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, milk lines) are evident in the embryo. In most mammals, paired breasts develop along these ridges, which extend from the base of the forelimb (future axilla) to the region of the hind limb (inguinal area). These ridges are not prominent in the human embryo and disappear after a short time, except for small portions that may persist in the pectoral region. Accessory breasts (polymastia) or accessory nipples (polythelia) may occur along the milk line when normal regression fails. Each breast develops when an ingrowth of ectoderm forms a primary tissue bud in the mesenchyme. The primary bud, in turn, initiates the development of 15 to 20 secondary buds. Epithelial cords develop from the secondary buds and extend into the surrounding mesenchyme. Major (lactiferous) ducts develop, which open into a shallow mammary pit. During infancy, a proliferation of mesenchyme transforms the mammary pit into a nipple. If there is failure of a pit to elevate above skin level, an inverted nipple results. This congenital malformation occurs in 4% of infants. At birth, the breasts are identical in males and females, demonstrating only the presence of major ducts. Enlargement of the breast may be evident and a secretion, referred to as witch's milk, may be produced. These transitory events occur in response to maternal hormones that cross the placenta. The breast remains undeveloped in the female until puberty, when it enlarges in response to ovarian estrogen and progesterone, which initiate proliferation of the epithelial and connective tissue elements. However, the breasts remain incompletely developed until pregnancy occurs. Absence of the breast (amastia) is rare and results from an arrest in mammary ridge development that occurs during the 6th fetal week. Breast hypoplasia also may be iatrogenically induced prior to puberty by trauma, infection, or radiation therapy. Symmastia is a rare anomaly recognized as webbing between the breasts across the midline. Accessory nipples (polythelia) occur in less than 1% of infants. Supernumerary breasts may occur in any configuration along the mammary milk line, but most frequently occur between the normal nipple location and the symphysis pubis. Accessory axillary breast tissue is uncommon and usually is bilateral. Functional Anatomy The breast is composed of 15 to 20 lobes, which are each composed of several lobules. Fibrous bands of connective tissue travel through the breast (suspensory ligaments of Cooper), insert perpendicularly into the dermis, and provide structural support. The mature female breast extends from the level of the 2nd/3rd rib to the inframammary fold at the 6th/7th rib. It extends transversely from the lateral border of the sternum to the anterior axillary line. The deep or posterior surface of the breast rests on the fascia of the pectoralis major, serratus anterior, and external oblique abdominal muscles, and the upper extent of the rectus sheath. The retromammary bursa may be identified on the posterior aspect of the breast between the investing fascia of the breast and the fascia of the pectoralis major muscles. The axillary tail of Spence extends laterally across the anterior axillary fold. The upper outer quadrant of the breast
contains a greater volume of tissue than do the other quadrants. Considerable variations in the size, contour, and density of the breast are evident between individuals. Nipple–areola Complex The epidermis of the nipple–areola complex is pigmented and is variably corrugated. During puberty, the pigment becomes darker and the nipple assumes an elevated configuration. During pregnancy, the areola enlarges and pigmentation is further enhanced. The areola contains sebaceous glands, sweat glands, and accessory glands, which produce small elevations on the surface of the areola (Montgomery tubercles). Smooth-muscle bundle fibers, which lie circumferentially in the dense connective tissue and longitudinally along the major ducts, extend upward into the nipple where they are responsible for the nipple erection that occurs with various sensory stimuli. The dermal papilla at the tip of the nipple contains numerous sensory nerve endings and Meissner's corpuscles. This rich sensory innervation is of functional importance as the sucking infant initiates a chain of neurohumoral events that results in milk letdown. Inactive and Active Breast Each lobe of the breast terminates in a major (lactiferous) duct (2 to 4 mm in dm), which opens through a constricted orifice (0.4 to 0.7 mm in dm) into the ampulla of the nipple. Immediately below the nipple–areola complex, each major duct has a dilated portion (lactiferous sinus), which is lined with stratified squamous epithelium. Major ducts are lined with two layers of cuboidal cells, while minor ducts are lined with a single layer of columnar or cuboidal cells. Myoepithelial cells of ectodermal origin reside between the epithelial cells in the basal lamina and contain myofibrils.
