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This fifth edition comes at a time when considerable progress has been made in the treatment of breast cancer. In the United States and in Western Europe, there has been a substantial decrease in the death rate from the disease, attributable to early detection with screening mammogra- phy and increasingly effective systemic treatment. Also, it is now established that effective local treatment is essential to decreasing breast cancer mortality. A key contributor to this decrease in breast cancer mortality has been the willingness of many thousands of women with breast cancer who have participated in clinical trials. Of importance as well to this progress are the many talented and dedicated laboratory and translational investigators and clinical researchers who
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have been committed to the breast cancer problem. This edition is dedicated to them.
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Efforts have also been made to understand and improve the quality of life of breast cancer patients. The widespread use of sentinel node biopsy as an alternative to axillary lymph node dissection is a prominent example. Systemic therapy is increasingly targeted and less toxic and advances in the molecular characterization of breast cancers have begun to explain the heterogeneity of the disease and allow for individualization of treatments. Radiation treatment has advanced by better incorporation of imaging modalities and more sophisticated irradiation techniques also allowing for more targeted, less toxic, and, in many cases, abbreviated courses of treatments. While there has been progress in the treatment of breast cancer, we are very aware that there are still many patients who die of the disease and that much more progress is needed.
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We hope that the fifth edition of Diseases of the Breast will be a useful resource for both clinicians and translational investigators and will foster the understanding and commu- nication necessary to provide optimal patient care and to help foster advances in managing diseases of the breast, especially breast cancer.
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Jay R. Harris, MD Marc E. Lippman, MD Monica Morrow, MD
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C. Kent Osborne, MD
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xv
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Interest in, and knowledge about, breast diseases, especially breast cancer, have increased greatly in recent years. A number of factors have contributed to this, the foremost of which are the high occurrence of breast cancer in western- ized countries and the dramatic upswing in this incidence during the past few decades. Clinical investigators have also helped define various benign diseases of the breast and have described their management and relation to subse- quent breast cancer development. Moreover, clinical trials performed throughout the world have contributed consid- erable information about the early detection and manage- ment of breast cancer using surgery, radiation therapy, and systemic therapies, including chemotherapy and hormonal interventions. Finally, rapid advances in the understanding of the molecular biology and genetics of both normal tissues and cancers have raised optimism that new, more specific methods can be developed to identify a woman’s risk for breast cancer, to prevent, or at least detect, the disease at an earlier stage, and, failing this, to cure it with minimal tox- icity. Ultimately a source of hope, these factors have never- theless caused considerable anxiety in the population, as well as provided a proliferation of information important for clinicians dealing with diseases that strike the breast.
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Diseases of the Breast is intended as a single-source com-
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pilation of the new knowledge on breast diseases presented in a form accessible to practicing clinicians. Although it is widely recognized that multidisciplinary interaction and information sharing are essential to effective clinical man- agement of diseases of the breast, new developments are
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rapidly demonstrating that clinicians also need to be knowl- edgeable about advances in basic science. A prominent example of how advances in basic science can rapidly enter the clinical arena is the discovery of the first genetic muta- tions at specific loci shown to be associated with a high risk of breast cancer. Clinicians are now faced with patient ques- tions about the nature and meaning of such testing as well as its risks and benefits. We believe that other advances in basic science will quickly be reflected in clinical practice.
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For Diseases of the Breast, we invited a large, diverse, and distinguished group of experts to summarize the cur- rent knowledge about breast diseases, including clinical features, management, and underlying biologic and epide- miologic factors. In assembling these contributions, we have tried to make the book comprehensive and timely, as well as accessible to practicing clinicians. We believe that this book will also be an aid to basic and translational scientists con- cerned about a breast cancer problem by providing clinical information that can help focus their energies and talents. We hope that Diseases of the Breast will be a useful resource for both clinicians and scientists and will foster the under- standing and communication necessary to provide optimal patient care and to rapidly achieve advances in managing diseases of the breast, especially breast cancer.
