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THE BREAST DURING PUBERTY, PREGNANCY AND LACTATION Dr. Varda Stahl-Kent DEPARTMENT OF RADIOLOGY AND THE M. FANNY BREAST CARE INSTITUTE ASSAF HAROFE MEDICAL CENTER EMBRIOLOGY OF THE BREAST At about the sixth week of embrionic life, breast precursor develops from ectodermal origin. The “milk line” extends from the axillary area to the groin region. Portions of the milk line atrophy except in the region of the fourth intercostal space, from which mammary tissue develops. When portions of the milk line do not regress, there is accessory breast tissue or accessory nipple. CHANGES IN THE BREAST DURING CHILDHOOD Branching of main ducts –terminal buds – TDLU’s Proliferation and enlargement of adipose cells Increasing of stroma and blood vessels ULTRASOUND APPEARANCE OF THE BREAST DURING CHILDHOOD BREAST DEVELOPMENT DURING PUBERTY Estrogen responsible for ductal development. Progesterone responsible for lobulo-alveolar development. Breast bud appearance – telarche – mean age 9.8 years. Premature breast development – before age 8. Delayed breast development – after 13. Asymmetric breast development not uncommon, not to be mistaken for a mass. TANNER PHASES OF PUBERTAL BREAST DEVELOPEMENT 1 – nipple elevation 2 – nipple and breast projection from chest wall, palpable tissue in subareolar region 3 - increased glandular tissue and areolar size 4 - development of nipple-areolar complex 5 - final adolescent development with smooth breast contour THE BREAST IN ADOLESCENCE ASYMMETRICAL DEVELOPMENT IN A 13YEAR-OLD GIRL DEVELOPMENTAL ANOMALIES Polymastia – aberrant breast – ectopic breast tissue with no nipple or areola, usually close to the normal breast (axilla, infraclavicular region etc). Cancer and fibroadenoma may occur. – Supernumerary breasts – have nipple, areola or both, with or without breast tissue. Anywhere from the axilla to the groin, but may occur in many other areas. ACCESSORY BREAST TISSUE SEPARATED FROM THE MAIN BUD ASYMMETRICAL DEVELOPMENT Poland’s syndrome – – Agenesis of pectoralis muscle and breast tissue on one side. Asymmetrical development of breast tissue only. POLAND’S SYNDROME MASSES IN THE PEDIATRIC AND ADOLESCENT PATIENT Mostly benign etiology: – – – – – – – – – Gynecomastia Cyst Fibroadenoma Phyllodes tumor (rare – only up to 10% under 20y) Lymph node Galactocele Duct ectasia Juvenile Papillomatosis Infection Only 0.2% of primary breast cancers occur in this age group. GYNECOMASTIA Neonatal period. Adolescence (peak at 13-14 years). Common, frequently resolves within 2 years. Elderly men. Pathologic processes: renal or liver diseases, testicular or adrenal tumors, hyperthyroidism Medications: estrogen, psychoactive drugs, cardiovascular drugs, diuretics, chemotherapy, drugs of abuse Ultrasound demonstrates hypoechogenic breast tissue in subareolar region. GYNECOMASTIA OF PUBERTY Common etiology: transient imbalance between estrogen and androgen. – By the end of puberty, estrogen increases X3 and testosterone X30 – the ratio estrogen : testosterone may be greater than normal for a certain period Breast tissue of affected individuals may be more sensitive to estrogen. Kleinfelter synd. (47 xxy) Significant association with varicocele in the ages 12-14 BILATERAL, ASYMMETRICAL GYNECOMASTIA ASSYMETRICAL GYNECOMASTIA CYST Most common in the ages 30-50, but may occur in any age group. Cysts are common - about 20% of the masses in the young age group Caused by dilation of the lobular acini – either from obstruction of ducts or from imbalance of production and absorption. On ultrasound: anechoic, smooth wall, through transmission (backwall enhancement). FIBROADENOMA The most common mass excised in the pediatric and adolescent age group (50-75%) Sometimes very large ( “giant fibroadenoma” if larger than 8 cm). Contains normal epithelial (mostly ductal ) and stromal elements Stimulated by hormonal changes Commonly regresses around the age of 40 Does not have a malignant potential On ultrasound: homogeneous, surrounded by a thin pseudocapsule, few large lobulations or none, may have backwall enhancement, usually a single vessel. 