In the inactive breast, the epithelium is sparse and consists primarily of ductal epithelium. In the early phase of the menstrual cycle, minor ducts are cord-like with small lumina. With estrogen stimulation at the time of ovulation, alveolar epithelium increase, in height, duct lumina become more prominent, and some secretions accumulate. When the hormonal stimulation decreases, the alveolar epithelium regresses.
plasma cells.With pregnancy. . and dense lysosomes. As the breast enlarges in response to hormonal stimulation. Two distinct substances are produced by the alveolar epithelium: (1) the protein component of milk. and eosinophils accumulate within the connective tissues.With parturition. The minor ducts branch and alveoli develop. which forms as free lipid droplets in the cytoplasm. the breast undergoes proliferative and developmental maturation. which is synthesized in the endoplasmic reticulum (merocrine secretion). Milk released in the first few days following parturition is called colostrum and has low lipid content but contains considerable quantities of antibodies. enlargement of the breasts occurs via hypertrophy of alveolar epithelium and accumulation of secretory products in the lumina of the minor ducts. and (2) the lipid component of milk (apocrine secretion). Golgi complexes. large mitochondria. Alveolar epithelium contains abundant endoplasmic reticulum. lymphocytes.
The three principal groups of veins are: • • • perforating branches of the internal thoracic vein perforating branches of the posterior intercostal veins tributaries of the axillary vein. and Lymphatics The breast receives its principal blood supply from: • • • perforating branches of the internal mammary artery lateral branches of the posterior intercostal arteries branches from the axillary artery(highest thoracic. The lateral thoracic artery gives off branches to the serratus anterior. and subscapularis muscles. pectoralis major and minor. lateral thoracic. With subsequent reduction in the number of these cells. Innervation. 3rd . It also gives rise to lateral mammary branches. and 4th anterior intercostal perforators and branches of the internal mammary artery arborize in the breast as the medial mammary arteries. Blood Supply. . the production of colostrum decreases and lipid-rich milk is released. and pectoral branches of the thoracoacromial artery) The 2nd .The lymphocytes and plasma cells that accumulate within the connective tissues of the breast are the source of the antibody component.
specifically the anterior branches of the supraclavicular nerve. The boundaries for lymph drainage of the axilla are not well demarcated. The intercostobrachial nerve is the lateral cutaneous branch of the 2nd intercostal nerve and may be visualized during surgical dissection of the axilla.The vertebral venous plexus of Batson. Cutaneous branches that arise from the cervical plexus. supply a limited area of skin over the upper portion of the breast. which invests the vertebrae and extends from the base of the skull to the sacrum. pelvic bones. and central nervous system. These branches exit the intercostal spaces between slips of the serratus anterior muscle. Resection of the intercostobrachial nerve causes loss of sensation over the medial aspect of the upper arm. The 6 axillary lymph node groups recognized by surgeons are: Axillary vein group (lateral) • • • consists of 4 to 6 lymph nodes lie medial or posterior to the vein receive most of the lymph drainage from the upper extremity External mammary group (anterior or pectoral group) • • • consists of 5 or 6 lymph nodes lie along the lower border of the pectoralis minor muscle contiguous with the lateral thoracic vessels receive most of the lymph drainage from the lateral aspect of the breast . may provide a route for breast cancer metastases to the vertebrae. skull. and there is considerable variation in the position of the axillary lymph nodes. Lateral cutaneous branches of the 3rd to 6th intercostal nerves provide sensory innervation of the breast (lateral mammary branches) and of the anterolateral chest wall.
