Breast Histopathology : Normal Breast Disease Modules I have designed a series of articulate modules to provide you with content to help you meet the block's objectives dealing with breast disease.    Each articulate module is designed for 10 to no more than 30 minutes. Each module contains review questions for you to answer. We will start with normal breast structure and proceed through the objectives dealing with Pathologic Changes of The Breast.     Good listening Med 2s. Dr. Charles Hitchcock, MD, PhD

Normal Breast Histology Primary Learning Objective Describe breast anatomy and function, including changes of lactation. Secondary Learning Objectives Describe the gross anatomy and normal histology of the female breast. Describe the changes that occur in the breast during puberty, pregnancy, and lactation.

Breast Anatomy The breast is a mixture of epithelial glandular tissue and fibroadipose stroma that is divided into 15-20 lobes that radiate out from the nipple.    Each lobe contains 20-40 lobules. Each lobe has a branching lactiferous duct that opens into its own lactiferous sinus that opens in the nipple.   The smooth muscle of the nipple acts as a sphincter. Each lobe contains numerous terminal duct lobular units (TDLUs) made up by the terminal ducts and the alveoli surrounded by dense interlobular stroma. Most invasive carcinomas arise in the TDLU.

Distribution of Tumors in the Breast UOQ UIQ 50% 10% 20% The breast can be divided into five zones   Upper outer quadrant Upper inner quadrant Lower outer quadrant Lower inner quadrants Areola   The distribution of ductal and glandular tissue varies in each of these zones.    The locations of breast carcinoma correlates with the amount of glandular tissue in the zones. The incidence of breast cancer will be highest in the upper outer quadrant which contains the most glandular tissue. 10% 10% LOQ LIQ

Breast Lymphatics Look at the left figure: Lymphatic drainage from the breast is mainly directed toward axillary lymph nodes (B and C) which then drain into the infraclavicular (D) and supraclavicular (E) nodes.   Medial areas of the breast tend to drain via lymphatics into internal mammary nodes (F).    Look at the right figure: Understanding the lymphatic drainage of the breast helps to locate the sentinel lymph node (SLN).  The sentinel lymph node is the first lymph node that an area of the breast drains into. It is thus the first node into which cancer cells are likely to spread.   Sampling of sentinel lymph nodes for cancer involves injection of a radioactive tracer and/or blue dye into the tumor.    The surgeon identifies the sentinel lymph node by its blue coloration and/or its radioactivity.   If the node lacks tumor on frozen section, the surgeon can halt further exploration of the axilla.  

1 2 The bulk of the breast is made up of adipose tissue (1) and dense, eosinophilic staining, collagenous interlobular stroma (2). The breast consists of system of branching ducts that end in terminal ducts (arrows) that rise to terminal duct lobular units (TDLU) (circles) that have the appearance of a cluster of grapes. The TDLUs are the functional unit of the breast.

TDLUs Interlobular Stroma Intralobular Stroma Interlobular Stroma The left image represents a 4x magnification of the normal breast that shows the terminal duct lobular units (TDLU) (circles) coming off the terminal (arrow). The right image is a 10x magnification. It the dense interlobular stroma between the TDLUs and the more delicate intralobular stroma that separates each of the acini within a lobule. Terminal Duct Interlobular Stroma

Intralobular Ducts Intralobular Stroma Acini Intralobular Stroma This 20x magnification of a TDLU demonstrates the intralobular ducts that are lined by two layers of basophilic (blue) staining cuboidal epithelial cells that end in glandular acini. Each TDLU contains 10-100 acini drain into the terminal duct. The acini are poorly developed in the non-secreting mammary glands. At this higher magnification you can see that the delicate intralobular stroma contains lymphocytes, macrophages, and plasma cells that surround the acini within the TDLU.  

Luminal Epithelial Cells Intralobular Stroma Myoepithelial Cells Luminal Epithelial Cells The intralobular ducts contain two cell types that rest on the basement membrane. The lumen of the intralobular ducts and acini is lined by cuboidal ductal epithelial (luminal) cells whose function is to produce milk an. The actin and myosin containing myoepithelial cells have a clear cytoplasm and are in close contact with the ductal epithelial cell. The myoepithelial cells’ contraction propels the luminal contents through the ducts. An absence of myoepithelial cells is associated with a neoplastic process. Also note the delicate collagen of the intralobular stroma along with mononuclear cells (lymphocyte, plasma cell, and macrophage) and fibroblasts. Basement Membrane

Physiologic Changes Pregnancy Inactive Lactation Prior to the onset of puberty, the TDLUs are small with prominent terminal ductules, small acini, and a larger portion of intralobular stroma. At puberty the ovaries start to secrete estrogen which stimulates the accumulation of adipose tissue and hypertrophy of the TDLUs. By fifth or sixth months of pregnancy the breasts are fully capable of producing milk. Hormonal stimulation has caused both hyperplasia and hypertrophy of the acinar cells. The lumen of the acini contain secretions.   Lactation

A B The resting mammary gland (A) undergoes a series of physiologic changes, both morphologic and functional, in response to hormonal stimulation. Estrogen stimulates milk production during pregnancy and lactation (B) where the terminal portions of the ductule proliferate and hypertrophy to form secretory acini. The lumen of the acini contain eosinophilic staining secretions. Review Dr. Danforth’s short eModule.  

These three images demonstrate the progressive morphologic changes that breast undergoes during life. The resting mammary gland (A) undergoes a series of physiologic changes, both morphologic and functional, in response to hormonal stimulation. Estrogen stimulates milk production during pregnancy and lactation (B). Low estrogen levels in menopause (C) leads to a loss of lobular tissue and an increase in fibroadipose stroma. The relative amount of this stromal tissue changes with hormonal stimulation and impacts the “readability” of a mammogram.

Key Points To Remember About the Normal Breast The TDLU, the functional unit of the breast, contains: Terminal duct and lobules lined by myoepithelial cells and ductal epithelial cells. Contains delicate intralobular stroma (gives rise to fibroadenoma) Dense collagenous stroma separates the TDLUs TDLUs respond to estrogen stimulation by proliferating and during pregnancy and lactation undergo marked hypertrophy and hyperplasia to produce milk. Withdraw of estrogen leads to glandular cellular atrophy and apoptosis.

Normal Breast 1 Quiz

Thank you! After reflecting on the normal breast histology, contact me if you have any questions at charles.hitchcock@osumc.edu After reflecting on the normal breast histology, contact me if you have any questions.

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