Breast , Embryology and Development; Classification of Benign Disease and Management of Fibrocystic Disease; Subcutaneous Mastectomy

Plastic Surgery Seminar Series University of Toronto

Daniel Martin November 1, 2006 Previous Author: Judy Ward

Discussors: Dr. M. Musgrave Dr. M. Quan

Table of Contents

Anatomy…………………………………………………………………………… 3 Embryology……………………………………………………………………...... 6 Development………………………………………………………………………. 7 Physiology…………………………………………………………………………. 8 Congenital Anomalies …………………………………………………………...... 9 Benign …………………………………………………………...... 11 Fibrocystic Disease………………………………………………………… 11 Neoplasms and Proliferative lesions………………………………...... 14 and variants……………………………….……….. 14 Phyllodes Tumors..……………………………………………….... 15 Adenomas………………………………………………………….. 16 Papillomas……………...…………………………………………... 17 Microglandular Adenosis………………………………………….. 18 Radial Sclerosing Lesions…………………………………………. 19 Granular Cell Tumors……………………………………………… 19 Fibromatosis………………………………………………………... 19 Breast Infarct………………………………………………………. 20 Other………..……………………………………………………… 20 Inflammatory and Reactive lesions………………………………………… 20 Mammary Ductal Ectasia……………..……………………………. 20 Nonpuerperal Breast Abscesses……………………………………. 21 Mammary Fistula…………………………………………………... 22 Puerperal and Abscess……………………………………. 22 Reaction to Foreign Material………………………………………. 23 Breast Trauma……………………………………………………………… 23 Hematoma………………………………………………………….. 23 Fat Necrosis………………………………………………………... 23 Mondor’s Disease………………………………………………….. 24 Miscellaneous……………………………………………………………… 24 …………………………………………………………. 24 Subcutaneous Mastectomy…………………………………………………………. 25 References………………………………………………………………………….. 26

2 Anatomy · 2nd rib to at 6th rib · Lateral border sternum to midaxillary line · Axillary tail (of Spence) extends superolaterally into anterior axillary fold

Contour · At maturity – glandular components take a protuberant conical form · Cone base roughly circular measuring 10-12cm diameter, 5-7cm in thickness · Variation in size, contour and density · Nulliparous – hemispheric, flattening above the · Multiparity – larger, pendulous form with increase in volume and density · Senescence – flattened, flaccid, pendulous, decreased volume

Composition · 15-20 lobes of glandular tissue (tubuloalveolar type) within superficial · Upper half, particularly upper outer quadrant, contains greater volume of glandular tissue · interposed and fibrous tissue connections between lobules · Subcutaneous connective tissue surrounds the gland and extend as septa between lobes and lobules · Deep layer of superficial fascia lies on posterior surface, adjacent to deep investing fascia of pectoralis major, serratus anterior, external oblique abdominal muscle and rectus shealth · Retromammary bursa – between deep layer of superficial fascia and deep fascia · Suspensory ligaments (of Cooper) – fibrous bands from deep fascia to

3 Nipple and · Highly pigmented, variably corrugated · Keratinized stratified squamous · Smooth muscle bundle fibres arranged radially and circumferentially in connective tissue and longitudinally along lactiferous ducts extend into nipple · Areola – sebaceous glands, sweat glands, accessory areolar glands · Accessory glands produce small elevations of areola (Montgomery tubercles) · Nipple contains numerous sensory nerve endings and Meissner’s corpuscles, areola contains few

Blood Supply 1. internal mammary artery via medial mammary branches (60%) 2. lateral thoracic artery via lateral mammary branches (30%) 3. 3rd to 5th posterior intercostal arteries via lateral mammary branches 4. thoracoacromial artery via pectoral branches 5. subscapular and thoracodorsal artery

Venous Drainage · primary venous drainage is towards 1. perforating branches of internal thoracic vein 2. tributaries of axillary vein 3. perforating branches of posterior intercostal veins

Lymphatic Drainage · axillary nodes (primary drainage, >75%) – to subclavian lymph trunk · internal mammary (parasternal) nodes · both axillary and parasternal groups receive lymph from all quadrants of the breast

Axillary nodes: 1. axillary vein group (lateral group) · medial or posterior to vein 2. external mammary group (anterior or pectoral group) · lower border of pec. minor contiguous with lateral thoracic vessels 3. scapular group (posterior or subscapular) · posterior axillary wall, lateral border of scapula, contiguous with subscapular vessels

4 4. central group · embedded within fat of axilla posterior to pectoralis minor 5. subclavicular group (apical) · posterior and superior to upper border of pectoralis minor 6. interpectoral (Rotter’s) group · between pectoralis major and minor

Levels I – nodes lateral to or below lower border of pectoralis minor · external mammary, axillary vein, and scapular groups II – nodes deep to or behind pectoralis minor · central group III – nodes medial to or above upper border or pectoralis minor · subcalvicular group

