Artículo original Anales de Radiología México 2016 Apr;15(2):120-130.

Image characteristics of male disorders.

Santana-Vela IA1, Córdova-Chávez NA1, Putz-Botello MD1, Onofre-Castillo JJ2, Cuevas-Betancourt RE1, Arreozola-Mayoral MA1

Abstract OBJECTIVE: review the image characteristics of different disor- ders in differential diagnosis of benign and malignant processes of the male breast. Discuss the most common diseases seen at Hospital Christus Muguerza Alta Especialidad.

MATERIAL AND METHODS: we studied 40 patients in the pe- riod from January 2011 through December 2015. We searched the database of Hospital Christus Muguerza Alta Especialidad to identify patients who underwent studies of , ultrasound, and subsequent of mammary lesions.

RESULTS: the disorder most commonly observed is of the benign variety; was the most common diagnosis (60.9%). We detected 4.3% of patients with malignant conditions; usually palpable tumors reported as invasive ductal adenocarcinomas. 1Médico radiólogo del Hospital Christus Muguerza Alta Especialidad con calificación agregada en ima- DISCUSSION: in our population we found a majority of benign gen de mama. conditions, with gynecomastia the most common diagnosis. 2Médico radiólogo del Hospital Christus Muguerza The malignancy reported most commonly was invasive ductal Alta Especialidad. Jefe Departamento de Imagen- ología del Hospital Christus Muguerza. adenocarcinoma, a finding concurring with the specialized Hospital Christus Muguerza Alta Especialidad. Hidal- literature. We should take into account the BI-RADS reporting go Pte. # 2525 Col. Obispado, 64060, Monterrey, N. L. system, which does not make the distinction between female Received:March 18, 2016 or male gender. Accepted: March 27, 2016

CONCLUSIONS: benign mammary disorders are the most Correspondence common in male patients, and gynecomastia is the disorder of Ingrid Anel Santana Vela greatest incidence. Although malignant of the male [email protected]

breast is uncommon, it is important to take into account the This article must be quoted as various clinical and image manifestations which suggest this Santana-Vela IA, Córdova-Chávez NA, Putz-Botello diagnosis, to provide comprehensive and opportune treatments. MD, Onofre-Castillo JJ, Cuevas-Betancourt RE, Arreozola-Mayoral MA. Características por imagen de afecciones de la mama masculina. Anales de KEYWORDS: male breast; mammography; ultrasound Radiología México 2016;15(2):120-130.

120 www.nietoeditores.com.mx Santana-Vela IA, et al. Diagnostic imaging of the male breast

INTRODUCTION registry of the Dirección General de Información en Salud, in 2008, reported 0.1% deaths from Before puberty, the development of the breast a malignant tumor in males, which agrees with is similar in males and females. During puberty, the figures reported in the international literature. the male breast develops ductal structures but, Breast cases per age group and type, without stimulation, the lobular struc- identified in the Registro Histopatológico de tures do not grow. Thus, most of the male breast Neoplasias Malignas en México [Histopathology diseases involve ductal structures, but if there is Registry of Malignant Neoplasms in Mexico] long term estrogen stimulation, a disease associ- 2004-2006 in the Northern area of the country, ated to lobular structures may occur.1 indicated that breast malignant tumors are found with greater frequency in 70-year-old males or The normal male breast in the adult is made older (23.5%) being more common than invasive of skin, subcutaneous fat, atrophic ducts and ductal carcinoma (up to 75.6%).5 stromal elements with no Cooper ligaments. The lobular development of the male breast Imaging tests of the male breast takes place during stimulation processes with estrogen and and it is an uncom- Since incidence in males is very mon condition. Therefore, conditions associated low to justify screening, radiological exams for with lobular proliferation such as , the male breast are performed when symptoms phyloides tumors, invasive or in situ lobular are present. Although there are no established carcinoma are extremely rare in males, while protocols for the radiological evaluation of conditions associated with ductal and stromal the male breast in symptomatic patients, most proliferation such as gynecomastia, invasive authors agree that the initial test must be a mam- ductal carcinoma and papillary tumors may oc- mography with standard views used in women: cur in males.2 CC (craniocaudal) and MLO (midlateral oblique). Additional views must be obtained, such as Clinical framework and epidemiology magnification views and spot compression based on findings on the initial mammography In the last two decades the rate of males with and they must be studied with targeted imaging. breast disorders has increased from 0.8 to 2.4%, After the mammography, targeted ultrasound and currently accounting for around 1% of all breast MRI can be performed to analyze the area with . However, most of the men that have clinical disturbances or any focal disturbance in breast symptoms have benign disease, often the mammography.6 Improvement in diagnostic gynecomastia or skin lesions.3 The symptoms techniques such as mammography and ultra- referred by men in clinical examination are sound has led to greater accuracy in screening palpable areas, volume increase and breast for disturbances in the male breast, in spite of pain. Most of the lesions are benign, but caution the small rate (< 1%) of annual studies.7 should be used in the evaluation since breast cancer incidence in males has increased as much Lesions of the male breast as 26% in the last decades.3 Most of the men that come for breast imaging Breast cancer in males is an uncommon clinical studies refer palpable tumors, breast enlargement entity, accounting for around 1% of cancer death or sensitivity. It is crucial to establish the differ- in males.4 In Mexico, according to the death ence between benign and malignant tumors, to

