Imaging of the male breast: Protocols for practice

Imaging of the male breast: Protocols for practice Poster No.: C-2188 Congress: ECR 2014 Type: Educational Exhibit Authors: J. Muscat, V. Attard ; Birkirkara/MT, Nadur/MT Keywords: Endocrine disorders, Cancer, Decision analysis, Biopsy, Ultrasound, Mammography, Radioprotection / Radiation dose, Breast DOI: 10.1594/ecr2014/C-2188 1 2 1 2 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 35

Learning objectives Guidelines and recommendations for the workup of female patients presenting with breast complaints to symptomatic clinics or for the assessment and characterization of screen-detected findings [1,2] are, in their main part, well-adopted, tested and tried. These revolve around triple assessment which consists of clinical examination, imaging correlation and tissue sampling. The principal aim for this practice is to rule out malignancy. The purpose of this poster presentation is to illustrate the salient clinical, radiological and pathological findings on workup of male breast symptomatology as compiled from a comprehensive review of the current literature with imaging examples from our actual practice. Also, this work may serve to highlight possible in-clinic over-investigation of lower risk male patients whilst every effort must be made to avoid missing opportunities for diagnosis and, perhaps where possible, preventive care in particular higher-risk individuals and their relatives. Background The male patient presenting with a breast-related complaint is statistically much more likely to be benign in aetiology as fewer than 1% of all patients with breast cancer are men [3]. A noticeable trend is, however, that more male patients are being referred for the work up of breast complaints with some breast units reporting an increase of referrals by up to 500% over the last decade or so [4]. Also, incidental findings on cross-sectional imaging - CT, MRI and PET-CT scanning constitute an alternative source of a number of asymptomatic lesions for assessment. Gynaecomastia: the commonest benign condition of the male breast Males may seek medical attention in the symptomatic breast clinic for such symptoms as breast enlargement, breast pain or palpable lump. The majority of breast conditions in the male patient are indeed benign and gynaecomastia is the commonest aetiology. Gynaecomastia is defined as an increase in breast size due to a proliferation of breast ducts and stromal tissue secondary to an increased oestrogen to testosterone ratio [5]. Page 2 of 35

Fig. 1: Histologically, florid gynaecomastia is characterized by intraductal epithelial hyperplasia and increased periductal cellularity and oedema. In the inactive fibrous phase, the epithelial cells are flat and the periductal stroma is hyalinised. References: Department of Histopathology, Mater Dei Hospital - Birkirkara/MT Pseudogynaecomastia is defined as a sole increase in the amount of adipose breast tissue. Gynaecomastia can present at any age but is most commonly seen during puberty and senescence -and hence described as physiologic - with the prevalence of asymptomatic gynaecomastia quoted as being as high as 60-90% in neonates, up to 60% in adolescence and approaching 70% in men aged 50-69 years [6]. Endocrine and systemic disease, drugs and some neoplasms are other potential causes of gynaecomastia [5,7]. Page 3 of 35

Table 1: Causes of Gynaecomastia References: Adapted from: Charlot M, Beatrix O, Chateau, F et al. (2013) Pathologies of the male breast. Diagnostic and Interventional Imaging 94:26#37 Clinically, gynaecomastia presents as a soft, mobile, tender, retroareolar mass. It may be a unilateral process (14%). Bilateral symmetrical or bilateral asymmetrical (84%) changes in the breast may be detected clinically [5]. The main differential for gynaecomastia is lipomastia or pseudogynaecomastia which is the deposition of increased adipose tissue subcutaneously. Images for this section: Page 4 of 35

Table 1: Causes of Gynaecomastia Page 6 of 35

Findings and procedure details Imaging workup of the Male Breast Radiologically, 3 patterns of gynaecomastia are described, namely the nodular pattern (Figure 2), the dendritic (Figure 3, Figure 4) and the diffuse glandular (Figure 5, Figure 6) patterns. Fig. 2: 41 year old gentleman referred to clinic for work up of gynaecomastia. Patient awaiting liver transplant for liver cirrhosis secondary to Hepatitis C. Bilateral asymmetrical nodular gynaecomastia on MLO views (a,b). Ultrasound demonstrates hypoechoic retroareolar areas surrounded by fatty elements (c,d). No suspicious masses identified. The nodular phase is described as the early phase of gynaecomastia. References: The Park Centre for Breast Care, Brighton and Sussex University Hospitals, Brighton, UK Page 7 of 35

