Radiation-induced changes in the skin of the breast are identical to those described in irradiated skin from other sites and include epidermal atrophy and telangiectasia.10 The nature of these changes is, in part, dependent upon the interval between irradiation and histological examination.

Patients with invasive cancer and DCIS treated by breast-conserving surgery and radiation therapy occasionally develop areas of fat necrosis in the vicinity of the primary tumor site. These lesions may clinically, mammographically, and macroscopically resemble carcinoma.11 Although the diagnosis of fat necrosis can be readily made on core-needle biopsy, whether the changes in the needle biopsy samples are fully representative of the lesion in the breast may be a matter of concern. In such cases, careful pathologic-radiologic-clinical correlation is essential in order to avoid the underdiagnosis of breast cancer recurrence. If there is doubt about whether or not the core-needle biopsy samples are representative, a surgical excision should be performed.

A characteristic constellation of histological changes is observed in non-neoplastic breast tissue in patients treated by breast-conserving surgery and radiation therapy.12 The most frequent finding is that of scattered atypical epithelial cells in the terminal duct lobular unit (TDLU), usually associated with variable degrees of lobular sclerosis and atrophy. These atypical cells are large, with enlarged, diffusely hyperchromatic nuclei, generally small or inconspicuous nucleoli, and finely vacuolated eosinophilic cytoplasm. The cells often protrude into the lumen of the involved duct or acinus but do not show evidence of proliferation such as cellular stratification, loss of polarity, or mitotic activity (Fig. 19.1, e-Figs. 19.1, 19.2 and 19.3).

Radiation effects in the TDLU must be distinguished from carcinoma to prevent an incorrect diagnosis of tumor recurrence. The distinction between radiation change and lobular carcinoma in situ is not difficult because of the characteristic histologic appearance of the latter (i.e., a monotonous population of relatively small cells that fill and distend small ducts and acini). The differentiation of radiation-induced changes from DCIS involving the TDLU (cancerization of lobules) may be more difficult. However, when DCIS involves the TDLU, there is generally evidence of cellular proliferation as characterized by cellular stratification, loss of polarity, and distension of the involved ducts and acini. In addition, the nuclei in carcinoma cells tend to show irregularly dispersed chromatin and variably prominent nucleoli. Finally, necrosis of varying degrees may be seen with DCIS, and mitoses may be apparent. Conversely, the epithelial cells in areas of radiation change generally show maintenance of cellular polarity and cohesion, lack of stratification, a diffuse homogeneous increase in chromatin, usually small or inconspicuous nucleoli, and no evidence of necrosis or mitotic activity. In some instances of radiation change, there may be extensive lobular fibrosis and atrophy with distortion of the lobular architecture. Entrapment of acini containing atypical epithelial cells may result in a pseudoinfiltrative pattern, thereby simulating invasive carcinoma. However, the lobulocentric configuration of such areas is usually apparent on low-power examination.

Additional pathological changes that may be observed in non-neoplastic irradiated breast tissue include epithelial atypia in large (extralobular) ducts, atypical fibroblasts in the stroma, and vascular changes, such as myointimal hyperplasia in small arteries and prominent capillary endothelial cells.12 However, these changes tend to be most pronounced in cases in which the alterations in the TDLU are marked. It is important to note that stromal fibrosis, a well-recognized feature of radiation effect in other organs, is so variable in both irradiated and non-irradiated breasts that it cannot by itself be considered a constant and reliable histological indicator of prior irradiation in the breast.

The key features of radiation changes in non-neoplastic breast tissue are summarized in Table 19.1.

Histopathologic alterations attributable to chemotherapy may be seen in both non-neoplastic breast tissue and breast cancers.