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decrease the patient`s anxiety and avoid unnec- and ketoconazole may displace sexual estrogen essary procedures. Most of the lesions found in from the hormone binding globulin resulting in the male breast are benign, with gynecomastia elevation of free estrogen concentrations.10 It as the most common while malignant lesions is the most common cause of in account for less than 1% of the total lesions in males; clinical manifestations include palpable males. Other conditions may arise from the skin, abnormalities, focal pain, burning sensation. It subcutaneous fat, blood vessels, lymphatics and can be unilateral or bilateral and clinical loca- 3 nerves. Diseases such as , fi- tion is subareolar. brocystic changes and adenosis are uncommon in males.8 Among the most common conditions On mammography three patterns are found: nodular, dendritic and diffuse. The early florid we can find bilateral gynecomastia (56%), unilat- changes have nodular appearance in mammo- eral gynecomastia (25%), pseudogynecomastia grams and represent hyperplasia of the intraductal (8), lipomas (4%) or normal studies (3%).9 epithelium with stromal edema. In this phase, the symptoms last less than a year. On ultrasound, a Gynecomastia subareolar nodule with low level echoes with a disc or fan shape is found and may be hypervas- Excessive growth of breast tissue in males. It may cular from stromal proliferation.3 If the symptoms be physiological or pathological. 10 Physiological persist more than a year, the quiescent phase may gynecomastia is found in three age groups: new- be seen, associated with the dendritic growth borns, adolescents and older adults. Hypertrophy pattern found in mammography and ultrasound, of the neonatal breast is a transient condition and where finger-like projections are seen, either common in up to 90% of all newborns (females radial or in the shape of flames, extending to the and males). It is caused by elevation of retroareolar tissue. The late histopathologic stage that cross the placenta. Gynecomastia of puberty is characterized by hyalinized stroma, consistent 3 can be found in 3.9-64.6% of children between with fibrous gynecomastia. The third pattern is diffuse gynecomastia that is associated with the ages of 10 to 13 years, with a typical onset exposure to exogenous estrogens.3 6 months after secondary sexual characteristics appear. A specific cause is unknown.10 Pseudogynecomastia Pathologic gynecomastia may be caused by an The male breast grows as a result of excessive increase in estrogens, decreased testosterone, accumulation of fatty tissue with no glandular medications, drug abuse or it could be idio- tissue. It is more common in older adults.11 pathic. The increase in estrogen concentrations may be due to testicular tumors (Leydig tumors) Lipoma or to adrenocortical tumors. The increased aro- matization of estrogen precursors may result in It is the second most common benign lesion of increased estrogens and be associated to gy- the male breast. These lesions are fat contain- necomastia from Sertoli cell tumors, tumors of ing and well defined. They present as palpable the testicular sexual cord, germinal cell tumors, tumors but, in general, they are asymptomatic. , hyperthyroidism or Klinefelter On ultrasound they are well circumscribed syndrome. Disorders with reduced testosterone masses, uniform, isoechoic, hypoechoic or hy- are those such as aplasia or congenital testicular perechoic, with a thin echogenic capsule. On hypoplasia, trauma, testicular torsion or viral mammography they have a fine capsule that orchitis. Medications such as spironolactone allows visualization of the radiolucent lesion.12

