucinous (colloid)
  • Papillary
  • Scirrhous
  • Tubular
  • Other

Lobular

  • In situ
  • Invasive with predominant in situ component
  • Invasive

Nipple

  • Paget's disease, NOS
  • Paget's disease with intraductal carcinoma
  • Paget's disease with invasive ductal carcinoma

Other

  • Undifferentiated carcinoma

Histopathologic evaluation of a breast cancer is necessary to provide the diagnosis of the tumor, to help determine a patient's prognosis, and to help understand the nature of breast cancer overall.

Invasive (infiltrating) ductal carcinoma is the most common cell type, comprising 70% to 80% of all cases. The tumors occur throughout the age range of breast carcinoma, being most common in women in their middle to late 50s. It is characterized by its solid core, which is usually hard and firm on palpation. An associated ductal carcinoma in-situ is frequently present and comedo necrosis may occur in both invasive areas and areas of intraductal carcinoma. Invasive ductal carcinoma commonly spreads to the regional lymph nodes and carries the poorest prognosis among various ductal types. Nuclear and histologic grade have shown to be effective predictors of prognosis.

Ductal carcinoma in-situ (DCIS) consists of malignant epithelial cells confined to the mammary ducts, without microscopic evidence of invasion through the basement membrane into the surrounding tissue. According to the tumor differentiation, DCIS can be further divided into low, intermediate, and high grade. Such stratification has prognostic implications.

There are five histologic subtypes of DCIS, namely comedo, papillary, micropapillary, cribriform, and solid. The comedo subtype carries the higher probability of high nuclear grade, microinvasion, and over expression of the her-2/neu oncogene. The most characteristic mammographic abnormality associated with DCIS is "clustered microcalcifications". New classification systems using a combination of architecture, nuclear grade, and necrosis have been proposed, but the merits of these systems remain to be proved.

Invasive lobular carcinoma is relatively uncommon, comprising only 5% to 10% of breast tumors. Invasive lobular carcinomas are characterized by greater proportion of multicentricity in the same or the opposite breast. The lesions tend to have ill-defined margins, and occasionally the only evidence is subtle thickening or induration. Patients with infiltrating lobular carcinoma are especially prone to have bilateral carcinoma. Stage by stage, invasive lobular carcinoma has a similar prognosis to infiltrating ductal carcinoma.

Lobular carcinoma in-situ (LCIS) generally lacks specific clinical or mammographic signs, and occurs more frequently in premenopausal women. By definition, these cancer cells are confined to the mammary lobules without invasion. LCIS is characterized microscopically by a solid proliferation of small cells. The cells have a low proliferative rate, are typically estrogen receptor positive, and rarely over express the her-2/neu oncogene. Since there is a reported risk of bilaterally in this disease, some investigators have recommended treatment with bilateral simple mastectomy with immediate breast reconstruction. If watchful waiting is elected, lifetime observation is mandatory since the increased risk of breast cancer persists indefinitely.

Tubular carcinoma is also known as a well-differentiated carcinoma. The frequency of axillary lymph node metastases is approximately 10%, lower than that of ductal carcinoma. The prognosis is considerably better than for invasive ductal carcinoma.

Medullary carcinoma is characterized by a prominent lymphocyte infiltrate. Patients with medullary carcinoma tend to be younger than those with other types of breast cancer. The prognosis is also believed to be better than for invasive ductal cancer.

Inflammatory Breast Carcinoma is characterized by diffuse skin edema, skin and breast redness, and firmness of the underlying tissue without a palpable mass. The clinical manifestation is primarily due to tumor embolization to dermal lymphatics (skin lymph channels) with associated engorgement of superficial capillaries. Inflammatory breast cancer carries a poor prognosis.

Paget's disease of the nipple is a rare form of breast cancer that is characterized clinically by eczematoid changes of the nipple. It is believed that Paget's disease represents the migration of malignant cells from subjacent mammary ducts in the nipple. The prognosis of patients with Paget's disease appears to be similar to that of women with other types of breast carcinoma, stage for stage.