* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
European Journal of Radiology 84 (2015) 1350–1364 Contents lists available at ScienceDirect European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad Review How to approach breast lesions in children and adolescents Yiming Gao a,b,∗ , Mansi A. Saksena b , Elena F. Brachtel b , Deborah C. terMeulen b , Elizabeth A. Rafferty b a b New York University Langone Medical Center, 221 Lexington Ave., New York, NY 10016, USA Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA a r t i c l e i n f o Article history: Received 16 October 2014 Received in revised form 10 April 2015 Accepted 11 April 2015 Keywords: Pediatric breast lesions Breast evaluation in children and adolescents Developing breast Breast cancer in children Breast ultrasound a b s t r a c t Assessment of a pediatric breast lesion always starts with clinical evaluation. When imaging of a pediatric breast is indicated, ultrasound is the mainstay. The vast majority of pediatric breast complaints are of benign etiology, therefore the diagnostic/management approach emphasizes “ﬁrst do no harm”. Correlation with age and clinical history helps to direct diagnosis. It is essential to be familiar with the imaging appearance of the normal developing breast at various Tanner stages, in order to diagnose physiologic breast ﬁndings and to minimize unnecessary biopsies in young breasts vulnerable to injury. Normal anatomic structures, developmental conditions, benign neoplastic and non-neoplastic lesions are common causes of breast complaints in children. Uncommon benign masses and rarely, secondary more than primary malignancies may present in a pediatric breast. Chest wall masses such as Ewing’s sarcoma or rhabdomyosarcoma occur in children and may involve the breast via contiguous growth or locoregional metastasis. In addition, special attention should be given to any breast lesion in a child with risk factors predisposing to breast cancer, such as known extramammary malignancy, genetic mutations, prior mantle irradiation, or strong family history of breast cancer, which usually requires biopsy to exclude the possibility of malignancy. Conclusion: The developing breast is vulnerable to injury, and because breast malignancy is uncommon in children, diagnostic and management approach emphasizes “ﬁrst do no harm”. Understanding normal breast development and the spectrum of common and uncommon pediatric breast lesions are key to the correct diagnosis. © 2015 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The relatively high prevalence of adult breast cancer is the source of worry in many parents of children with breast complaints. One in every eight women in the United States develops invasive breast cancer during her lifetime . Yet breast cancer hardly ever afﬂicts children or adolescents. For example, the reported prevalence of breast cancer in females under the age of 20 is well below 0.1 per 100,000 . With that in mind, a tailored diagnostic and management approach is necessary for pediatric breast complaints. Furthermore, because the developing breast is uniquely vulnerable to iatrogenic injury, which can lead to permanent disﬁgurement, biopsy should be reserved only for lesions of high suspicion. ∗ Corresponding author at: 221 Lexington Ave., New York, NY 10016, USA. Tel.: +1 203 606 9310. E-mail address: [email protected] (Y. Gao). http://dx.doi.org/10.1016/j.ejrad.2015.04.011 0720-048X/© 2015 Elsevier Ireland Ltd. All rights reserved. Clinical evaluation is an essential component of complete assessment of pediatric breast complaints. With pertinent history and physical exam, many pediatric breast complaints can be correctly categorized as normal developmental processes or physiologic changes, which require only reassurance. Occasionally, imaging can be helpful in conﬁrming a normal ﬁnding such as an asymmetric breast bud, or may be necessary when an abnormality is suspected. When necessary, ultrasound is the primary imaging modality used in assessing breast lesions in children, given its diagnostic speciﬁcity and lack of ionizing radiation. Mammography is seldom used, but is the modality of choice to visualize calciﬁcations in select cases. Cross-sectional imaging modalities such as CT or MR are usually reserved for evaluation of disease extent and occasionally, problem solving. The vast majority of pediatric breast complaints are of benign etiology. Normal anatomic structures can mimic breast masses. Non-neoplastic benign entities in the pediatric breast include cyst, hematoma, mastitis/abscess, and galactocele. Clinical history helps clinch the diagnosis in some of these cases. The most common benign solid mass in the pediatric breast is a ﬁbroadenoma. Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 A 2–3 cm probably benign mass on ultrasound in a child without atypical features or rapid enlargement is rarely malignant and is safe to follow, as has been shown in multiple studies. Biopsy should be considered however if the mass is larger than 4–5 cm or undergoing rapid enlargement, to exclude the possibility of a phyllodes tumor. Other rare benign masses in the pediatric breast include hamartoma, intraductal papilloma, juvenile papillomatosis (a marker for familial breast cancer), and ﬁbrous nodule. Malignant lesions in the pediatric breast are exceedingly rare, more commonly metastatic disease to the breast and occasionally primary breast malignancy. Phyllodes tumor is the most common primary breast malignancy in children. Invasive ductal carcinoma is rare in children, of which the secretory subtype is the most common. In young people with risk factors predisposing to breast cancer, such as strong family history of breast cancer, known extramammary malignancy, genetic mutations, or prior mantle irradiation, biopsy is often required to exclude malignancy regardless of the imaging appearance of the breast lesion. In this article, we will review embryology and development of the breast, discuss the appropriate imaging and management approach of pediatric breast complaints, and explore the spectrum of common and uncommon pediatric breast lesions. 2. Imaging approach to the pediatric breast Because pediatric breast cancer is so rare, diagnostic imaging emphasizes “First Do No Harm”. Evaluation of pediatric breast complaints always begins with clinical assessment, which then determines the need for imaging. Ultrasound remains the primary and often the only necessary modality for the evaluation of breast complaints in the pediatric population, given its high sensitivity for detection of lesions in younger denser breasts  and the lack of ionizing radiation. In contrast, the utility of mammography is limited in the pediatric population, both due to low diagnostic sensitivity in young and dense breasts, and radiation risks associated with mammography in this age group. MRI and other cross sectional imaging modalities are generally reserved for assessment of disease extent, for assessment of deep chest wall lesions or vascular anomalies, or occasionally for correlation with ultrasound ﬁndings. Breast Imaging Reporting and Data System lexicon (currently 5th edition) is the gold standard for describing and stratifying breast lesions into categories which correlate with likelihood of malignancy by imaging appearance (Table 1). Although this is used both in adults and in children, because it is based on the likelihood of malignancy, which is exceedingly low in children , its utility may be limited in this setting. For example, the vast majority of pediatric breast lesions are benign and will be categorized BIRADS 2 or 3, emphasizing appropriate conservative management to “First Do No Harm”. Highly suspicious lesions or lesions in high risk pediatric patients may warrant biopsy and are categorized BIRADS 4 or above, but are few and far in between. 