Terminal Duct-Lobular Unit
Functional unit of the breast. 15-20 lobes in each breast each containing many TDLU. Consist of Acini connected to terminal duct, embedded within intralobular stroma.
Terminal Duct -> Subsegmental Duct -> Segmental Duct -> Lactiferous duct.
Cellular composition: The ducts and acini have a bilayer architecture — this is fundamental to understanding breast pathology:
- Inner luminal epithelial cells: These are the secretory cells. They express oestrogen receptor (ER), progesterone receptor (PR), and are the cells from which most carcinomas arise. They produce milk during lactation.
- Outer myoepithelial cells: These contractile cells sit on the basement membrane, express smooth muscle actin, p63, and calponin. They're crucial because they have tumour-suppressive properties — they secrete basement membrane components, produce protease inhibitors (like maspin and TIMP-1), and suppress angiogenesis. Their intact presence is what distinguishes in-situ from invasive disease. When a pathologist stains for p63 or CK5/6 and sees an intact myoepithelial layer, they can confidently call it DCIS rather than invasion.
The intralobular stroma is distinct from the interlobular stroma. It's hormone-responsive, loose, cellular, and oedematous — it swells with the menstrual cycle and contains immune cells. The interlobular stroma by contrast is dense, fibrous, and less hormonally responsive. This distinction matters: fibroadenomas arise from intralobular stroma, whereas phyllodes tumours show a more aggressive stromal proliferation with leaf-like architecture.
Why almost everything arises here: The TDLU is a high-turnover, hormone-responsive environment with constant proliferation and apoptosis — the perfect setup for accumulating mutations. Fibroadenomas, cysts, ADH, DCIS, LCIS, invasive ductal and lobular carcinoma all originate from the TDLU. Even "ductal" carcinoma is a misnomer — it arises from the TDLU, not the larger ducts. The only common lesion arising from the large ducts is intraductal papilloma.