18 Y-O, FIBROADENOMA TUBULAR ADENOMA An uncommon benign mass with a dominant uniform tubular element and sparse stroma, hence “true” adenoma Occurs mostly in young, non-pregnant women. Unrelated to contraceptives. On ultrasound – resembles fibroadenoma In older patients – may contain microcalcifications seen on mammography and ultrasound. 14 Y-O,TUBULAR ADENOMA JUVENILE PAPILLOMATOSIS Approximately 50% by age 20 Solitary mass clinically resembling FA Pathology: multiple cysts separated by firm fibrous septae, may be filled with secretions Complete excision recommended – 1015% risk of Ca. JUVENILE PAPILLOMATOSIS INFECTION Most common organisms – staphylococcus and streptococcus. Diabetic patients or patients under steroids – more prone. MALIGNANCY IN THE BREAST DURING PUBERTY Primary breast cancer exceedingly rare – previous irradiation a predisposing factor Metastases – from Rhabdomyosarcoma, Non-Hodjkin lymphoma, leukemia, malignant melanoma Metastases may present as round, regular masses. NON-HODJKIN LYMPHOMA NODULES IN THE BREAST CHANGES OF THE BREAST DURING PREGNANCY Early in the first trimester: – Proliferating glandular epithelium causes branching of the ducts. – Amount of fat and connective tissue decreases. Second trimester: – Alveolar epithelium differentiates into a secretory epithelium. – Arborization of the alveoli causes enlargement of the breast. – Colloid accumulates in the alveoli CHANGES OF THE BREAST DURING PREGNANCY Third trimester: – Differentiation of the of the milk-producing cells and synthesis of milk. – In the last days before delivery - increase of blood flow in the breast and filling of the alveoli and ducts with colostrum THE BREAST IN THE LAST TRIMESTER CHANGES OF THE BREAST DURING AND AFTER LACTATION Immediate post partum enlargement due to colostrum accumulation Milk secreted into alveoli 3 – 7 days post partum Breastfeeding stimulates further release of prolactin Post lactational changes – Periductal and perivascular stromal tissue increases – Alveolar cells and ductal branches regress THE BREAST DURING LACTATION IMAGING Diffuse increase in density on mammography - typical May have little or no change in density Mild increase in parenchymal echogenicity on ultrasound. Post lactational benign calcifications reported. LACTATING BREAST NORMAL LACTATING BREAST DUCT CONTAINING MILK INDICATIONS FOR IMAGING OF THE PREGNANT OR LACTATING PATIENT Palpable lump Persistence of inflammatory process Suspected breast abscess Persistent bloody nipple discharge Pagetoid changes of the nipple Axillary adenopathy SCREENING OF THE ASYMPTOMATIC PREGNANT PATIENT IS NOT INDICATED INFLUENCE OF PREGNANCY AND LACTATION ON BREAST EVALUATION Clinical examination extremely difficult. Breast masses may be masked or believed to resolve as the breast enlarges. Malignant masses may incorrectly be attributed to benign processes. PATHOLOGICAL CONDITIONS IN THE BREAST DURING PREGNANCY AND LACTATION Infection – Mastitis – Abscess Benign tumors – related to P & L – Lactating adenoma – Galactocele Other benign tumors, not necessarily related to P&L – Fibroadenoma – Hamartoma -Phyllodes tumor -Lipoma - Papilloma Malignant tumors – Primary - Secondary BREAST IMAGING METHODS DURING PREGNANCY AND LACTATION Ultrasound examination directed at the region of interest If lesion still suspicious or malignancy is proven – mammography , with limiting the number of exposures. Dose to fetus 0.4 mrad (10 rad or greater shown to cause malformations) DENSITY OF THE BREAST INCREASES DURING PREGNANCY AND EVEN MORE DURING LACTATION. RETURN OF THE DENSITY TO THE PRE-PREGNANT STATE OCCURS 1 – 5 MONTHS POST LACTATION. INFECTIONS DURING PREGNANCY AND LACTATION More common during lactation. Causative organisms are staphylococcus aureus or streptococcus, from the infant’s nose or throat. Usually resolve with antibiotics – penicillin An abscess should be drained, preferably under US guidance. MASTITIS Erythema, pain and induration Usually no need for imaging – Imaging performed if there is no response to antibiotics, or