5 Alternate Pathways – important when physiological routes obstructed - deep, substernal cross drainage to contralateral internal mammary chain - superficial presternal crossover - lateral intercostals - mediastinal - rectus abdominal muscle sheath to subdiaphragmatic and subperitoneal plexus – Gerota Pathway - direct spread to liver and retroperitoneal lymph nodes

Innervation · lateral and anterior cutaneous branches of 2nd to 6th intercostal nerves · lateral branch of 4th intercostal nerve – dominant to nipple · upper portion of breast – anterior or medial branches of the supraclavicular nerve from cervical plexus

Embryology

Independent of Placental Hormones Fetal weeks Stage Development 5 Ectodermal primitive milk streak (galactic band) develops from axilla to groin In region of , band develops to form , remaining band regresses 7-8 Milk hill Thickening in mammary anlage Disk Invagination into chest wall Globular Tridimensional growth 10-14 Cone Further invasion of chest wall mesenchyme results in flattening of ridge 12-16 Mesenchymal cells differentiate into the smooth muscle of the nipple and areola

Budding Development of epithelial buds 16 Branching Epithelial buds branch to form 15-25 strips of epithelium (future secretory alveoli) · secondary mammary anlage then develops – differentiation of follicle, sebaceous gland and sweat gland elements (only sweat glands develop fully at this time) · special apocrine glands develop to form Montgomery’s glands around nipple

Dependent on Placental Hormones Fetal weeks Stage Development 20-32 Canalization Canalization of the branched epithelial tissues 32-40 End-vesicle Parenchymal differentiation with development of lobular-alveolar structures that contain colostrum Lactiferous ducts open into a shallow pit which everts and gives rise to the nipple Nipple-areola complex develops and becomes pigmented

Neonate · stimulated mammary tissue secretes colostral milk (witch’s milk) – can be expressed from the nipple for 4-7 days postpartum in most neonates of either sex · colostral secretion declines over 3-4 weeks – involution of breast after withdrawal of placental hormones

Early Childhood · end vesicles become further canalized and develop into ductal structures by additional growth and branching · dense fibrous stroma and ducts lined by epithelium

Development · puberty in girls begins at age 10-12 yrs. · (immature ovarian follicles) o stimulate longitudinal ductal growth of ductal epithelium o Terminal ductules form buds that precede further breast lobules o Periductal connective tissue increases in volume and elasticity, with enhanced vascularity and fat deposition · (mature ovarian follicles) o Stimulates acinar epithelium, reduces estrogen binding to epithelium, limits tubular proliferation o Together with estrogen, produce full ductular-lobular-alveolar development o Relative role of each hormone not clear · Microanatomy o Growing and dividing ducts that form terminal end buds (TEB) o TEBs form new branches, twigs and small ductules termed alveolar buds o Alveolar buds differentiate into ductules o Alveolus = resting secretory unit o Acines = fully developed secretory unit of and o Lobules – develop during the first few years after menarche; alveolar buds cluster around a terminal · Tanner staging of

7

Physiology Menstrual Cylce - follicular phase: increasing estrogen stimulates epithelial proliferation - luteal phase: mammary ducts dilate, alveolar epithelial cells differentiate into secretory cells, increased mammary blood flow, increased interlobular edema - and pain may occur – cyclic mastalgia

Pregnancy - ductular, lobular and alveolar growth occurs – estrogen, progesterone, placental lactogen, chorionic gonadotropin, increasing levels of - breast enlargement significant at 5-8 weeks – dilatation of superficial veins, heaviness, increasing pigmentation of nipple-areolar complex - second half of pregnancy – increasing breast size from increasing dilatation of alveoli with colostrums and hypertrophy of myoepithelial cells, connective tissue and fat

Lactation - triggered by sudden loss withdrawal of placental hormones with continued production of prolactin - prolactin, in presence of growth hormone, insulin and cortisol, converts mammary epithelial cells from presecretory to secretory state - milk ejection – activation of sensory nerve endings in nipple-areolar complex causes prolactin secretion from anterior pituitary and from posterior pituitary - oxytocin acts on myoepithelial cells, which contract and eject milk from alveoli into lactiferous ducts and sinuses

Menopause - regression of epithelial structures and stroma, increased fat deposition - duct system remains but lobules shrink and collapse

8 Congenital Anomalies

Ø two general categories: 1. presence of supernumerary breast tissue o incomplete involution of milk line o 2-6% females, 1-3% males o may enlarge with puberty, pregnancy or lactation; potential site of CA

2. absence or underdevelopment of breast tissue o may be unilateral or bilateral o result from partial or complete underdevelopment of mammary bud o – complete absence of glandular tissue, nipple and areola o hypoplasia – presence of small rudimentary breast o – absence of nipple and areola, glandular tissue present o – nipple present, breast tissue lacking