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Jay R. Harris, MD Marc E. Lippman, MD Monica Morrow, MD Samuel Hellman, MD
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xvi
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Dedication v Contributors vi
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Preface to the Fifth Edition xv Preface to the First Edition xvi
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S E C T I O N I
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Breast Anatomy and
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Development
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C H A P T E R 1
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Breast Anatomy and Development
| null | null | null |
Michael P. Osborne and Susan K. Boolbol
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Breast Anatomy and Development
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CHAPTER CONTENTS
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Embryology
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Breast Anatomy and Development
|
CHAPTER CONTENTS
| null | null |
Developmental Abnormalities Congenital Abnormalities Acquired Abnormalities
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Breast Anatomy and Development
|
CHAPTER CONTENTS
| null | null |
Normal Breast Development during Puberty Morphology
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Breast Anatomy and Development
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CHAPTER CONTENTS
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Adult Breast
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Breast Anatomy and Development
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CHAPTER CONTENTS
| null | null |
Vascular Anatomy of the Breast Lymphatic Drainage of the Breast
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Breast Anatomy and Development
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CHAPTER CONTENTS
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Muscular and Neural Anatomy Microanatomy of Breast Development Microscopic Anatomy of the Adult Breast Anatomy of the Nipple and Breast Ducts
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Breast Anatomy and Development
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CHAPTER CONTENTS
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Physiology
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Breast Anatomy and Development
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CHAPTER CONTENTS
| null | null |
Microscopy, Morphology, and the Menstrual Cycle Breast Changes during Pregnancy
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Breast Anatomy and Development
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CHAPTER CONTENTS
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Lactation Menopause
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Breast Anatomy and Development
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CHAPTER CONTENTS
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Mammary glands are a distinguishing feature of mammals. Nursing of the young in the animal kingdom has many physi- ologic advantages for the mother, such as aiding postpar- tum uterine involution, and for the neonate, in terms of the transfer of immunity and bonding. It has become increas- ingly apparent that the advantages of nursing are substan- tial for both mother and child.
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Breast Anatomy and Development
|
CHAPTER CONTENTS
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An understanding of the morphology and physiology of the breast, and the many endocrine interrelationships of both, is essential to the study of the pathophysiology of the breast and the management of benign, preneoplastic, and neoplastic disorders.
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Breast Anatomy and Development
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EMBRYOLOGY
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During the fifth week of human fetal development, the ecto- dermal primitive milk streak, or “galactic band,” develops from axilla to groin on the embryonic trunk (1). The ecto- derm over the thorax invaginates into the surrounding mes- enchyme, with subsequent epithelial budding and branching
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Breast Anatomy and Development
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EMBRYOLOGY
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(2). In the region of the thorax, the band develops to form a mammary ridge, whereas the remaining galactic band regresses. Incomplete regression or dispersion of the primi- tive galactic band leads to accessory mammary tissues, found in 2% to 6% of women in the form of accessory nipples or axillary breast tissue.
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Breast Anatomy and Development
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EMBRYOLOGY
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At 7 to 8 weeks’ gestation, a thickening occurs in the mammary anlage (milk hill stage), followed by invagina- tion into the chest wall mesenchyme (disc stage) and tridi- mensional growth (globular stage). Further invasion of the chest wall mesenchyme results in a flattening of the ridge (cone stage) at 10 to 14 weeks’ gestation. Between 12 and
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Breast Anatomy and Development
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EMBRYOLOGY
| null | null |
16 weeks’ gestation, mesenchymal cells differentiate into the smooth muscle of the nipple and areola. Epithelial buds
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Breast Anatomy and Development
|
EMBRYOLOGY
| null | null |
develop (budding stage) and then branch to form 15 to 25 strips of epithelium (branching stage) at 16 weeks’ ges- tation; these strips represent the future secretory alveoli
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Breast Anatomy and Development
|
EMBRYOLOGY
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(3). The secondary mammary anlage then develops, with differentiation of the hair follicle, sebaceous gland, and sweat gland elements, but only the sweat glands develop fully at this time. Phylogenetically, the breast parenchyma is believed to develop from sweat gland tissue. In addition, apocrine glands develop to form the Montgomery glands around the nipple. The developments described thus far are independent of hormonal influences.
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Breast Anatomy and Development
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EMBRYOLOGY
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During the third trimester of pregnancy, placental sex hormones enter the fetal circulation and induce canaliza- tion of the branched epithelial tissues (canalization stage)
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Breast Anatomy and Development
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EMBRYOLOGY
| null | null |
(4). This process continues from the 20th to the 32nd week of gestation. At term, 15 to 25 mammary ducts have been formed, with coalescence of approximately 10 major ducts and sebaceous glands near the epidermis (5). Parenchymal differentiation occurs at 32 to 40 weeks with the develop- ment of lobuloalveolar structures that contain colostrum (end-vesicle stage). A fourfold increase in mammary gland mass occurs at this time, and the nipple–areolar complex develops and becomes pigmented. Externally the nipple is small and flattened, although rudimentary sebaceous glands and Montgomery tubercles are present. The circu- lar smooth muscle fibers that lead to the erectile function of the nipple are developed by this stage.
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Breast Anatomy and Development
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EMBRYOLOGY
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In the neonate, the stimulated mammary tissue secretes colostral milk (sometimes called witch’s milk), which can be expressed from the nipple for 4 to 7 days postpartum in most neonates of either sex. At birth, the withdrawal of maternal steroids results in the secretion of neonatal pro- lactin. It is this hormone that stimulates newborn breast secretion. In the newborn, colostral secretion declines over a 3- to 4-week period owing to involution of the breast after
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Breast Anatomy and Development
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EMBRYOLOGY
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3
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Breast Anatomy and Development
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EMBRYOLOGY
| null | null |
withdrawal of placental hormones. During early childhood, the end vesicles become further canalized and develop into ductal structures by additional growth and branching.