if an abscess is suspected clinically. Fluid and edema seen among tissue planes, thickened skin. NORMAL RT. BREAST MASTITIS LT.BREAST BREAST ABSCESS Round or oval mass , may be irregular Through sound transmission Thick walls Fluid/debris level Occasional air in cavity with bright reflections Increased vascularity in the periphery of the lesion Management is by aspiration and antibiotics. ABSCESS AFTER DELIVERY AIR IN AN ABSCESS GALACTOCELE - DEFINITIONS A milk-containing cyst that results from occlusion of a lactiferous duct and is lined by flattened cuboidal epithelium Retention of milk-like fluid (fatty material) in areas of cystic duct dilatation appearing usually during or shortly after lactation – SOME GALACTOCELES HAVE BEEN REPORTED WITH NO HISTORY OF LACTATION AND EVEN PREGNANCY, PROBABLY DUE TO DUCTAL OBSTRUCTION OF ANOTHER ETIOLOGY. GALACTOCELE – CLINICAL CONSIDERATIONS Palpable, firm, mobile mass in pregnant, lactating or early post lactational patient. May be seen up to several years post lactation May be seen in chronic galactorrhea, in patients receiving prolactin stimulating agents or in pituitary adenoma May occur after breast augmentation Rarely reported in postmenopausal women, in males and in infants GALACTOCELE – IMAGING FINDINGS Well-circumscribed mass Echogenicity depends on the amount of fat and protein within the milk Frequently subareolar but may be anywhere in the breast Solitary, multiple, unilateral or bilateral Average size 2 cm, may exceed 5 cm. GALACTOCELE -MAMMOGRAPHIC FINDINGS -Mammograhy performed only if appearance on ultrasound is suspicious. -Circumscribed mass of variable density. -Fat-fluid level on lateral film, fluid-calcium level, peripheral curvilinear calcifications. -Often obscured by surrounding dense tissue. GALACTOCELE – CYSTIC, WITH SEPTATIONS AND THICK FLUID CONTENTS COMPLEX-CYST APPEARANCE 25 CC OF MILK WERE DRAINED FAT FLUID LEVEL FAT - FLUID LEVEL WITH SHADOWING FAT-FLUID LEVEL WITH A CLOT OF MILK MOVING OF THE FAT-FLUID LEVEL GALACTOCELE CONTAINING FAT ONLY (LIPOMA TYPE) PSEUDOHAMARTOMA LIKE GALACTOCELE GALACTOCELE WITH PERIPHERAL CALCIFICATIONS INFECTED GALACTOCELEA COMPLEX CYSTIC MASS RESOLUTION OF A GALACTOCELE INCOMPLETE RESOLUTION OF A GALACTOCELE GALACTOCELE MIMICKING A TUMOR GALACTOCELE – MANAGEMENT Usually spontaneous resolution No need for treatment unless suspicious or unless symptomatic relief needed. Aspiration under ultrasound guidance After core biopsy fistulae may occur. ASPIRATED GALACTOCELE CONTENTS LACTATING ADENOMA – KEY FACTS The most common breast mass in a young pregnant patient. Well-differentiated benign tumor . Clinically soft , mobile, palpable mass. Spontaneous regression after completion of breastfeeding. Presentation may be delayed – up to 10 months after cessation of nursing. 5% undergo infarction and become painful No malignant potential. LACTATING ADENOMA – PROPOSED ORIGINS De novo in hormonally stimulated breast Arises from pre-existing fibroadenoma, tubular adenoma or lobular hyperplasia Premature lactational changes, out of phase with surrounding breast tissue. LACTATING ADENOMA – IMAGING - 1 Oval or macrolobulated hypoechoic mass. Parallel to skin. Hyperechoic bands and pseudocapsule. Posterior enhancement. Most often in anterior portion of breast Hypervascular on doppler exam. 20-30% compressibility LACTATING ADENOMA – IMAGING - 2 Size – usually 2 – 4 cms, the largest reported - 21 cms. May be multiple. Less common findings – Posterior shadowing (occurs with infarction) Angulated or ill-defined margins. Hyperechoic or isoechoic. VASCULAR LACTATING ADENOMA INFARCTED LACTATING ADENOMA LACTATING ADENOMA – D.D.