Inverted nipple – lactiferous ducts fail to evert as a nipple, 2-4% incidence

Polythelia () · most frequent abnormality · present in 2-5% of general population, male:female equal · most cases sporadic, 6% familial AD inheritance · most common site – inframammary region (> 90%) · may be misdiagnosed as nevi · occur anywhere along mammary ridges (axilla to groin) · association: renal disease (cysts, duplications, unilateral renal agenesis, neoplasm), congenital

heart defect, arrhythmias, essential HTN, pyloric stenosis, epilepsy, ear anomlies · treatment: simple excision

Polymastia (supernumerary breast) · 1-2% of female population · most cases sporadic, may be part of a syndrome – Turner’s, Fleischer’s (lateral displacement of , renal hypoplasia) · most common site: axilla, followed by inframammary region · may present in pregnancy as axillary fullness · may or may not be associated nipple-areola complex; most commonly nipple and areola absent or rudimentary

9 · treatment: excision of ectopic breast tissue · lower chest wall and inframammary approached through inframammary incision · inframammary breast often confluent with lower pole of primary breast o must be careful not to injure primary developing breast bud in preadolescent or in patient with developing breasts

Hypoplasia · congenital vs. acquired secondary to injury of breast bud · may occur in patients with – Turner syndrome, congenital adrenal hyperplasia, delayed menarche · underdevelopment of the breast; nipple and glands present · management o delay reconstruction until 13 years of age, if possible o saline-filled permanent expander-implant – exchanged for permanent implant when breast development complete o nipple-areola reconstruction at completion of expansion

Congenital Absence – 3 groups 1. Bilateral associated with congenital ectodermal defect · Sex-linked recessive, 50% penetrance from mother to son · Mother to daughter transmission causes 10-30% of heterozygous girls to show manifestations, less severe than boys · Skin and appendages, teeth and nails affected · Cleft lip and palate, microphthalmia, corneal dysplasia

2. Unilateral absence (Poland’s syndrome) · incidence: 1 in 30 000 live births · most cases sporadic; familial pattern is AD · more common on right side · male:female = 3:1 · deformity varies greatly and may include: o absence of 2nd to 4th ribs o absence of pectoralis major muscle o aplasia/hypoplasia of the breast o hypoplasia of muscles of shoulder girdle (including latissimus dorsi) o brachysyndactyly – with hypoplasia of the middle phalanges and central skin webbing o shortening of forearm bones o deficiency of subcutaneous fat o absence of axillary hair · may also involve aplasia or hypoplasia of nipple-areolar complex · associated anomalies – scoliosis, dextrocardia, congenital spherocytosis, leukemia · management may involve:

10 o temporary expander to provide symmetry during breast development; exchanged for permanent implant at completion of development o latissimus dorsi muscle – inadequate subcutaneous tissue, or to reconstruct infraclavicular hollowness or anterior axillary fold o autologous reconstruction: TRAM – reconstruction of breast, infraclavicular areas and anterior axillary fold

3. Bilateral absence of the breast · May occur in isolation · Associated with cleft palate, high-arched palate, scant axillary and pubic hair, absence of a finger, and ‘lobster claw’ deformity of the hands and feet · Inheritance – autosomal dominant

Acquired Abnormalities · injudicious biopsy of a precociously developing breast or treatment of neonatal mastitis – excision of most of breast bud with subsequent deformity during puberty · radiation therapy – prepubertal treatment of hemangioma or intrathoracic lesion · severe burn – burn wound contracture

Benign Breast Disease

Fibrocystic Disease · not a distinct entity, either clinically or pathologically · a heterogeneous group of abnormalities that may occur separately or together · synonyms: ‘chronic cystic mastitis’ and ‘mammary dysplasia’ · incidence: 50% of women have palpable irregularities · etiology: exaggerated response of the breast stroma and epithelium to hormones and growth factors, theories include: o increased estrogen o altered sensitivity to estrogen

11 o progesterone deficiency in luteal phase o prolactin – elevated basal level or exaggerated release o altered hepatic steroid mechanisms

· early manifestations may occur by age 20, but most patients are mid-30s and 40s (disease primarily of premenopausal women) · microscopic evidence of fibrocystic disease may persist after menopause but symptomatic disease, including nodularity, should not (exception – hormone replacement therapy)

· clinical presentation: o diffuse, often bilateral – most frequently in upper, outer quadrant, with radiation to the axilla o palpable breast masses/irregularities – solid, cystic lumps o fluctuation with menstrual cycle o o symptomatic for months to years

· pathological changes include: o macroscopic and microscopic cysts o stromal fibrosis o apocrine metaplasia o a variety of proliferative lesions

· 3 groups (different relative risks for subsequent development of ): 1. Nonproliferative lesions 2. Proliferative lesions without atypia 3. Atypical hyperplasias