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Fig. 3: 82 year old gentleman referred for imaging of a lump in the right breast Clinical grade 3 Unilateral dendritic gynaecomastia on Right MLO and Right CC views (a,c). The left breast is normal (c,d). References: The Park Centre for Breast Care, Brighton and Sussex University Hospitals, Brighton, UK Fig. 4: Ultrasound, of same patient in Figure 3, demonstrates a wedge-shaped opacity with its apex in the subareolar region with irregular margins posteriorly extending into echogenic fibrous breast tissue. In view of P3 clinical grading, patient's age and unilaterality, ultrasound guided tissue sampling was, at the time, performed confirming gynaecomastia. References: The Park Centre for Breast Care, Brighton and Sussex University Hospitals, Brighton, UK Page 9 of 35

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Fig. 5: 54 year old gentleman presenting with a 6 month history of left breast swelling and tenderness - Clinical grade 2 Diffuse glandular pattern of gynaecomastia bilaterally on MLO and CC views (a,b,c,d). References: The Park Centre for Breast Care, Brighton and Sussex University Hospitals, Brighton, UK Fig. 6: Ultrasound of same patient in Figure 5 confirms diffuse glandularity (a,b,c). Hyperechoic fibrous breast tissue (*) arranged as per sonographic assessment of the female breast. References: The Park Centre for Breast Care, Brighton and Sussex University Hospitals, Brighton, UK Other benign breast lesions may be demonstrated in the male breast such as cutaneous conditions, fat necrosis, cysts (Figure 7), abscesses and intramammary lymph nodes may also occur in the male breast. Page 11 of 35

Fig. 7: 17 year old young man noticed to have a growing lump in the left breast. Simple cysts - anechoic, thin-walled and demonstrating through transmission measuring up to 11mm in the lateral part of retroareolar gynaecomastia/glandular elements. No solid, complex elements demonstrated. References: The Park Centre for Breast Care, Brighton and Sussex University Hospitals, Brighton, UK The workup and imaging modality of choice for assessment of the male breast varies - with some centres opting for mammography first-line, and targeted ultrasound being performed as an adjunct assessment when required. Other breast units opt for ultrasound assessment of the male breast. Barkeji et al [8] identified that out of 142 male patients imaged over a twelve month period, 44% had a biopsy performed and 5 were found to have a malignancy. 124 of these patients had imaging findings which were classified as normal or benign and 45 of these individuals had a biopsy. None of these biopsies were malignant or altered management. Correlation of imaging and clinical findings may safely reduce the number of unnecessary breast interventions performed in these individuals. It is found that, in both female and male breast cancer, the biggest risk factor is age. Nonetheless, as is true for much of medicine, a "one size fits all" universal model is not necessarily appropriate or safe. Men younger than 40 years of age - with clinical gynaecomastia - may not need imaging assessment. If imaging is requested, ultrasound may be considered sufficient. Patients over the age of 40 years may be initially assessed mammographically with a near 100% specificity when both clinical examination and mammographic findings are benign and hence no further assessment (tissue biopsy) warranted [3]. Correlation with clinical findings and any initial imaging findings should guide triple diagnostic assessment as required. Making use of a standardized reporting breast imaging classification is useful to communicate findings with referrers and also outline the level of suspicion for malignancy. The Royal College of Radiologists Breast Group formulated a national classification for use by Breast Imagers in the UK [9]. The main contrasting element between this system and the American College of Radiologists BIRADS classification lies in Category 3 classification: BI-RADS deems lesions in this group to be most likely benign but recommends follow-up imaging in 6 months than annually for a year or two. The RCRBG's classification defines category 3 lesions as indeterminate/ probably benign but necessitating further investigation (Table 2). Page 12 of 35

Table 2: RCRBG and BI-RADS Imaging Classification Systems Compared References: Adapted from: Maxwell A, Ridley N, Rubin G et al. (2009) The Royal College of Radiologists Breast Group breast imaging classification. Clin Radiol 64(1):624#627 Male Breast Cancer Page 13 of 35

Male breast cancer is uncommon representing circa 0.6% of all breast cancers. It constitutes less than 1% of all malignancies in men [10] and male breast cancer has an annual incidence in Europe of 1 in 100000 [5]. In 2012, the National Cancer Institute in the US, estimated 226,870 newly diagnosed female breast cancers and 2190 newly diagnosed male breast cancers. Several risk factors for male breast cancer have been identified (Table 3)[11]. Although some of these risk factors may also be those for gynaecomastia, the latter does not infer an increased risk of breast cancer development. Gynaecomastia is a much commoner encountered clinical entity. In 20% of men with breast cancer there is a family history of breast cancer in first degree female relatives with mutations of BRCA2 being commonest. Page 14 of 35

