Radiologic evaluation of lumps in the male breast

Introduction

Investigation of lumps in the male breast is a common reason for referrals, most of which are made directly from primary care physicians. At our Breast Imaging Center patients are not scheduled for consultation with a breast surgeon before imaging; the radiologist reads the mammograms and decides whether supplemental ultrasound and fine needle aspiration cytology (FNAC) should be performed. While performing the ultrasound procedure, the radiologist will also do a clinical examination of both breasts and axillae.

The male breast consists mainly of glandular tissue, subcutaneous fat, and skin. Mammary glands are located sub- and retroareolarly. Retroareolar breast tissue is a normal finding, particularly in the elderly (1). Gynecomastia is defined as breast tissue exceeding 2 cm measured on mammography or ultrasound imaging. It is the most common cause of lumps in the male breast, and is caused by disturbed balance of male and female hormones (2).

Gynecomastia is the most common cause of male breast lumps (3,4) and is classified into three patterns according to mammographic appearance: (i) nodular (florid) gynecomastia (Fig. 1a) is often reversible within 1 year if the cause is treated, and the breast is usually tender; (ii) a dendritic pattern (Fig. 1b) is irreversible, being characterized by more fibrosis and less tenderness; (iii) diffuse glandular (Fig. 1c) gynecomastia is strongly affected by estrogen, with a mammographic appearance resembling the female breast. OPEN IN VIEWER

In obese men, breast enlargement is often caused by proliferation of adipose tissue, a condition termed pseudogynecomastia which is often bilateral.

Male breast cancer (Figs. 2 and 3) is uncommon, and is usually found in adults aged older than 60 years. In most cases the exact cause is unknown, but certain risk factors do exist, in particular BRCA2-mutations and Klinefelter syndrome (5), as well as obesity, testicular retention, chest irradiation, and hyperthyroidism (6,7). On the contrary, gynecomastia is not a risk factor for developing male breast cancer (8). OPEN IN VIEWER

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Fig. 3.

A 64-year-old male patient referred for evaluation of a firm fixed mass in the right breast. Mammography shows a solid tumor with irregular margins and retraction of the mamilla, confirmed to be an invasive ductal carcinoma.

In women with breast lumps, the triple diagnostic approach consisting of clinical examination, imaging, and FNAC (or better core-needle biopsy, CNB) is recommended in numerous guidelines (9), including those of the Norwegian Breast Cancer Group (NBCG) (10). In contrast, no Norwegian guidelines for imaging of male patients with breast lumps exist. To our knowledge, there is also a lack of international consensus on the use of mammography and ultrasound in the evaluation of men with breast symptoms. The female guidelines are not easily adaptable to the male population, who rarely suffer from breast cancer. Thus by adhering to the female breast cancer guidelines and personal intuition, radiologists might have performed unnecessary imaging and FNAC on a significant number of men with breast lumps. Hence, we reviewed the radiological findings of breast lumps in 539 men to assess whether performing ultrasound and FNAC is necessary when mammography shows classical gynecomastia.

Material and Methods

This study has been approved by the Committee for research and quality assurance in the Southern and Eastern Norway Regional Health Authority.

We have retrospectively collected data on male patients referred for breast imaging in Vestre Viken Health Trust during the period from 1 January 2011 to 31 December 2013. The vast majority of the patients were referred to mammography by their general practitioner.

Digital mammograms (Mammomat Inspiration, Siemens Healthcare, Erlangen, Germany) of 539 male patients were reviewed retrospectively. In all cases, one mediolateral oblique projection was obtained of each breast. A marker was attached to the skin of patients with a palpable lump – making it possible to correlate it to the mammographic findings. All mammograms were reviewed by two radiologists in consensus.

Ultrasound examinations were performed in most of the patients to reassure the diagnosis from the mammograms. The ultrasound procedure was conducted by one radiologist using a 6–15 or a 5–17 MHz linear array transducer (Logiq E9, GE Healthcare, Milwaukee, WI, USA or Philips iU22, Philips Healthcare, Bothell, WA, USA).

When both mammography and ultrasound were performed, the images were analyzed by the same radiologist. Each record contained information about the radiologic findings; it was noted whether the mammograms were normal, if gynecomastia or other benign changes were present, or if there were any malignant characteristics.

FNAC was performed in 355 patients, and the procedure was ultrasound-guided in all of them (Sterican 25 G needle 0.5 × 40 mm, B. Braun, Melsungen, Germany). If pathological conditions other than gynecomastia were suspected on mammograms, FNAC was always performed. Furthermore, FNAC was performed on several patients to reassure the diagnosis despite mammograms and ultrasound suggesting classical gynecomastia. As no uniform guidelines or criteria for performing FNAC exist, there were no selection criteria. The decisions were made at the radiologist’s discretion.