external mammary. The lymph node groups are assigned levels according to their relationship to the pectoralis minor muscle. Scapular group (posterior or subscapular) • • • consists of 5 to 7 lymph nodes lie along the posterior wall of the axilla at the lateral border of the scapula contiguous with the subscapular vessels receive lymph drainage principally from the lower posterior neck. level I lymph nodes • • Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle axillary vein. The lymph fluid that passes through the interpectoral group of lymph nodes passes directly into the central and subclavicular groups. external mammary. which are embedded in the fat of the axilla lie immediately posterior to the pectoralis minor muscle receive lymph drainage both from the axillary vein. the posterior trunk. and scapular groups of lymph nodes and directly from the breast Subclavicular group (apical) • • • consists of 6 to 12 sets of lymph nodes lie posterior and superior to the upper border of the pectoralis minor muscle receive lymph drainage from all of the other groups of axillary lymph nodes Interpectoral group (Rotter's) • • • • consists of 1 to 4 lymph nodes interposed between the pectoralis major and pectoralis minor muscles receive lymph drainage directly from the breast. and the posterior shoulder Central group • • • consists of 3 or 4 sets of lymph nodes. and scapular groups level II lymph nodes • • Lymph nodes located superficial or deep to the pectoralis minor muscle central and interpectoral groups .
From the upper part of the breast. The plexus of lymph vessels in the breast arises in the interlobular connective tissue and in the walls of the lactiferous ducts and communicates with the subareolar plexus of lymph vessels. Estrogen. including estrogen. and growth hormone. During the 3rd trimester. Pregnancy. The axillary lymph nodes usually receive more than 75% of the lymph drainage from the breast. the areolar skin darkens. prolactin. and LH secretion. level III lymph nodes • • Lymph nodes located medial to or above the upper border of the pectoralis minor muscle subclavicular group. These physiologic events initiate an increase in GnRH. fat droplets accumulate in the alveolar . and Senescence A dramatic increase in circulating ovarian and placental estrogens and progestins is evident during pregnancy. there is a decrease in the sensitivity of the hypothalamic pituitary axis to negative feedback and an increase in its sensitivity to positive feedback by estrogen. cortisol. oxytocin. flows through the lymph vessels that accompany the perforating branches of the internal mammary artery. thyroid hormone. the minor ducts branch and develop. Some lymph vessels may travel directly to the subscapular (posterior. Estrogen initiates ductal development. and prolactin especially have profound trophic effects that are essential to normal breast development and function. Efferent lymph vessels from the breast pass around the lateral edge of the pectoralis major muscle and pierce the clavipectoral fascia ending in the external mammary (anterior. The rest is derived primarily from the medial aspect of the breast. and ultimately an increase in estrogen and progesterone secretion by the ovaries. progesterone. In the female neonate. and the accessory areolar glands of Montgomery become prominent. which initiates striking alterations in the form and substance of the breast. Prolactin is the primary hormonal stimulus for lactogenesis in late pregnancy and the postpartum period. It upregulates hormone receptors and stimulates epithelial development. circulating estrogen and progesterone levels decrease after birth and remain low throughout childhood because of the sensitivity of the hypothalamic pituitary axis to negative feedback by these hormones. With the onset of puberty. progesterone. The breast enlarges as the ductal and lobular epithelium proliferates. while progesterone is responsible for differentiation of epithelium and for lobular development. Lactation. a few lymph vessels pass directly to the subclavicular (apical) group of lymph nodes. FSH. scapular) group of lymph nodes. leading to establishment of the menstrual cycle. and enters the parasternal (internal mammary) group of lymph nodes. Physiology of the Breast Breast Development and Function Breast development and function are initiated by a variety of hormonal stimuli. pectoral) group of lymph nodes. In the 1st and 2nd trimesters.