· Non-proliferative lesions (70%) o Cysts – fluid-filled round to ovoid, vary in size from microscopic to gross, derived from terminal duct lobular unit o Papillary apocrine change – proliferation of ductal epithelial cells, cells show apocrine features o Epithelial-related calcifications – may be present in normal ducts and lobules, or virtually any pathological breast condition (may also be found in stroma and blood vessel walls) o Mild hyperplasia of the usual type– increased number of epithelial cells within a duct (more than 2 but not more than 4 cells in depth) o Fibroadenoma – see below

· Proliferative lesions without atypia (26%) o Moderate or florid hyperplasia of the usual type - intraductal epithelial proliferations (> 4 epithelial cells in depth), cells are cytologically benign o Intraductal papillomas – see below

12 o Sclerosing adenosis – proliferation of glandular (acinar) structures and stroma; stroma may distort glandular elements producing a pattern that mimics infiltrating carcinoma; may be associated with calcifications

· Atypical hyperplasia (4%) o Proliferative lesions that possess some, but not all, of the features of carcinoma in situ o Atypical ductal hyperplasias – some of the architectural or cytological features of ductal CA in situ: nuclear monomorphism, regular cell placement, round regular spaces, in at least least part of the involved duct o Atypical lobular hyperplasias – changes similar to those of lobular CA in situ, but lack complete criteria

· management o P/E o Mammogram – cystic change, calcification o U/S – differentiate between cystic and solid mass o Need aspiration – most effective therapy Ø both diagnostic and therapeutic Ø simple cyst should completely resolve following aspiration Ø biopsy if: mass does not completely resolve, cyst fluid is bloody, cyst recurs multiple times – concern is an adjacent carcinoma or intracystic carcinoma Ø cytological analysis of cyst fluid not routinely recommended – poor yield o excision of any suspicious mass – firm, irregular lesion with asymmetry from contralateral side o adjunctive treatment (mastalgia): Ø warm compresses, analgesics Ø avoidance of methylxanthines (caffeine, chocolate); low fat diet, high fibre diet, primrose oil, pyridoxine – none have proven benefit Ø Danazol (antigonadotropin) – FDA approved for treatment of mastalgia, eliminates monthly fluctuation in sex steroid production Ø Oral contraceptive pill – decreased estrogen and adequate progesterone Ø Bromocriptine (prolactin inhibitor) – cyclic mastalgia

· Prognosis – relative risk (RR) of subsequent breast cancer o Non-proliferative lesions Ø Not increased (RR=0.89), even in patients with a family history Ø However, increased risk if: gross cysts + family history Ø Gross cysts alone (RR=1.5), but when combined with family history (RR = 3.0) o Proliferative lesions without atypia Ø Mildly elevated risk (RR=1.6)

13 Ø Increased risk: proliferative lesions + family history (RR=2.1) o Atypical hyperplasia Ø Significantly increased risk of developing breast CA (RR=4.4) Ø Atypical hyperplasia + family history (RR=8.9)

Neoplasms and Proliferative Lesions

Fibroadenomas · Among the most common causes of benign mass · Incidence: o May appear at any age o Most common in young women (peak incidence in late 20s - early 30s) o 12-16% bilateral o Most common cause of mass in adolescent (76%) o Much less common in women over 55 yrs. (1.4%) o Generally, no racial differences in frequency or age of presentation (some studies have found increased prevalence and younger age of presentation in black women) o Not increased by OCP · Etiology o Hyperplasia and distortion of normal breast lobules – involve single terminal ductal lobular unit and surrounding connective tissue stroma o Hormonally responsive tissue, arise in women with a relative excess level of circulating estradiol over progesterone · Pathology o Gross appearance: pseudoencapsulated, sharply delimited from surrounding tissue o Epithelial and stromal components o Epithelial component – well-defined, gland-like and duct-like spaces; varying degrees of hyperplasia o Estrogen (localized to epithelial component) and progesterone receptors present

· Clinical features o Clinical diagnosis accurate in only 50-73% of cases o Discrete, mobile, usually non-tender o Rounded or lobulated contour, firm to rubbery texture o No dimpling or retraction of overlying skin o Grow until they reach 2-3cm in size o May enlarge during pregnancy and lactation o Rarely, infarction may occur during pregnancy – relative vascular insufficiency in face of increased metabolic demands o Rate of growth not affected by OCP o involute after menopause

14 · Investigations o May be diagnosed by FNA – cytological examination o Mammogram or U/S – discrete mass with distinct round borders

· Treatment o Women < 25 (perhaps as old as 35), typical 2-3cm fibroadenoma – FNA and regular follow up o Older women – excision to exclude carcinoma; not more than a few mm of surrounding normal breast parenchyma