Gynecomastia was diagnosed based on characteristic mammographic findings: A fan-shaped opacity extending from the nipple which gradually becomes more transparent towards the surrounding adipose tissue is typically found (11,12). Male breast cancer is usually seen subareolar and eccentric to the nipple (11). Furthermore, malignant lesions are usually characterized by more distinct margins and higher density. Most other benign changes usually originate from skin or subcutaneous tissue (e.g. lipomas, epidermal cysts, and fat necrosis). For each patient we recorded whether ultrasound and FNAC were performed, as well as the final diagnosis after all diagnostic procedures were completed.

Referrals to the Breast Imaging Center often contained incomplete information. In cases where medications and clinical findings were included, this information was registered and used in the study.

Results

A total of 539 male patients were referred for investigation of a breast mass between 1 January 2011 and 31 December 2013. The mean age of patients was 54.9 years (median age, 58 years; age range, 15–91 years). Forty-eight percent were aged over 60 years. The mean age among patients with breast cancer was 64.2 years (median age, 64 years; age range, 42–89 years). Of the patients, 80.1% were referred due to an enlarged breast or a breast mass. Tenderness was reported in the referrals of 265 patients, and a firm mass in 116 patients.

In all patients, bilateral mammography was performed. Furthermore, mammography was supplemented by ultrasonography in 483 cases, and FNAC was done in 335 patients. In addition, 12 core biopsies and two surgical excision biopsies were taken (Fig. 4). Benign diagnoses, including gynecomastia, were made in 452 patients. Ten patients received a malignant diagnosis (Table 1). OPEN IN VIEWER

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Table 1.

An overview displaying results from all of the investigations during the 3-year observation period, divided into normal, benign, and malignant findings.

Findings	Cases (n)
Normal	77
Benign diagnoses (n = 452)
Gynecomastia	350
Unilateral	213
Bilateral	137
Pseudogynecomastia	39
Lipoma	34
Atheroma	11
Fat necrosis	10
Abcess	2
Other*	6
Malignant diagnoses (n = 10)
Invasive ductal carcinoma (IDC)	6
Metastasis – malignant melanoma	1
Skin tumor – malignant melanoma	1
Metastasis – squamous cell carcinoma	1
Lymphoma	1

*

The following findings are included under “Other” benign diagnoses: eczema (n = 1), hemangioma (n = 1), hematoma (n = 1), pilomatrixoma (n = 1), schwannoma (n = 1), and vein (n = 1).

In total, 350 of the 539 patients (mean age, 55 years; median age, 60 years; age range, 15–91 years) were diagnosed with gynecomastia by a characteristic appearance on mammography. Further evaluation was performed in almost all of these subjects; ultrasonography was done in 340 (97%) of the patients and FNAC was performed in 261 patients (75%) without altering the original diagnosis. Biopsy was taken in four patients (1%), but the main diagnosis remained unchanged after the biopsy results. In one patient, an additional diagnosis was made (eczematous reaction).

After performing mammography and ultrasound, the diagnosis remained uncertain in 13 patients. However, supplemental FNAC or biopsy confirmed benign diagnoses in all of these patients. Furthermore, one patient was diagnosed with a fibroadenoma at a private radiology institute, and cytology demonstrated possibly irregular cells. The patient was referred to our Breast Imaging Center for further investigation. Additional imaging was performed and demonstrated typical findings consistent with gynecomastia. Since cytology was inconclusive, a breast biopsy was performed, and the diagnosis was confirmed. Contrary to women, fibroadenoma of the breast rarely occurs in men.

A complete list of the benign diagnoses is displayed in Table 1.

Among the subjects with malignant diagnoses, six suffered from infiltrating carcinomas, one of which was bilateral. Furthermore, one patient was diagnosed with a metastasis from a malignant melanoma (the patient had been recurrence-free for 11 years after the initial treatment and was referred due to a recently discovered breast mass); a skin tumor which was shown to be a malignant melanoma was found in another patient; one subject was diagnosed with metastasis from a squamous cell carcinoma; finally, one patient suffered from a large B-cell lymphoma. In all of these patients, malignant imaging features were found in both the mammogram and the ultrasound examination (Table 1).

Discussion

Benign changes were seen in 83.9% of the patients who underwent mammography as part of the investigation of a breast lump. Gynecomastia comprised 77.4% of the benign diagnoses. In agreement with previous reports, lipoma was the second most common benign tumor in the male breast (11). In 14% of the cases, imaging did not reveal any abnormalities. Ten patients (1.9%) received a malignant diagnosis, six of whom (1.1%) were diagnosed with breast cancer (infiltrative ductal carcinoma). Our findings suggest that breast cancer is a rare diagnosis among men with breast lumps, and similar numbers are obtained from other countries (3,4,13).