3. Normal breast development The breast begins normal development during the 5–6th week of fetal gestation , with ectodermal cells invaginating into the deeper mesenchyme to form the mammary ridges or milk lines, which extend symmetrically along the anterior torso from the axillae to the groin (Fig. 1). Over time, there is normal involution of the milk lines except at the level of the 4th intercostal space, where normal breast buds form. If normal involution is incomplete, ectopic or accessory nipples and/or breast tissue may form anywhere along these milk lines. At the 4th intercostal space, the primary breast buds (invaginated epidermal cells) evolve into secondary buds and further branch into lactiferous ducts within the breast parenchyma. Overlying the breast bud at the skin surface, a small depression or mammary pit forms, which further evolves into the nipple–areolar complex (Fig. 2). Prior to puberty, the breast is composed of epithelium lined lactiferous ducts supported by stromal connective tissue . Enlargement of these ducts are a common cause of self-limited bilateral palpable subareolar nodules in both male and female infants in the ﬁrst 6–12 months of life due to maternal hormonal inﬂuence . With the onset of puberty, the breast undergoes further maturation. The term thelarche refers to the onset of normal pubertal phase of breast development in females, with estrogen stimulating ductal growth and progesterone promoting lobular and alveolar differentiation, completing the terminal duct lobular unit. The normal age of onset of thelarche in the U.S. ranges between 9 and 10 years of age, with the average onset of thelarche in African American girls generally being earlier compared to that in Caucasian girls . Premature thelarche therefore, is deﬁned as early onset of breast development in prepubertal girls, typically before age 7–8. Thelarche after 12 years of age is considered delayed . Idiopathic premature thelarche generally occurs in younger children between ages 1–3 , and is unusual after age 4 . Idiopathic premature thelarche is benign and generally self-limited. This can however mimic a mass when unilateral, and thus frequently comes to clinical attention. The role of ultrasound is to conﬁrm the presence of normal developing breast tissue or thelarche (whether premature or appropriate), in the absence of a discrete mass. Clinical reassurance and followup usually sufﬁce for idiopathic isolated premature thelarche, but occasionally short term imaging followup may be appropriate. Other possible Table 1 BI-RADS assessment categories and likelihood of cancer. American College of Radiology BI-RADS© Atlas 2013. BI-RADS category Assessment Likelihood of cancer 0 Incomplete – need additional imaging evaluation Negative Benign Probably Benign Suspicious Highly suggestive of malignancy Known biopsy-proven malignancy N/A 1 2 3 4 5 6 Essentially 0% Essentially 0% >0%, ≤2% >2%, <95% ≥95% N/A 1351 Fig. 1. Milk lines or Milk ridges (Y. Gao). 1352 Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 Fig. 2. Breast development – Ectodermal cells invaginate to form the primary breast bud, which branches into secondary buds, and then subsequently branch and elongate further to form the lactiferous ducts. Externally a mammary pit or indentation is formed in the skin, which evolves into the nipple areolar complex (Susanne Loomis, MS, FBCA of MGH REMS Media Service). Fig. 3. Clinical tanner stages of normal breast development (Susanne Loomis, MS, FBCA of MGH REMS Media Service). factors linked to isolated premature thelarche include high body mass index  and herbal intake . Premature thelarche can also occur in conjunction with precocious puberty. It is important to ensure that there are no other signs of sexual maturation associated with premature thelarche such as development of axillary and pubic hair, in which case further imaging and laboratory workup would be indicated to exclude hormonally active adrenal or gonadal neoplasms as potential causes for precocious puberty. There are ﬁve Tanner stages of normal pubertal breast development based on the clinical appearance of the developing breast (Fig. 3). Ultrasound appearances of the breast at various Tanner stages have been well described and familiarity with these appearances is critical for the radiologist performing pediatric breast evaluation [6,12]. Sonographically, the Tanner stage 1 breast appears as mildly heterogeneous retroareolar tissue. The Tanner stage 2 breast appears as a hyperechoic nodule with central linear or stellate areas of hypoechogenicity which represent evolving ductal structures. Tanner stage 3 and 4 breast tissues demonstrate appearance of further expansion of the hyperechoic ﬁbroglandular elements, with the central retroareolar hypoechoic regions evolving into more branching and eventually nodular conﬁgurations. The Tanner stage 5 breast shows the appearance of mature echogenic breast tissue without central hypoechogenicity, as seen in the adult breast. 4. Common causes of pediatric breast complaints 4.1. Normal anatomic structures 4.1.1. Normal lymph node Normal lymph nodes reside in the axilla, axillary tail, and breast parenchyma, and can become clinically palpable. Intramammary lymph nodes are most commonly found in the upper outer quadrants of the breasts. A prominent node in an otherwise healthy young patient is most commonly due to reactive nodal Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 1353 Fig. 4. 17 year old girl with prominence of left axillary tail following intended weight loss. Ultrasound was performed of the left axilla in the area of clinical concern, demonstrating a normal lymph node with hypoechoic cortex of normal thickness (<3 mm) and hyperechoic central fatty hilus. Fig. 6. 3 year old boy with rhabdomyosarcoma and normal asymmetric breast buds (arrows) on post treatment surveillance CT. hypertrophy, or occasionally from relative loss of soft tissue surrounding a lymph node (for example, weight loss), causing it to become clinically more prominent. Ultrasound is deﬁnitive in the identiﬁcation of a normal lymph node, which appears as a bean shaped or oval structure with hypoechoic sub-3-mm cortex and echogenic central fatty hilus (Fig. 4). Hilar vascular ﬂow is helpful for diagnosis at real time sonography. A normal lymph node is a benign ﬁnding and clinical followup sufﬁces. The typical appearance of reactive nodal hypertrophy is mild diffuse cortical thickening. Common causes of reactive axillary lymphadenopathy include viral illness and vaccination, both frequently encountered in children. Sonographic evidence of abnormal ﬁndings such as eccentric cortical thickening or displacement of central fatty hilum suggest possible malignant nodal involvement and warrant tissue sampling. 4.1.2. Normal breast bud Asymmetric normal breast development is a common cause of unilateral subareolar mass in children. Asymmetry between the breast buds is common, with differences of up to 2 years in the phase of development between the breasts considered to be within the normal spectrum . Ultrasound may be performed to conﬁrm the presence of normal breast buds and the absence of other abnormalities (Fig. 5). Early development of the breast bud is called premature thelarche, which is most common in children under age 3. Benign isolated premature thelarche usually regresses on its own. Imaging ﬁndings of normal or premature development of breast buds are similar. Ultrasound shows subareolar hypoechoic stellate breast tissue without associated mass (Fig. 5). Although CT is not indicated in this setting, normal breast asymmetry incidentally noted on CT performed for another indication can occasionally lead to concern for a breast mass (Fig. 6). It is important to be familiar with the appearances of normal breast buds at different stages of evolution in order to avoid unnecessary biopsy which places the young patient at risk for iatrogenic hypomastia or amastia. Once benign breast bud asymmetry is conﬁrmed, clinical follow up is appropriate. Further imaging is usually not indicated. 