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Table 3: Risk factors for Male Breast Cancer References: Adapted from: Ruddy KJ, Winer EP. (2013) Male breast cancer: risk factors, biology, diagnosis, treatment and survivorship. Annals of Oncology 24:1434-1443 The peak incidence of male breast cancer occurs a decade or so later than does female breast cancer - with patients presenting at a median age of 67. Patients tend to present at a more advanced stage of disease. This may be due to less breast awareness in male patients and a relative lack of clinical suspicion by physicians [10]. The clinical presentation is typically that of a nontender eccentric subareolar mass. (Figure 8 and Figure 9). Page 16 of 35

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Fig. 8: 75 year old gentleman presenting with a 4 month history of a lump in the right breast. Clinical grade 3/4. Father had breast cancer at age 75. Mammogram demonstrates a well-defined mass and some variable calcification at 9 o'clock in the right breast. Background gynaecomastia noted bilaterally. Right breast (a,c): M4. Left breast (b,d): M2. Ultrasound guided core performed: G3 Invasive Ductal carcinoma. Axilla normal at ultrasound assessment. At surgery, G3 IDC confirmed with associated high-grade DCIS. No lymphovascular invasion. Normal axillary nodes. References: The Park Centre for Breast Care, Brighton and Sussex University Hospitals, Brighton, UK Page 18 of 35

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Fig. 9: 42 year old male presenting with a right P3 lump. Right MLO and CC views (a,b) demonstrate an irregular mass with microcalcifications behind and superomedial to the nipple: M5. Sonographically a U5 irregular hypoechoic mass (c) is demonstrated. Core biopsy performed. Histology: Grade 2 Invasive Ductal Carcinoma. Macrometasis demonstrated at surgery - pt2,pn1 References: The Park Centre for Breast Care, Brighton and Sussex University Hospitals, Brighton, UK Also, the less standardized use of breast imaging in male patients implies a lack of familiarity with the imaging characteristics of male breast cancer. Pathologically, the vast majority of breast cancer in males is invasive ductal carcinoma. Ductal carcinoma in situ is not frequently diagnosed as most patients present with a symptomatic lump as opposed to screen detected findings. Male breast tissue is predominately composed of undeveloped ductal components encircled by connective, adipose, and subcutaneous tissues. Lobular carcinoma is therefore rare. Simple breast cysts are uncommon and complexity must be excluded as neoplastic papillary lesions may manifest as complex cystic lesions. Fibroadenomas are also very rare in men - as these are also of lobular origin [12,13]. The imaging appearances of breast carcinoma in males are variable. Even well-defined lesions - which perhaps would be considered benign in the female breast (Figure 10) merit further investigation in the male breast. Page 20 of 35

Fig. 10: 87 year old male presenting with a 2cm firm, not very mobile lump in the left breast and vague skin dimpling - P4. Bilateral MLO views only performed (a,b) - Left M4 opacity. Ultrasound demonstrated a well-defined, hypoechoic, gently lobulated lesion with through-transmission. In the female breast this would not be regarded as highly suspicious (M3) however in a male this is still most in keeping with a carcinoma (M4) - US guided biopsy performed confirming Grade 3 Invasive Ductal Carcinoma. References: The Park Centre for Breast Care, Brighton and Sussex University Hospitals, Brighton, UK NICE guidance for Familial Breast Cancer [14] outlines that individuals with a first degree male relative with breast cancer should be offered referral to Secondary Care. Referral to a Specialist Genetic Clinic may be recommended if there are additional family members with breast cancer and a male relative with breast cancer. The diagnosis of a male breast cancer - rare as it may be - therefore has broader repercussions. Images for this section: Page 21 of 35

Fig. 2: 41 year old gentleman referred to clinic for work up of gynaecomastia. Patient awaiting liver transplant for liver cirrhosis secondary to Hepatitis C. Bilateral asymmetrical nodular gynaecomastia on MLO views (a,b). Ultrasound demonstrates hypoechoic retroareolar areas surrounded by fatty elements (c,d). No suspicious masses identified. The nodular phase is described as the early phase of gynaecomastia. Page 22 of 35

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Fig. 3: 82 year old gentleman referred for imaging of a lump in the right breast - Clinical grade 3 Unilateral dendritic gynaecomastia on Right MLO and Right CC views (a,c). The left breast is normal (c,d). Fig. 4: Ultrasound, of same patient in Figure 3, demonstrates a wedge-shaped opacity with its apex in the subareolar region with irregular margins posteriorly extending into echogenic fibrous breast tissue. In view of P3 clinical grading, patient's age and unilaterality, ultrasound guided tissue sampling was, at the time, performed confirming gynaecomastia. Page 24 of 35