(US) – Fibroadenoma – Galactocele – Complicated cyst – Tubular adenoma – Well-circumscribed carcinoma. LACTATING ADENOMA - MANAGEMENT Spontaneous regression after completion of lactation. If suspicious – core biopsy needed (FNA not diagnostic) If very large and/or painful – Bromocriptine has been reported to reduce size, through suppression of Prolactin. FIBROADENOMA Most common benign tumor in all women under 35 Benign fibroepithelial tumor May develop or markedly enlarge during pregnancy Variable appearance on ultrasound, usually oval or macrolobulated, homogeneously hypoechoic . FIBROADENOMA WITH INCREASED VASCULARITY PHYLLODES TUMOR Rare tumor, histologically similar to fibroadenoma, but 16 – 28% recur locally after excision. Low incidence of metastases. Solid, macrolobulated hypoechoic mass sometimes not homogeneous, or with cystic spaces. May have posterior enhancement. PHYLLODES TUMOR - MANAGEMENT F.N.A and core biopsy not reliable in differentiating Phyllodes tumor from fibroadenoma. Excisional biopsy recommended. If proven Phyllodes tumor – excision with clean margins indicated. BLOODY NIPPLE DISCHARGE DURING PREGNANCY Usually appears during the third trimester. The cause is increased vascularity, and a minor trauma. Usually ceases with the onset of nursing, but may persist during lactation. Cytological analysis may be false positive. US should be performed. If normal exams – follow-up every month. If pathological cause suspected (mass, positive cytology )- galactography and biopsy. PREGNANCY-ASSOCIATED BREAST CANCER Definition: breast cancer that occurs during pregnancy or within 12 months thereafter Incidence – 1:3,000 – 1:10,000 pregnancies (most common cancer and cause of cancer death in pregnancy) 0.2 – 3.8% of all breast cancers Approximately 7 – 14% of newly diagnosed breast cancers in women under 40 are associated with pregnancy. PREGNANCY-ASSOCIATED BREAST CANCER Distribution of histologic types – same as in nonpregnant patients. 2 – 4% - inflammatory carcinomas. No evidence that pregnancy itself is a risk factor for the development of breast cancer. Cancer is found frequently in an advanced stage. Prognosis similar to the non-pregnant patients when matched for age and stage. INFLAMMATORY CARCINOMA Erythema, warmth and induration with or without “peau d’orange” Typically evolves over 3 months or less The cause is embolization of dermal lymphatics by tumor. Frequently misdiagnosed as mastitis or abscess Biopsy should be performed when an abscess is drained during pregnancy CAUSES FOR DELAY IN DIAGNOSIS DURING PREGNANCY AND LACTATION Difficulty in physical examination. Attribution of a mass to a benign process. Hormones causing growth enhancement. Higher percentage of ER negative tumors which are more aggressive. Rich blood supply probably enhances growth of metastases. EVALUATION OF A PALPABLE MASS IN THE PREGNANT OR LACTATING PATIENT Ultrasound – Cystic or galactocele – follow up. – Solid – biopsy. If lesion is clinically suspicious – F.N.A or core biopsy. If malignancy proven– tailored mammography to the lesion and contralateral MLO. – Dose to fetus 0.5mGy (natural background radiation during pregnancy 1.0 mGy) MRI IN THE PREGNANT PATIENT Safety not clear. Gadolinium crosses the placenta , causes fetal malformations in rats, and is to be used only if benefits outweigh the risk, and only after the first trimester. BREAST BIOPSY DURING PREGNANCY F.N.A may give false positive result. Core or open biopsy preferred - but may cause milk fistula or infection. Excisional biopsy or incisional biopsy may be performed under local anesthesia. Bleeding more common than in nonpregnant patients. STAGEING BREAST CANCER IN THE PREGNANT PATIENT Chest x-ray performed with abdominal shielding. CT avoided because of inability to shield the abdomen and because of the use of iodine contrast material which may cause hypothyroidism in the newborn. Radionuclide bone scan is contraindicated (dose is 20mCi) Sentinel lymph node mapping – not recommended. TAKE-HOME MESSAGE - 1 Breast pathological conditions may be found at all ages, but are uncommon in the younger age group , under 30. Ultrasound is the method of choice for evaluating children, adolescents, pregnant and lactating patients. Need for biopsy determined by imaging findings and/or clinical impression. TAKE-HOME MESSAGE - 2 A DOMINANT MASS IN THE PREGNANT OR LACTATING PATIENT SHOULD BE PROMPTLY EVALUATED. SCREENING MAMMOGRAPHY IN HIGH RISK PATIENTS OVER 40 SHOULD NOT BE POSTPONED. SHOULD BE PERFORMED AFTER NURSING.