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Surgery_Schwartz. sarcoma. AIDS. 2009;23(13):1701-1706. 177. Martinez V, Caumes E, Gambotti L, et al. Remission from Kaposi’s sarcoma on HAART is associated with suppression of HIV replication and is independent of protease inhibitor therapy. Br J Cancer. 2006;94(7):1000-1006. 178. Aiba S, Tabata N, Ishii H, Ootani H, Tagami H. Dermatofi-brosarcoma protuberans is a unique fibrohistiocytic tumour expressing CD34. Br J Dermatol. 1992;127(2):79-84. 179. Abenoza P, Lillemoe T. CD34 and factor XIIIa in the differ-ential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans. Am J Dermatopathol. 1993;15(5):429-434. 180. Fields RC, Hameed M, Qin L-X, et al. Dermatofibrosarcoma protuberans (DFSP): predictors of recurrence and the use of systemic therapy. Ann Surg Oncol. 2011;18(2):328-336. 181. Meguerditchian A-N, Wang J, Lema B, Kraybill WG, Zeitouni NC, Kane JM 3rd. Wide excision or Mohs micrographic sur-gery for the treatment of primary dermatofibrosarcoma protu-berans. Am J Clin Oncol.


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Surgery_Schwartz. A-N, Wang J, Lema B, Kraybill WG, Zeitouni NC, Kane JM 3rd. Wide excision or Mohs micrographic sur-gery for the treatment of primary dermatofibrosarcoma protu-berans. Am J Clin Oncol. 2009;33(3):1. 182. Requena L, Sangueza OP. Cutaneous vascular proliferations. Part III. Malignant neoplasms, other cutaneous neoplasms with significant vascular component, and disorders errone-ously considered as vascular neoplasms. J Am Acad Dermatol. 1998;38(2 pt 1):143-175. 183. Holden CA, Spittle MF, Jones EW. Angiosarcoma of the face and scalp, prognosis and treatment. Cancer. 1987;59(5):1046-1057. 184. Wagner G, Sachse MM. Extramammary Paget disease— clinical appearance, pathogenesis, management. JDDG J der Dtsch Dermatologischen Gesellschaft. 2011;9(6):448-454.Brunicardi_Ch16_p0511-p0540.indd 54019/02/19 3:09 PM


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Surgery_Schwartz. The BreastCatherine C. Parker, Senthil Damodaran, Kirby I. Bland, and Kelly K. Hunt 17chapterA BRIEF HISTORY OF BREAST CANCER THERAPYBreast cancer has captured the attention of surgeons throughout the ages. The Smith Surgical Papyrus (3000–2500 b.c.) is the earliest known document to refer to breast cancer. The cancer was in a man, but the description encompassed most of the common clinical features. In reference to this cancer, the author concluded, “There is no treatment.”1 There were few other historical references to breast cancer until the first century. In De Medicina, Celsus commented on the value of operations for early breast cancer: “None of these may be removed but the cacoethes (early cancer), the rest are irritated by every method of cure. The more violent the operations are, the more angry they grow.”2 In the second century, Galen inscribed his classical clinical observation: “We have often seen in the breast a tumor exactly resembling the animal the crab. Just as the


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Surgery_Schwartz. the more angry they grow.”2 In the second century, Galen inscribed his classical clinical observation: “We have often seen in the breast a tumor exactly resembling the animal the crab. Just as the crab has legs on both sides of his body, so in this disease the veins extending out from the unnatural growth take the shape of a crab’s legs. We have often cured this disease in its early stages, but after it has reached a large size, no one has cured it. In all operations we attempt to excise the tumor in a circle where it borders on the healthy tissue.”3The Galenic system of medicine ascribed cancers to an excess of black bile and concluded that excision of a local bodily outbreak could not cure the systemic imbalance. Theories espoused by Galen dominated medicine until the Renaissance. In 1652, Tulp introduced the idea that cancer was contagious when he reported an elderly woman and her housemaid who both developed breast cancer (N. Tulp, Observationes medi-cae 1652). This single


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Surgery_Schwartz. In 1652, Tulp introduced the idea that cancer was contagious when he reported an elderly woman and her housemaid who both developed breast cancer (N. Tulp, Observationes medi-cae 1652). This single incidence was accepted as conclusive A Brief History of Breast Cancer Therapy541Embryology and Functional Anatomy of the Breast543Embryology / 543Functional Anatomy / 544Physiology of the Breast547Breast Development and Function / 547Pregnancy, Lactation, and Senescence / 548Gynecomastia / 549Infectious and Inflammatory Disorders of the Breast550Bacterial Infection / 550Mycotic Infections / 550Hidradenitis Suppurativa / 550Mondor’s Disease / 550Common Benign Disorders and Diseases of the Breast551Aberrations of Normal Development and Involution / 551Pathology of Nonproliferative Disorders / 552Pathology of Proliferative Disorders Without Atypia / 553Pathology of Atypical Proliferative Diseases / 553Treatment of Selected Benign Breast Disorders and Diseases / 554Risk Factors for Breast


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Surgery_Schwartz. / 552Pathology of Proliferative Disorders Without Atypia / 553Pathology of Atypical Proliferative Diseases / 553Treatment of Selected Benign Breast Disorders and Diseases / 554Risk Factors for Breast Cancer555Hormonal and Nonhormonal Risk Factors / 555Risk Assessment Models / 555Risk Management / 556BRCA Mutations / 558Epidemiology and Natural History of Breast Cancer561Epidemiology / 561Natural History / 562Histopathology of Breast Cancer563Carcinoma In Situ / 563Invasive Breast Carcinoma / 565Diagnosis of Breast Cancer567Examination / 567Imaging Techniques / 567Breast Biopsy / 574Breast Cancer Staging and Biomarkers575Breast Cancer Staging / 575Biomarkers / 575Overview of Breast Cancer Therapy580In Situ Breast Cancer (Stage 0) / 580Early Invasive Breast Cancer (Stage I, IIA, or IIB) / 582Advanced Local-Regional Breast Cancer (Stage IIIA or IIIB) / 585Internal Mammary Lymph Nodes / 587Distant Metastases (Stage IV) / 587Local-Regional Recurrence / 587Breast Cancer Prognosis /


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Surgery_Schwartz. IIB) / 582Advanced Local-Regional Breast Cancer (Stage IIIA or IIIB) / 585Internal Mammary Lymph Nodes / 587Distant Metastases (Stage IV) / 587Local-Regional Recurrence / 587Breast Cancer Prognosis / 587Surgical Techniques in Breast Cancer Therapy588Excisional Biopsy With Needle Localization / 588Sentinel Lymph Node Dissection / 590Breast Conservation / 591Mastectomy and Axillary Dissection / 591Modified Radical Mastectomy / 592Reconstruction of the Breast and Chest Wall / 593Nonsurgical Breast Cancer Therapies594Radiation Therapy / 594Chemotherapy Adjuvant / 594Antiestrogen Therapy / 597Ablative Endocrine Therapy / 598Anti-HER2 Therapy / 598Special Clinical Situations599Nipple Discharge / 599Axillary Lymph Node Metastases in the Setting of an Unknown Primary Cancer / 600Breast Cancer During Pregnancy / 600Male Breast Cancer / 600Phyllodes Tumors / 600Inflammatory Breast Carcinoma / 601Rare Breast Cancers / 602Brunicardi_Ch17_p0541-p0612.indd 54101/03/19 5:04 PM 542evidence


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Surgery_Schwartz. During Pregnancy / 600Male Breast Cancer / 600Phyllodes Tumors / 600Inflammatory Breast Carcinoma / 601Rare Breast Cancers / 602Brunicardi_Ch17_p0541-p0612.indd 54101/03/19 5:04 PM 542evidence and started an idea which persisted into the 20th century among some lay people. The majority of respected sur-geons considered operative intervention to be a futile and ill-advised endeavor. The Renaissance and the wars of the 16th and 17th centuries brought developments in surgery, particularly in anatomical understanding. However, there were no new theories espoused in relation to cancer. Beginning with Morgagni, surgi-cal resections were more frequently undertaken, including some early attempts at mastectomy and axillary dissection. The 17th century saw the start of the Age of Enlightenment, which lasted until the 19th century. In terms of medicine, this resulted in the abandonment of Galen’s humoral pathology, which was repudi-ated by Le Dran, and the subsequent rise in cellular


Surgery_Schwartz

Surgery_Schwartz. which lasted until the 19th century. In terms of medicine, this resulted in the abandonment of Galen’s humoral pathology, which was repudi-ated by Le Dran, and the subsequent rise in cellular pathology as espoused by Virchow. Le Dran stated that breast cancer was a local disease that spread by way of lymph vessels to axillary lymph nodes. When operating on a woman with breast cancer, he routinely removed any enlarged axillary lymph nodes.4In the 19th century, Moore, of the Middlesex Hospital, London, emphasized complete resection of the breast for cancer and stated that palpable axillary lymph nodes also should be removed.5 In a presentation before the British Medical Asso-ciation in 1877, Banks supported Moore’s concepts and advo-cated the resection of axillary lymph nodes even when palpable lymphadenopathy was not evident, recognizing that occult involvement of axillary lymph nodes was frequently present. In 1894, Halsted and Meyer reported their operations for treatment of breast


Surgery_Schwartz

Surgery_Schwartz. lymphadenopathy was not evident, recognizing that occult involvement of axillary lymph nodes was frequently present. In 1894, Halsted and Meyer reported their operations for treatment of breast cancer.6 By demonstrating superior local-regional con-trol rates after radical resection, these surgeons established radi-cal mastectomy as state-of-the-art treatment for that era. Halsted and Meyer advocated complete dissection of axillary lymph node levels I to III. Both routinely resected the long thoracic nerve and the thoracodorsal neurovascular bundle with the axil-lary contents. In 1943, Haagensen and Stout described the grave signs of breast cancer, which included: (a) edema of the skin of the breast, (b) skin ulceration, (c) chest wall fixation, (d) an axillary lymph node >2.5 cm in diameter, and (e) fixed axillary lymph nodes. Women with two or more signs had a 42% local recurrence rate and only a 2% 5-year disease-free survival rate.7 Based on these findings, they declared that women


Surgery_Schwartz

Surgery_Schwartz. and (e) fixed axillary lymph nodes. Women with two or more signs had a 42% local recurrence rate and only a 2% 5-year disease-free survival rate.7 Based on these findings, they declared that women with grave signs were beyond cure by radical surgery. In 1948, Patey and Dyson of the Middlesex Hospital, London, advocated a modi-fied radical mastectomy for the management of advanced oper-able breast cancer, explaining, “Until an effective general agent for treatment of carcinoma of the breast is developed, a high proportion of these cases are doomed to die.”8 Their technique included removal of the breast and axillary lymph nodes with preservation of the pectoralis major muscle. They showed that removal of the pectoralis minor muscle allowed access to and clearance of axillary lymph node levels I to III.During the 1970s, there was a transition from the Halsted radical mastectomy to the modified radical mastectomy as the surgical procedure most frequently used by American surgeons to