4.1.3. Osseous structures Osseous structures can occasionally account for areas of clinical concern in the region of the breast, particularly in thin patients or patients with rib and chest wall deformities such as pectus excavatum, pectus carinatum, or in the setting of Poland syndrome (Fig. 7). Clinical exam usually reveals a ﬁxed ﬁrm mass contiguous to the remainder of bony structures. If uncertainty remains after physical examination, chest radiography could obtained to assess for osseous abnormalities, and ultrasound can be performed to evaluate the focal area of concern and to exclude a mass or other abnormality. Poland syndrome is an autosomal recessive disorder, marked by unilateral partial or complete absence of the pectoralis muscle, associated with breast hypoplasia or aplasia, rib and chest wall deformities, as well as ipsilateral limb abnormalities (Fig. 8). It is important to recognize that breast cancer occurs in the hypoplastic breast in a patient with Poland syndrome, and that routine mammographic screening is indicated in these patients in adulthood [13–15]. Of the reported cases of breast cancer in the setting Fig. 5. 5 year old boy with mobile subareolar right breast mass discovered by mother. Ultrasound demonstrates asymmetric but normal breast buds, right larger than left. There is no mass in the subareolar right breast in the area of clinical concern. 1354 Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 Fig. 7. 17 year old girl with Poland syndrome notes a ﬁrm lump along the right sternal border. (a) Ultrasound shows a hypoechoic shadowing structure at the right costomanubrial junction, felt to be related to the thoracic skeleton. (b) Chest radiograph demonstrates near complete absence of the right breast shadow consistent with Poland syndrome and conﬁrms the source of clinical concern to be a normal anterior rib. of Poland syndrome, the vast majority involve the ipsilateral hypoplastic breast [13–15]. 4.2. Developmental abnormalities 4.2.1. Ectopic breast tissue Ectopic or accessory breast tissue refers to breast tissue located somewhere other than the expected location of the normal breast in the 4th intercostal space, usually along the mammary ridge or milkline, which extends from the axilla to the vulva. The ectopic breast tissue represents incomplete involution of the ectodermal mammary ridge (embryonic progenitors to breast tissue). Ectopic breast tissue may contain some or all of the components of the mammary gland, including glandular tissue, areola, and nipple. Both benign and malignant breast masses arising from ectopic breast tissue have been described in the literature. Because ectopic breast tissue is responsive to hormonal inﬂuence as much as normal breast tissue, it is a common source of clinical complaints of swelling and discomfort, including in children and adolescents. The most common site of ectopic breast tissue is the axilla . Approximately 2–6% women have axillary ectopic breast tissue . On ultrasound, ectopic axillary breast tissue appears as a heterogeneously echogenic area of focal tissue, similar in sonotexture to normal breast parenchyma  (Fig. 9). It is important to be familiar with the sonographic appearance of ectopic breast tissue, as recognition and correct diagnosis obviate the need for intervention, particularly in children and adolescents. On mammography (despite limited utility in children), ectopic axillary breast tissue is best visualized on mediolateral oblique and exaggerated craniocaudal views and appears as ﬁbroglandular density separate from the dominant breast mound overlying the pectoralis muscle. Fig. 8. MLO mammographic views demonstrate absence of the left pectoralis major muscle and left breast hypoplasia in a patient with Poland syndrome. 4.2.2. Gynecomastia Gynecomastia is excess breast tissue development in males, which can present clinically as subareolar tenderness and or a palpable mass. It can be unilateral or bilateral, and it has been reported to be familial. The cause of gynecomastia is unknown but Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 1355 4.3. Non-neoplastic lesions Fig. 9. 20 year old woman with enlarging left axillary lump. Ultrasound of the left axilla demonstrates focal area of normal ﬁbroglandular tissue. Fig. 10. 17 year old boy with right subareolar tender swelling. Ultrasound of the right breast shows prominent ﬁbroglandular tissue directly deep to the nipple, consistent with gynecomastia. thought to be related to relative elevation of circulating estrogen with respect to testosterone. In adults, gynecomastia may be idiopathic or has been associated with chronic liver disease, excess body fat, marijuana or exogenous steroid intake, or medications such as cimetidine, digitalis, and tricyclic antidepressants. In children, gynecomastia is often physiologic and is most common in neonates and adolescents. Up to 90% of neonates have transient breast hypertrophy due to maternal hormonal inﬂuence , and clinical reassurance usually sufﬁces. During puberty, gynecomastia is present in up to two thirds of 10–13 year old boys , which usually subsides within two years, and clinical followup is appropriate. Ultrasound is the modality of choice in children, and typically demonstrates increased retroareolar ﬁbroglandular tissue similar to the appearance of the early developing female breast (Fig. 10), consistent with gynecomastia. In adult males, mammograms are diagnostic for gynecomastia, most commonly showing retroareolar ﬂame shaped breast tissue. If however gynecomastia presents in prepubertal boys, other causes should be considered. Estrogen producing tumors such as testicular Leydig cell tumor, adrenal cortical tumor, or gonadotropin secreting tumors such as hepatoblastoma, ﬁbrolamellar hepatocellular carcinoma, or choriocarcionoma can cause gynecomastia. Other causes include prolactinoma, testicular feminization, Klinefelter syndrome, neuroﬁbromatosis type 1, medications, and herbal remedies [3,6]. In prepubertal boys, clinical exam suggestive of gynecomastia should prompt correlation with clinical history and further imaging and laboratory exams to exclude underlying disease. 4.3.1. Cyst Cysts (within the spectrum of ﬁbrocystic change) in the breast are most common in women between ages 35–50, but they can also occur in children and adolescents . Cysts may arise from dilatation of the lobular acini possibly due to imbalance of ﬂuid secretion and resorption, or due to obstruction of the duct leading to the lobule . Cysts are more commonly solitary than multiple in children , and can often present as a palpable abnormality in the breast, occasionally associated with tenderness when associated with inﬂammation or infection. Most cysts are treated conservatively, with some rarely requiring antibiotic therapy or drainage if infection is suspected. On ultrasound, if a simple cyst is demonstrated as an anechoic structure with imperceptible wall and posterior acoustic enhancement (Fig. 11), benign diagnosis is conﬁrmed and no further imaging or intervention is indicated. However if the cyst appears to be thick walled and or contains internal echoes, diagnostic considerations should include a complicated cyst, an abscess, a galactocele, or focal duct ectasia in the appropriate clinical contexts. 4.3.2. Hematoma A hematoma is an area of localized hemorrhage. In children and adolescents, hematomas in the breast are often seen in conjunction with sports injuries, iatrogenic trauma, or activity related injuries such as bike handle bar injury. A clear history of trauma and careful physical exam for signs of superﬁcial bruising over the breast help conﬁrm the diagnosis. On ultrasound, a hematoma can appear as a solid or complex cystic mass. Sonographic appearance of a hematoma varies depending on the age of the blood products. More acutely, a hematoma appears hyperechoic. It becomes progressively more anechoic as it regresses over time . Because blood products can incite reactive changes, a hematoma can have irregular or even spiculated margins, mimicking malignancy (Fig. 12). This highlights the importance of a thorough clinical history and a careful clinical exam, which can obviate unnecessary biopsy. When the diagnosis of hematoma is established, short-term follow up by ultrasound is recommended to ensure resolution. 