Uncommon organisms may be encountered and long-term antibiotic therapy may be required. and retromammary abscesses (unicentric or multicentric). Breast abscesses are typically seen in staphylococcal infections and present with point tenderness. which permits full expression of the lactogenic action of prolactin. In late pregnancy. visual. Oxytocin release results from the auditory. The surrounding fibrous connective tissue increases in density. and hyperthermia.. erythema. and breast tissues are replaced by adipose tissues. possibly with recurrent abscess formation. Hospital-acquired puerperal infections of the breast are much less common now. aureus that are transmitted via the suckling neonate and may result in substantial morbidity and occasional mortality. which is best accomplished via circumareolar incisions or incisions paralleling Langer's lines. but nursing women who present with milk stasis or noninfectious inflammation may still develop this problem. cultures are taken to identify acid-fast bacilli. Following delivery of the placenta. prolactin and oxytocin release decrease. While staphylococcal infections tend to be more localized and may be located deep in the breast tissues. subareolar. Infectious and Inflammatory Disorders of the Breast Excluding the postpartum period. streptococcal infections usually present with diffuse superficial involvement. After weaning of the infant. anaerobic and aerobic bacteria. In this situation. Dormant milk causes increased pressure within the ducts and alveoli resulting in atrophy of the epithelium. Breast infections may be chronic. including warm compresses. Preoperative ultrasonography is effective in delineating the extent of the drainage procedure. Bacterial Infection Staphylococcus aureus and Streptococcus species are the organisms most frequently recovered from nipple discharge from an infected breast. thoracic cavity). e. skin. Milk production and release are controlled by neural reflex arcs that originate in nerve endings of the nipple–areola complex.g. They are treated with local wound care. Epidemic puerperal mastitis is initiated by highly virulent strains of methicillinresistant S. necessitating operative drainage of fluctuant areas. Oxytocin initiates contraction of the myoepithelial cells resulting in compression of alveoli and expulsion of milk into the lactiferous sinuses. progression of a staphylococcal infection may result in subcutaneous. These abscesses are related to lactation and occur within the first few weeks of breast-feeding. and the administration of intravenous antibiotics (penicillins or cephalosporins).epithelium and colostrum fills the alveolar and ductal spaces. In this . interlobular (periductal). prolactin stimulates the synthesis of milk fats and proteins. circulating progesterone and estrogen levels decrease. and olfactory stimuli associated with nursing. Pus frequently may be expressed from the nipple. With menopause there is a decrease in the secretion of estrogen and progesterone by the ovaries and involution of the ducts and alveoli of the breast. Maintenance of lactation requires regular stimulation of these neural reflexes resulting in prolactin secretion and milk letdown. and fungi. infections of the breast are rare and are classified as intrinsic (2nd to abnormalities in the breast) or extrinsic (2nd to an infection in an adjacent structure.
Therapy involves the removal of predisposing factors such as maceration and the topical application of nystatin. It is widely accepted that this range of changes is the consequence of an exaggeration and distortion of the cyclic breast changes that occur normally in the menstrual cycle. breast-feeding is stopped. All tend to arise during reproductive life but may persist after the menopause. calcifications. Intraoral fungi that are inoculated into the breast tissue by the suckling infant initiate these infections. scaly lesions of the inframammary or axillary folds. Pus mixed with blood may be expressed from sinus tracts. and surgical therapy is initiated.circumstance. This therapy generally eliminates the necessity of surgical intervention. The patient develops nipple fissuring and milk stasis. having lost its normal delicate. The addition of antibiotics results in a satisfactory outcome in more than 95% of cases. and related lesions • Cysts . Pathology of Nonproliferative Disorders Nonproliferative disorders of the breast account for 70% of benign breast conditions and carry no increased risk for the development of breast cancer. may be necessary to eradicate a persistent fungal infection. myxomatous appearance. duct ectasia. Scrapings from the lesions demonstrate fungal elements (filaments and binding cells). fibroadenomas. A stromal lymphocytic infiltrate is common in this and all other variants of fibrocystic change. The proliferative lesions include a range of banal to atypical duct or ductular epithelial cell hyperplasias and sclerosing adenosis. The nonproliferative lesions include cysts and/or fibrosis without epithelial cell hyperplasia. Candida albicans affecting the skin of the breast presents as erythematous. Mycotic Infections Fungal infestations of the breast are rare and usually involve blastomycosis or sporotrichosis. periductal mastitis. This category includes cysts and apocrine metaplasia. The alterations are here subdivided into nonproliferative and proliferative patterns. which initiate a retrograde bacterial infection. but occasionally drainage of an abscess. antibiotics are started. The stroma surrounding all forms of cysts is usually compressed fibrous tissue. Amphotericin B is the most effective antifungal agent for the treatment of systemic (noncutaneous) infections. Emptying of the breast by using breast suction pumps shortens the duration of symptoms and reduces the incidence of recurrences. It is characterized by an increase in fibrous stroma associated with dilation of ducts and formation of cysts of various sizes. known as simple fibrocystic change. Fibrocystic Changes This designation is applied to a miscellany of changes in the female breast that range from those that are innocuous to patterns associated with an increased risk of breast carcinoma. which present as mammary abscesses in close proximity to the nipple–areola complex. Nonepidemic (sporadic) puerperal mastitis refers to involvement of the interlobular connective tissue of the breast by an infectious process. or even partial mastectomy.