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Surgery_Schwartz. levels I to III.During the 1970s, there was a transition from the Halsted radical mastectomy to the modified radical mastectomy as the surgical procedure most frequently used by American surgeons to treat breast cancer. This transition acknowledged that: (a) fewer patients were presenting with advanced local disease with or without the grave signs described by Haagensen, (b) extirpation of the pectoralis major muscle was not essential for local-regional control in stages I and II breast cancer, and (c) neither the modified radical mastectomy nor the Halsted radi-cal mastectomy consistently achieved local-regional control of stage III breast cancer. Radiation therapy was incorporated into the management of advanced breast cancer and demonstrated improvements in local-regional control. The National Surgical Key Points1 The breast receives its principal blood supply from per-forating branches of the internal mammary artery, lateral branches of the posterior intercostal arteries, and


Surgery_Schwartz

Surgery_Schwartz. The National Surgical Key Points1 The breast receives its principal blood supply from per-forating branches of the internal mammary artery, lateral branches of the posterior intercostal arteries, and branches from the axillary artery, including the highest thoracic, lat-eral thoracic, and pectoral branches of the thoracoacromial artery.2 The axillary lymph nodes usually receive >75% of the lymph drainage from the breast, and the rest flows through the lymph vessels that accompany the perforating branches of the internal mammary artery and enters the parasternal (internal mammary) group of lymph nodes.3 Breast development and function are initiated by a variety of hormonal stimuli, with the major trophic effects being modulated by estrogen, progesterone, and prolactin.4 Benign breast disorders and diseases are related to the nor-mal processes of reproductive life and to involution, and there is a spectrum of breast conditions that ranges from normal to disorder to disease (aberrations


Surgery_Schwartz

Surgery_Schwartz. and diseases are related to the nor-mal processes of reproductive life and to involution, and there is a spectrum of breast conditions that ranges from normal to disorder to disease (aberrations of normal devel-opment and involution classification).5 To calculate breast cancer risk using the Gail model, a woman’s risk factors are translated into an overall risk score by multiplying her relative risks from several cat-egories. This risk score is then compared with an adjusted population risk of breast cancer to determine the wom-an’s individual risk. This model is not appropriate for use in women with a known BRCA1 or BRCA2 mutation or women with lobular or ductal carcinoma in situ.6 Routine use of screening mammography in women ≥50 years of age reduces mortality from breast cancer by 25%. Magnetic resonance imaging (MRI) screening is recom-mended in women with BRCA mutations and may be con-sidered in women with a greater than 20% to 25% lifetime risk of developing breast


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Surgery_Schwartz. by 25%. Magnetic resonance imaging (MRI) screening is recom-mended in women with BRCA mutations and may be con-sidered in women with a greater than 20% to 25% lifetime risk of developing breast cancer.7 Core-needle biopsy is the preferred method for diagnosis of palpable or nonpalpable breast abnormalities.8 When a diagnosis of breast cancer is made, the surgeon should determine the clinical stage, histologic characteris-tics, and appropriate biomarker levels before initiating local therapy.9 Sentinel node dissection is the preferred method for stag-ing of the regional lymph nodes in women with clinically node-negative invasive breast cancer. Axillary dissection may be avoided in women with one to two positive senti-nel nodes who are treated with breast conserving surgery, whole breast radiation, and systemic therapy.10 Local-regional and systemic therapy decisions for an indi-vidual patient with breast cancer are best made using a multidisciplinary treatment approach. The sequencing


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Surgery_Schwartz. and systemic therapy.10 Local-regional and systemic therapy decisions for an indi-vidual patient with breast cancer are best made using a multidisciplinary treatment approach. The sequencing of therapies is dependent on patient and tumor related factors including breast cancer subtype.Brunicardi_Ch17_p0541-p0612.indd 54201/03/19 5:04 PM 543THE BREASTCHAPTER 17Adjuvant Breast and Bowel Project (NSABP) conducted a ran-domized trial in the early 1970s to determine the impact of local and regional treatments on survival in operable breast cancer. In the B-04 trial, 1665 women were enrolled and stratified by clinical assessment of the axillary lymph nodes. The clinically node-negative women were randomized into three treatment groups: (a) Halsted radical mastectomy; (b) total mastectomy plus radiation therapy; and (c) total mastectomy alone. Clini-cally node-positive women were randomized to Halsted radical mastectomy or total mastectomy plus radiation therapy. This trial accrued


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Surgery_Schwartz. plus radiation therapy; and (c) total mastectomy alone. Clini-cally node-positive women were randomized to Halsted radical mastectomy or total mastectomy plus radiation therapy. This trial accrued patients between 1971 and 1974, an era that pre-dated widespread availability of effective systemic therapy for breast cancer and therefore reflect survival associated with local-regional therapy alone. There were no differences in survival between the three groups of node-negative women or between the two groups of node-positive women. These overall survival equivalence patterns persisted at 25 years of follow-up.9The next major advance in the surgical management of breast cancer was the development of breast conserving surgery. Breast conserving surgery and radium treatment was first reported by Geoffrey Keynes of St Bartholomew’s Hospital, London in the British Medical Journal in 1937.10 Several decades later, the NSABP launched the B-06 trial, a phase 3 study that randomized 1851


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Surgery_Schwartz. by Geoffrey Keynes of St Bartholomew’s Hospital, London in the British Medical Journal in 1937.10 Several decades later, the NSABP launched the B-06 trial, a phase 3 study that randomized 1851 patients to total mastec-tomy, lumpectomy alone, or lumpectomy with breast irradia-tion. The results showed no difference in disease-free, distant disease-free, and overall survival among the three groups; how-ever, the omission of radiation therapy resulted in significantly higher rates of ipsilateral breast tumor recurrence in those who received lumpectomy alone.11 The B-06 trial excluded patients who had palpable axillary lymph nodes, and those patients randomized to breast conserving surgery had frozen sections performed. If on frozen section the margins were involved, the surgeon proceeded to perform a mastectomy, but the patient was included in the analysis as having had a breast conserv-ing operation. Furthermore, in B-06, local in-breast recurrences were regarded as “nonevents” in terms


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Surgery_Schwartz. a mastectomy, but the patient was included in the analysis as having had a breast conserv-ing operation. Furthermore, in B-06, local in-breast recurrences were regarded as “nonevents” in terms of disease-free survival. Both the NSABP B-04 and B-06 trials were taken to refute the Halstedian concept that cancer spread throughout a region of the breast to lymphatics and then on to distant sites. Bernard Fisher proposed the “alternative hypothesis” that breast cancer was a systemic disease at diagnosis and that tumor cells had access to both the blood and lymphatic systems and that regional lymph nodes were a marker of systemic disease and not a barrier to the dissemination of cancer cells. He proposed that host factors were important in the development of metastasis and that varia-tions in the local-regional approach to breast cancer treatment were not likely to substantially impact survival. This idea was dominant for a number of years but has been challenged by the Early Breast Cancer


Surgery_Schwartz

Surgery_Schwartz. local-regional approach to breast cancer treatment were not likely to substantially impact survival. This idea was dominant for a number of years but has been challenged by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview analysis, which reported that “the avoidance of recur-rence in a conserved breast . . . avoids about one breast cancer death over the next 15 years for every four such recurrences avoided,”12 indicating that not all breast cancer is a systemic disease at presentation.During the 1970s, clinical trials were initiated to determine the value of systemic therapy in the postoperative setting as an adjuvant to surgery. The EBCTCG was established in 1985 to coordinate the meta-analysis of data from randomized clinical trials in order to examine the impact of adjuvant treatments for breast cancer on recurrence and mortality. The EBCTCG overview has demonstrated that anthracycline containing regimens are superior to cyclophosphamide, methotrexate, and


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Surgery_Schwartz. of adjuvant treatments for breast cancer on recurrence and mortality. The EBCTCG overview has demonstrated that anthracycline containing regimens are superior to cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), and more recently, that the addition of a taxane to an anthracycline-based regimen reduces breast cancer mortality by one-third.11 The overview has also demonstrated that tamoxifen is of benefit only in patients with estrogen recep-tor (ER) positive breast cancer and that tamoxifen may decrease mortality from breast cancer by as much as 30%.13 Importantly, the EBCTCG data have shown that proportional reduction in risk was not significantly affected by standard clinical and pathologic factors such as tumor size, ER status, and nodal status.14 This underscores the importance of stratification of risk in determining adjuvant therapy decisions in order to minimize the toxicities of therapies in those unlikely to benefit, yet real-ize the substantial benefits gained in


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Surgery_Schwartz. of stratification of risk in determining adjuvant therapy decisions in order to minimize the toxicities of therapies in those unlikely to benefit, yet real-ize the substantial benefits gained in local-regional control and survival in those at higher risk.Many early randomized clinical trials considered all patients similarly in terms of treatment viewing breast cancer as more of a homogeneous disease. Breast cancer has traditionally been defined by pathologic determinants using conventional light microscopy and basic histologic techniques. In the 1980s, immunohistochemistry allowed assessment of the expression of individual tumor markers (most commonly proteins) while DNA was initially assessed in terms of its ploidy status. Sub-sequently, breast cancer specimens have been interrogated at the level of the DNA by labeling genes of interest and allow-ing fluorescent dyes to quantify the abundance of a particular gene and comparing a large number of genes simultaneously in a single


Surgery_Schwartz

Surgery_Schwartz. at the level of the DNA by labeling genes of interest and allow-ing fluorescent dyes to quantify the abundance of a particular gene and comparing a large number of genes simultaneously in a single breast cancer specimen. Gene expression arrays have shown that breast cancers cluster according to their intrinsic gene expression patterns into at least five intrinsic subtypes and these intrinsic subtypes correlate with breast cancer outcomes.15 Breast cancers are now classified by molecular subtypes and these are being used for risk stratification and decision making in terms of local-regional and systemic therapies.Currently, 50% of American women will consult a sur-geon regarding breast disease, 25% will undergo breast biopsy for diagnosis of an abnormality, and 12% will develop some variant of breast cancer. Considerable progress has been made in the integration of surgery, radiation therapy, and systemic therapy to control local-regional disease, enhance survival, and improve the