4.3.3. Abscess Although more commonly encountered in lactating women, mastitis and abscess can occur in childhood. Mastitis occurs most frequently in infants (age < 2 months; i.e. mastitis neonatorum) and later childhood (age 8–17), and is thought to be related to skin infection and or ductal obstruction . Typically, suppurative mastitis presents with edema and erythema, occasionally with fever and leukocytosis. Ongoing mastitis can lead to the development of phlegmon and abscess. The most common pathogen is Staphylococcus aureus, followed by Streptococcus and less commonly Enterococcus species . Ultrasound should be performed Fig. 11. 17 year old girl presents with persistent “nodule” in the upper outer right breast. Ultrasound shows a nonvascular circumscribed thin-walled anechoic structure with posterior acoustic enhancement, consistent with a simple cyst. 1356 Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 Fig. 12. 15 year old girl with known sports related trauma to the chest presents with an area of palpable concern. Targeted ultrasound to this site of trauma demonstrates a non-vascular irregular anti-parallel predominantly hypoechoic mass, with mild adjacent soft tissue induration, consistent with hematoma. This resolved completely on the follow up ultrasound six weeks later. in patients with clinical symptoms of infection to exclude presence of a drainable ﬂuid collection. The ultrasound typically shows skin thickening and hyperechoic indurated breast tissue associated with hyperemia (mastitis). Occasionally, a hypoechoic complex mass (phlegmon or developing abscess), or an organized thick walled complex ﬂuid collection is present (frank abscess) (Fig. 13). Treatment includes antibiotic therapy and prompt ultrasound guided drainage, which helps facilitate healing and provides material for culture and sensitivity testing to further tailor therapy. 4.3.4. Galactocele Galactoceles are retention cysts of milky ﬂuid in the breast, most commonly seen in pregnant, lactating, or early post lactational women, but can occasionally present in children and young infants with or without endocrinopathy [3,6]. A galactocele likely results from occlusion of a lactiferous duct, therefore histologically represents a cyst with walls lined by cuboidal to columnar epithelium . Galactoceles can persist up to several years post lactation. Sonographically, a galactocele appears as a complex cystic mass with variable internal echotexture depending on the relative milk (hyperechoic) versus water (hypoechoic/anechoic) Fig. 14. 15 year old Somali refugee who is 1 month postpartum and breast feeding, presents with right breast lump. Ultrasound shows a circumscribed oval cystic mass of mixed internal echogenicity, in the setting of breast feeding, suggestive of fatty milky contents. This was aspirated for symptom relief, yielding milky ﬂuid, consistent with a galactocele. contents (Fig. 14). Occasionally, a fat-ﬂuid level may be present, which is visualized on ultrasound as well as on mammography. This is diagnostic of a galactocele. Clinical history and imaging appearance often suggestive the diagnosis. Aspiration of milky ﬂuid conﬁrms the diagnosis of a galactocele in the setting of complex and or atypical imaging appearance, and provides symptomatic relief. 4.4. Benign masses 4.4.1. Fibroadenoma Fibroadenomas are benign ﬁbroepithelial tumors and are the most common solid breast masses found in adolescent girls . Because ﬁbroadenomas arise from proliferation of specialized connective tissue stroma surrounding breast lobules, they do not usually occur in the male breast where lobules are typically absent, although male ﬁbroadenomas have been reported in rare cases. Fibroadenomas are estrogen sensitive tumors and may grow rapidly during puberty and pregnancy. The classic clinical presentation of a typical ﬁbroadenoma is a nontender palpable mobile rubbery mass usually 2–3 cm in size  (Fig. 15). At ultrasound, ﬁbroadenomas are usually parallel, circumscribed, oval hypoechoic masses, but may exhibit macrolobulations and become irregular in shape as they grow into larger masses . A pseudocapsule may be seen in certain cases  (Fig. 15). The internal echotexture Fig. 13. 14 year old girl with left areolar swelling, redness, pain, and fever for 1 week. Targeted ultrasound to the periareolar left breast demonstrates skin thickening and an underlying complex ﬂuid collection, consistent with abscess (a, b). The abscess was drained to completion under ultrasound guidance (c), yielding 3–4 cc of purulent ﬂuid. This was sent for culture and grew Staphylococcus Aureus. Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 1357 angular margin, marked hypoechogenicity, or shadowing warrants sampling  (Fig. 16). Rarely, a “complex ﬁbroadenoma” has been described, which appears less homogeneous on ultrasound and contains foci of sclerosis, adenosis, papillary apocrine metaplasia, cyst, or calciﬁcations histologically . When present in children, complex ﬁbroadenomas are associated with a minimally increased risk of developing breast cancer later in life [23,4]. A histologic variant of ﬁbroadenoma is the juvenile ﬁbroadenoma which is discussed in a separate section. 5. Uncommon causes of pediatric breast complaints 5.1. Uncommon benign masses Fig. 15. 16 year old girl with hard lump in the right breast. Ultrasound shows a circumscribed oval mass of heterogeneous internal echotexture and a pseudocapsule. Surgical excision was performed for histologic conﬁrmation, yielding ﬁbroadenoma. of ﬁbroadenomas can be either homogeneous or heterogeneous. Posterior acoustic features vary. Although in the past most palpable solid breast masses underwent biopsy despite benign features, we now know that short term followup of solid masses with probably benign sonographic features is a safe alternative to biopsy in the absence of atypical features or rapid enlargement [26–29]. A palpable breast mass meeting the criteria for a probably benign lesion at ultrasound has less than 1% chance of being malignant in multiple series for all age groups [26–29], and the chance of such a lesion being malignant in a pediatric patient is even lower. In a developing pediatric breast which is prone to iatrogenic injury, biopsy of a mass with typically benign sonographic features should be avoided in favor of periodic imaging surveillance. Surgical excision remains indicated in rapidly enlarging or symptomatic breast masses in children and adolescents regardless of benign sonographic features or initially benign pathology at biopsy (Fig. 16), because a phyllodes tumor cannot be excluded. A probably benign appearing mass on ultrasound at initial presentation in children with a personal history of malignancy, prior local radiation, or genetic mutations known to increase risk of breast cancer such as BRCA1 or 2 mutations, still requires biopsy. Presence of any malignant features such as spiculation, microlobulation, 5.1.1. Juvenile ﬁbroadenomas Juvenile ﬁbroadenoma (cellular ﬁbroadenoma) is an uncommon variant of ﬁbroadenoma, in part due to a lack of consensus in histologic diagnostic criteria. Histologic features include stromal hypercellularity accompanied by intraductal epithelial hyperplasia . These can be comparable in size to classic ﬁbroadenomas, but often undergo rapid enlargement. When growth reaches greater than 5–10 cm , these lesions are referred to as juvenile giant ﬁbroadenomas. Juvenile ﬁbroadenomas are more common in the African American population [30,31]. Given their frequent large size and rapid progressive growth, surgical excision is indicated to exclude the possibility of a phyllodes tumor. Deﬁnitive diagnosis of phyllodes tumors may be difﬁcult in a core biopsy, often necessitating surgical excision for complete pathologic evaluation. Sonographically, juvenile ﬁbroadenomas appear similar to classic ﬁbroadenomas, but demonstrate progressive growth and strikingly large size (Fig. 17). 5.1.2. Hamartoma Hamartomas are benign tumors of disorganized mature breast tissue elements. Despite this being a relatively common lesion in the adult breast, hamartomas are rare in children and adolescents . Hamartomas can grow to be very large in size (>10 cm) and mimic a juvenile giant ﬁbroadenoma . A hamartoma is a benign mass not associated with any known increased risk of later breast cancer. The clinical presentation is usually a painless mass, similar to that of the more common ﬁbroadenoma. On ultrasound, hamartomas appear as well circumscribed oval or round masses which can be hypoechoic, isoechoic, or heterogeneous in echotexture  (Fig. 18), mimicking the appearance of the more common ﬁbroadenoma. Although seldom used in children, mammography often shows a classic “breast within breast” appearance in hamartomas Fig. 16. 