122 Santana-Vela IA, et al. Diagnostic imaging of the male breast

Epidermal inclusion cyst or more ducts. It may be a palpable finding or there may be discharge. Mammograms It is common in males, accounting for the third show dense tubular structures converging in the most common benign lesion of the male breast. areola-nipple complex; they may have calcifica- It is the result of the obstruction of a hair follicle tions. On ultrasound they are tubular branched or can be post-traumatic, after an insect bite or structures, anechoic, full of discharge and that surgery. Physical examination shows typically may contain cell debris; they may be central palpable lesions, and the glandular orifice can be or peripherally located, the latter favoring a seen as a black dot on the tumor. On ultrasound malignancy.16 they appear as an ovoid tumor, circumscribed, and hypoechoic. On mammography it is an Hamartoma ovoid tumor, circumscribed, with high density 12 and adjacent to the skin. They are benign, mixed, circumscribed lesions that contain glandular elements, fibrous and fatty tissue. It is uncommon, with a 0.1-0.7% reported incidence. There may be invasive ductal It is the infection of breast tissue that can lead to carcinoma or in situ ductal carcinoma in remote an abscess and areas of duct ectasia. On mam- cases. On mammography lesions are ovoid, well mography it is found as a unilateral growth of circumscribed with lucencies, dense elements the breast, with trabecular and skin thickening. that represent glandular and fibrous tissue. On An abscess may be found as an irregular tumor, ultrasound the echotexture may be hyperechoic, with or without calcifications, so it is difficult to isoechoic or heterogenous.17 differentiate from a malignancy. It is important to establish a correct correlation of the clinical Costochondritis findings with the patient´s history, in order to give 13 an accurate diagnosis. It is a self-limited condition defined as an in- flammation of the costochondral or costosternal Intramammary lymph node junction, usually in multiple levels with no inflammation or induration. Pain is elicited with It is a well-defined nodule in the upper outer intentional palpation of the affected cartilage and quadrant of the breast, with a radiolucent may irradiate to the chest wall.18 center. It is considered pathognomonic of an intramammary lymph node.14 On ultrasound Cancer reniform tumors are described with fatty hilum, a hypoechoic cortex and echogenic hilum. They Breast cancer in males accounts for approxi- may be found anywhere in the breast, but they mately 1% of all breast cancers and around are more common in the upper outer quadrant, 0.17% of all cancers in males. The average age especially towards the axillary extension; they of presentation is 59 years.3 It presents as an 15 range from 0.3 to 1 cm in size. irregular tumor, subareolar, with retraction of the nipple and skin, ulceration and thickening. Duct ectasia Thelorrhagia is reported up to 25%.3

It predominantly involves the retroareolar ducts Risk factors to develop male breast cancer and is defined as a non-specific dilatation of one include advanced age, chronic exposure to

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estrogens, BRCA2 genetic predisposition, crypt- lation seen at the Hospital Christus Muguerza orchidism, testicular lesions, liver dysfunction Alta Especialidad. and .3 In 85% of cases it has been shown to be an invasive ductal ad- DESIGN enocarcinoma, with carcinoma in situ in half the cases.3 Most of the patients present with a Descriptive, observational, cross-sectional, ret- palpable tumor and it may be associated with rospective study. gynecomastia; however, gynecomastia is not recognized as a risk factor for the development Inclusion criteria of carcinoma.3 All male patients who had mammography or On mammography tumors appear with high ultrasound and interventional procedures from January, 2011 to December, 2015 were included density, they are irregular, spiculated and with in the study, regardless of age. lobulated margins. A remarkable feature in male breast cancer is that microcalcifications are not MATERIAL AND METHODS documented in most of the cases, for they are only found in 13 to 30% of cases and they are Mammograms were performed with Hologic not as thick and are less linear than those seen Selenia® y Hologic Selenia DimensionsÒ equip- 3 in female cancers. On ultrasound, a solid, ment in mid lateral oblique (MLO) view and hypoechoic tumor is found, irregularly shaped, additional views according to the case. For 3 spiculated or with lobulated margins. complementation, Phillips iU22® and Phillips Epic 5® ultrasound equipment was used with a Treatment of male breast cancer lineal transducer of 12 and 18 MHz, using color Doppler and qualitative elastography. Surgical treatment includes simple or modified mastectomy with axillary assessment and senti- Protocol for interventional procedures in male nel node or biopsy.3 at the Hospital Christus Muguerza Alta Especialidad OBJECTIVE In some patients a percutaneous biopsy is per- Imaging studies of the male breast are used formed in real time using a BARD gun, with a for the evaluation of clinical anomalies such 14 gauge needle. Approximately 6 fragments are obtained from the lesions, which are all placed a breast growth, palpable tumors, pain, nipple in jars to be sent to the Pathology department for discharge or skin lesions. Since this is a disease definitive study. that is becoming more common, it is important to know the differences between benign and Each study was examined by three radiologist malignant findings. Imaging and pathological certified on breast imaging of our institution. characteristics were reviewed in the differential They evaluated the findings documented on diagnosis of benign and malignant tumors in the mammography and ultrasound. In cases where male breast. The most common conditions will an interventional procedure was performed, be discussed as well as the different reasons to the imaging and histopathology findings were perform breast imaging studies in the male popu- assessed.