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Surgery_Schwartz. of breast cancer. Considerable progress has been made in the integration of surgery, radiation therapy, and systemic therapy to control local-regional disease, enhance survival, and improve the quality of life of breast cancer survivors. Surgeons are traditionally the first physician consulted for breast care, and it is critical for them to be well trained in all aspects of the breast from embryologic development, to growth and development, to benign and malignant disease processes. This will allow the greatest opportunity to achieve optimal outcomes for patients and their families.EMBRYOLOGY AND FUNCTIONAL ANATOMY OF THE BREASTEmbryologyAt the fifth or sixth week of fetal development, two ventral bands of thickened ectoderm (mammary ridges, milk lines) are evident in the embryo.16 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


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Surgery_Schwartz. 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 Brunicardi_Ch17_p0541-p0612.indd 54301/03/19 5:04 PM 544SPECIFIC CONSIDERATIONSPART IIFigure 17-1. The mammary milk line. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Figure 17-2. Anatomy of the breast. Tangential and cross-sectional (sagittal) views of the breast and associated chest wall. (Reproduced with permission from Bland KI, Copeland EMI: The Breast: Comprehensive Management of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)occur along the milk line (Fig. 17-1) when normal regression fails. Each breast develops when an ingrowth of


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Surgery_Schwartz. of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)occur along the milk line (Fig. 17-1) 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. Dur-ing 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 pres-ence of major ducts. Enlargement of the breast may be evi-dent, and a secretion, historically referred to as witch’s milk, may be produced. These transitory events occur in response to


Surgery_Schwartz

Surgery_Schwartz. only the pres-ence of major ducts. Enlargement of the breast may be evi-dent, and a secretion, historically 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 mam-mary ridge development that occurs during the sixth fetal week. Poland’s syndrome consists of hypoplasia or complete absence of the breast, costal cartilage and rib defects, hypoplasia of the subcutaneous tissues of the chest wall, and brachysyndactyly. Breast hypoplasia also may be iatrogenically induced before puberty by trauma, infection, or radiation therapy. Symmastia is a rare anomaly


Surgery_Schwartz

Surgery_Schwartz. tissues of the chest wall, and brachysyndactyly. Breast hypoplasia also may be iatrogenically induced before 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 <1% of infants and may be associated with abnormalities of the urinary and cardiovascular systems. 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. Turner’s syndrome (ovarian agenesis and dysgenesis) and Fleischer’s syndrome (displacement of the nipples and bilateral renal hypoplasia) may have polymastia as a component. Accessory axillary breast tissue is uncommon and usually is bilateral.Functional AnatomyThe breast is composed of 15 to 20 lobes (Fig. 17-2), which are each composed of several lobules.17 Fibrous bands of con-nective tissue travel through the breast (Cooper’s


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Surgery_Schwartz. bilateral.Functional AnatomyThe breast is composed of 15 to 20 lobes (Fig. 17-2), which are each composed of several lobules.17 Fibrous bands of con-nective tissue travel through the breast (Cooper’s suspensory ligaments), insert perpendicularly into the dermis, and provide structural support. The mature female breast extends from the level of the second or third rib to the inframammary fold at the sixth or seventh 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 pecto-ralis major, serratus anterior, and external oblique abdominal muscles, and the upper extent of the rectus sheath. The retro-mammary 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 quad-rant of the


Surgery_Schwartz

Surgery_Schwartz. 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 quad-rant of the breast contains a greater volume of tissue than do the other quadrants. The breast has a protuberant conical form. The base of the cone is roughly circular, measuring 10 to 12 cm in diameter. Considerable variations in the size, contour, and den-sity of the breast are evident among individuals. The nulliparous breast has a hemispheric configuration with distinct flattening above the nipple. With the hormonal stimulation that accom-panies pregnancy and lactation, the breast becomes larger and increases in volume and density, whereas with senescence, it assumes a flattened, flaccid, and more pendulous configuration with decreased volume.Nipple-Areola Complex. The epidermis of the nipple-are-ola complex is pigmented and is variably corrugated. During puberty, the pigment becomes darker and the


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Surgery_Schwartz. configuration with decreased volume.Nipple-Areola Complex. The epidermis of the nipple-are-ola complex is pigmented and is variably corrugated. During puberty, the pigment becomes darker and the nipple assumes an elevated configuration. Throughout pregnancy, the areola Brunicardi_Ch17_p0541-p0612.indd 54401/03/19 5:04 PM 545THE BREASTCHAPTER 17Figure 17-3. Inactive human breast (100x). The epithelium, which is primarily ductal, is embedded in loose connective tissue. Dense connective tissue surrounds the terminal duct lobular units (TDLU). (Used with permission from Dr. Sindhu Menon, Consultant Histo-pathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)Figure 17-4. Active human breast: pregnancy and lactation (160x). The alveolar epithelium becomes conspicuous during the early pro-liferative period. The alveolus is surrounded by cellular connective tissue. (Used with permission from Dr. Sindhu Menon, Consultant


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Surgery_Schwartz. The alveolar epithelium becomes conspicuous during the early pro-liferative period. The alveolus is surrounded by cellular connective tissue. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)enlarges and pigmentation is further enhanced. The areola con-tains sebaceous glands, sweat glands, and accessory glands, which produce small elevations on the surface of the areola (Montgomery’s tubercles). Smooth muscle bundle fibers, which lie circumferentially in the dense connective tissue and longi-tudinally 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 Meiss-ner’s corpuscles. This rich sensory innervation is of functional importance because the sucking of the infant


Surgery_Schwartz

Surgery_Schwartz. dermal papilla at the tip of the nipple contains numerous sensory nerve endings and Meiss-ner’s corpuscles. This rich sensory innervation is of functional importance because the sucking of the infant initiates a chain of neurohumoral events that results in milk letdown.Inactive and Active Breast. Each lobe of the breast termi-nates in a major (lactiferous) duct (2–4 mm in diameter), which opens through a constricted orifice (0.4–0.7 mm in diameter) into the ampulla of the nipple (see Fig. 17-2). Immediately below the nipple-areola complex, each major duct has a dilated portion (lactiferous sinus), which is lined with stratified squa-mous epithelium. Major ducts are lined with two layers of cuboidal cells, whereas minor ducts are lined with a single layer of columnar or cuboidal cells. Myoepithelial cells of ectoder-mal 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


Surgery_Schwartz

Surgery_Schwartz. cells of ectoder-mal 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 (Fig. 17-3). 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 increases in height, duct lumina become more prominent, and some secretions accumulate. When the hormonal stimulation decreases, the alveolar epithe-lium regresses.With pregnancy, the breast undergoes proliferative and developmental maturation. As the breast enlarges in response to hormonal stimulation, lymphocytes, plasma cells, and eosin-ophils accumulate within the connective tissues. The minor ducts branch and alveoli develop. Development of the alveoli is asymmetric, and variations in the degree of development may occur within a single lobule (Fig. 17-4). With parturition, enlargement of the breasts occurs via


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Surgery_Schwartz. develop. Development of the alveoli is asymmetric, and variations in the degree of development may occur within a single lobule (Fig. 17-4). With parturition, enlargement of the breasts occurs via hypertrophy of alveolar epithelium and accumulation of secretory products in the lumina of the minor ducts. Alveolar epithelium contains abundant endo-plasmic reticulum, large mitochondria, Golgi complexes, and dense lysosomes. Two distinct substances are produced by the alveolar epithelium: (a) the protein component of milk, which is synthesized in the endoplasmic reticulum (merocrine secretion); and (b) the lipid component of milk (apocrine secretion), which forms as free lipid droplets in the cytoplasm. Milk released in the first few days after parturition is called colostrum and has low lipid content but contains considerable quantities of anti-bodies. The lymphocytes and plasma cells that accumulate within the connective tissues of the breast are the source of the antibody component.


Surgery_Schwartz

Surgery_Schwartz. content but contains considerable quantities of anti-bodies. The lymphocytes and plasma cells that accumulate within the connective tissues of the breast are the source of the antibody component. With subsequent reduction in the number of these cells, the production of colostrum decreases and lipid-rich milk is released.Blood Supply, Innervation, and Lymphatics. The breast receives its principal blood supply from: (a) perforating branches of the internal mammary artery; (b) lateral branches of the poste-rior intercostal arteries; and (c) branches from the axillary artery, including the highest thoracic, lateral thoracic, and pectoral branches of the thoracoacromial artery (Fig. 17-5). The second, third, and fourth anterior intercostal perforators and branches of the internal mammary artery arborize in the breast as the medial mammary arteries. The lateral thoracic artery gives off branches to the serratus anterior, pectoralis major and pectoralis minor, and subscapularis muscles. It


Surgery_Schwartz

Surgery_Schwartz. arborize in the breast as the medial mammary arteries. The lateral thoracic artery gives off branches to the serratus anterior, pectoralis major and pectoralis minor, and subscapularis muscles. It also gives rise to lateral mammary branches. The veins of the breast and chest wall follow the course of the arteries, with venous drainage being toward the axilla. The three principal groups of veins are: (a) per-forating branches of the internal thoracic vein, (b) perforating branches of the posterior intercostal veins, and (c) tributaries of the axillary vein. Batson’s vertebral venous plexus, which invests the vertebrae and extends from the base of the skull to the sacrum, may provide a route for breast cancer metastases to the vertebrae, skull, pelvic bones, and central nervous system. Lymph vessels generally parallel the course of blood vessels.1Brunicardi_Ch17_p0541-p0612.indd 54501/03/19 5:04 PM 546SPECIFIC CONSIDERATIONSPART IIFigure 17-5. Arterial supply to the breast, axilla,


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Surgery_Schwartz. vessels generally parallel the course of blood vessels.1Brunicardi_Ch17_p0541-p0612.indd 54501/03/19 5:04 PM 546SPECIFIC CONSIDERATIONSPART IIFigure 17-5. Arterial supply to the breast, axilla, and chest wall. (Reproduced with permission from Bland KI, Copeland EMI: The Breast: Comprehensive Management of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)Figure 17-6. Lymphatic pathways of the breast. Arrows indicate the direction of lymph flow. (Visual Art: © 2013. The University of Texas MD Anderson Cancer Center.)Figure 17-7. Axillary lymph node groups. Level I includes lymph nodes located lateral to the pectoralis minor muscle; level II includes lymph nodes located deep to the pectoralis minor; and level III includes lymph nodes located medial to the pectoralis minor. The axillary vein with its major tributaries and the supracla-vicular lymph node group are also illustrated. (Visual Art: © 2013.The University of Texas MD Anderson Cancer


Surgery_Schwartz

Surgery_Schwartz. to the pectoralis minor. The axillary vein with its major tributaries and the supracla-vicular lymph node group are also illustrated. (Visual Art: © 2013.The University of Texas MD Anderson Cancer Center.)Lateral cutaneous branches of the third through sixth inter-costal nerves provide sensory innervation of the breast (lateral mammary branches) and of the anterolateral chest wall. These branches exit the intercostal spaces between slips of the serratus anterior muscle. Cutaneous branches that arise from the cervical plexus, specifically the anterior branches of the supraclavicular nerve, supply a limited area of skin over the upper portion of the breast. The intercostobrachial nerve is the lateral cutane-ous branch of the second intercostal nerve and may be visual-ized during surgical dissection of the axilla. Resection of the intercostobrachial nerve causes loss of sensation over the medial aspect of the upper arm.The boundaries for lymph drainage of the axilla are not well