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Breast Anatomy and Development
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EMBRYOLOGY
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After birth, the male breast undergoes minimal addi- tional development and remains rudimentary. In the female, the breasts undergo extensive further development, which is regulated by hormones that influence reproduction. The breast has reached its major development by 20 years of age and will usually begin to undergo atrophic changes in the fifth decade of life.
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Breast Anatomy and Development
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DEVELOPMENTAL ABNORMALITIES
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The developmental abnormalities may be unilateral or bilat- eral and involve both the nipple and the breast or both. These abnormalities are usually isolated to the breast, but there are reports of being associated with a variety of other abnormali- ties. The most common association is with upper limb and urinary tract abnormalities.
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Breast Anatomy and Development
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DEVELOPMENTAL ABNORMALITIES
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Congenital Abnormalities
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Polythelia and Polymastia
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The most frequently observed abnormality seen in both sexes is an accessory nipple (polythelia). Ectopic nipple tissue may be mistaken for a pigmented nevus, and it may occur at any point along the milk streak from the axilla to the groin. The reported incidence of polythelia varies greatly in the literature. In a prospective study, Mimoumi et al. (6) found the incidence of polythelia to be 2.5%. Urbani and Betti
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Breast Anatomy and Development
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DEVELOPMENTAL ABNORMALITIES
|
Congenital Abnormalities
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Polythelia and Polymastia
|
(7) evaluated the association between polythelia and kidney and urinary tract malformations. These data indicate a sig- nificantly higher frequency of kidney and urinary tract mal- formations in patients with polythelia. This is a controversial issue, and many studies in the literature do not find any con- nection between polythelia and renal anomalies (8,9).
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Breast Anatomy and Development
|
DEVELOPMENTAL ABNORMALITIES
|
Congenital Abnormalities
|
Polythelia and Polymastia
|
Rarely, accessory true mammary glands develop; these are most often located in the axilla (polymastia). During pregnancy and lactation, an accessory breast may enlarge; occasionally, if it has an associated nipple, the accessory breast may function.
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Breast Anatomy and Development
|
DEVELOPMENTAL ABNORMALITIES
|
Congenital Abnormalities
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Hypoplasia and Amastia
|
Hypoplasia is the underdevelopment of the breast; congeni- tal absence of a breast is termed amastia. When breast tis- sue is lacking but a nipple is present, the condition is termed amazia. A wide range of breast abnormalities have been described and can be classified as follows (10,11):
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Breast Anatomy and Development
|
DEVELOPMENTAL ABNORMALITIES
|
Congenital Abnormalities
|
Hypoplasia and Amastia
|
Unilateral hypoplasia, contralateral normal Bilateral hypoplasia with asymmetry Unilateral hyperplasia, contralateral normal Bilateral hyperplasia with asymmetry
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Breast Anatomy and Development
|
DEVELOPMENTAL ABNORMALITIES
|
Congenital Abnormalities
|
Hypoplasia and Amastia
|
Unilateral hypoplasia, contralateral hyperplasia Unilateral hypoplasia of breast, thorax, and pectoral mus-
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Breast Anatomy and Development
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DEVELOPMENTAL ABNORMALITIES
|
Congenital Abnormalities
|
Hypoplasia and Amastia
|
cles (Poland’s syndrome)
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Breast Anatomy and Development
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DEVELOPMENTAL ABNORMALITIES
|
Congenital Abnormalities
|
Hypoplasia and Amastia
|
Most of these abnormalities are not severe. The most severe deformity, amastia or marked breast hypoplasia, is associ- ated with hypoplasia of the pectoral muscle in 90% of cases (12), but the reverse does not apply. Of women with pec- toral muscle abnormalities, 92% have a normal breast (13). Congenital abnormalities of the pectoral muscle are usu- ally manifested by the lack of the lower third of the muscle and an associated deformity of the ipsilateral rib cage. The association among absence of the pectoral muscle, chest wall deformity, and breast abnormalities was first recog- nized by Poland in 1841. The original description, however,
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Breast Anatomy and Development
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DEVELOPMENTAL ABNORMALITIES
|
Congenital Abnormalities
|
Hypoplasia and Amastia
|
did not note the concomitant abnormalities of the hand (symbrachydactyly, with hypoplasia of the middle phalan- ges and central skin webbing) (14), and considerable con- troversy has evolved concerning the validity of the eponym for this congenital syndrome (15,16).
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Breast Anatomy and Development
|
DEVELOPMENTAL ABNORMALITIES
|
Congenital Abnormalities
|
Athelia
|
The congenital absence of the nipple areolar complex is a rare entity and is usually associated with absence of the breast. This condition is typically associated with other anomalies.