so a more conservative approach is reasonable. the mass must disappear completely after aspiration 2. but if there is an anaerobic infection. and solitary fibroadenomas in young women are frequently removed to alleviate patient concern. and perhaps excisional biopsy are recommended. • Fibroadenomas Removal of all fibroadenomas has been advocated irrespective of patient age or other considerations. and excision of the fibroadenoma may be avoided. Any fluid obtained is submitted for cytology and for culture using a transport medium appropriate for the detection of anaerobic organisms. should the problem recur. If either of these conditions is not met. Recurrent abscess with fistula is a difficult . simple drainage is preferred. a subareolar abscess is usually unilocular and often is associated with a single duct system. Yet most fibroadenomas are self-limiting and many go undiagnosed. recurrent infection frequently develops. Antibiotics are then continued based on sensitivity tests.2 mL of fluid are taken for cytology mass is then imaged with ultrasound and any solid area on the cyst wall is biopsied by needle The 2 cardinal rules of safe cyst aspiration are: 1. Preoperative ultrasound will accurately delineate its extent. and the fluid is discarded Bloodstained. which is fixed by fingers of the nondominant hand. If the fluid that is aspirated is: not bloodstained. then ultrasound. The surgeon may either undertake simple drainage with a view toward formal surgery. needle biopsy. In the absence of pus. • Periductal Mastitis Painful and tender masses behind the nipple–areola complex are aspirated with a 21gauge needle attached to a 10-mL syringe.cyst is aspirated to dryness. The volume of a typical cyst is 5 to 10 mL. In a woman of childbearing age.A 21-gauge needle attached to a 10-mL syringe is placed directly into the mass. the fluid must not be bloodstained. Careful ultrasound examination with core-needle biopsy will provide for an accurate diagnosis. Unlike puerperal abscesses. the patient is counseled concerning the biopsy results. but it may be 75 mL or more. Subsequently. women are started on a combination of metronidazole and dicloxacillin while awaiting the results of culture. when there is considerable pus present. surgical treatment is recommended. or proceed with definitive surgery.
but occasionally presents as a palpable mass Benign calcifications are often associated with this disorder Excisional biopsy and histologic examination are frequently necessary to exclude the diagnosis of cancer • Radial scars and complex sclerosing lesions Central sclerosis and varying degrees of epithelial proliferation. complex sclerosing lesions. apocrine metaplasia. Treatment of Recurrent Subareolar Sepsis Suitable for Fistulectomy Small abscess localized to one segment Recurrence involving the same segment Mild or no nipple inversion Patient unconcerned about nipple inversion Younger patient No discharge from other ducts No prior fistulectomy Suitable for Total Duct Excision Large abscess affecting more than 50% of the areolar circumference Recurrence involving a different segment Marked nipple inversion Patient requests correction of nipple inversion Older patient Purulent discharge from other ducts Recurrence after fistulectomy Pathology of Proliferative Disorders Without Atypia Proliferative breast disorders without atypia include sclerosing adenosis. ductal epithelial hyperplasia. and intraductal papillomas. and papilloma formation characterize radial scars and complex sclerosing lesions of the breast . depending on the circumstances. • Sclerosing adenosis prevalent during the childbearing and perimenopausal years marked intralobular fibrosis and proliferation of small ductules and acini distorted breast lobules and usually occurs in the context of multiple microcysts. radial scars.problem and may be treated by fistulectomy or by major duct excision.