Surgery_Schwartz

Surgery_Schwartz. dissection of the axilla. Resection of the intercostobrachial nerve causes loss of sensation over the medial aspect of the upper arm.The boundaries for lymph drainage of the axilla are not well demarcated, and there is considerable variation in the posi-tion of the axillary lymph nodes. The six axillary lymph node groups recognized by surgeons (Figs. 17-6 and 17-7) are: (a) the axillary vein group (lateral), which consists of four to six lymph nodes that lie medial or posterior to the vein and receive most of the lymph drainage from the upper extremity; (b) the external mammary group (anterior or pectoral group), which consists of five to six lymph nodes that lie along the lower border of the pectoralis minor muscle contiguous with the lateral thoracic vessels and receive most of the lymph drainage from the lat-eral aspect of the breast; (c) the scapular group (posterior or subscapular), which consists of five to seven lymph nodes that lie along the posterior wall of the axilla at the


Surgery_Schwartz

Surgery_Schwartz. drainage from the lat-eral aspect of the breast; (c) the scapular group (posterior or subscapular), which consists of five to seven lymph nodes that lie along the posterior wall of the axilla at the lateral border of the scapula contiguous with the subscapular vessels and receive lymph drainage principally from the lower posterior neck, the posterior trunk, and the posterior shoulder; (d) the central group, which consists of three or four sets of lymph nodes that are embedded in the fat of the axilla lying immediately posterior to the pectoralis minor muscle and receive lymph drainage both from the axillary vein, external mammary, and scapular groups of lymph nodes, and directly from the breast; (e) the subcla-vicular group (apical), which consists of six to twelve sets of lymph nodes that lie posterior and superior to the upper bor-der of the pectoralis minor muscle and receive lymph drainage from all of the other groups of axillary lymph nodes; and (f) the interpectoral group


Surgery_Schwartz

Surgery_Schwartz. that lie posterior and superior to the upper bor-der of the pectoralis minor muscle and receive lymph drainage from all of the other groups of axillary lymph nodes; and (f) the interpectoral group (Rotter’s lymph nodes), which consists of one to four lymph nodes that are interposed between the pec-toralis major and pectoralis minor muscles and receive lymph drainage directly from the breast. The lymph fluid that passes Brunicardi_Ch17_p0541-p0612.indd 54601/03/19 5:04 PM 547THE BREASTCHAPTER 17through the interpectoral group of lymph nodes passes directly into the central and subclavicular groups.As indicated in Fig. 17-7, the lymph node groups are assigned levels according to their anatomic relationship to the pectoralis minor muscle. Lymph nodes located lateral to or below the lower border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the axillary vein, external mammary, and scapular groups. Lymph nodes located superficial or deep to the


Surgery_Schwartz

Surgery_Schwartz. border of the pectoralis minor muscle are referred to as level I lymph nodes, which include the axillary vein, external mammary, and scapular groups. Lymph nodes located superficial or deep to the pectoralis minor muscle are referred to as level II lymph nodes, which include the central and interpectoral groups. Lymph nodes located medial to or above the upper border of the pectoralis minor muscle are referred to as level III lymph nodes, which consist of the subclavicular group. 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. 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, pectoral) group of lymph nodes. Some lymph vessels may travel directly to the subscapular (pos-terior, scapular) group of lymph nodes. From the


Surgery_Schwartz

Surgery_Schwartz. fascia, ending in the external mammary (anterior, pectoral) group of lymph nodes. Some lymph vessels may travel directly to the subscapular (pos-terior, scapular) group of lymph nodes. From the upper part of the breast, a few lymph vessels pass directly to the subclavicular (api-cal) group of lymph nodes. The axillary lymph nodes usually receive >75% of the lymph drainage from the breast. The rest is derived primarily from the medial aspect of the breast, flows through the lymph vessels that accompany the per-forating branches of the internal mammary artery, and enters the parasternal (internal mammary) group of lymph nodes.PHYSIOLOGY OF THE BREASTBreast Development and FunctionBreast development and function are initiated by a variety of hormonal stimuli, including estrogen, progesterone, prolactin, oxytocin, thyroid hormone, cortisol, and growth hormone.17,18 Estrogen, progesterone, and prolactin especially have profound trophic effects that are essential to normal breast


Surgery_Schwartz

Surgery_Schwartz. prolactin, oxytocin, thyroid hormone, cortisol, and growth hormone.17,18 Estrogen, progesterone, and prolactin especially have profound trophic effects that are essential to normal breast develop-ment and function. Estrogen initiates ductal development, whereas progesterone is responsible for differentiation of epithe-lium and for lobular development. Prolactin is the primary hor-monal stimulus for lactogenesis in late pregnancy and the postpartum period. It upregulates hormone receptors and stimu-lates epithelial development. Fig. 17-8 depicts the secretion of neurotrophic hormones from the hypothalamus, which is respon-sible for regulation of the secretion of the hormones that affect the breast tissues. The gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) regulate the release of estrogen and progesterone from the ovaries. In turn, the release of LH and FSH from the basophilic cells of the anterior pituitary is regulated by the secretion of


Surgery_Schwartz

Surgery_Schwartz. (FSH) regulate the release of estrogen and progesterone from the ovaries. In turn, the release of LH and FSH from the basophilic cells of the anterior pituitary is regulated by the secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Positive and negative feedback effects of circulating estrogen and progesterone regulate the secretion of LH, FSH, and GnRH. These hormones are respon-sible for the development, function, and maintenance of breast tissues (Fig. 17-9A). In the female neonate, circulating estrogen and progesterone levels decrease after birth and remain low throughout childhood because of the sensitivity of 23GRFLH-RHDopamineOxy/ADHTRHCRF-Figure 17-8. Overview of the neuroendocrine con-trol of breast development and function. ADH = antidiuretic hormone; CRF = corticotropin-releasing factor; GRF = growth hormone releasing factor; LH-RH = luteinizing hormone–releasing hormone; Oxy = oxytocin; TRH = thyrotropin-releasing hor-mone. (Reproduced with


Surgery_Schwartz

Surgery_Schwartz. CRF = corticotropin-releasing factor; GRF = growth hormone releasing factor; LH-RH = luteinizing hormone–releasing hormone; Oxy = oxytocin; TRH = thyrotropin-releasing hor-mone. (Reproduced with permission from Bland KI, Copeland EMI: The Breast: Comprehensive Man-agement of Benign and Malignant Diseases, 4th ed. Philadelphia, PA: Elsevier/Saunders; 2009.)Brunicardi_Ch17_p0541-p0612.indd 54701/03/19 5:04 PM 548SPECIFIC CONSIDERATIONSPART IIABCDFigure 17-9. The breast at different physi-ologic stages. The central column contains three-dimensional depictions of microscopic structures. A. Adolescence. B. Pregnancy. C. Lactation. D. Senescence.the hypothalamic-pituitary axis to negative feedback from these hormones. With the onset of puberty, there is a decrease in the sensitivity of the hypothalamic-pituitary axis to negative feed-back and an increase in its sensitivity to positive feedback from estrogen. These physiologic events initiate an increase in GnRH, FSH, and LH secretion


Surgery_Schwartz

Surgery_Schwartz. hypothalamic-pituitary axis to negative feed-back and an increase in its sensitivity to positive feedback from estrogen. These physiologic events initiate an increase in GnRH, FSH, and LH secretion and ultimately an increase in estrogen and progesterone secretion by the ovaries, leading to establish-ment of the menstrual cycle. At the beginning of the menstrual cycle, there is an increase in the size and density of the breasts, which is followed by engorgement of the breast tissues and epi-thelial proliferation. With the onset of menstruation, the breast engorgement subsides and epithelial proliferation decreases.Pregnancy, Lactation, and SenescenceA dramatic increase in circulating ovarian and placental estro-gens and progestins is evident during pregnancy, which initiates striking alterations in the form and substance of the breast (see Fig. 17-9B).17-19 The breast enlarges as the ductal and lobular epithelium proliferates, the areolar skin darkens, and the acces-sory areolar glands


Surgery_Schwartz

Surgery_Schwartz. in the form and substance of the breast (see Fig. 17-9B).17-19 The breast enlarges as the ductal and lobular epithelium proliferates, the areolar skin darkens, and the acces-sory areolar glands (Montgomery’s glands) become prominent. In the first and second trimesters, the minor ducts branch and develop. During the third trimester, fat droplets accumulate in the alveolar epithelium, and colostrum fills the alveolar and duc-tal spaces. In late pregnancy, prolactin stimulates the synthesis of milk fats and proteins.After delivery of the placenta, circulating progesterone and estrogen levels decrease, permitting full expression of the lactogenic action of prolactin. Milk production and release are controlled by neural reflex arcs that originate in nerve endings of the nipple-areola complex. Maintenance of lactation requires regular stimulation of these neural reflexes, which results in prolactin secretion and milk letdown. Oxytocin release results from the auditory, visual, and olfactory


Surgery_Schwartz

Surgery_Schwartz. of lactation requires regular stimulation of these neural reflexes, which results in prolactin secretion and milk letdown. Oxytocin release results from the auditory, visual, and olfactory stimuli associated with nursing. Oxytocin initiates contraction of the myoepithelial cells, which results in compression of alveoli and expulsion of milk into the lactiferous sinuses. After weaning of the infant, prolactin and oxytocin release decreases. Dormant milk causes increased pressure within the ducts and alveoli, which results in atrophy of the epithelium (Fig. 17-9C). With menopause, there is a decrease in the secretion of estrogen and progesterone by Brunicardi_Ch17_p0541-p0612.indd 54801/03/19 5:04 PM 549THE BREASTCHAPTER 17Table 17-1Pathophysiologic mechanisms of gynecomastia I. Estrogen excess states A. Gonadal origin 1. True hermaphroditism 2. Gonadal stromal (nongerminal) neoplasms of the testis a. Leydig cell (interstitial) b. Sertoli cell c. Granulosa-theca cell 3. Germ cell


