1. Jacob J. Adler

2.  The following slides are meant to supplement the background text in the manuscript. It is not meant to be presented alone.  The large amount of text on slides are not meant to be presented in class, but are placed here to help you connect concepts with the pictures.

3. Breast, Testicular, Ovarian

4. http://www.okc.cc.ok.us/deanderson/dennis-tutorial/histology.html#anchor1038249 Main Functions of Epithelial Cells Absorbtion – Enterocytes (absorptive epithelial cells) in the intestine have microvilli on apical surface allowing selective uptake of nutrients from the gut. Protection – Epithelial cells tightly adhere to each other to form a barrier to external toxins and pathogens in tissues such as the skin and intestines. Filtration – Podocytes form precise slits to form a Filtration Barrier in Glomerulus of Kidney Main Functions of Epithelial Cells Absorbtion – Enterocytes (absorptive epithelial cells) in the intestine have microvilli on apical surface allowing selective uptake of nutrients from the gut. Protection – Epithelial cells tightly adhere to each other to form a barrier to external toxins and pathogens in tissues such as the skin and intestines. Filtration – Podocytes form precise slits to form a Filtration Barrier in Glomerulus of Kidney Over 90 % of all Cancers arise from Epithelial Cells

5. Change is constantly happening: Pregnancy, lactation, puberty, menstruation, menopause The breast comprises a branching system of ducts leading down from the lactiferous sinus ending in glands (acini aggregated into lobules) which have the potential to secrete milk. Approximately 12 large ducts emerge from the breast as lactiferous ducts. Their subdivisions form rather complicated breast segments that are discrete physiologically but probably interdigitate with each other at their boundaries. The ducts branch repeatedly ultimately giving rise to the terminal duct lobular unit (TDLU).

6. The duct lumen is clearly visible (white center surrounded by cells. Nuclei are healthy and appropriate size and shape. Connective tissue that surrounds the duct has little to no inflammatory white blood cells nor invasive epithelial cells. = indicates the lobular units

7. During the proliferative phase of the menstrual cycle lobules are small, mitoses are infrequent and specialized stroma is condensed. In the secretory phase of the cycle the TDLUs increase in size with a more loose oedematous (FLUID FILLED) stroma. They show epithelial mitotic activity and the cytoplasm is vacuolated. In the peri-menstrual phase there may be some sloughing of epithelium (similar to the process of uterial epithelial renewal aka menstruation) into the TDLU lumen evident as debris and a mild lymphocytic intraepithelial infiltrate can be seen. These variations do not give rise to diagnostic problems in routine practice.

8. NORMAL Terminal Ductal Lobular Unit (TDLU) LATE STAGE PREGNANCY/PREPARING FOR LACTATION Late pregnancy changes in the breast: Expansion of TDLUs Epithelium accumulates fat droplets Luminal portion of cytoplasm vacuolated Non-specialized stroma apparently diminished - TDLUs crowded Lactation: Epithelial cells vacuolated,cytoplasm generally diminished in comparison with late pregnancy - Secretion with residual nuclei post-secretion protruding into lumen

9. NORMAL TLDU The postmenopausal breast shows a reduction in the amount of glandular tissue and relatively increased stroma. Glandular units show fewer acini and specialised stroma is diminished in amount. Also the epithelial and myoepithelial cells are smaller. There may be areas of dense fibrosis and benign vascular calcification may be seen. The entire spectrum of premenopausal lobular appearances can be seen in quite elderly post menopausal women. POST-MENOPAUSAL BREASTNORMAL Terminal Ductal Lobular Unit (TDLU)

12. Normal Mammary Duct Normal Mammary Duct IDC Invasive Ductal Carcinoma DCIS Ductal Carcinoma in situ DCIS Ductal Carcinoma in situ Invasion of Breast Cancer Cells into the Stroma

13. HyperplasiaNormal

14. HyperplasiaMild dysplasiaNormal

15. Carcinoma in Situ Mild dysplasia Carcinoma in situ (severe dysplasia) NormalHyperplasia

16. Mild dysplasia Carcinoma in situ (severe dysplasia) Cancer (invasive) NormalHyperplasia