· Prognosis (risk of carcinoma) o Frequency of CA within fibroadenoma – 0.1-0.3% o Predominant carcinoma – lobular carcinoma in situ o Mean age – 45 yrs. o Normal surrounding tissue – no increased risk o Proliferative surrounding tissue or complex fibroadenoma – RR 3.1 · Complex fibroadenoma – cyst > 3mm, sclerosing adenosis, epithelial calcification or papillary changes o With positive family history – RR 3.87 o 10-15% with CA in fibroadenoma will eventually develop CA in contralateral breast

Fibroadenoma variants Giant Fibroadenoma · 5cm, usually breast of pregnant or lactating woman · delay excision until after pregnancy, if possible

Juvenile Fibroadenoma · adolescent females, arise shortly before or after menarche · 2% of all , 7% of all breast lesions in females under 20 yrs. of age · Rapidly enlarging, well-circumscribed, non-tender breast mass 1.0-2.0cm or more · Distortion of overlying skin, prominent veins · Pathology: more floridly glandular, greater stromal cellularity than adult-type fibroadenoma · DDx – adult fibroadenoma, unilateral virginal hypertrophy, phylloides tumor, periductal fibrosarcoma · Benign lesion, never been shown to undergo malignant transformation · Excise – preserving central breast bud and as much normal breast tissue as possible

Phyllodes Tumor (formerly cystosarcoma phyllodes) · Unusual fibroepithelial tumor that shares some characteristics with fibroadenoma · Incidence: rare – 2.0-4.4% of all fibroadenomas · Spectrum of disease – benign, intermediate, malignant (25%) · Significant local recurrence rate – 20% (incomplete surgical excision)

15 · Metastases: 5% · Pathology (may be indistinguishable from large fibroadenoma) o Variable tumor size (1cm to larger than 40cm) o Gross: well circumscribed, compression/distortion of surrounding normal parenchyma o Epithelial elements and connective tissue - bulk of the mass is connective tissue – mixed gelatinous, edematous or dense areas o Characteristics of stroma determine classification as benign or malignant and differentiates from fibroadenoma o cystic components – sites of infarction, degeneration and necrosis

· Clinical features o Mean age – 4th decade, 10-20 yrs. older than mean age for fibroadenoma o Painless breast mass, smooth, multinodular, bulky and rounded o Long duration of continuous growth or rapid growth in a previously stable, long-standing nodule o Grows large rapidly – shiny, stretched, attenuated skin, varicose veins, skin ulceration (stretching and pressure), erythema resulting from necrosis as it outgrows its blood supply o Nipple effacement o Absence of suspicious axillary lymph nodes, despite large mass o Necrotic, infected, ulcerated tumor can cause enlarged nodes o Rarely bilateral

· Investigations o Mammogram – smooth, polylobulated margins (like fibroadenoma); some margins may be irregular suggesting local invasion o U/S – fluid-filled elongated spaces or cleft within otherwise solid mass

· Treatment o Similarity with fibroadenoma – often initially enucleated with small margin o Recommended margin – 2 cm o If suspicion of malignant elements – re-excision of biopsy scar to ensure complete local excision o Large tumor or histologically malignant – simple mastectomy o Axillary dissection – generally not recommended; lymph node metastasis occurs rarely o Metastatic lesions resemble sarcoma – lung (66%), bone (28%), liver, heart, distant lymph nodes – may be resectable o Adjuvant systemic therapy – based on guidelines for treating sarcomas

Adenomas · Well-circumscribed tumors composed of: o benign epithelial elements o sparse, inconspicuous stroma (compared with fibroadenoma)

16 · Tubular o Young women o Well-define, freely movable nodules; clinically resemble fibroadenoma o Pathology: proliferation of uniform, small tubular structures, scant amount of intervening stroma; tubules resemble normal breast acini

· Lactating o Freely movable mass that develops during pregnancy or postpartum o Pathology: composed of glands with identical lactational changes seen during pregnancy and puerperium

Papillomas Solitary · Presentation: o 30-50 yrs. of age o Bloody nipple discharge (70-80%) o +/- palpable mass o Mass frequently found close to areola, usually 0.3-0.5cm in size o Rarely bilateral · Pathology: o Tumor of major lactiferous ducts o Multiple, branching, interanastomosing papillae, central fibrovascular core covered with epithelium · Investigations: o Mammogram – mass or calcification o Ductogram – identify affected duct o Cytological analysis of nipple discharge · Management: o Total duct excision or limited duct excision (if affected duct can be determined) · Prognosis: o Slightly increased risk for development of carcinoma relative to general population – RR 3.3

Multiple Peripheral Papillomas · Much less frequent than solitary papillomas · Indistinct mass – multiple papillary lesions, groups of peripheral ducts · Nipple discharge infrequent · Located peripherally, 15% bilateral · Pathology o originate from terminal ductlobular unit o associated with atypical ductal hyperplasia – 43% · Management o complete local excision o close follow-up