Surgery_Schwartz

Surgery_Schwartz. excess states A. Gonadal origin 1. True hermaphroditism 2. Gonadal stromal (nongerminal) neoplasms of the testis a. Leydig cell (interstitial) b. Sertoli cell c. Granulosa-theca cell 3. Germ cell tumors a. Choriocarcinoma b. Seminoma, teratoma c. Embryonal carcinoma B. Nontesticular tumors 1. Adrenal cortical neoplasms 2. Lung carcinoma 3. Hepatocellular carcinoma C. Endocrine disorders D. Diseases of the liver—nonalcoholic and alcoholic cirrhosis E. Nutrition alteration states II. Androgen deficiency states A. Senescence B. Hypoandrogenic states (hypogonadism) 1. Primary testicular failure a. Klinefelter’s syndrome (XXY) b. Reifenstein’s syndrome c. Rosewater-Gwinup-Hamwi familial gynecomastia d. Kallmann syndrome e. Kennedy’s disease with associated gynecomastia f. Eunuchoidal state (congenital anorchia) g. Hereditary defects of androgen biosynthesis h. Adrenocorticotropic hormone deficiency 2. Secondary testicular


Surgery_Schwartz

Surgery_Schwartz. disease with associated gynecomastia f. Eunuchoidal state (congenital anorchia) g. Hereditary defects of androgen biosynthesis h. Adrenocorticotropic hormone deficiency 2. Secondary testicular failure a. Trauma b. Orchitis c. Cryptorchidism d. Irradiation C. Renal failure III. Pharmacologic causes IV. Systemic diseases with idiopathic mechanismsthe ovaries and involution of the ducts and alveoli of the breast. The surrounding fibrous connective tissue increases in density, and breast tissues are replaced by adipose tissues (Fig. 17-9D).GynecomastiaGynecomastia refers to an enlarged breast in the male.20 Physi-ologic gynecomastia usually occurs during three phases of life: the neonatal period, adolescence, and senescence. Common to each of these phases is an excess of circulating estrogens in relation to circulating testosterone. Neonatal gynecomastia is caused by the action of placental estrogens on neonatal breast tissues, whereas in adolescence, there is an excess of estradiol


Surgery_Schwartz

Surgery_Schwartz. in relation to circulating testosterone. Neonatal gynecomastia is caused by the action of placental estrogens on neonatal breast tissues, whereas in adolescence, there is an excess of estradiol relative to testosterone, and with senescence, the circulating testosterone level falls, which results in relative hyperestrin-ism. In gynecomastia, the ductal structures of the male breast enlarge, elongate, and branch with a concomitant increase in epithelium. During puberty, the condition often is unilateral and typically occurs between ages 12 and 15 years. In contrast, senescent gynecomastia is usually bilateral. In the nonobese male, breast tissue measuring at least 2 cm in diameter must be present before a diagnosis of gynecomastia may be made. Mammography and ultrasonography are used to differentiate breast tissues. Dominant masses or areas of firmness, irregular-ity, and asymmetry suggest the possibility of a breast cancer, particularly in the older male. Gynecomastia generally does


Surgery_Schwartz

Surgery_Schwartz. breast tissues. Dominant masses or areas of firmness, irregular-ity, and asymmetry suggest the possibility of a breast cancer, particularly in the older male. Gynecomastia generally does not predispose the male breast to cancer. However, the hypoandro-genic state of Klinefelter’s syndrome (XXY), in which gyneco-mastia is usually evident, is associated with an increased risk of breast cancer. Gynecomastia is graded based on the degree of breast enlargement, the position of the nipple with reference to the inframammary fold, and the degree of breast ptosis and skin redundancy: Grade I—mild breast enlargement without skin redundancy; Grade IIa—moderate breast enlargement without skin redundancy; Grade IIb—moderate breast enlargement with skin redundancy; and Grade III—marked breast enlargement with skin redundancy and ptosis.Table 17-1 identifies the pathophysiologic mechanisms that may initiate gynecomastia: estrogen excess states; andro-gen deficiency states; pharmacologic causes; and


Surgery_Schwartz

Surgery_Schwartz. with skin redundancy and ptosis.Table 17-1 identifies the pathophysiologic mechanisms that may initiate gynecomastia: estrogen excess states; andro-gen deficiency states; pharmacologic causes; and idiopathic causes. Estrogen excess results from an increase in the secretion of estradiol by the testicles or by nontesticular tumors, nutri-tional alterations such as protein and fat deprivation, endocrine disorders (hyperthyroidism, hypothyroidism), and hepatic dis-ease (nonalcoholic and alcoholic cirrhosis). Refeeding gyne-comastia is related to the resumption of pituitary gonadotropin secretion after pituitary shutdown. Androgen deficiency may initiate gynecomastia. Concurrently occurring with decreased circulating testosterone levels is an elevated level of circulating testosterone-binding globulin, which results in a reduction of free testosterone. This senescent gynecomastia usually occurs in men age 50 to 70 years. Hypoandrogenic states can be from primary testicular failure or


Surgery_Schwartz

Surgery_Schwartz. globulin, which results in a reduction of free testosterone. This senescent gynecomastia usually occurs in men age 50 to 70 years. Hypoandrogenic states can be from primary testicular failure or secondary testicular failure. Kline-felter’s syndrome (XXY) is an example of primary testicular failure that is manifested by gynecomastia, hypergonadotropic hypogonadism, and azoospermia. Secondary testicular failure may result from trauma, orchitis, and cryptorchidism. Renal failure, regardless of cause, also may initiate gynecomastia.Pharmacologic causes of gynecomastia include drugs with estrogenic activity (digitalis, estrogens, anabolic steroids, marijuana) or drugs that enhance estrogen synthesis (human chorionic gonadotropin). Drugs that inhibit the action or syn-thesis of testosterone (cimetidine, ketoconazole, phenytoin, spironolactone, antineoplastic agents, diazepam) also have been implicated. Drugs such as reserpine, theophylline, verapamil, tricyclic antidepressants, and


Surgery_Schwartz

Surgery_Schwartz. (cimetidine, ketoconazole, phenytoin, spironolactone, antineoplastic agents, diazepam) also have been implicated. Drugs such as reserpine, theophylline, verapamil, tricyclic antidepressants, and furosemide induce gynecomastia through idiopathic mechanisms.When gynecomastia is caused by androgen deficiency, then testosterone administration may cause regression. When it is caused by medications, then these are discontinued if possi-ble. When endocrine defects are responsible, then these receive specific therapy. As soon as gynecomastia is progressive and does not respond to other treatments, surgical therapy is con-sidered. Techniques include local excision, liposuction or sub-cutaneous mastectomy. Attempts to reverse gynecomastia with danazol have been successful, but the androgenic side effects of the drug are considerable.Brunicardi_Ch17_p0541-p0612.indd 54901/03/19 5:04 PM 550SPECIFIC CONSIDERATIONSPART IIINFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREASTInfections in the


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Surgery_Schwartz. effects of the drug are considerable.Brunicardi_Ch17_p0541-p0612.indd 54901/03/19 5:04 PM 550SPECIFIC CONSIDERATIONSPART IIINFECTIOUS AND INFLAMMATORY DISORDERS OF THE BREASTInfections in the postpartum period remain proportionately the most common time for breast infections to occur. Infections of the breast unrelated to lactation are proportionately less com-mon, however, are still a relatively common presentation to breast specialists. The latter are classified as intrinsic (second-ary to abnormalities in the breast) or extrinsic (secondary to an infection in an adjacent structure, e.g., skin, thoracic cavity) the most common being probably periductal mastitis and infected sebaceous cysts, respectively.Bacterial InfectionStaphylococcus aureus and Streptococcus species are the organisms most frequently recovered from nipple discharge from an infected breast.17 Typically breast abscesses are seen in staphylococcal infections and present with point tenderness, erythema, and


Surgery_Schwartz

Surgery_Schwartz. organisms most frequently recovered from nipple discharge from an infected breast.17 Typically breast abscesses are seen in staphylococcal infections and present with point tenderness, erythema, and hyperthermia. When these abscesses are related to lactation they usually occur within the first few weeks of breastfeeding. If there is progression of a staphylococcal infec-tion, this may result in subcutaneous, subareolar, interlobular (periductal), and retromammary abscesses (unicentric or multi-centric). Previously almost all breast abscesses were treated by operative incision and drainage, but now the initial approach is antibiotics and repeated aspiration of the abscess, usually ultra-sound-guided aspiration.21 Operative drainage is now reserved for those cases that do not resolve with repeated aspiration and antibiotic therapy or cases in which there is some other indica-tion for incision and drainage (e.g., thinning or necrosis of the overlying skin). Preoperative ultrasonography


Surgery_Schwartz

Surgery_Schwartz. repeated aspiration and antibiotic therapy or cases in which there is some other indica-tion for incision and drainage (e.g., thinning or necrosis of the overlying skin). Preoperative ultrasonography is effective in delineating the required extent of the drainage procedure. While staphylococcal infections tend to be more localized and may be situated deep in the breast tissues, streptococcal infections usually present with diffuse superficial involvement. They are treated with local wound care, including application of warm compresses, and the administration of IV antibiotics (penicillins or cephalosporins). Breast infections may be chronic, possibly with recurrent abscess formation. In this situation, cultures are performed to identify acid-fast bacilli, anaerobic and aerobic bacteria, and fungi. Uncommon organisms may be encountered, and long-term antibiotic therapy may be required.Biopsy of the abscess cavity wall should be considered at the time of incision and drainage to rule


Surgery_Schwartz

Surgery_Schwartz. and fungi. Uncommon organisms may be encountered, and long-term antibiotic therapy may be required.Biopsy of the abscess cavity wall should be considered at the time of incision and drainage to rule out underlying breast cancer in patients where antibiotics and drainage have been ineffective.Nowadays hospital-acquired puerperal infections of the breast are much less common, but nursing women who pres-ent with milk stasis or noninfectious inflammation may still develop this problem. Epidemic puerperal mastitis is initiated by highly virulent strains of methicillin-resistant S aureus that are transmitted via the suckling neonate and may result in sub-stantial morbidity and occasional mortality. Purulent fluid may be expressed from the nipple. In this circumstance, breastfeed-ing is stopped, antibiotics are started, and surgical therapy is initiated. Nonepidemic (sporadic) puerperal mastitis refers to involvement of the interlobular connective tissue of the breast by an infectious


Surgery_Schwartz

Surgery_Schwartz. antibiotics are started, and surgical therapy is initiated. Nonepidemic (sporadic) puerperal mastitis refers to involvement of the interlobular connective tissue of the breast by an infectious process. The patient develops nipple fissuring and milk stasis, which initiates a retrograde bacterial infection. Emptying of the breast using breast suction pumps shortens the duration of symptoms and reduces the incidence of recurrences. The addition of antibiotic therapy results in a satisfactory out-come in >95% of cases.Zuska’s disease, also called recurrent periductal mastitis, is a condition of recurrent retroareolar infections and abscesses.22,23 Smoking has been implicated as a risk factor for this condition.24,25 This syndrome is managed symptomatically by antibiotics coupled with incision and drainage as necessary. Attempts to obtain durable long-term control by wide debride-ment of chronically infected tissue and/or terminal duct resec-tion have been reported and can be curative, but


