FIGURE 15.1

Normal breast. The majority of the breast is composed of stromal tissue, largely mature adipose and fibrous tissue. Within this lie the physiologically and pathologically important breast epithelial structures, from which most breast lesions are derived. The lobules of the breast form well-defined islands of small tubular structures (acini) (e.g. lower left) surrounded by intralobular stroma. The ducts are lined by a double layer of inner cuboidal or columnar epithelium over a layer of myoepithelial cells (centre).

FIGURE 15.2

High-power view of lactating breast. During later pregnancy and lactation, the epithelium of the lobules becomes vacuolated with lipid-rich material, which is secreted into the lumen.

FIGURE 15.3

Fat necrosis. The main picture and higher power inset both show fat spaces surrounded by an inflammatory response including swollen macrophages (pale blue) which have taken up released lipid.

FIGURE 15.4

Fibroadenoma. A core biopsy of a fibroadenoma seen as a well-defined mass of loose myxoid connective tissue bearing ductal structures resembling tubules. A small portion of adjacent normal breast is present (bottom left).

FIGURE 15.5

Hyalinized fibroadenoma with stromal microcalcification. Core biopsies from a fibroadenoma with a more hyalinized fibrous stroma than seen in Figure 15.4. Large foci of microcalcification are seen in the core on the right as irregular haematoxyphilic islands.

FIGURE 15.6

Fibrocystic change. Cysts arise from the terminal duct lobular unit and bear secretions. Most are less than 1 cm in diameter.

FIGURE 15.7

Microcyst in fibrocystic change. Small cysts are common in fibrocystic change. The epithelium is flattened (compare to adjacent normal epithelial lined ducts). The lumen bears flocculent secretions.

FIGURE 15.8

Apocrine metaplasia in fibrocystic change. Breast cysts in fibrocystic change are commonly lined by apocrine epithelium (seen in the left of this photomicrograph). The cells in apocrine metaplasia are larger than normal epithelium (compared to the normal epithelial cells on the right), more columnar in shape and have abundant eosinophilic cytoplasm.

FIGURE 15.9

Epithelial hyperplasia of usual type in fibrocystic change. The duct space is no longer lined by a single layer of luminal epithelial cells but by a hyperplastic proliferation, which almost fills the ducts in this case. The cells, however, do not show significant pleomorphism or increase in size and mitoses are not prominent.

FIGURE 15.10

Sclerosing adenosis. Sclerosing adenosis is a proliferation of the terminal duct lobular unit seen as a disorderly proliferation of acinar structures and intralobular stromal cells. The small tubular structures of the disorganized lobular proliferation may be mistaken by the unwary for invasive carcinoma.

FIGURE 15.11

Radial scar. The central portion of a radial scar seen as fibrosis and elastosis bearing entrapped ductal structures. Some of these show usual type epithelial hyperplasia.

FIGURE 15.12

High-grade ductal carcinoma in situ (DCIS). Duct spaces are completely filled by a solid neoplastic proliferation of large, highly malignant cells. In this case the DCIS extends into the lobules as ‘cancerization’ of lobules; this may mimic invasion, but the process in both ducts and lobules has a surrounding myoepithelium (not shown). The DCIS within ducts bears central comedo-type necrosis.

FIGURE 15.13

Paget’s disease of the nipple. When DCIS extends along major ducts as far as the nipple, groups of carcinoma cells may enter the deeper layer of the epidermis and spread within it through the nipple and areola in the form of Paget’s disease of the nipple. In this case, atypical malignant cells with abundant cytoplasm and large nuclei are seen in the basal layers of the nipple.

FIGURE 15.14

Invasive breast carcinoma of no special type (ductal). Invasive carcinoma is formed from irregular islands of pleomorphic malignant cells. These have no surrounding myoepithelial cells and diffusely infiltrate into the stroma. The higher power inset shows the malignant cells in more detail, with numerous mitoses.

FIGURE 15.15

Infiltrating lobular carcinoma. This subtype of invasive carcinoma is composed of small, relatively regular cancer cells. Typically linear cords of carcinoma cells infiltrate diffusely as ‘single files’.

FIGURE 15.16

Tubular carcinoma. This subtype of invasive carcinoma is formed from elongated tubular structures infiltrating through a cellular fibroblastic stroma. The tubules are lined by a single layer of relatively regular cancer cells, without an associated myoepithelial layer, and with central lumina.

FIGURE 15.17

Lymph node metastasis. Section of lymph node with metastatic carcinoma cells seen as large pleomorphic cancer cells (top of image) compared with normal-sized lymphoid cells (bottom of photomicrograph).

FIGURE 15.18

Core biopsy of fibrous tissue infiltrated by invasive carcinoma. The tumour is forming tubular structures. An adjacent benign cyst is present. Inset of higher power of the same cancer shows irregular islands of carcinoma with a reactive fibroblastic stroma.

FIGURE 15.19

Macroscopic specimen of wide local excision. The wide local excision specimen has been received in the laboratory and the different aspects painted with inks so that the margins can be identified histologically. This is undertaken according to orientation sutures placed on the specimen by the surgeon; e.g. the surgeon may mark the medial aspect with medium length suture, the lateral with long suture and superior with a short suture according to local protocol. In the incised specimen the invasive cancer can be seen centrally as a pale area with an irregular outline within the normal yellow fatty tissue.

FIGURE 15.20

Overall survival curves for patients with invasive primary operable breast carcinoma according to the Nottingham Prognostic Index (NPI) groups from data from the Nottingham Tenovus Primary Operable Breast Cancer Series. Each of the five lines shows survival for women within that range of NPI scores, namely excellent, good, moderate 1, moderate 2 and poor prognostic groups.

FIGURE 15.21

Oestrogen receptor immunohistochemistry in invasive breast carcinoma. Sheets of invasive breast carcinoma cells stained immunohistochemically with antibody against oestrogen receptor. The nuclei of this cancer all show strong reactivity (as intense brown staining) and this tumour is strongly oestrogen-receptor-positive, indicating a good chance of response to hormone therapy.

FIGURE 15.22

HER2-positive breast cancer. Invasive breast cancer with strong positive staining of HER2 protein on the surface of the cell membranes (3 + staining).

FIGURE 15.23

Fluorescent in-situ hybridization (FISH) for the HER2 gene. The number of copies of the HER2 gene in the tumour cell nucleus is assessed with fluorescence microscopy and the number of signals (red dots) is counted per cell and compared with the number of signals for chromosome 17 (green dots). A ratio of HER2 gene to chromosome 17 of more than 2 is considered positive, as here.