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Breast Anatomy and Development
|
DEVELOPMENTAL ABNORMALITIES
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Acquired Abnormalities
| null |
The most common—and avoidable—cause of amastia is iatrogenic. Injudicious biopsy of a precociously develop- ing breast results in excision of most of the breast bud and subsequent marked deformity during puberty. The use of radiation therapy in prepubertal girls to treat either heman- gioma of the breast or intrathoracic disease can also result in amastia. Traumatic injury of the developing breast, such as that caused by a severe cutaneous burn, with subsequent contracture, can also result in deformity.
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Breast Anatomy and Development
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NORMAL BREAST DEVELOPMENT DURING PUBERTY
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Puberty in girls begins at the age of 10 to 12 years as a result of the influence of hypothalamic gonadotropin-releasing hor- mones secreted into the hypothalamic–pituitary portal venous system. The basophilic cells of the anterior pituitary release follicle-stimulating hormone and luteinizing hormone. Follicle- stimulating hormone causes the primordial ovarian follicles to mature into Graafian follicles, which secrete estrogens, pri- marily in the form of 17-estradiol. These hormones induce the growth and maturation of the breasts and genital organs (17). During the first 1 to 2 years after menarche, hypothalamic– adenohypophyseal function is unbalanced because the matu- ration of the primordial ovarian follicles does not result in ovulation or a luteal phase. Therefore, ovarian estrogen syn- thesis predominates over luteal progesterone synthesis. The physiologic effect of estrogens on the maturing breast is to stimulate longitudinal growth of ductal epithelium. Terminal ductules also form buds that precede formation of breast lob- ules. Simultaneously, periductal connective tissues increase in volume and elasticity, with enhanced vascularity and fat deposition. These initial changes are induced by estrogens synthesized in immature ovarian follicles, which are anovula- tory; subsequently, mature follicles ovulate, and the corpus luteum releases progesterone. The relative role of these hor- mones is not clear. In experimental studies, estrogens alone induce a pronounced ductular increase, whereas progester- one alone does not. The two hormones together produce full ductular–lobular–alveolar development of mammary tissues
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Breast Anatomy and Development
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NORMAL BREAST DEVELOPMENT DURING PUBERTY
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(17). The marked individual variation in development of the
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Breast Anatomy and Development
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NORMAL BREAST DEVELOPMENT DURING PUBERTY
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breast makes it impossible to categorize histologic changes on the basis of age (4). Breast development by age has been described by external morphologic changes. The evolution of the breast from childhood to maturity has been divided into five phases by Tanner (18), as shown in Table 1-1.
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Breast Anatomy and Development
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MORPHOLOGY
|
Adult Breast
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The adult breast lies between the second and sixth ribs in the vertical axis and between the sternal edge and the midax- illary line in the horizontal axis (Fig. 1-1). The average breast
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Breast Anatomy and Development
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MORPHOLOGY
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Adult Breast
| null |
measures 10 to 12 cm in diameter, and its average thickness centrally is 5 to 7 cm. Breast tissue also projects into the axilla as the axillary tail of Spence. The contour of the breast varies but is usually dome-like, with a conical configuration in the nulliparous woman and a pendulous contour in the parous woman. The breast is comprised of three major struc- tures: skin, subcutaneous tissue, and breast tissue, with the last comprising both parenchyma and stroma. The paren- chyma is divided into 15 to 20 segments that converge at the nipple in a radial arrangement. The collecting ducts that drain each segment are 2 mm in diameter, with subareolar lactiferous sinuses of 5 to 8 mm in diameter. Approximately 10 major collecting milk ducts open at the nipple (5).
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Breast Anatomy and Development
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MORPHOLOGY
|
Adult Breast
| null |
The nomenclature of the duct system is varied. The branching system can be named in a logical fashion, starting with the collecting ducts in the nipple and extending to the ducts that drain each alveolus, as shown in Table 1-2. Each duct drains a lobe made up of 20 to 40 lobules. Each lob- ule consists of 10 to 100 alveoli or tubulosaccular secretory units (5,19). The stroma and subcutaneous tissues of the breast contain fat, connective tissue, blood vessels, nerves, and lymphatics.
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Breast Anatomy and Development
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MORPHOLOGY
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Adult Breast
| null |
The skin of the breast is thin and contains hair fol- licles, sebaceous glands, and eccrine sweat glands. The nipple, which is located over the fourth intercostal space in the nonpendulous breast, contains abundant
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Breast Anatomy and Development
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MORPHOLOGY
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Adult Breast
| null |
sensory nerve endings, including Ruffini-like bodies and end bulbs of Krause. Moreover, sebaceous and apo- crine sweat glands are present, but not hair follicles. The areola is circular and pigmented, measuring 15 to 60 mm in diameter. The Morgagni tubercles, located near the periphery of the areola, are elevations formed by openings of the ducts of the Montgomery glands. The Montgomery glands are large sebaceous glands capable of secreting milk; they represent an intermediate stage between sweat and mammary glands. Fascial tissues envelop the breast; the superficial pectoral fascia envelops the breast and is contin- uous with the superficial abdominal fascia of Camper. The undersurface of the breast lies on the deep pectoral fascia, covering the pectoralis major and anterior serratus mus- cles. Connecting these two fascial layers are fibrous bands (Cooper suspensory ligaments) that represent the “natural” means of support of the breast.