Surgery_Schwartz

Surgery_Schwartz. and drainage as necessary. Attempts to obtain durable long-term control by wide debride-ment of chronically infected tissue and/or terminal duct resec-tion have been reported and can be curative, but they can also be frustrated by postoperative infections.26Mycotic InfectionsFungal infections of the breast are rare and usually involve blas-tomycosis or sporotrichosis.27 Intraoral fungi that are inoculated into the breast tissue by the suckling infant initiate these infec-tions, which present as mammary abscesses in close proxim-ity to the nipple-areola complex. Pus mixed with blood may be expressed from sinus tracts. Antifungal agents can be adminis-tered for the treatment of systemic (noncutaneous) infections. This therapy generally eliminates the necessity of surgical inter-vention, but occasionally drainage of an abscess, or even partial mastectomy, may be necessary to eradicate a persistent fungal infection. Candida albicans affecting the skin of the breast presents as


Surgery_Schwartz

Surgery_Schwartz. but occasionally drainage of an abscess, or even partial mastectomy, may be necessary to eradicate a persistent fungal infection. Candida albicans affecting the skin of the breast presents as erythematous, scaly lesions of the inframammary or axillary folds. Scrapings from the lesions demonstrate fungal elements (filaments and binding cells). Therapy involves the removal of predisposing factors such as maceration and the topi-cal application of nystatin.Hidradenitis SuppurativaHidradenitis suppurativa of the nipple-areola complex or axilla is a chronic inflammatory condition that originates within the accessory areolar glands of Montgomery or within the axillary sebaceous glands.27 Women with chronic acne are predisposed to developing hidradenitis. When located in and about the nipple-areola complex, this disease may mimic other chronic inflammatory states, Paget’s disease of the nipple, or invasive breast cancer. Involvement of the axillary skin is often multifo-cal and contiguous.


Surgery_Schwartz

Surgery_Schwartz. complex, this disease may mimic other chronic inflammatory states, Paget’s disease of the nipple, or invasive breast cancer. Involvement of the axillary skin is often multifo-cal and contiguous. Antibiotic therapy with incision and drain-age of fluctuant areas is appropriate treatment. Excision of the involved areas may be required. Large areas of skin loss may necessitate coverage with advancement flaps or split-thickness skin grafts.Mondor’s DiseaseMondor’s disease is a variant of thrombophlebitis that involves the superficial veins of the anterior chest wall and breast.28 In 1939, Mondor described the condition as “string phlebitis,” a thrombosed vein presenting as a tender, cord-like structure.29 Frequently involved veins include the lateral thoracic vein, the thoracoepigastric vein, and, less commonly, the superficial epi-gastric vein. Typically, a woman presents with acute pain in the lateral aspect of the breast or the anterior chest wall. A ten-der, firm cord is found to


Surgery_Schwartz

Surgery_Schwartz. and, less commonly, the superficial epi-gastric vein. Typically, a woman presents with acute pain in the lateral aspect of the breast or the anterior chest wall. A ten-der, firm cord is found to follow the distribution of one of the major superficial veins. Rarely, the presentation is bilateral, and most women have no evidence of thrombophlebitis in other ana-tomic sites. This benign, self-limited disorder is not indicative of a cancer. When the diagnosis is uncertain, or when a mass is present near the tender cord, biopsy is indicated. Therapy for Mondor’s disease includes the liberal use of anti-inflammatory medications and application of warm compresses along the symptomatic vein. The process usually resolves within 4 to 6 weeks. When symptoms persist or are refractory to therapy, excision of the involved vein segment may be considered.Brunicardi_Ch17_p0541-p0612.indd 55001/03/19 5:04 PM 551THE BREASTCHAPTER 17COMMON BENIGN DISORDERS AND DISEASES OF THE BREASTBenign breast


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Surgery_Schwartz. of the involved vein segment may be considered.Brunicardi_Ch17_p0541-p0612.indd 55001/03/19 5:04 PM 551THE BREASTCHAPTER 17COMMON BENIGN DISORDERS AND DISEASES OF THE BREASTBenign breast disorders and diseases encompass a wide range of clinical and pathologic entities. Surgeons require an in-depth understanding of benign breast disorders and diseases so that clear explanations may be given to affected women, appropriate treat-ment is instituted, and unnecessary long-term follow up is avoided.Aberrations of Normal Development and InvolutionThe basic principles underlying the aberrations of normal devel-opment and involution (ANDI) classification of benign breast conditions are the following: (a) benign breast disorders and diseases are related to the normal processes of reproductive life and to involution; (b) there is a spectrum of breast conditions that ranges from normal to disorder to disease; and (c) the ANDI classification encompasses all aspects of the breast condition,


Surgery_Schwartz

Surgery_Schwartz. life and to involution; (b) there is a spectrum of breast conditions that ranges from normal to disorder to disease; and (c) the ANDI classification encompasses all aspects of the breast condition, including pathogenesis and the degree of abnormality.30 The horizontal component of Table 17-2 defines ANDI along a spectrum from normal, to mild abnormality (disorder), to severe abnormality (disease). The vertical component indi-cates the period during which the condition develops.Early Reproductive Years. Fibroadenomas are seen and pres-ent symptomatically predominantly in younger women age 15 to 25 years (Fig. 17-10).31 Fibroadenomas usually grow to 1 or 2 cm in diameter and then are stable but may grow to a larger size. Small fibroadenomas (≤1 cm in size) are considered nor-mal, whereas larger fibroadenomas (≤3 cm) are disorders, and giant fibroadenomas (>3 cm) are disease. Similarly, multiple fibroadenomas (more than five lesions in one breast) are very uncommon and are considered


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Surgery_Schwartz. larger fibroadenomas (≤3 cm) are disorders, and giant fibroadenomas (>3 cm) are disease. Similarly, multiple fibroadenomas (more than five lesions in one breast) are very uncommon and are considered disease. It is noted that with the introduction of mammographic screening, asymptomatic 4Table 17-2ANDI classification of benign breast disorders NORMALDISORDERDISEASEEarly reproductive years (age 15–25 y) Lobular developmentStromal developmentFibroadenomaAdolescent hypertrophyGiant fibroadenomaGigantomastia Nipple eversionNipple inversionSubareolar abscess Mammary duct fistulaLater reproductive years (age 25–40 y)Cyclical changes of menstruationCyclical mastalgiaIncapacitating mastalgia Nodularity Epithelial hyperplasia of pregnancyBloody nipple discharge Involution (age 35–55 y)Lobular involutionMacrocysts— Sclerosing lesions Duct involution DilatationDuct ectasiaPeriductal mastitis SclerosisNipple retraction— Epithelial turnoverEpithelial hyperplasiaEpithelial hyperplasia with


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Surgery_Schwartz. lesions Duct involution DilatationDuct ectasiaPeriductal mastitis SclerosisNipple retraction— Epithelial turnoverEpithelial hyperplasiaEpithelial hyperplasia with atypiaANDI = aberrations of normal development and involution.Reproduced with permission from Mansel RE, Webster D, Sweetland H: Hughes, Mansel & Webster’s Benign Disorders and Diseases of the Breast, 3rd ed. London: Elsevier/Saunders; 2009.Figure 17-10. Fibroadenoma (40x). These benign tumors are typi-cally well circumscribed and are comprised of both stromal and glandular elements. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consultant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)fibroadenomas are sometimes found in an older screened popu-lation. The precise etiology of adolescent breast hypertrophy is unknown. A spectrum of changes from limited to massive stro-mal hyperplasia (gigantomastia) is seen. Nipple inversion is a disorder of


Surgery_Schwartz

Surgery_Schwartz. The precise etiology of adolescent breast hypertrophy is unknown. A spectrum of changes from limited to massive stro-mal hyperplasia (gigantomastia) is seen. Nipple inversion is a disorder of development of the major ducts, which prevents nor-mal protrusion of the nipple. Mammary duct fistulas arise when nipple inversion predisposes to major duct obstruction, leading to recurrent subareolar abscess and mammary duct fistula.Brunicardi_Ch17_p0541-p0612.indd 55101/03/19 5:04 PM 552SPECIFIC CONSIDERATIONSPART IIABFigure 17-11. A. Ductal epithelial hyperplasia. The irregular intra-cellular spaces and variable cell nuclei distinguish this process from carcinoma in situ. B. Lobular hyperplasia. The presence of alveo-lar lumina and incomplete distention distinguish this process from carcinoma in situ. (Used with permission from Dr. R.L. Hackett.)Table 17-3Cancer risk associated with benign breast disorders and in situ carcinoma of the breastABNORMALITYRELATIVE RISKNonproliferative lesions


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Surgery_Schwartz. in situ. (Used with permission from Dr. R.L. Hackett.)Table 17-3Cancer risk associated with benign breast disorders and in situ carcinoma of the breastABNORMALITYRELATIVE RISKNonproliferative lesions of the breastNo increased riskSclerosing adenosisNo increased riskIntraductal papillomaNo increased riskFlorid hyperplasia1.5 to 2-foldAtypical lobular hyperplasia4-foldAtypical ductal hyperplasia4-foldDuctal involvement by cells of atypical ductal hyperplasia7-foldLobular carcinoma in situ10-foldDuctal carcinoma in situ10-foldData from Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease, N Engl J Med. 1985 Jan 17; 312(3):146-151.Table 17-4Classification of benign breast disordersNonproliferative disorders of the breast Cysts and apocrine metaplasia Duct ectasia Mild ductal epithelial hyperplasia Calcifications Fibroadenoma and related lesionsProliferative breast disorders without atypia Sclerosing adenosis Radial and complex sclerosing


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Surgery_Schwartz. ectasia Mild ductal epithelial hyperplasia Calcifications Fibroadenoma and related lesionsProliferative breast disorders without atypia Sclerosing adenosis Radial and complex sclerosing lesions Ductal epithelial hyperplasia Intraductal papillomasAtypical proliferative lesions Atypical lobular hyperplasia Atypical ductal hyperplasiaData from Godfrey SE: Is fibrocystic disease of the breast precancerous? Arch Pathol Lab Med. 1986 Nov;110(11):991.include ductal and lobular hyperplasia, both of which display some features of carcinoma in situ. Women with atypical ductal or lobular hyperplasia have a fourfold increase in breast cancer risk (Table 17-3).Pathology of Nonproliferative DisordersOf paramount importance for the optimal management of benign breast disorders and diseases is the histologic differentia-tion of benign, atypical, and malignant changes.32,33 Determin-ing the clinical significance of these changes is a problem that is compounded by inconsistent nomenclature. The