17 · Prognosis – subsequent ipsilateral breast carcinoma – 10-33%

Papillomatosis (Epitheliosis) · Component of benign epithelial hyperplasia, often associated with other elements of fibrocystic disease · Biopsy often performed because of a mass, less often because of nipple discharge · Pathology o epithelial proliferation extending into the lumen of the ductules o little connective tissue, thin fibrovascular stalks · Management – close follow-up · Prognosis – incidence of subsequent cancer mildly elevated

Juvenile Papillomatosis · Adolescents and young women (mean age 23) · Painless, circumscribed, mobile mass · Mistaken clinically for fibroadenoma · Pathologic findings: o Duct papillomatosis, apocrine and nonapocrine cysts, papillary apocrine hyperplasia, sclerosing adenosis, duct stasis o Epithelial proliferation, cytological atypia · Associated with a positive family history of breast cancer · Management – excision and follow-up

Papillomatosis of the Nipple () · 40-50 yrs. of age · Presentation: o tumor – bulge beneath nipple, slow enlargement o nipple surface – ulceration, serous or bloody discharge o rarely painful · Clinical diagnosis confused with Paget’s disease or carcinoma · Pathology: spectrum – sclerosing papillomatosis, papillomatosis adenosis, adenosis · Associated with concurrent CA: 12-20% · Subsequent development of CA in ipsilateral breast rare · Management: o Once diagnosed, search for ipsilateral CA o Excision of lesion – in absence of CA

Microglandular Adenosis · Presentation: o palpable mass o incidental finding in breast tissue excised for other lesions · > 40 yrs. of age · Pathology:

18 o Ill-defined area of firm, rubbery tissue, usually 3-4cm o Microscopically – poorly circumscribed, haphazard proliferation of small, round glands in the stroma and adipose tissue o May be mistaken for well-differentiated (tubular) carcinoma · No increased risk of CA · Management – local excision

Radial Sclerosing Lesions · Also referred to as: sclerosing papillary proliferation, nonencapsulated sclerosing lesion, radial scar · Importance: may simulate carcinoma on mammography, gross and microscopic examination · Most frequently incidental finding – tissue excised for fibrocystic disease · Occasionally detected by mammography – soft-tissue densities with irregular, serrated edges; similar appearance to carcinoma · Pathology: o < 1cm (> 1cm = complex sclerosing lesions) o Microscopically – stellate configuration; central, fibroelastic core with entrapped glandular elements; ducts radiate from core, varying degrees of epithelial hyperplasia and papillomatosis · Treatment – local excision · Prognosis – no increased risk of CA

Granular Cell Tumors · Simulate carcinoma on clinical, mammographic and pathologic examination · More common in blacks than whites · Occur between puberty and menopause · Most common site of occurrence – upper, inner quadrant of the breast · Presentation o Palpable mass o May be associated with skin retraction or fixation to chest wall muscles · Mammogram – resemble scirrhous carcinoma · Pathology – poorly circumscribed proliferation of clusters of cells, prominent granularity of the cytoplasm · Management – wide local excision

Fibromatosis · Locally invasive, non-encapsulated proliferation of well-differentiated fibroblasts · Recur locally; do not metastasize · Presentation o Palpable mass o Sometimes associated with skin retraction or fixation to underlying muscle · Mammography – indistinguishable from carcinoma · Pathology – interlacing bundles of spindle-shaped cells surrounded by collagen

19 · Management – wide local excision

Breast Infarct · Infarction of breast tissue producing discrete mass – pregnancy and lactation · Etiology: possibly related to increased metabolic demands of pregnancy/lactation · Firm or rubbery lobulated masses 1-10cm · No history of trauma, no signs/symptoms of infection · Pathology: coagulation necrosis within infracted tissue – physiologic lobular hyperplasia of pregnancy, lactational adenoma, or fibroadenoma · Management: excision to rule out malignancy

Other Masses · Adenomatous tumors (resembling dermal sweat gland neoplasms) o Breast parenchyma (clear cell hidradenoma, eccrine spiradenoma) o Nipple (syringomatous adenoma) · Pleomorphic adenoma · Lipoma and Adenolipoma · Benign hemangiomas · Pseudoangiomatous hyperplasia of the mammary stroma · Chondromatous lesions · Leiomyomas · Neurofibromas and neurilemomas (schwannomas) · Adenomyoepitheliomas · Hamartomas

Inflammatory and Reactive Lesions

Mammary Duct Ectasia and Periductal Mastitis · mammary duct ectasia – periductal mastitis o chronic inflammatory process occurring in and around the terminal subareolar ducts of the breast · duct ectasia – dilated, thinned, secretion-filled ducts, keratin plugs · periductal mastitis – inflammatory process around the ducts · incidence: 5.5-25%, peak incidence 40-49 yrs. · pathology: o mononuclear cell infiltrate, plasma cells around terminal mammary ducts o inflammatory reaction may be scant or intense o dilated ducts filled with cellular debris and lipid-rich material · etiology: o duct dilatation, accumulation of lipid material and cellular debris, leakage of this material through thinned, damaged wall provoking inflammation in surrounding tissues o duct obstruction may be primary event – keratin plug or nipple inversion