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Breast Anatomy and Development
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MORPHOLOGY
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Vascular Anatomy of the Breast
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The principal blood supply to the breast is derived from the internal mammary and lateral thoracic arteries. Approximately 60% of the breast, mainly the medial and central parts, is sup- plied by the anterior perforating branches of the internal mammary artery. Approximately 30% of the breast, mainly the upper, outer quadrant, is supplied by the lateral thoracic artery. The pectoral branch of the thoracoacromial artery; the lateral branches of the third, fourth, and fifth intercostal arteries; and the subscapular and thoracodorsal arteries all make minor contributions to the blood supply.
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Breast Anatomy and Development
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MORPHOLOGY
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Vascular Anatomy of the Breast
| null |
The principal veins involved in the venous drainage of the thoracic wall and the breast are the perforating branches of the internal thoracic vein, tributaries of the axillary vein, and perforating branches of posterior intercostal veins.
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Breast Anatomy and Development
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MORPHOLOGY
|
Lymphatic Drainage of the Breast
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Lymph Vessels
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The lymphatic drainage of the breast is of great importance in the spread of malignant disease of the breast. The subepi- thelial or papillary plexus of the lymphatics of the breast is confluent with the subepithelial lymphatics over the surface of the body. These valveless lymphatic vessels communi- cate with subdermal lymphatic vessels and merge with the Sappey subareolar plexus. The subareolar plexus receives lymphatic vessels from the nipple and areola and commu- nicates by way of vertical lymphatic vessels equivalent to those that connect the subepithelial and subdermal plexus elsewhere (20). Lymph flows unidirectionally from the super- ficial to deep plexus and from the subareolar plexus through the lymphatic vessels of the lactiferous ducts to the peril- obular and deep subcutaneous plexus. The periductal lym- phatic vessels lie just outside the myoepithelial layer of the duct wall (21). Flow from the deep subcutaneous and intra- mammary lymphatic vessels moves centrifugally toward the axillary and internal mammary lymph nodes. Injection studies with radiolabeled colloid (22) have demonstrated the physiology of lymph flow and have countered the old hypothesis of centripetal flow toward the Sappey subareolar plexus (23). Approximately 3% of the lymph from the breast is estimated to flow to the internal mammary chain, whereas 97% flows to the axillary nodes (24).
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Breast Anatomy and Development
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MORPHOLOGY
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Lymphatic Drainage of the Breast
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Lymph Vessels
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New insight into lymphatic anatomy and the physiol-
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Breast Anatomy and Development
|
MORPHOLOGY
|
Lymphatic Drainage of the Breast
|
Lymph Vessels
|
ogy of lymph flow has been gained from sentinel lymph node studies. It has been observed that the dermal and parenchymal lymphatics drain to the same axillary lymph nodes that are the main basin for lymph draining from the breast (25–30). This might be expected considering the embryology of the breast described earlier in this chapter.
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Breast Anatomy and Development
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MORPHOLOGY
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Lymphatic Drainage of the Breast
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Lymph Vessels
|
FIGURE 1-1 Normal anatomy of the breast and pectoralis major muscle. 1. Perforating branches from internal mammary artery and vein; 2. Pectoral branches from thoracoacro- mial artery and vein; 3. External mammary branch from lateral thoracic artery and vein;
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Breast Anatomy and Development
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MORPHOLOGY
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Lymphatic Drainage of the Breast
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Lymph Vessels
|
4. Branches from subscapular and thoracodorsal arteries and veins; 5. Lateral branches of third, fourth, and fifth intercostal arteries and veins; 6. Internal mammary artery and veins;
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Breast Anatomy and Development
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MORPHOLOGY
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Lymphatic Drainage of the Breast
|
Lymph Vessels
|
7. Sternocostal head of pectoralis major muscle; 8. Clavicular head of pectoralis major muscle; 9. Axillary artery and vein; 10. Cephalic vein; 11. Axillary sheath; 12. Latissimus dorsi muscle; 13. Serratus anterior muscle; 14. External abdominal oblique muscle.