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Surgery_Schwartz. histologic differentia-tion of benign, atypical, and malignant changes.32,33 Determin-ing the clinical significance of these changes is a problem that is compounded by inconsistent nomenclature. The classifica-tion system originally developed by Page separates the various types of benign breast disorders and diseases into three clini-cally relevant groups: nonproliferative disorders, proliferative disorders without atypia, and proliferative disorders with atypia (Table 17-4). Nonproliferative disorders of the breast account for 70% of benign breast conditions and carry no increased risk Later Reproductive Years. Cyclical mastalgia and nodular-ity usually are associated with premenstrual enlargement of the breast and are regarded as normal. Cyclical pronounced mastal-gia and severe painful nodularity are viewed differently than are physiologic discomfort and lumpiness. Painful nodularity that persists for >1 week of the menstrual cycle is considered a disor-der. In epithelial


Surgery_Schwartz

Surgery_Schwartz. painful nodularity are viewed differently than are physiologic discomfort and lumpiness. Painful nodularity that persists for >1 week of the menstrual cycle is considered a disor-der. In epithelial hyperplasia of pregnancy, papillary projections sometimes give rise to bilateral bloody nipple discharge.Involution. Involution of lobular epithelium is dependent on the specialized stroma around it. However, an integrated invo-lution of breast stroma and epithelium is not always seen, and disorders of the process are common. When the stroma invo-lutes too quickly, alveoli remain and form microcysts, which are precursors of macrocysts. The macrocysts are common, often subclinical, and do not require specific treatment. Sclerosing adenosis is considered a disorder of both the proliferative and the involutional phases of the breast cycle. Duct ectasia (dilated ducts) and periductal mastitis are other important components of the ANDI classification. Periductal fibrosis is a sequela of


Surgery_Schwartz

Surgery_Schwartz. and the involutional phases of the breast cycle. Duct ectasia (dilated ducts) and periductal mastitis are other important components of the ANDI classification. Periductal fibrosis is a sequela of periductal mastitis and may result in nipple retraction. About 60% of women ≥70 years of age exhibit some degree of epi-thelial hyperplasia (Fig. 17-11). Atypical proliferative diseases Brunicardi_Ch17_p0541-p0612.indd 55201/03/19 5:04 PM 553THE BREASTCHAPTER 17for the development of breast cancer. This category includes cysts, duct ectasia, periductal mastitis, calcifications, fibroad-enomas, and related disorders.Breast macrocysts are an involutional disorder, have a high frequency of occurrence, and are often multiple. Duct ecta-sia is a clinical syndrome characterized by dilated subareolar ducts that are palpable and often associated with thick nipple discharge. Haagensen regarded duct ectasia as a primary event that led to stagnation of secretions, epithelial ulceration, and leakage


Surgery_Schwartz

Surgery_Schwartz. ducts that are palpable and often associated with thick nipple discharge. Haagensen regarded duct ectasia as a primary event that led to stagnation of secretions, epithelial ulceration, and leakage of duct secretions (containing chemically irritating fatty acids) into periductal tissue.34 This sequence was thought to pro-duce a local inflammatory process with periductal fibrosis and subsequent nipple retraction. An alternative theory considers periductal mastitis to be the primary process, which leads to weakening of the ducts and secondary dilatation. It is possible that both processes occur and together explain the wide spec-trum of problems seen, which include nipple discharge, nipple retraction, inflammatory masses, and abscesses.Calcium deposits are frequently encountered in the breast. Most are benign and are caused by cellular secretions and debris or by trauma and inflammation. Calcifications that are associated with cancer include microcalcifications, which vary in shape and


Surgery_Schwartz

Surgery_Schwartz. Most are benign and are caused by cellular secretions and debris or by trauma and inflammation. Calcifications that are associated with cancer include microcalcifications, which vary in shape and density and are <0.5 mm in size, and fine, linear calcifications, which may show branching. Fibroadenomas have abundant stroma with histologically normal cellular elements. They show hormonal dependence similar to that of normal breast lobules in that they lactate during pregnancy and invo-lute in the postmenopausal period. Adenomas of the breast are well circumscribed and are composed of benign epithelium with sparse stroma, which is the histologic feature that differentiates them from fibroadenomas. They may be divided into tubular adenomas and lactating adenomas. Tubular adenomas are seen in young nonpregnant women, whereas lactating adenomas are seen during pregnancy or during the postpartum period. Ham-artomas are discrete breast tumors that are usually 2 to 4 cm in diameter, firm, and


Surgery_Schwartz

Surgery_Schwartz. young nonpregnant women, whereas lactating adenomas are seen during pregnancy or during the postpartum period. Ham-artomas are discrete breast tumors that are usually 2 to 4 cm in diameter, firm, and sharply circumscribed. Adenolipomas con-sist of sharply circumscribed nodules of fatty tissue that contain normal breast lobules and ducts.Fibrocystic Disease. The term fibrocystic disease is nonspe-cific. Too frequently, it is used as a diagnostic term to describe symptoms, to rationalize the need for breast biopsy, and to explain biopsy results. Synonyms include fibrocystic changes, cystic mastopathy, chronic cystic disease, chronic cystic mas-titis, Schimmelbusch’s disease, mazoplasia, Cooper’s disease, Reclus’ disease, and fibroadenomatosis. Fibrocystic disease refers to a spectrum of histopathologic changes that are best diagnosed and treated specifically.Pathology of Proliferative Disorders Without AtypiaProliferative breast disorders without atypia include sclerosing adenosis,


Surgery_Schwartz

Surgery_Schwartz. histopathologic changes that are best diagnosed and treated specifically.Pathology of Proliferative Disorders Without AtypiaProliferative breast disorders without atypia include sclerosing adenosis, radial scars, complex sclerosing lesions, ductal epithe-lial hyperplasia, and intraductal papillomas.32,33 Sclerosing ade-nosis is prevalent during the childbearing and perimenopausal years and has no malignant potential. Histologic changes are both proliferative (ductal proliferation) and involutional (stro-mal fibrosis, epithelial regression). Sclerosing adenosis is char-acterized by distorted breast lobules and usually occurs in the context of multiple microcysts, but occasionally presents as a palpable mass. Benign calcifications are often associated with this disorder. Sclerosing adenosis can be managed by observa-tion as long as the imaging features and pathologic findings are concordant. Central sclerosis and various degrees of epithelial proliferation, apocrine metaplasia, and


Surgery_Schwartz

Surgery_Schwartz. can be managed by observa-tion as long as the imaging features and pathologic findings are concordant. Central sclerosis and various degrees of epithelial proliferation, apocrine metaplasia, and papilloma formation characterize radial scars and complex sclerosing lesions of the breast. Lesions up to 1 cm in diameter are called radial scars, whereas larger lesions are called complex sclerosing lesions. Radial scars originate at sites of terminal duct branching where the characteristic histologic changes radiate from a central area of fibrosis. All of the histologic features of a radial scar are seen in the larger complex sclerosing lesions, but there is a greater disturbance of structure with papilloma formation, apocrine metaplasia, and occasionally sclerosing adenosis. Distinguish-ing between a radial scar and invasive breast carcinoma can be challenging based on core-needle biopsy sampling. Often the imaging features of a radial scar (which can be quite similar to an invasive


Surgery_Schwartz

Surgery_Schwartz. between a radial scar and invasive breast carcinoma can be challenging based on core-needle biopsy sampling. Often the imaging features of a radial scar (which can be quite similar to an invasive cancer) will dictate the need for either a vacuum-assisted biopsy or surgical excision in order to exclude the pos-sibility of carcinoma.Mild ductal hyperplasia is characterized by the presence of three or four cell layers above the basement membrane. Moder-ate ductal hyperplasia is characterized by the presence of five or more cell layers above the basement membrane. Florid duc-tal epithelial hyperplasia occupies at least 70% of a minor duct lumen. It is found in >20% of breast tissue specimens, is either solid or papillary, and is associated with an increased cancer risk (see Table 17-3). Intraductal papillomas arise in the major ducts, usually in premenopausal women. They generally are <0.5 cm in diameter but may be as large as 5 cm. A common presenting symptom is nipple discharge, which


Surgery_Schwartz

Surgery_Schwartz. papillomas arise in the major ducts, usually in premenopausal women. They generally are <0.5 cm in diameter but may be as large as 5 cm. A common presenting symptom is nipple discharge, which may be serous or bloody. Grossly, intraductal papillomas are pinkish tan, fri-able, and usually attached to the wall of the involved duct by a stalk. They rarely undergo malignant transformation, and their presence does not increase a woman’s risk of developing breast cancer (unless accompanied by atypia). However, multiple intraductal papillomas, which occur in younger women and are less frequently associated with nipple discharge, are susceptible to malignant transformation.Pathology of Atypical Proliferative DiseasesThe atypical proliferative diseases have some of the features of carcinoma in situ but either lack a major defining feature of car-cinoma in situ or have the features in less than fully developed form.34 Atypical ductal hyperplasia (ADH) appears similar to low grade ductal


Surgery_Schwartz

Surgery_Schwartz. in situ but either lack a major defining feature of car-cinoma in situ or have the features in less than fully developed form.34 Atypical ductal hyperplasia (ADH) appears similar to low grade ductal carcinoma in situ (DCIS) histologically and is composed of monotonous round, cuboidal, or polygonal cells enclosed by basement membrane with rare mitoses. A lesion will be considered to be ADH if it is up to 2 or 3 mm in size but would be called DCIS if it is larger than 3 mm. The diagnosis can be difficult to establish with core-needle biopsy specimen alone and many cases will require excisional biopsy specimen for classification. Individuals with a diagnosis of ADH are at increased risk for development of breast cancer and should be counseled appropriately regarding risk reduction strategies.In 1978, Haagensen et al described lobular neoplasia, a spectrum of disorders ranging from atypical lobular hyperplasia to lobular carcinoma in situ (LCIS).35 Atypical lobular hyper-plasia (ALH)


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Surgery_Schwartz. 1978, Haagensen et al described lobular neoplasia, a spectrum of disorders ranging from atypical lobular hyperplasia to lobular carcinoma in situ (LCIS).35 Atypical lobular hyper-plasia (ALH) results in minimal distention of lobular units with cells that are similar to those seen in LCIS. The diagnosis of LCIS is made when small monomorphic cells that distend the terminal ductal lobular unit are noted. In cases of LCIS, the acini are full and distended while the overall lobular architec-ture is maintained (Fig. 17-12). Classic LCIS is not associated with a specific mammographic or palpable abnormality but is Brunicardi_Ch17_p0541-p0612.indd 55301/03/19 5:04 PM 554SPECIFIC CONSIDERATIONSPART IIFigure 17-12. Lobular carcinoma in situ (100x). There are small monomorphic cells that distend the terminal duct lobular unit, with-out necrosis or mitoses. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consul-tant Histopathologist and Lead Breast