20 o alternatively – periductal inflammation may lead to scared dilated ducts o cause of primary periductal mastitis not known § autoimmune § bacterial infection · clinical presentation may include: o subareolar tenderness o nipple retraction or inversion o hard mass, clinically indistinguishable from carcinoma or o doughy tubular masses beneath areola (dilated, secretion-filled ducts) o nipple discharge – cream to green +/- occult blood o chronic recurring abscesses and chronic fistulas to periareolar skin · investigations o mammogram – spherical and tubular calcifications in the lumen and walls of dilated ducts · Management o Mass § biopsy to rule out malignancy § if frozen-section diagnosis suggests periductal mastitis – broad- specturm antibiotics that cover anaerobes o nipple discharge § biopsy, cytology § bloody or cytologically suspicious – duct excision

Nonpuerperal Breast Abscesses · more common than puerperal · 8.5% of breast abscesses occur in puerperium · 3% actually lactating · Subareolar – most common o indolent and relapsing course o not systemically ill o tenderness, erythema, induration · Peripheral o resemble puerperal mastitis o predisposing conditions – diabetes, steroid therapy, other infected skin lesions · Organisms o Usually multiple, including anaerobes o Anaerobes: Bacteroides, peptostreptococcus, proprionibacterium o Aerobes: staph aureus, coagulase-negative staph · Treatment o I&D,broad-spectrum antibiotics, including anaerobes o Biopsy of wall of abscess cavity – rule out carcinoma o However, high recurrence rate – particularly in subareolar or periareolar o Excision of major ducts beneath areola after resolution of acute inflammation

21 Mammary Fistula · Uncommon complication of duct ectasia · Long-standing may form fistulous tract · May arise following o surgical or spontaneous drainage of subareolar abscess o breast biopsy · fistula exits in periareolar skin · organisms – similar to those found in nonpuerperal breast abscesses · treatment o marsupialization, wedge resection of portion of areola o important to excise tract, involved and portion of nipple through which involved duct passed

Puerperal Mastitis and Abscess · cellulites of the lactating breast – may progress to abscess

Sporadic · most common during early weeks of nursing · infection around, rather than within, the ductal system · presentation: o cellulitis in a wedge-shaped pattern over a portion of the breast skin o cracked or irritated nipple – portal of entry for bacteria o fever and systemic symptoms, no purulent nipple drainage · organism – staph aureus (most common) · management – antibiotics, continue to breast-feed or pump, warmth, manual compression

Epidemic · hospital acquired – uncommon · infant transmits pathogen to mother’s breast, seeding multiple ducts · involved areas – erythematous, warm, tender · organism – staph aureus (most common) · management – wean infant, antibiotics, warmth, manual compression, pumping

Abscess · progression of puerperal mastitis · fluctuant mass may not be palpable, therefore suspect if: o tenderness and erythema of puerperal mastitis do not resolve on antibiotics o worsening of local symptoms · diagnosis uncertain – U/S to rule out deep abscess · management: o I&D – break up all loculations o Biopsy abscess wall – rule out carcinoma · Heal rapidly, recurrence and development of fistulas rare

22 Other Breast Infections · Tuberculosis, Actinomycosis, Blastomycosis, Sporotrichosis, Syphilis, Candidal Intertrigo

Other Inflammatory Lesions · Sarcoidosis, granulomatous lobular mastitis, neonatal mastitis

Reaction to Foreign Material · Foreign body-type granulomatous inflammation – following injection or implantation of a variety of substances (paraffin, silicone) · Multiple firm nodules · Capsule formation around prosthesis

Breast Trauma · Often overlooked, usually self-limiting · Significant trauma may be marker for more serious thoracic injuries · Clinical presentation – ecchymosis, erythema, edema, soft tissue disruption from penetrating injuries · severe breast trauma – subcutaneous rupture of the breast secondary to seat belt o ecchymosis and visible furrow in the breast o sequela – fat necrosis with deformity which may require cosmetic surgery · blunt trauma in women who have undergone augmentation mammoplasty o implant rupture o rupture of fibrous capsule · Sequelae – hematoma and fat necrosis

Hematoma · Most common sequelae following trauma · Clinical presentation – ecchymosis, painful mass · May occur after relatively minor trauma – needle aspiration, biopsy · Mammography – usually not helpful o poor margins, raising possibility of CA o may obscure other abnormalities · management: o small hematoma or diffuse in breast – analgesics, observation o larger discrete lesions with overlying skin necrosis or hematoma occurring after biopsy – surgical drainage o post surgery and expanding – return to OR