15 year old lacrosse player presents with left breast lump. Ultrasound demonstrates a parallel non-vascular hypoechoic mass with slightly irregular margins anteriorly and posterior acoustic enhancement, prompting biopsy showing a ﬁbroadenoma (a, b). A year later, the patient returns feeling “the lump is a lot bigger”. Ultrasound shows interval enlargement of the same mass, with surgical excisional biopsy recommended, yielding ﬁnal pathology of ﬁbroadenoma. 1358 Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 Fig. 17. 13 year old girl with rapidly enlarging breast mass. Ultrasound shows a large circumscribed mass exceeding the span of the linear ultrasound probe, estimated up to 10 cm in the largest dimension, with relatively homogeneous internal echotexture. This was surgically excised with pathology demonstrating juvenile ﬁbroadenoma. or serosanguinous nipple discharge. Intraductal papillomas are uncommon in children, and rare in boys [5,4,31] (Fig. 19). On ultrasound, a solid intraductal mass is present within a dilated duct ﬁlled with anechoic ﬂuid, occasionally with associated vascularity (Fig. 19). Surgical excision is the treatment of choice, to exclude rarely associated malignancy. Histologically, a papilloma is a mass consisting of multiple papillary structures, each deﬁned by a ﬁbrovascular core made up of connective tissue and small blood vessels, and lined by benign epithelium (Fig. 19). Fig. 18. 18 year old girl with right breast palpable mass. Ultrasound shows a partially circumscribed oval hypoechoic mass which underwent ultrasound guided core biopsy, demonstrating hamartoma. due to interspersed areas of radiodense ﬁbroglandular components and radiolucent fatty components within an encapsulated mass. When representative tissue is available from core biopsy sampling, hamartomas are readily differentiated from ﬁbroadenomas. Hamartomas appear histologically as disorganized lobules and adipose tissue, usually with a well-deﬁned boundary between the lesion and normal surrounding tissue . Fibroadenomas are deﬁned histologically by proliferation of specialized stroma around lobules. Lobules and fat are usually not present in a ﬁbroadenoma . Occasionally however, hamartomas may be difﬁcult to reliably distinguish from ﬁbroepithelial lesions at core needle biopsy, as hamartomatous elements can mimic normal background breast tissue, particularly if tissue sampling is inadequate . Hamartomas should be included in the differential considerations of a probably benign appearing breast mass on ultrasound, and is safe to follow in children and adolescents. In the event the lesion undergoes rapid progressive growth, surgical excision would be indicated. Hamartomas can recur if excision is incomplete . 5.1.3. Intraductal papilloma (solitary central papilloma) Intraductal papilloma represents a lesion of epithelial proliferation within a lactiferous duct. They are usually solitary and located in a subareolar duct, often causing post obstructive ductal dilatation. The clinical presentation is usually spontaneous serous 5.1.4. Juvenile papillomatosis (multiple peripheral papillomas) Juvenile papillomatosis is a rare localized proliferative process in the breast, in which multiple peripheral papillomas are present (in peripheral ducts). This is distinct from intraductal papilloma, in which a solitary central intraductal papilloma is present (in a central subareolar duct). Juvenile papillomatosis is a marker for familial breast cancer . Histologically, juvenile papillomatosis lacks the ﬁbrovascular core (Fig. 19d) which is typical in the central papilloma. On ultrasound, papillomatosis may appear as ill-deﬁned irregular hypoechoic tissue or masses, occasionally containing cystic spaces (Fig. 20) [6,36]. There may be associated clustered microcalciﬁcations . On MRI, papillomatosis presents as lobulated masses with cystic spaces well seen on T2 weighted sequences which enhance with gadolinium . Juvenile papillomatosis is a benign condition, but is associated with carcinoma in up to 15% of the cases , therefore surgical resection to negative margins to prevent recurrence is indicated. A disproportionate number of patients with juvenile papillomatosis have family history of breast cancer (up to 58%) [37,38], and should be closely monitored due to increased risk of developing breast cancer later in life. 5.1.5. Fibrous nodule Fibrous nodules are benign breast lesions of focally dense collagenous stroma surrounding atrophic epithelial elements . They most commonly present as ﬁrm palpable masses in premenopausal women, but rarely may be seen in the pediatric population (Fig. 21). Other names synonymous with ﬁbrous nodule include focal ﬁbrosis, ﬁbrous disease, ﬁbrous mastopathy, ﬁbrosis of the breast, and ﬁbrous tumor . The imaging appearance of ﬁbrous nodules is not well described in the literature, but small series have shown them to be small noncalciﬁed lesions (0.6–3.5 cm in Harvey et al.) at mammography, and solid hypoechoic masses with circumscribed or indistinct, and occasionally irregular margins at ultrasound . Histology of Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 1359 Fig. 19. 16 year old boy with serosanguinous left nipple discharge for one month. Ultrasound of the subareolar left breast shows an oval iso- to hyperechoic intraductal mass outlined by ﬂuid within a dilated duct (b). Ultrasound needle localized surgical excision was performed. Whole slide pathology image (a) shows histologic–radiologic correlation of the intraductal mass. A solitary papilloma is present within an epithelium-lined lactiferous duct (c). Higher power microscopy shows a papillary structure consisting of a ﬁbrovascular core (d) (black arrows) with connective tissues and small blood vessels, lined by benign epithelium (black arrowhead). myoﬁbroblastoma . Fibrous nodule is an acceptable benign histologic diagnosis for a discrete mass at mammography or ultrasound [39,40]. Periodic imaging surveillance of any mass meeting deﬁned imaging criteria is a reasonable and safe approach. However if there are any imaging features suspicious for malignancy, sampling and excision should be considered. 5.2. Malignant masses Fig. 20. 22 year old woman with Juvenile papillomatosis. Ultrasound shows a masslike area of hypoechoic tissue containing multiple anechoic cystic spaces, consistent with papillomatosis at histology (Courtesy of Dr. Katherine Humphrey). these lesions shows dense ﬁbroconnective tissue similar to that in adjacent breast tissue with scant or absent adipose tissue, as well as an absence of features of other stromal lesions such as pseudoangiomatous stromal hyperplasia, ﬁbroadenoma, lymphocytic or diabetic mastopathy, nodular fasciitis, ﬁbromatosis, or 5.2.1. Metastatic disease Malignant masses are rare in the pediatric breast, of which, metastatic disease is more common than primary breast malignancy. Primary tumors known to metastasize to the breast in children include rhabdomyosarcoma, neuroblastoma, lymphoma, leukemia, Ewing sarcoma, melanoma, and renal cell carcinoma [41,42]. An enlarging breast mass in a child with a known history of primary malignancy warrants sampling even if probably benign in imaging appearance. Metastatic disease in the breast can be solitary or multiple masses, involving one or both breasts. Imaging appearances of metastatic lesions in the breast are variable. Ultrasound may show a circumscribed or irregularly marginated mass which is heterogeneous or hypoechoic in echotexture . Mammography is less relevant in the pediatric population, but can show a circumscribed, partially obscured, or 1360 Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 lymphoma. Aggressive subtypes of CTCL include Sézary syndrome, primary cutaneous CD8+ aggressive epidermotropic T cell lymphoma, primary cutaneous gamma/delta T cell lymphoma, and extranodal natural killer/T cell lymphoma . Physical exam may show palpable masses or persistent papular rash involving the skin. Comprehensive physical examination including a thorough skin examination is indicated to assess for multifocal disease. These masses are hypervascular and often appear hypoechoic/anechoic but may appear hyperechoic on ultrasound. They enhance on MRI and are FDG avid on PET CT  (Fig. 22). Mammography plays a minor role in children, but CTCL appears as multiple and occasionally solitary superﬁcial irregular masses. Treatment focuses on systemic and topical therapy, with stem cell transplantation reserved for refractory, progressive cases. Fig. 21. 