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Surgery_Schwartz. the terminal duct lobular unit, with-out necrosis or mitoses. (Used with permission from Dr. Sindhu Menon, Consultant Histopathologist and Dr. Rahul Deb, Consul-tant Histopathologist and Lead Breast Pathologist, Royal Derby Hospital, Derby, UK.)an incidental finding noted on breast biopsy. There is a variant of LCIS that has been termed pleomorphic LCIS. In the case of pleomorphic LCIS, there can be calcifications or other suspi-cious mammographic changes that dictate the need for biopsy. Classic LCIS is not treated with excision as the patient is at risk for developing invasive breast cancer in either breast and therefore the patient is counseled regarding appropriate risk reduction strategies. Pleomorphic LCIS can be difficult to dis-tinguish from high-grade DCIS and there are some proponents who have suggested that patients with pleomorphic LCIS be managed similar to those with DCIS with attention to margins and consideration for radiation therapy in the setting of breast


Surgery_Schwartz

Surgery_Schwartz. some proponents who have suggested that patients with pleomorphic LCIS be managed similar to those with DCIS with attention to margins and consideration for radiation therapy in the setting of breast conserving treatment. The use of immunohistochemical stain-ing for E-cadherin can help to discriminate between LCIS and DCIS. In lobular neoplasias, such as ALH and LCIS, there is a lack of E-cadherin expression, whereas the majority of ductal lesions will demonstrate E-cadherin reactivity.Treatment of Selected Benign Breast Disorders and DiseasesCysts. Because needle biopsy of breast masses may produce artifacts that make mammography assessment more difficult, many multidisciplinary teams prefer to image breast masses before performing either fine-needle aspiration or core-needle biopsy.36,37 In practice, however, the first investigation of pal-pable breast masses may be a needle biopsy, which allows for the early diagnosis of cysts. A 21-gauge needle attached to a 10-mL syringe is


Surgery_Schwartz

Surgery_Schwartz. In practice, however, the first investigation of pal-pable breast masses may be a needle biopsy, which allows for the early diagnosis of cysts. A 21-gauge needle attached to a 10-mL syringe is placed directly into the mass, which is fixed by fingers of the nondominant hand. The volume of a typical cyst is 5 to 10 mL, but it may be 75 mL or more. If the fluid that is aspirated is not bloodstained, then the cyst is aspirated to dryness, the needle is removed, and the fluid is discarded because cytologic examination of such fluid is not cost effec-tive. After aspiration, the breast is carefully palpated to exclude a residual mass. In most cases, however, imaging has been per-formed prior to a needle being introduced into the breast, and indeed the majority of cysts are now aspirated under ultrasound guidance. If a mass was noted on initial ultrasound or there is a residual mass post aspiration, then a tissue specimen is obtained, usually by core biopsy. When cystic fluid is bloodstained,


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Surgery_Schwartz. guidance. If a mass was noted on initial ultrasound or there is a residual mass post aspiration, then a tissue specimen is obtained, usually by core biopsy. When cystic fluid is bloodstained, fluid can be sent for cytologic examination. A simple cyst is rarely of concern, but a complex cyst may be the result of an underlying malignancy. A pneumocystogram can be obtained by injecting air into the cyst and then obtaining a repeat mammogram. When this technique is used, the wall of the cyst cavity can be more carefully assessed for any irregularities.Fibroadenomas. Most fibroadenomas are self-limiting and many go undiagnosed, so a more conservative approach is reasonable. Careful ultrasound examination with core-needle biopsy will provide for an accurate diagnosis. Ultrasonogra-phy may reveal specific features that are pathognomonic for fibroadenoma, and in a young woman (e.g., under 25 years) where the risk of breast cancer is already very low a core-needle biopsy may not be necessary.


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Surgery_Schwartz. specific features that are pathognomonic for fibroadenoma, and in a young woman (e.g., under 25 years) where the risk of breast cancer is already very low a core-needle biopsy may not be necessary. In patients where biopsy is performed, the patient is counseled concerning the ultra-sound and biopsy results, and surgical excision of the fibroad-enoma may be avoided. Cryoablation and ultrasound-guided vacuum-assisted biopsy are approved treatments for fibroad-enomas of the breast, especially lesions <3 cm. Larger lesions are often still best treated by excision. With short-term follow-up, a significant percentage of fibroadenomas will decrease in size and will no longer be palpable.38 However, many will remain palpable, especially those larger than 2 cm.39 There-fore, women should be counseled that the options for treat-ment include surgical removal, cryoablation, vacuum assisted biopsy, or observation.Sclerosing Disorders. The clinical significance of scleros-ing adenosis lies in its


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Surgery_Schwartz. that the options for treat-ment include surgical removal, cryoablation, vacuum assisted biopsy, or observation.Sclerosing Disorders. The clinical significance of scleros-ing adenosis lies in its imitation of cancer. On physical exami-nation, it may be confused with cancer, by mammography, and at gross pathologic examination. Excisional biopsy and histologic examination are frequently necessary to exclude the diagnosis of cancer. The diagnostic work-up for radial scars and complex sclerosing lesions frequently involves stereo-tactic biopsy. It usually is not possible to differentiate these lesions with certainty from cancer by mammographic features, so a larger tissue biopsy is recommended either by way of vacuum-assisted biopsy or an open surgical excisional biopsy. The mammographic appearance of a radial scar or sclerosing adenosis (mass density with spiculated margins) will usually lead to an assessment that the results of a core-needle biopsy specimen showing benign disease are


Surgery_Schwartz

Surgery_Schwartz. of a radial scar or sclerosing adenosis (mass density with spiculated margins) will usually lead to an assessment that the results of a core-needle biopsy specimen showing benign disease are discordant with the radiographic findings.Periductal Mastitis. Painful and tender masses behind the nipple-areola complex are aspirated with a 21-gauge needle attached to a 10-mL syringe. Any fluid obtained is submitted for culture using a transport medium appropriate for the detec-tion of anaerobic organisms. In the absence of pus, women are started on a combination of antibiotics to cover polymicrobial infections while awaiting the results of culture. Antibiotics are then continued based on sensitivity tests. Many cases respond satisfactorily to antibiotics alone, but when considerable puru-lent material is present, repeated ultrasound guided aspiration is performed, and ultimately in a proportion of cases surgical treatment is required. Unlike puerperal abscesses, a subareo-lar abscess is


Surgery_Schwartz

Surgery_Schwartz. material is present, repeated ultrasound guided aspiration is performed, and ultimately in a proportion of cases surgical treatment is required. Unlike puerperal abscesses, a subareo-lar abscess is usually unilocular and often is associated with a single duct system. Ultrasound will accurately delineate its extent. In those cases that come to surgery, the surgeon may either undertake simple drainage with a view toward formal Brunicardi_Ch17_p0541-p0612.indd 55401/03/19 5:04 PM 555THE BREASTCHAPTER 17Table 17-5Treatment of recurrent subareolar sepsisSUITABLE FOR FISTULECTOMYSUITABLE FOR TOTAL DUCT EXCISIONSmall abscess localized to one segmentLarge abscess affecting >50% of the areolar circumferenceRecurrence involving the same segmentRecurrence involving a different segmentMild or no nipple inversionMarked nipple inversionPatient unconcerned about nipple inversionPatient requests correction of nipple inversionYounger patientOlder patientNo discharge from other ductsPurulent


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Surgery_Schwartz. or no nipple inversionMarked nipple inversionPatient unconcerned about nipple inversionPatient requests correction of nipple inversionYounger patientOlder patientNo discharge from other ductsPurulent discharge from other ductsNo prior fistulectomyRecurrence after fistulectomyModified with permission from Mansel RE, Webster DJT: Benign Disorders and Diseases of the Breast: Concepts and Clinical Management, 2nd ed. London: Elsevier/Saunders; 2000.surgery, should the problem recur, or proceed with definitive surgery. In a woman of childbearing age, simple drainage is preferred, but if there is an anaerobic infection, recurrent infection frequently develops. Recurrent abscess with fistula is a difficult problem. Treatment of periductal fistula was ini-tially recommended to be opening up of the fistulous track and allowing it to granulate.40 This approach may still be used, especially if the fistula is recurrent after previous attempts at fistulectomy. However, nowadays the preferred


Surgery_Schwartz

Surgery_Schwartz. of the fistulous track and allowing it to granulate.40 This approach may still be used, especially if the fistula is recurrent after previous attempts at fistulectomy. However, nowadays the preferred initial surgical treatment is by fistulectomy and primary closure with anti-biotic coverage.41 Excision of all the major ducts is an alter-native option depending on the circumstances (Table 17-5). When a localized periareolar abscess recurs at the previous site and a fistula is present, the preferred operation is fistulec-tomy, which has minimal complications and a high degree of success. However, when subareolar sepsis is diffused rather than localized to one segment or when more than one fistula is present, total duct excision is the most expeditious approach. The first circumstance is seen in young women with squamous metaplasia of a single duct, whereas the latter circumstance is seen in older women with multiple ectatic ducts. Age is not always a reliable guide, however, and fistula


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Surgery_Schwartz. in young women with squamous metaplasia of a single duct, whereas the latter circumstance is seen in older women with multiple ectatic ducts. Age is not always a reliable guide, however, and fistula excision is the preferred initial procedure for localized sepsis irrespective of age. Antibiotic therapy is useful for recurrent infection after fistula excision, and a 2to 4-week course is recommended before total duct excision.Nipple Inversion. More women request correction of con-genital nipple inversion than request correction for the nipple inversion that occurs secondary to duct ectasia. Although the results are usually satisfactory, women seeking correction for cosmetic reasons should always be made aware of the surgi-cal complications of altered nipple sensation, nipple necrosis, and postoperative fibrosis with nipple retraction. Because nipple inversion is a result of shortening of the subareolar ducts, a com-plete division of these ducts is necessary for permanent correc-tion of


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Surgery_Schwartz. fibrosis with nipple retraction. Because nipple inversion is a result of shortening of the subareolar ducts, a com-plete division of these ducts is necessary for permanent correc-tion of the disorder.RISK FACTORS FOR BREAST CANCERHormonal and Nonhormonal Risk FactorsIncreased exposure to estrogen is associated with an increased risk for developing breast cancer, whereas reducing exposure is thought to be protective.42-48 Correspondingly, factors that increase the number of menstrual cycles, such as early men-arche, nulliparity, and late menopause, are associated with increased risk. Moderate levels of exercise and a longer lacta-tion period, factors that decrease the total number of menstrual cycles, are protective. The terminal differentiation of breast epi-thelium associated with a full-term pregnancy is also protective, so older age at first live birth is associated with an increased risk of breast cancer. Finally, there is an association between obesity and increased breast cancer