and late menopause . which may be serous or bloody rarely undergo malignant transformation However. usually in premenopausal women generally ˂ 0.5 cm in dm but may be as large as 5 cm A common presenting symptom is nipple discharge. whereas reducing exposure is thought to be protective.≥5 cell layers above the basement membrane Severe. which occur in younger women and are less frequently associated with nipple discharge. while larger lesions are called complex sclerosing lesions Excisional biopsy and histologic examination are frequently necessary to exclude the diagnosis of cancer • Ductal hyperplasia mild.Lesions up to 1 cm in dm are called radial scars.occupies at least 70% of a minor duct lumen either solid or papillary carries an increased cancer risk • Intraductal papillomas arise in the major ducts. are susceptible to malignant transformation Pathology of Atypical Proliferative Diseases Atypical lobular hyperplasia (ALH) Atypical ductal hyperplasia (ADH) have some of the features of carcinoma in situ (CIS) but either lack a major defining feature of CIS or have the features in less than fully developed form Risk Factors for Breast Cancer Hormonal and Nonhormonal Risk Factors Increased exposure to estrogen is associated with an increased risk for developing breast cancer. early menarche. multiple intraductal papillomas. nulliparity.3/4 cell layers above the basement membrane Moderate.
which are more likely to be well differentiated and to express hormone receptors than BRCA-1–associated breast cancer. and for each gene. . such as an early age of onset when compared with sporadic cases. and are hormone receptor–negative BRCA-1 associated breast cancers have a number of distinguishing clinical features. and the presence of associated cancers in some affected individuals. older age at first live birth obesity . alcohol consumption radiation exposure BRCA Mutations BRCA-1 located on chromosome 17q contains 22 coding exons functions as tumor-suppressor gene. men with germline mutations in BRCA-2 have an estimated breast cancer risk of 6% BRCA-2–associated breast cancers are invasive ductal carcinomas. but like BRCA-1. loss of both alleles is required for the initiation of cancer a role in transcription. while lower than for BRCA-1. cell-cycle control. and DNA damage repair pathways germline mutations in BRCA-1 represent a predisposing genetic factor in as many as 45% of hereditary breast cancers and in at least 80% of hereditary ovarian cancers Female mutation carriers have up to a 90% lifetime risk for developing breast cancer and up to a 40% lifetime risk for developing ovarian cancer Breast cancer in these families appears as an autosomal dominant trait with high penetrance BRCA-1–associated breast cancers are invasive ductal carcinomas. specifically ovarian cancer and possibly colon and prostate cancers BRCA-2 located on chromosome 13q contains 26 coding exons biologic function of BRCA-2 is not well defined. are poorly differentiated. it is postulated to play a role in DNA damage response pathways breast cancer risk for BRCA-2 mutation carriers is close to 85% and the lifetime ovarian cancer risk. a higher prevalence of bilateral breast cancer. is still estimated to be close to 20% Breast cancer in BRCA-2 families is an autosomal dominant trait and has a high penetrance Unlike male carriers of BRCA-1 mutations.