Importantly, none of the malignant cases were interpreted as benign lesions on mammography. Indeed, a negative predictive value (NPP) larger than 99% for excluding male breast cancer by mammography has also been found in other studies (3,14,15). Furthermore, both the sensitivity and the specificity of mammography has been estimated to be more than 90% (14). Hence, mammography is an accurate modality for distinguishing benign and malignant causes of male breast lumps.

Mammography is a reliable method for detecting gynecomastia due to the typical morphology of gynecomastia, characterized by a fan-shaped opacity extending from the central retroareolar area towards the surrounding adipose tissue (Fig. 1). In contrast, breast cancers are usually located subareolarly and eccentric to the nipple (16,17) (Figs. 2 and 3). Malignant lesions typically appear more discrete and solid, and retraction of the nipple may occur (16). Metastases to the breast usually occur in widespread malignancies, commonly presenting as large, round, solid, and well demarcated densities on mammograms. Primary tumors are often lung cancers, prostate cancers, or malignant melanomas.

The patient record and clinical examination often gives important information about the cause of a breast lump. Hormonal abnormalities as well as breast cancer must be ruled out. Manual testicular examination should always be performed. Referral should include information about whether the mass is unilateral or bilateral, its consistency (soft, firm, mobile, fixed) as well as the tenderness. The presence of enlarged axillary lymph nodes should also be noted.

There are particular characteristics that point towards benign diagnoses. The largest risk factor for both female and male breast cancer is age. Taylor et al. (15) found that only 3% of male breast cancers occur in men under the age of 40 years. Increased amount of breast tissue is a common physiological finding in adolescent boys from puberty until the age of 18 years (18–20), and these changes will spontaneously regress with age (19). In our material, four patients were aged under 18 and overweight. Pseudogynecomastia is frequently found in overweight boys (21) and does not warrant radiologic evaluation. In general, it has been suggested that radiologic evaluation of lumps should not be routine in men aged less than 40 years (15,18).

Gynecomastia may also be a side-effect of medication; it is reported that gynecomastia could be related to misuse of prescription drugs in up to 25% of the patients (22). Patients using anabolic steroids are often at risk of developing gynecomastia (23). Furthermore, several cardiovascular medications (spironolactone, digitalis, nifedipine, and other calcium blockers), hormone therapy for prostate cancer, H2-blockers, HIV antiviral medication, and first-generation antipsychotics may cause gynecomastia (6). Some studies also suggest an association between recreational use of cannabis and gynecomastia, but the findings are conflicting (22). Gynecomastia is common in several groups of patients, including those with cirrhosis of the liver, severe renal failure, and testicular atrophy, as well as hyperthyroidism (24).

If the clinical investigation suggests a probable cause of the gynecomastia, this cause should be treated, and the patient should be re-examined at a later stage. Initially, imaging is not necessary in these cases (3). If the clinical information does not reveal an underlying cause, liver and thyroid function tests as well as creatinine should be measured. If the latter tests are normal, further hormonal investigations should include estradiol, testosterone, SHBG, LH, FSH, hCG, and prolactin (25).

When mammography is performed, we suggest that the following three questions should be asked while analyzing a mammogram:

– Is the breast normal?

When the mammographic appearance is inconsistent with gynecomastia, FNAC or CNB might be of important diagnostic value. Some of our patients were diagnosed with benign conditions with uncertain findings on mammograms and ultrasound; a Schwannoma, hemangioma, and pilomatrixoma were found. In these cases, FNAC or CNB was required for the final diagnosis. All of these lesions were later surgically excised, but the diagnoses remained unaltered. We also observed breast abscesses, and these lesions had a characteristic clinical and sonographic appearance, although abscesses are hard to identify on mammography alone.

Despite the fact that breast cancer is rare in men, the incidence of male breast cancer in the USA has increased from 1973 to 1998 (26). However, data from the Cancer Registry of Norway shows a stable rate of 0.4 per 100,000 person years during all 5-year periods from 1983 to 2007 in Norway (27). On the other hand, breast cancer was found in 38 Norwegian men in 2013, and 28 were diagnosed with cancer in both 2011 and 2012. In contrast, only 15 and 13 were diagnosed in 2009 and 2010, respectively. This shift can be due to random variation, but we are eager to investigate the incidence of male breast cancer in the years to come.

Our results reveal that unnecessary imaging and FNAC has been performed in a large proportion of patients with clinical characteristics and mammographic findings suggesting benign diagnoses. In general, there is a risk of overuse and defensive medicine when guidelines are lacking (28). Hence, improving the routines for imaging of tumors in the male breast is important; overuse of resources can be reduced, and costs can be avoided.

In conclusion, performing supplementary ultrasound and FNAC is redundant and contributes to unnecessary costs when mammograms show classical gynecomastia.