16 year old boy with multiple small left breast nodules. Ultrasound shows multiple circumscribed hypoechoic masses with a representative lesion displayed here, which shows an echogenic rim. Fine needle aspiration was performed, showing ﬁbroconnective tissue with scant adipose tissue, suggestive of a ﬁbrous nodule. irregular. Particular attention should be given to children and adolescents with known history of extramammary malignancies and genetic mutations linked to breast cancer, who present with a breast complaint. 5.2.2. Hematologic malignancy/Cutaneous T-cell lymphoma Lymphoma and leukemia are among the most common malignancies to metastasize to the breast secondarily . Primary breast lymphoma however, is extremely rare and usually manifests as non-Hodgkin’s lymphoma. Of the primary breast lymphomas, the majority are of B-cell type (Burkitt’s); T-cell lymphomas are exceedingly rare . Cutaneous T-cell lymphomas (CTCLs) are an uncommon subgroup of non-Hodgkin’s lymphoma that arises primarily in the skin, and can rarely present as a breast mass (Fig. 22) with or without involvement of axillary lymph nodes. CTCLs account for about 4% of all cases of non-Hodgkin’s lymphoma. The age-adjusted annual incidence of cutaneous T-cell lymphoma is approximately six cases per million . CTCLs increase in incidence with age and primarily affect adults, but can affect people of all ages, including children. More indolent subtypes of CTCL include mycosis fungoides, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, subcutaneous panniculitis-like T cell lymphoma, and primary cutaneous CD4+ small/medium pleomorphic T cell 5.2.3. Chest wall malignancies Chest wall malignancies in children may occasionally involve the breast via contiguous growth or locoregional metastasis. The most frequent chest wall malignancies in children are the malignant small round cell tumors (Ewing’s sarcoma, PNET/Primitive Neuroectodermal Tumor), followed by various sarcomas including rhabdomyosarcoma, osteosarcoma, or chondrosarcoma. Disease commonly involves extramammary chest structures, and diagnosis relies on cross sectional imaging tools such as CT, MR, or FDG PET. Ultrasound and mammography are helpful in isolated breast lesions without known history of primary chest wall malignancy. Treatment usually includes local surgical resection and adjuvant chemotherapy. 5.2.4. Phyllodes tumors Phyllodes tumors are rare ﬁbroepithelial lesions which arise from the specialized connective tissues around mammary lobules with indeterminate malignant potential. Phyllodes tumors were previously termed cystosarcoma phyllodes due to their cystic appearance and sarcoma-like characteristics including a propensity for hematogenous spread, therefore metastasizing to the lung rather than axillary lymph nodes. Phyllodes tumors are rare, but nevertheless represent the most common primary breast malignancy in children and adolescents when malignant . Phyllodes tumors are histologically categorized into low, intermediate, and high grade, all of which may recur, and rarely, metastasize. There is signiﬁcant clinical, imaging, and histologic overlap between phyllodes tumors and juvenile ﬁbroadenomas, thus biopsy of any rapidly enlarging breast mass is warranted to evaluate for phyllodes tumor. Phyllodes tumors tend to be large (>6 cm) at clinical presentation , and appear as circumscribed, oval or round masses which are hypoechoic or heterogeneous, often with posterior acoustic enhancement on ultrasound . Intralesional cysts and clefts (Fig. 23) are highly suggestive of the diagnosis, although these may also be present in juvenile ﬁbroadenomas . Ultrasound guided biopsy is indicated in any large or rapidly Fig. 22. 16 year old girl with cutaneous T cell lymphoma involving the right breast, initially presenting as non healing rash. CT shows an irregular inﬁltrative mass along the superﬁcial aspect of the right breast (a), which is FDG avid on PET CT (b), and consistent with subcutaneous panniculitis-like cutaneous T cell at biopsy. Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 1361 Fig. 23. 13 year old girl notes a subcutaneous mass in the right breast, present for 6 weeks. Ultrasound shows a large solid and cystic complex mass with heterogeneous internal echotexture and interspersed linear anechoic clefts (a, arrows). Biopsy was the mass was performed, with whole pathology slide (b) demonstrating an intermediate grade phyllodes tumor with overall variegated architecture consisting of fronds, classic for phyllodes tumor. Spaces between fronds correlate well with the sonographic feature of clefts often seen in these tumors. enlarging breast mass in children (more speciﬁc features of a phyllodes tumor). Surgical excision with wide margins is required for all phyllodes tumors. Low grade phyllodes tumors are generally associated with lower rate of recurrence . In children, recurrence rate of phyllodes tumor is even lower, estimated at approximately 10% . Local recurrence does not alter prognosis. Histologic features of phyllodes tumors include increased stromal cellularity, cellular atypia, stromal overgrowth, and presence of sarcomatous elements, the latter of which used to deﬁne the malignant type . Based on these histologic criteria, phyllodes tumors are generally classiﬁed into low-grade, intermediate-grade, or high-grade (malignant) tumors (Fig. 23). Classiﬁcation into benign and malignant lesions is occasionally used. Phyllodes tumors exhibit an overall variegated architecture (Fig. 23b), and consist of fronds (cellular stromal tissue lined by epithelium), allowing for cystic or cleft like spaces between abutting fronds on ultrasound (Fig. 23a). 5.2.5. Invasive secretory carcinoma Primary breast carcinomas are exceedingly rare in the pediatric population. Primary breast cancer incidence is noted to be approximately 0.1 case per million in females younger than 20 years of age . Boys are even less affected (Figs. 24 and 25). The most common subtype of invasive breast cancer in children is invasive secretory carcinoma, which carries a more favorable prognosis as compared to the less common subtypes of breast cancer seen in children (invasive ductal, invasive lobular, medullary, inﬂammatory, and anaplastic carcinomas) [5,50,51]. Secretory carcinomas are small circumscribed masses (usually < 3 cm) that present as painless palpable masses (Fig. 24). On ultrasound, they typically appear as circumscribed or partially microlobulated hypoechoic masses with heterogeneous internal echotexture  (Fig. 24). Secretory carcinoma contains bubbles of secretory components or cytoplasmic vacuoles on histology, which are characteristically positive by PAS stain (Fig. 24b). Treatment is surgical excision, sentinel node biopsy, with or without systemic adjuvant therapy depending on the disease extent. 5.2.6. Post radiation breast cancer Children who receive high dose mantle irradiation for Hodgkin’s disease are at signiﬁcantly increased risk for developing breast cancer later in life. This population has a cumulative incidence of breast cancer of 12–20% by about age 40, comparable to that in the BRCA (breast cancer susceptibility) gene mutation carriers (10–19%), whereas in the general population, women of the same age group have a cumulative incidence of breast cancer of 1% . Young women at the greatest risk are those treated with therapeutic radiation between ages 10–16, with the majority of the tumors developing in the radiation ﬁeld . The risk of breast cancer increases with years post irradiation, therefore routine screening is important. Annual screening mammogram with adjunctive MRI screening are generally recommended in young women at least 25 years of age, 8–10 years following completion of radiation therapy as per the American College of Radiology guidelines . The imaging appearance of breast cancer arising after therapeutic irradiation is not different from other primary breast cancers. 