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Fig. 5: 54 year old gentleman presenting with a 6 month history of left breast swelling and tenderness - Clinical grade 2 Diffuse glandular pattern of gynaecomastia bilaterally on MLO and CC views (a,b,c,d). Fig. 6: Ultrasound of same patient in Figure 5 confirms diffuse glandularity (a,b,c). Hyperechoic fibrous breast tissue (*) arranged as per sonographic assessment of the female breast. Fig. 7: 17 year old young man noticed to have a growing lump in the left breast. Simple cysts - anechoic, thin-walled and demonstrating through transmission - measuring up to 11mm in the lateral part of retroareolar gynaecomastia/glandular elements. No solid, complex elements demonstrated. Page 26 of 35

Table 2: RCRBG and BI-RADS Imaging Classification Systems Compared Page 27 of 35

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Table 3: Risk factors for Male Breast Cancer Page 29 of 35

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Fig. 8: 75 year old gentleman presenting with a 4 month history of a lump in the right breast. Clinical grade 3/4. Father had breast cancer at age 75. Mammogram demonstrates a well-defined mass and some variable calcification at 9 o'clock in the right breast. Background gynaecomastia noted bilaterally. Right breast (a,c): M4. Left breast (b,d): M2. Ultrasound guided core performed: G3 Invasive Ductal carcinoma. Axilla normal at ultrasound assessment. At surgery, G3 IDC confirmed with associated highgrade DCIS. No lymphovascular invasion. Normal axillary nodes. Page 31 of 35

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Conclusion Importance of history taking, clinical examination and standardised categorization of clinical findings: P1: Normal, P2: Benign; P3: Equivocal; P4: Suspicious; P5: Benign. P1 and P2 findings in young individuals (< 40 years) - imaging may not be necessary. Correlation of imaging and clinical findings - is further investigation required? Gynaecomastia in its multiple forms: nodular, dendritic, diffuse. Risk factors for gynaecomastia are multiple. Gynaecomastia is NOT a precursor of breast carcinoma. Male breast cancer is rare - but significance of the occurrence of breast cancer in a first-degree male relative cannot be underestimated in family history screening. Personal information J Muscat, Specialist Trainee Medical Imaging Department, Mater Dei Hospital, Malta Clinical Fellow in Breast and Paediatric Imaging at BSUH NHS, UK jessica.muscat@gov.mt V Attard, Specialist Trainee Department of Pathology, Histopathology Section Mater Dei Hospital, Malta References 1. 2. Willett AM, Michell MJ, Lee MJR (eds). Best practice diagnostic guidelines for patients presenting with breast symptoms. London: Department of Health, 2010. Wilson R, Liston J. Quality assurance guidelines for breast screening radiology. Second Edn. NHSBSP publication no 59: Sheffield NHS Cancer Screening Programmes, 2011. Page 34 of 35

3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Taylor K, Ames V, Wallis M. The diagnostic value of clinical examination and imaging used as part of an age#related protocol when diagnosing male breast disease: An audit of 1141 cases from a single centre. The Breast 2013; 22: 268#272. Al#Allak A, Govindarajulu S, Shere M, et al. Gynaecomastia: A decade of experience. The Surgeon 2011; 9:255#258. Charlot M, Beatrix O, Chateau, F et al. Pathologies of the male breast. Diagnostic and Interventional Imaging 2013; 94:26#37. Madhukar M, Chetlen A. Multimodality imaging of benign and malignant male breast disease. Clin Radiol 2013; 68:e698#e706. Barter S, Dobson H, Sinnatamby R. Radiology- Integrated Training Initiative 4a Breast Module. Male Breast Disease. Barkeji M, Sher A, Murden M. Diagnostic guidelines for male breast cancer: Are we probing too deep? http://www.ejso.com/article/ S0748-7983(13)00092-9/abstract Maxwell A, Ridley N, Rubin G et al. The Royal College of Radiologists Breast Group breast imaging classification. Clin Radiol 2009; 64(1):624#627. Giordano SH, Cohen DS, Buzdar AIJ, et al. Breast carcinoma in men: a population based study. Cancer 2004; 101:51#57. Ruddy KJ, Winer EP. Male breast cancer: risk factors, biology, diagnosis, treatment and survivorship. Annals of Oncology 2013; 24:1434-1443. Doyle S, Steel J, Porter G. Imaging male breast cancer. Clin Radiol. 2011; 66:1079#1085. Colfry, AJ. Miscellaneous Syndromes and Their Management: Occult Breast Cancer, Breast Cancer in Pregnancy, Male Breast Cancer, Surgery in Stage IV Disease. Surg Clin N Am 2013; 93:519-531. Familial breast cancer: Classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer. NICE Clinical Guideline 164, 2013. Page 35 of 35