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Breast Anatomy and Development
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MORPHOLOGY
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Lymphatic Drainage of the Breast
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Lymph Vessels
|
Lymphoscintigraphic studies have also shown that deeper parenchymal or retromammary lymphatics preferentially drain to the internal mammary lymph nodes when compared to intradermal or subdermal injection (31–35). There has been controversy over the direction of parenchymal lymph
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Breast Anatomy and Development
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MORPHOLOGY
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Lymphatic Drainage of the Breast
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Lymph Vessels
|
flow in relation to the subareolar plexus. Isotope injection of technetium-99m–labeled sulfur colloid into the subareolar region results in localization of isotope in the axillary sentinel lymph node (36–38). A detailed isotope study of subareolar injection and the lymphatic channels leading to the sentinel lymph node showed that in 90% of cases a single channel exited the areolar margin superiorly or laterally and termi- nated in an axillary sentinel lymph node (39). Secondary lymphatic channels exited the areola in 75% of cases. None entered the internal mammary lymph node chain.
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Breast Anatomy and Development
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MORPHOLOGY
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Lymphatic Drainage of the Breast
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Lymph Vessels
|
Suami et al. (40) studied 24 breasts in 14 fresh human cadavers to examine the lymphatic drainage. Lymph collect- ing vessels were found evenly spaced at the periphery of the anterior upper torso draining radially into the axillary nodes. As identified in cross-section analysis, as these collecting vessels reached the breast some passed over and some through the breast parenchyma. Perforating lymph vessels that coursed beside the branches of the internal mammary vessels and drained into the ipsilateral internal mammary
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Breast Anatomy and Development
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MORPHOLOGY
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Lymphatic Drainage of the Breast
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Lymph Vessels
|
lymphatics were also found. Some of these findings are discordant with current knowledge and may explain some of the false-negative rates of sentinel lymph node biopsy.
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Breast Anatomy and Development
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MORPHOLOGY
|
Lymphatic Drainage of the Breast
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Axillary Lymph Nodes
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The topographic anatomy of the axillary lymph nodes has been studied as the major route of regional spread in primary mammary carcinoma. The anatomic arrangement of the axil- lary lymph nodes has been subject to many different classifi- cations. The most detailed studies are those of Pickren (41), which show the pathologic anatomy of tumor spread. Axillary lymph nodes can be grouped as the apical or subclavicular nodes, lying medial to the pectoralis minor muscle, and the axillary vein lymph nodes, grouped along the axillary vein from the pectoralis minor muscle to the lateral limit of the axilla; the interpectoral (Rotter) nodes, lying between the pectoralis major and minor muscles along the lateral pectoral nerve (42,43); the scapular group, comprising the nodes lying along the subscapular vessels; and the central nodes, lying beneath the lateral border of the pectoralis major muscle and below the pectoralis minor muscle (Fig. 1-2). Other groups can be identified, such as the external mammary nodes lying over the axillary tail, intramammary lymph nodes, which are found in 28% of breasts (44), and the paramammary nodes located in the subcutaneous fat over the upper, outer quad- rant of the breast.
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Breast Anatomy and Development
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MORPHOLOGY
|
Lymphatic Drainage of the Breast
|
Axillary Lymph Nodes
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An alternative method of delineating metastatic spread, for the purposes of determining pathologic anatomy and met- astatic progression, is to divide the axillary lymph nodes into arbitrary levels (45). Level I lymph nodes lie lateral to the lat- eral border of the pectoralis minor muscle, level II nodes lie behind the pectoralis minor muscle, and level III nodes are located medial to the medial border of the pectoralis minor muscle (Fig. 1-3). These levels can be determined accurately only by marking them with tags at the time of surgery.
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Breast Anatomy and Development
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MORPHOLOGY
|
Lymphatic Drainage of the Breast
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Internal Mammary Lymph Nodes
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The internal mammary nodes lie in the intercostal spaces in the parasternal region. The nodes lie close to the inter- nal mammary vessels in extrapleural fat and are distributed in the intercostal spaces, as shown in Figure 1-3. From the second intercostal space downward, the internal mammary nodes are separated from the pleura by a thin layer of fascia in the same plane as the transverse thoracic muscle. The number of lymph nodes described in the internal mammary chain varies. The nodes lie medial to the internal mammary vessels in the first and second intercostal spaces in 88% and 76% of cases, respectively, whereas they lie lateral to the vessels in the third intercostal space in 79% of cases. The prevalence of nodes in each intercostal space is as follows: first space, 97%; second space, 98%; third space, 82%; fourth space, 9%; fifth space, 12%; and sixth space, 62% (46). The pathologic anatomy of this route of lymphatic drainage in the spread of breast disease has been described by Handley and Thackray (47) and Urban and Marjani (48).