5.2.7. Hereditary breast cancer/Cowden syndrome Approximately 10% breast cancers are hereditary. Known associated factors include not only the BRCA1 and BRCA2 mutations, but also rare germline mutations such as TP53 mutations in LiFraumeni syndrome, STK11 mutations in Peutz-Jeghers syndrome, and PTEN mutations in Cowden syndrome . New mutations continue to emerge with further advances in genomic technology. The hallmark of hereditary breast cancer is early onset of disease, highlighting the importance of early screening. Cowden syndrome is also known as multiple hamartoma syndrome. Together with Bannayan-Riley-Ruvalcaba syndrome, Cowden syndrome belongs to the spectrum of hamartomatous overgrowth syndromes associated with germ line mutations in the tumor suppressor PTEN gene which is located on 10q23.3, with an autosomal dominant inheritance. However, not all patients with clinical diagnosis of Cowden syndrome have an identiﬁable PTEN mutation . PTEN mutation carriers are at signiﬁcantly increased risks for breast, thyroid, endometrial, and renal cell carcinomas (Fig. 26). Cowden syndrome patients carry a cumulative breast cancer risk of 77% by age 70, and 75% of these patients have breast lesions of some kind (Fig. 26) . Given the markedly elevated risks for breast cancer, guidelines have proposed commencing clinical breast exam and screening breast ultrasound at age 25, and starting screening mammogram and MRI at age 30 or 5 years before earliest known breast cancer in the family . 1362 Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 Fig. 24. 8 year old boy with family history of breast cancer presents with a painless right periareolar breast lump for 1.5 years with recent increase in size. Ultrasound shows a circumscribed oval predominantly hypoechoic mass (a) which corresponds well with whole slide pathology mount (b). Surgical excisional biopsy shows invasive secretory carcinoma, solid variant, and in situ secretory carcinoma. Mastectomy was ultimately performed for positive surgical margin at the initial resection. Sentinel node biopsy was negative. Higher power microscopy of the mass shows jagged edges of invasive tumor cells along the periphery (c. arrows). PAS stain is positive, highlighting the presence of intracytoplasmic vacuoles (arrows). 6. Management algorithm Fig. 25. A 29 year old woman found to have breast cancer 15 years post mantle radiation for Hodgkin’s disease as a girl at the age of 14. Ultrasound shows a taller than wide irregular hypoechoic mass with echogenic halo, consistent with an invasive ductal carcinoma at biopsy. Given the risk of iatrogenic injury to the developing breast and the extremely low incidence of malignancy in children, an algorithm for diagnosis and management is proposed, emphasizing “ﬁrst do no harm” (Fig. 27). All pediatric breast complaints should begin with a clinical assessment, taking into account the patient’s age, presentation, past medical history, family history, and symptoms. Newborns with subareolar nodules and nipple discharge likely experience these symptoms due to maternal hormonal inﬂuence, and parents should be reassured. Similarly, subareolar nodules in infants under age 1 are likely due to maternal hormonal inﬂuence, which are generally self limited. Prepubertal children with asymmetric breast buds can present with a palpable subareolar mass in the breast, which can be conﬁrmed using ultrasound if clinical exam is uncertain. These are common and usually resolve by puberty. In older children and adolescents, ultrasound remains the primary diagnostic tool to evaluate breast complaints. Normal structures such as a lymph node or benign lesions such as a simple cyst or a lipoma can be diagnosed at ultrasound without need for further imaging. In the setting of known trauma, a hematoma can be assessed and followed to resolution using ultrasound. In the setting of infection, ultrasound can exclude the presence of a phlegmon or abscess, the latter of which can be drained under sonographic guidance to facilitate healing while under antibiotic treatment. Probably benign masses (circumscribed margin, oval shape, parallel orientation) measuring up to 3–4 cm in young girls are most likely to be ﬁbroadenomas and are safe to follow by ultrasound whether palpable or not, except when atypical features exist or rapid enlargement Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 1363 Fig. 26. 15 year old girl with Cowden syndrome presents with innumerable palpable bilateral circumscribed homogeneous breast masses with a representative example displayed here on ultrasound (a). The patient had already undergone prior bilateral breast biopsies demonstrating benign histologies including a complex sclerosing lesion with PASH (b), therefore surveillance of the remaining masses rather than biopsy was recommended. This patient also has a history of papillary thyroid cancer requiring thyroidectomy, and has over 50 polyps throughout the gastrointestinal tract in the esophagus, stomach, and colon. Fig. 27. How to approach breast lesions in children and adolescents – a diagnostic and management algorithm. occurs. Larger than 5 cm masses meeting criteria as probably benign cannot be readily differentiated from phyllodes tumors, and therefore, biopsy is indicated. Mass lesions with malignant features on ultrasound (indistinct/angular/microlobulated/spiculated margin, irregular shape, and anti-parallel orientation) should be biopsied. Initial discovery of any breast mass, regardless of appearance in patients with known extramammary malignancy, prior mantle radiation, genetic mutations or syndromes, warrants sampling. Other cross sectional imaging modalities such as CT, MR, FDG-PET are often helpful in deﬁning disease extent. Gynecomastia is most commonly physiologic in neonates and teenage boys. A clinical and laboratory workup should be considered however, in prepubertal boys with gynecomastia to exclude estrogen secreting tumors in rare cases. Children with nipple discharge should be examined and ultrasound may rarely show an intraductal papilloma or juvenile papillomatosis, both of which require surgical resection, the latter of which is associated with elevated risk of developing breast cancer later in life. 7. Conclusion Breast malignancy is exceedingly rare in children. Diagnostic and management approach of the pediatric breast is therefore appropriately conservative. It is important to understand that the spectrum of pediatric breast disease differs from that of the adult breast. Knowledge of common and uncommon benign and 1364 Y. Gao et al. / European Journal of Radiology 84 (2015) 1350–1364 malignant pediatric breast lesions and their appearances on imaging help direct diagnosis and management. Conﬂicts of interest The authors declare no conﬂicts of interest. References  http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancerkey-statistics, American Cancer Society (last medical review 11.09.13, last revised 24.10.13, viewed 22.12.13).  SEER Cancer Statistics Factsheets: Breast Cancer. National Cancer Institute, Bethesda, MD, http://seer.cancer.gov/statfacts/html/breast.html  Kaneda HJ, Mack J, Kasales CJ, Schetter S. AJR 2013;200:W204–12, http://dx.doi.org/10.2214/AJR.12.9560.  Greydanus DE, Matytsina L, Gains M. Breast disorders in children and adolescents. Prim Care 2006;33:455–502.  Cofﬁn CM. The breast. In: Stocker JT, Dehner LP, editors. Pediatric pathology. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2002. p. 993–1015.  Chung EM, Cube R, Hall GJ, Gonzalez C, Stocker JT, Glassman LM. Breast masses in children and adolescents: radiologic–pathologic correlation. RadioGraphics 2009;29:907–31.  Kaplowitz PB, Overﬁeld SE. Drug and Therapeutics and Executive Committee of the Lawson Wilkins Pediatric Endocrine Society. Reexamination of the age limit for deﬁning when puberty is precocious in girls in the United States: implications for evaluation and treatment. Pediatrics 1999;104: 936–41.  