Fat Necrosis · etiology – trauma, breast biopsy, lumpectomy and radiation, reduction mammoplasty, infection, duct ectasia, injection of foreign material, autologous fat transplantation, TRAM

23 · clinical features: o difficult to distinguish from carcinoma clinically and on mammography o overweight, middle-aged women, large pendulous breasts o painless mass – firm, ill-defined, poorly mobile o subareolar region, superficial tissues o associated skin thickening or retraction · pathology: cystic spaces surrounded by lipid-laden macrophages and foreign body-type giant cells; variable acute inflammatory cell infiltrate; focal hemorrhage · mammographic features – poorly defined spiculated masses; associated skin thickening or retraction; microcalcifications; lipid-filled cysts · management: o trauma with ecchymosis and palpable mass – observe; mass may increase in size initially then regress, or may remain unchanged for yrs. o absence of trauma – biopsy to establish diagnosis – FNA, core biopsy or needle localization excisional biopsy

Mondor’s Disease · superficial thrombophlebitis of lateral thoracic or superior thoracoepigastric veins · etiology: trauma, infection, breast surgery, excessive physical strain, rheumatoid arthritis, 2-12.7% associated with CA · clinical presentation – tender subcutaneous cord in the breast +/- dimpling of the skin, no systemic signs of infection · investigations – mammogram if cancer suspected · management – self-limiting, resolving in 2-10 weeks; local application of heat; analgesics; persistent – ligation of vein

Miscellaneous

Galactocele · milk filled cyst, round, well circumscribed, mobile, usually centrally located · usually occurs after cessation of lactation or when feeding frequency has curtailed significantly · pathogenesis unclear – inspissated milk within a large lactiferous duct · needle aspiration – diagnostic and therapeutic o thick, creamy material confirms diagnosis; may by tinged dark-green or brown, but is sterile · operation indicated for – cyst that cannot be aspirated or super infection

24 Subcutaneous Mastectomy

· removes 75-95% of breast tissue while preserving nipple-areola complex and breast skin (vs. total mastectomy which removes 95%) · risk reducing procedure as opposed to cancer preventing – significant portion of cancers originate in the NAC · rationale – allow for superior cosmetic result (compared with total mastectomy) · benefit over surveillance or chemoprevention has not been consistently demonstrated

· Indications – none absolute: · Selected women with a significant risk of developing breast cancer o Hereditary/familial breast CA o Bilateral atypical hyperplasia and 2 or more 1st degree relatives with premenopausal or bilateral breast CA o Bilateral atypical hyperplasia in a premenopausal woman o Bilateral multifocal DCIS o Unilateral DCIS or LCIS with contralateral atypical hyperplasia o Hx of breast CA with a good prognosis and DCIS, LCIS, or atypical hyperplasia in contralateral remaining breast or strong family history · Severe mastodynia, chronic suppurative mastitis · Breasts that are mammographically and/or clinically difficult to evaluate: o dense, fibronodular o women with multiple previous biopsies

· Technique o Inframammary incision, elevation of skin flap in subdermal plane o Variable amount of glandular tissue beneath NAC spared for viability o Other areas where breast tissue remains – axillary tail, skin flaps (particularly inferior) and infra-clavicular area o Alternative approaches – oblique, lateral wedge incisions

· Complications (10-60% for prophylactic mastectomy in general) o 5-15% incidence of nipple and areola necrosis o Skin ischemia Ø between areola and inframammary incision Ø scar of previous biopsy - cutaneous fistula and skin necrosis o Hematoma, infection o Coolness of the overlying skin o Unsatisfactory cosmetic result o Psychological and psycho-emotional morbidity

· No proven benefit over life long surveillance or chemotherapy · 70-80% of women with invasive breast cancer are candidates for conservative surgery – prevention more radical than established treatment

25 References

Bentz, M. L. Pediatric Plastic Surgery. Appleton & Lange, 1998. Chp 32.

El-Wakeel, H., Umpleby, H. C. Systematic review of fibroadenoma as a risk factor for breast cancer. The Breast. 12:302-307, 2003.

Harris, J. R. Diseases of the Breast. Lippincott, 1996. Chps 1-3.

Lin, K. Y., Nguyen, D. B., Williams, R. M. Complete Breast Absence Revisited. Plastic and Reconstructive Surgery. 106: 98-101, 2000.

Netter, F. H. Atlas of Anatomy.

Revis, D. R. and Caffee, H. H. Breast Embryology. www.emedicine.com. Updated March 2006

Sakorafas, G. H., and Tsiotou, A. G. Prophylactic mastectomy; evolving perspectives. European Journal of Cancer. 36:567-578, 2000.

Schwartz, S. I. Principles of Surgery. 7th edition. McGraw-Hill, 1999. Chp 14.

Ward, J. Breast anatomy, embryology and development; classification of benign breast disease; management of fibrocystic disease; subcutaneous mastectomy. Plastic Surgery Seminar Series, 2003

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