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Breast Anatomy and Development
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MORPHOLOGY
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Lymphatic Drainage of the Breast
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Internal Mammary Lymph Nodes
|
In the presence of nodal metastases, obstruction of the physiologic routes of lymphatic flow may occur, and alter- native pathways may then become important. The alterna- tive routes that have been described are deep, substernal, cross-drainage to the contralateral internal mammary chain (49,50); superficial presternal crossover, lateral intercostal, and mediastinal drainage (51); and spread through the rec- tus abdominis muscle sheath to the subdiaphragmatic and subperitoneal plexus (the Gerota pathway). This last route allows the direct spread of tumor to the liver and retroperi- toneal lymph nodes. Substernal crossover is demonstra- ble by isotope imaging of the lymph nodes and may be of significance in early breast cancer (52).
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Breast Anatomy and Development
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MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
The important muscles in the region of the breast are the pectoralis major and minor, serratus anterior, and latissimus dorsi muscles, as well as the aponeurosis of the external oblique and rectus abdominis muscles (Fig. 1-2).
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Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
The pectoralis minor muscle arises from the outer aspect of the third, fourth, and fifth ribs and is inserted into the medial border of the upper surface of the coracoid pro- cess of the scapula. The muscle is usually prefixed, rather than postfixed, and is innervated by the medial pectoral nerve, which arises mainly from the medial cord of the bra- chial plexus (cervical vertebra number, or C8, T1 segmental origin) and descends posteriorly to the muscle crossing the axillary vein anteriorly. The nerve enters the interpectoral space, passing through the muscle itself in 62% of cases and around the lateral border as a single branch in 38% of cases (53). Varying numbers of branches passing through the muscle provide motor supply to the lateral part of the pectoralis major muscle. The terms medial and lateral pec- toral nerves are confusing: The standard terminology refers to their brachial plexus origin rather than their anatomic positions. Changes in terminology have been proposed but have not yet been generally accepted. The arrangement of these nerves is of particular importance in performing an axillary dissection.
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Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
The serratus anterior muscle stabilizes the scapula on the chest wall. The muscle arises by a series of digitations from the upper eight ribs laterally; its origin from the first rib is in the posterior triangle of the neck. At its origin from the fifth, sixth, seventh, and eighth ribs, the serratus anterior muscle interdigitates with the origin of the external oblique muscle. The muscle inserts into the vertebral border of the scapula on its costal surface and is supplied by the long thoracic nerve of Bell (the nerve to the serratus anterior muscle). The origin of this important nerve is the posterior aspect of the C5, C6, and C7 roots of the brachial plexus. It passes posteriorly to the axillary vessels, emerging on the chest wall high in the medial part of the subscapular fossa. The nerve lies superfi- cial to the deep fascia overlying the anterior serratus muscle and marks the posterior limit of dissection of the deep fas- cia. Preservation of the nerve to the serratus anterior muscle as it passes downward is essential to avoid “winging” of the scapula and loss of shoulder power.
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
The latissimus dorsi muscle, the largest muscle in the body, is characterized by a wide origin from the spinous processes and supraspinous ligaments of the seventh thoracic vertebra downward, including all the lumbar and sacral vertebrae. The muscle inserts, by a narrow tendon forming the posterior axillary fold, into a 2.5-cm insertion in the bicipital groove of the humerus. As the muscle spirals around the teres major muscle, the surfaces of the muscle become reversed to the point of insertion. The muscle is supplied by the thoracodorsal nerve (the nerve to the latissimus dorsi muscle), which arises from the posterior cord of the brachial plexus, with segmental origin from C6, C7, and C8. The nerve passes behind the axillary ves- sels, approaches the subscapular vessels from the medial side, and then crosses anterior to these vessels to enter the medial surface of the muscle. As the nerve passes through the axilla it is intimately involved in the scapular group of lymph nodes. Resection of the nerve does not result in any important cosmetic or functional defect; nevertheless, it should be preserved when possible.