Bock K, Duda VF, Hadji P, Ramaswamy A, Schulz-Wendtland R, Klose KJ, et al. Pathologic breast conditions in childhood and adolescence. J Ultrasound Med 2005;24:1347–54.  Diamantopolous S, Bao Y. Gynecomastia and premature thelarche: a guide for practitioners. Pediatr Rev 2007;28(9):57–68.  Atay Z, Turan S, Guran T, Furman A, Bereket A. The prevalence and risk factors of premature thelarche and pubarche in 4- to 8-year-old girls. Acta Paediatr 2012;101(2):71–5.  Okdemir D, Hatipoglu N, Kurtoglu S, Akin L, Kendirci M. Premature thelarche related to fennel tea consumption? J Pediatr Endocrinol Metab 2013:1–5, http://dx.doi.org/10.1515/jpem-2013-0308.  Garciı́a CJ, Espinoza A, Dinamarca V, Navarro O, Daneman A, Garcia H, et al. Breast US in children and adolescents. Radiographics 2000;20:1605–12.  Mojallal A, La Marca S, Shipkov C, Sinna R, Braye F. Poland syndrome and breast tumor: a case report and review of the literature. Aesth Surg J 2012;32(1):77–83.  Zhang F, Qi XW, Xu Y, Zhou Y, Zhang Y, Fan L, et al. Breast cancer and Poland syndrome: a case report and literature review. Breast J 2011;17(2):196–200, http://dx.doi.org/10.1111/j.1524-4741.2010.01042.x.  Wang X, Ning L. Breast carcinoma associated with Poland syndrome: one case report and literature review. Chin J Clin Oncol 2008;5(3):223–5, http://dx.doi.org/10.1007/s11805-008-0223-z.  Dixon JM, Mansel RE. ABC of breast diseases: congenital problems and aberrations of normal breast development and involution. BMJ 1994;309:797, http://dx.doi.org/10.1136/bmj.309.6957.797.  Adler DD, Rebner M, Pennes DR. Accessory breast tissue in the axilla: mammographic appearance. Radiology 1987;163:709–11.  Park JE, Sohn YM, Kim EK. Sonographic ﬁndings of axillary masses. J Ultrasound Med 2013;32(7):1261–70.  Nordt CA, DiVasta AD. Gynecomastia in adolescents. Curr Opin Pediatr 2008;20:375–82.  Weinstein SP, Conant EF, Orel SG, Zuckerman JA, Bellah R. Spectrum of US ﬁndings in pediatric and adolescent patients with palpable breast masses. Radiographics 2000;20:1613–21.  Siegel MJ. Chest. In: Siegel MJ, editor. Pediatric sonography. 3rd ed. Philadelphia, PA: Lippincott Williams & Williams; 2002. p. 201–11.  Faden H. Mastitis in children from birth to 17 years. Pediatr Infect Dis J 2005;24:1113.  Sanchez R, Ladino-Torres MF, Bernat JA, Joe A, DiPietro MA. Breast ﬁbroadenomas in the pediatric population: common and uncommon sonographic ﬁndings. Pediatr Radiol 2010;40:1681–9.  Simmons PS. Diagnostic considerations in breast disorders of children and adolescents. Obstet Gynecol Clin North Am 1992;19:91–102.  Stavros AT, Thickman D, Rapp CL, Dennis MA, Parker SH, Sisney GA. Solid breast nodules: use of sonography to distinguish between benign and malignant lesions. Radiology 1995;196(1):123–34.  Graf O, Helbich TH, Fuchsjaeger MH, Hopf G, Morgun M, Graf C, et al. Follow-up of palpable circumscribed noncalciﬁed solid breast masses at mammography and US: can biopsy be averted? Radiology 2004;233:850–6.  Giess CS, Smeglin LZ, Meyer JE, Ritner JA, Birdwell RL. Risk of malignancy in palpable solid breast masses considered probably benign or low suspicion. J Ultrasound Med 2012;31:1943–9.  Harvey JA, Nicholson BT, Lorusso AP, Cohen MA, Bovbjerg VE. Short-term follow-up of palpable breast lesions with benign imaging features: evaluation of 375 lesions in 320 women. AJR Am J Roentgenol 2009;193:1723–30.  Raza S, Chikarmane SA, Neilsen SS, Zorn LM, Birdwell RL. BI-RADS 3, 4, and 5 lesions: value of US in management – followup and outcome. Radiology 2008;248:773–81.  Pike AM. Juvenile (cellular) adenoﬁbromas, a clinicopathologic study. Am J Surg Pathol 1985;9:730–6.  Pettinato G, Manivel JC, Kelly DR, Wold LE, Dehner LP. Lesions of the breast in children exclusive of typical ﬁbroadenoma and gynecomastia. Pathol Annu 1989;24:296–328.  Chang HL, Lerwill MF, Goldstein AM. Breast hamartomas in adolescent females. Breast J 2009;15(5):515–20.  Georgian-Smith D, Kricun B, McKee G, Yeh E, Rafferty EA, D’Alessandro HA, et al. The mammary hamartoma: appreciation of additional imaging characteristics. J Ultrasound Med 2004;23(10):1267–73.  Lerwill MF. Biphasic lesions of the breast. Semin Diagn Pathol 2004;21:48–56.  Gill J, Greenall M. Juvenile papillomatosis and breast cancer. J Surg Educ 2007;64(4):234–6.  Kopans DB. Breast imaging. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. p. 797–8.  Rosen PP. Benign mesenchymal neoplasms. In: Rosen’s breast pathology. Philadelphia, PA: Lippincott-Raven; 1996. p. 658–705.  Bazzocchi F, Santini D, Martinelli G, Piccaluga A, Taffurelli M, Grassigli A, et al. Juvenile papillomatosis (epitheliosis) of the breast: a clinical and pathologic study of 13 cases. Am J Clin Pathol 1986;86:745–8, 797–798.  Harvey SC, Denison CM, Lester SC, DiPiro PJ, Smith DN, Meyer JE. Fibrous nodules found at large-core needle biopsy of the breast: imaging features. Radiology 1999;211(2):535–40.  Berg WA, Hruban RH, Kumar D, Singh HR, Brem RF, Gatewood OM. Lessons from mammographic–histopathologic correlation of large-core needle breast biopsy. Radiographics 1996;16:1111–30.  Boothroyd A, Carty H. Breast masses in childhood and adolescence: a presentation of 17 cases and a review of the literature. Pediatr Radiol 1994;24:81–4.  Chateil JF, Arboucalot F, Perel Y, Brun M, Boisserie-Lacroix M, Diard F. Breast metastases in adolescent girls: US ﬁndings. Pediatr Radiol 1998;28:832–5.  Aguilera NS, Tavassoli FA, Chu WS, Abbondanzo SL. T-cell lymphoma presenting in the breast: a histologic, imunophenotypic and molecular genetic study of four cases. Mod Pathol 2000;13(6):599–605.  Chihara D, Ito H, Matsuda T, Shibata A, Katsumi A, Nakamura S, et al. Differences in incidence and trends of haematological malignancies in Japan and the United States. Br J Haematol 2014;164(4):536–45.  Swerdlow E, Campo N, Harris NL, Pileri S, Stein H, Jaffe ES. WHO classiﬁcation of tumors of hematopoietic and lymphoid tissues. 4th ed. France: IARC Press Lyon; 2008.  Uematsu T, Kasami M. 3T-MRI, elastography, digital mammography, and FDGPET CT ﬁndings of subcutaneous panniculitis-like T cell lymphoma (SPTCL) of the breast. Jpn J Radiol 2012;30(9):766–71.  Dehner LP, Hill DA, Deschryver K. Pathology of the breast in children, adolescents, and young adults. Semin Diagn Pathol 1999;16:235–47.  Tse GM, Niu Y, Shi HJ. Phyllodes tumor of the breast: an update. Breast Cancer 2010;17:29–34.  Rajan PB, Cranor ML, Rosen PP. Cystosarcoma phyllodes in adolescent girls and young women: a study of 45 patients. Am J Surg Pathol 1998;22:64–9.  Murphy JJ, Morzaria S, Gow KW, Magee JF. Breast cancer in a 6-year-old child. J Pediatr Surg 2000;35:765–7.  Horowitz DP, Sharma CS, Connolly E, Gidea-Addeo D, Deutsch I. Secretory carcinoma of the breast: results from the survival, epidemiology and end results database. Breast 2012;21:350–3.  Mun SH, Ko EY, Han BK, Shin JH, Kim SJ, Cho EY. Secretory carcinoma of the breast: sonographic features. J Ultrasound Med 2008;27:947–54.  Freitas V, Saranelo A, Menezes R, Kulkarni S, Hodgson D, Crystal P. Added cancer yield of breast magnetic resonance imaging screening in women with a prior history of chest radiation therapy. Cancer 2013;119(3):495–503.  Lee CH, Dershaw DD, Kopans D, Evans P, Monsees B, Monticciolo D, et al. Breast cancer screening with imaging: recommendations from the Society of Breast Imaging and the ACR on the use of mammography, breast MRI, breast ultrasound, and other technologies for the detection of clinically occult breast cancer. J Am Coll Radiol 2010;7:18–27.  Apostolou P, Fostira F. Hereditary breast cancer: the era of new susceptibility genes. Biomed Res Int 2013:747318, http://dx.doi.org/10.1155/2013/747318.  Piccione M, Fragapane T, Antona V, Giachino D, Cupido F, Corsello G. PTEN hamartoma tumor syndromes in childhood: description of two cases and a proposal for follow-up protocol. Am J Med Genet Part A 2013;161A:2902–8.  Bubien V, Bonnet F, Brouste V, Hoppe S, Barouk-Simonet E, David A, et al. High cumulative risks of cancer in patients with PTEN hamartoma tumour syndrome. J Med Genet 2013;50(4):255–63.