and Chemoprevention The Primary Breast Cancer More than 80% of breast cancers show productive fibrosis that involves the epithelial and stromal tissues. especially the axillary lymph nodes. Eventually the lymph nodes adhere to each other and form a conglomerate mass. but become firm or hard with continued growth of the metastatic cancer. gallbladder. colon. cancer cells invade the skin and eventually ulceration occurs. and the presence of associated cancers in some affected individuals. more than 60% are distant. up to 20% of breast cancer recurrences are locoregional. bile duct. Localized edema (peau d'orange) develops when drainage of lymph fluid from the skin is disrupted. a higher prevalence of bilateral breast cancer. Typically. the accompanying desmoplastic response entraps and shortens the suspensory ligaments of Cooper to produce a characteristic skin retraction. compared to as much as a 75% risk for node-positive women. and stomach cancers. some cancer cells are shed into cellular spaces and transported via the lymphatic network of the breast to the regional lymph nodes. such as an early age of onset compared with sporadic cases. Distant Metastases . While more than 95% of the women who die of breast cancer have distant metastases. as well as melanoma Cancer Prevention for BRCA Mutation Carriers Risk management strategies for BRCA-1 and BRCA-2 carriers include: Prophylactic mastectomy and reconstruction. prostate. Intensive surveillance for breast and ovarian cancer. small satellite nodules appear near the primary ulceration In general. Lymph nodes that contain metastatic cancer are at first ill-defined and soft. As new areas of skin are invaded. axillary lymph nodes are involved sequentially from the low (level I) to the central (level II) to the apical (level III) lymph node groups. specifically ovarian. With growth of the cancer and invasion of the surrounding breast tissues. Cancer cells may grow through the lymph node capsule and fix to contiguous structures in the axilla including the chest wall. pancreas. BRCA-2–associated breast cancer has a number of distinguishing clinical features. With continued growth. Prophylactic oophorectomy and hormone replacement therapy. Node-negative women have less than a 30% risk of recurrence. and 20% are both locoregional and distant Axillary Lymph Node Metastases As the size of the primary breast cancer increases. the most important prognostic correlate for disease-free and overall survival is axillary lymph node status.
For 10 years following initial treatment. and liver. pleura. metastases may become evident as late as 20 to 30 years after treatment of the primary cancer. nipple discharge Microcalcifications 1/3 2–46% 40–80% 10–20% 1–2% 25–70% Ipsilateral Ductal 44–47 2–5% None None 2/3 5% 60–90% 50–70% 1% 25–35% Bilateral Ductal 15–20 years 5–10 years Among biopsies of mammographically detected breast lesions. These cells are scavenged by natural killer lymphocytes and macrophages. Histopathology of Breast Cancer Carcinoma In Situ Cancer cells are in situ or invasive depending on whether or not they invade through the basement membrane.5 cm in diameter.At approximately the 20th cell doubling. distant metastases are the most common cause of death in breast cancer patients. breast cancers acquire their own blood supply (neovascularization). Salient Characteristics of In Situ Ductal (DCIS) and Lobular (LCIS) Carcinoma of the Breast LCIS Age (years) Incidence a Clinical signs Mammographic signs Premenopausal Incidence of synchronous invasive carcinoma Multicentricity Bilaterality Axillary metastasis Subsequent carcinomas: Incidence Laterality Interval to diagnosis Histology a DCIS 54–58 5–10% Mass. in order of frequency. pain. are bone. While 60% of the women who develop distant metastases will do so within 24 months of treatment. Multicentricity--occurrence of a second breast cancer outside the breast quadrant of the primary cancer . soft tissues. Successful implantation of metastatic foci from breast cancer predictably occurs after the primary cancer exceeds 0. which courses the length of the vertebral column. lung. which corresponds to the 27th cell doubling. Common sites of involvement. cancer cells may be shed directly into the systemic venous blood to seed the pulmonary circulation via the axillary and intercostal veins or the vertebral column via Batson's plexus of veins. Thereafter.