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
An important landmark in the apex of the axilla is the origin of the subclavius muscle, which arises from the cos- tochondral junction of the first rib. At the tendinous part of the lower border of this muscle, two layers of the cla- vipectoral fascia fuse together to form a well-developed
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
FIGURE 1-2 Chest wall muscles and vascular anatomy. 1. External abdominal oblique muscle; 2. Rectus sheath; 3. Rectus abdominis muscle; 4. Internal intercostal muscle;
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
5. Transverse thoracic muscle; 6. Pectoralis minor muscle; 7. Perforating branches from internal mammary artery and vein; 8. Internal mammary artery and vein; 9. Cut edge of pectoralis major muscle; 10. Sternoclavicular branch of thoracoacromial artery and vein;
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
11. Subclavius muscle and Halsted ligament; 12. External intercostal muscle; 13. Axillary vein; 14. Axillary artery; 15. Lateral cord of brachial plexus; 16. Lateral pectoral nerve (from the lateral cord); 17. Cephalic vein; 18. Thoracoacromial vein; 19. Intercostobrachial nerve; 20. Lateral cutaneous nerves; 21. Lateral thoracic artery and vein; 22. Scapular branches of lateral thoracic artery and vein; 23. Medial pectoral nerve (from medial cord); 24. Ulnar nerve; 25. Pectoralis minor muscle; 26. Coracoclavicular ligament;
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
27. Coracoacromial ligament; 28. Cut edge of deltoid muscle; 29. Acromial and humeral branches of thoracoacromial artery and vein; 30. Musculocutaneous nerve; 31. Medial cutaneous nerve of arm; 32. Subscapularis muscle; 33. Lower subscapular nerve; 34. Teres major muscle; 35. Long thoracic nerve; 36. Serratus anterior muscle; 37. Latissimus dorsi muscle; 38. Latissimus dorsi muscle; 39. Thoracodorsal nerve; 40. Thoracodorsal artery and vein; 41. Scapular circumflex artery and vein; 42. Branching of intercostobrachial nerve; 43. Teres major muscle; 44. Medial cutaneous nerve of forearm; 45. Subscapular artery and vein; 46. Posterior humeral circumflex artery and vein; 47. Median nerve;
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
48. Coracobrachialis muscle; 49. Pectoralis major muscle; 50. Biceps brachii muscle, long head; 51. Biceps brachii muscle, short head; 52. Brachial artery; 53. Basilic vein;
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
54. Pectoral branch of thoracoacromial artery and vein.
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
FIGURE 1-3 Lymphatic drainage of the breast showing lymph node groups and levels.
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
1. Internal mammary artery and vein; 2. Substernal cross-drainage to contralateral internal mammary lymphatic chain; 3. Subclavius muscle and Halsted ligament; 4. Lateral pectoral nerve (from the lateral cord); 5. Pectoral branch from thoracoacromial vein; 6. Pectoralis minor muscle; 7. Pectoralis major muscle; 8. Lateral thoracic vein; 9. Medial pectoral nerve (from the medial cord); 10. Pectoralis minor muscle; 11. Median nerve; 12. Subscapular vein; 13. Thoracodorsal vein; A. Internal mammary lymph nodes; B. Apical lymph nodes;
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
C. Interpectoral (Rotter) lymph nodes; D. Axillary vein lymph nodes; E. Central lymph nodes; F. Scapular lymph nodes; G. External mammary lymph nodes; Level I lymph nodes: lateral to lateral border of pectoralis minor muscle; Level II lymph nodes: behind pectoralis minor muscle; Level III lymph nodes: medial to medial border of pectoralis minor muscle.
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
| null |
band, the costocoracoid ligament, which stretches from the coracoid process to the first costochondral junction (the Halsted ligament). At this point, the axillary vessels (the vein being anterior and inferior to the artery) enter the tho- rax, passing over the first rib and beneath the clavicle. Many unnamed small branches enter the axillary vein at its lower border. Near the apex, a small artery, the highest thoracic artery, arises from the axillary artery and lies on the first and second ribs.
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
|
Muscular Abnormalities
|
Congenital absence of the sternocostal head of the pec- toralis major muscle and its associated abnormalities (Poland’s syndrome) have been described earlier in this chapter. In 5% of cadavers, a sternalis muscle can be
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
|
Muscular Abnormalities
|
found lying longitudinally between the sternal insertion of the sternocleidomastoid muscle and the rectus abdomi- nis muscle. The pectoralis minor muscle is inserted into the head of the humerus as well as the coracoid process of the scapula in 15% of cases. Part of the tendon then passes between the two parts of the coracoacromial liga- ment to insert into the coracohumeral ligament. Rarely, the axillopectoral muscle arises as a separate part of the latissimus dorsi muscle and inferolaterally crosses the base of the axilla superficially, passing deep to the pecto- ralis major muscle to join its insertion or to continue to the coracoid process (the axillohumeral arch of Langer). This anatomic arrangement can cause compression of the axillary vessels (54) and difficulty in orientation during axillary dissection.
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
|
Muscular Abnormalities
|
FIGURE 1-4 Normal duct in adolescent female breast.
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Muscular and Neural Anatomy
|
Muscular Abnormalities
|
Rudimentary lobules are seen to be “budding” from the parent duct. Hematoxylin and eosin (H&E) stain. (Photomicrograph courtesy of Dr. Syed Hoda.)
|
Breast Anatomy and Development
|
MORPHOLOGY
|
Microanatomy of Breast Development
| null |
The developing breast at puberty has been described in detail by Russo and Russo (55) as growing and dividing ducts that form club-shaped terminal end buds. Growing terminal end buds form new branches, twigs, and small ductules termed alveolar buds (Fig. 1-4). Alveolar buds subsequently differentiate into the terminal structure of the resting breast, named the acines by German pathologists or the ductule by Dawson (4). The term alveolus is best applied to the resting secretory unit, and acines to the fully developed secretory unit of pregnancy and lactation (55).
|
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