and comedo types papillary and cribriform types of DCIS probably transform to invasive cancer over a longer time frame and are of lower grade solid and comedo types of DCIS are generally higher-grade lesions and probably invade over a shortened natural history Invasive Breast Carcinoma Foote and Stewart originally proposed the following classification for invasive breast cancer: I. which may be subtle. Paget's disease of the nipple presents as a chronic. Histologically. solid. but may progress to an ulcerated. DCIS is characterized by a proliferation of the epithelium that lines the minor ducts. resulting in papillary growths within the duct lumina four morphologic categories are prototypes of pure lesions: Papillary. cribriform. which are large but maintain a normal nuclear:cytoplasmic ratio Cytoplasmic mucoid globules are a distinctive cellular feature calcifications associated with LCIS typically occur in adjacent tissues occurs 12x more frequently in white women than in African American women Ductal Carcinoma In Situ(intraductal carcinoma) predominantly seen in the female breast accounts for 5% of male breast cancers. vacuolated cells (Paget's cells) in the rete pegs of the epithelium Surgical Tx .Multifocality--occurrence of a second cancer within the same breast quadrant as the primary cancer Lobular Carcinoma In Situ originates from the terminal duct lobular units only develops in the female breast characterized by distention and distortion of the terminal duct lobular units by cancer cells. pale. weeping lesion A palpable mass may or may not be present associated with extensive DCIS and may be with an invasive cancer Bx of the nipple • • population of cells that are identical to the underlying DCIS cells (pagetoid features or pagetoid change) Pathognomonic of this cancer is the presence of large. eczematous eruption of the nipple.
or modified radical mastectomy. NST) 80% presents with macroscopic or microscopic axillary lymph node metastases in 60% of cases perimenopausal or postmenopausal women in the 5th to 6th decades of life as a solitary. mesenchymal metaplasia or anaplasia is noted Because of the intense lymphocyte response associated with the cancer. The cancer cells arranged in small clusters.• lumpectomy. and fewer than 10% demonstrate hormone receptors In rare circumstances. depending on the extent of involvement and the presence of invasive cancer II. large pleomorphic nuclei that are poorly differentiated and show active mitosis. Invasive ductal carcinoma a. the cancer is soft and hemorrhagic A rapid increase in size may occur secondary to necrosis and hemorrhage Bilaterality is reported in 20% of cases Microscopically characterized by • • • a dense lymphoreticular infiltrate composed predominantly of lymphocytes and plasma cells. and a sheet-like growth pattern with minimal or absent ductal or alveolar differentiation Approximately 50% of these cancers are associated with DCIS. and there is a broad spectrum of histologies with variable cellular and nuclear grades b. mastectomy. which is characteristically present at the periphery of the cancer. Mucinous (colloid) carcinoma 2% . Adenocarcinoma with productive fibrosis (scirrhous. simplex. firm mass poorly defined margins and its cut surfaces show a central stellate configuration with chalky white or yellow streaks extending into surrounding breast tissues. Medullary carcinoma 4% A frequent phenotype of BRCA-1 hereditary breast cancer Grossly. benign or hyperplastic enlargement of the lymph nodes of the axilla may contribute to erroneous clinical staging Women with this cancer have a better 5-year survival rate than those with NST or invasive lobular carcinoma c.
Tubular carcinoma (and ICC) 2% Tubular carcinoma is another special-type breast cancer and accounts for 2% of all invasive breast cancers. will develop axillary lymph node metastases. which are usually confined to the lowest axillary lymph nodes (level I). a special-type cancer closely related to tubular carcinoma. Papillary carcinoma 2% It generally presents in the 7th decade of life and occurs in a disproportionate number of nonwhite women Typically. the presence of metastatic disease in one or two axillary lymph nodes does not adversely affect survival. Approximately 10% of women with tubular carcinoma or with invasive cribriform carcinoma. which surround aggregates of low-grade cancer cells The cut surface of this cancer is glistening and gelatinous in quality Fibrosis is variable. Under low-power magnification. However. Distant metastases are rare in tubular carcinoma and invasive cribriform carcinoma. papillary carcinomas are small and rarely attain a size of 3 cm in diameter Defined by papillae with fibrovascular stalks and multilayered epithelium low frequency of axillary lymph node metastases e. Long-term survival approaches 100%. It is reported in as many as 20% of women whose cancers are diagnosed by mammography screening and is usually diagnosed in the perimenopausal or early menopausal periods. and when abundant it imparts a firm consistency to the cancer Approximately 66% of mucinous carcinomas display hormone receptors Lymph node metastases occur in 33% of cases d. a haphazard array of small. randomly arranged tubular elements is seen. . Typically presents in the elderly population as a bulky tumor This cancer is defined by extracellular pools of mucin.