124 Santana-Vela IA, et al. Diagnostic imaging of the male breast

Analysis Table 1. Imaging diagnostics

Statistical analysis: The statistical programs from Disease Number of % Mean age cases Microsoft Office Excel® 2010 were used to ana- lyze the results. Gynecomastia 28 60.9 42 Lymph nodes 5 10.9 41 Others 3 6.5 50 Ethics Mastitis 2 4.3 40 Costochondritis 2 4.3 35 Patients who underwent interventional pro- Pseudogynecomastia 2 4.3 56 cedures were requested to sign an informed Invasive ductal 2 4.3 73 consent form in which the physician or tech- adenocarcinoma nologist explained the risks and care after the Ductal ectasia 1 2.2 17 procedure. A report was made in cases where Inclusion cyst 1 2.2 29 a complication was documented and follow-up was based on the severity of symptoms.

RESULTS matory process of the breast was found in 4.3% (n=2), as in patients with costochondritis. Some Forty male patients who came to our breast patients presented because of mammary gland diagnosis center to have an imaging study were growth and were diagnosed as having pseudo- found, accounting for 0.21% of the total number gynecomastia (4.3%, n=2). Another patient 4.3% of breast studies performed in our hospital. Out (n=2) had palpable tumors and nipple retraction of 15,218 mammograms, 26 were performed in with a diagnosis of invasive ductal adenocarci- males (0.17%) and of a total of 17,915 breast noma. In ductal disease we saw a patient with ultrasound studies, 45 were in the male popula- ectasia of retroalveolar predominance (2.2%) tion (0.25%) in the study period. and among skin and adnexal diseases one pa- tient was documented (2.2%) with a diagnosis of When imaging studies were performed in our epidermal inclusion cyst (Table 1, Figures 1-6). diagnostic center, ages ranged between 10 (in Considering the frequency documented in our the youngest patient) and 92 years, with a mean study, gynecomastia was found to be the most of 42 years of age ( ). The reasons for hav- Table 1 common diagnosis in our population: 20 patients ing the study were documented for each patient had unilateral disease (71.5%) while only 8 pa- and the most common were palpable areas, tients had bilateral disease (28.6%). pain, breast tissue growth, palpable tumors and . Laterality of the lesions was evaluated in this work: 37% (n=17) were found in the left breast, The diagnoses reported in order of frequency were: gynecomastia (60.9%, n=28), palpable 37% (n=17) in the right breast and 26% (n=12) nodes with focal or diffuse cortical thickening presented lesions in both breasts (Table 2). Con- (10.9%, n=5) and other miscellaneous distur- sidering the characteristics and diagnosis of the bances (6.5%, n=3) such as hamartoma (n=1), lesions, a BI-RADS category was assigned. Most deep giant lipoma with pectoral muscle involve- of the patients were BI-RADS-2, who were ap- ment (n=1) and prominent and palpable fatty proximately 36 patients accounting for 90% of lobule (n=1). Concerning frequency, the inflam- the population studied. In BI-RADS-4 category

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A A

B

B Figure 1. Right side gynecomastia in quiescent pha- se. Left pseudogynecomastia. BI-RADS-2 category. 62-year-old male with palpable tumor in the right breast. History of prostate cancer. A) MLO mam- mogram of both breasts: retroareolar tissue in flame shape. Subcutaneous tissue in the left breast with no disturbances. B) Right breast ultrasound: hyopechoic retroareolar radial tissue in the right breast, homo- genous tissue, of mixed echotexture, fibroglandular Figure 2. Abnormal intramammary lymph node. BI- predominance located in the retroareolar area. RADS-4 category. 39-year-old male with palpable tumor in the right breast. A) Lateral view in mam- mography of the right breast: isodense nodule with radiolucent center, associated with trabecular thicke- ning. B) Right breast ultrasound: intramammary lymph there were 2 patients (5%), one of them had node with focal cortical thickening, avascular, with cortical focal thickness and another one in cat- qualitative elastography showing hard consistency. egory 4C had a spiculated tumor associated with calcifications and abnormal lymph nodes. For DISCUSSION category BI-RADS-3 and 5 we found one patient in each (2.5%, respectively), and we found no Due to an increased incidence of male breast cases in category BI-RADS-1 (Table 3). diseases in the last decades, including malig-

126 Santana-Vela IA, et al. Diagnostic imaging of the male breast

A A

B B

Figure 3. Deep right giant lipoma. Left pseudogyne- comastia. BI-RADS-2 category. 57-year-old male with palpable tumor in the right breast. A) MLO mammo- Figure 4. Mastitis. BI-RADS-2 category. 42-year-old gram of both breasts and CC of the right breast: radio- male referred for percutaneous biopsy with BI-RADS- lucent tumor involving the pectoral muscle. In the left 4A report. A) Ultrasound: tissue with heterogenous breast subcutaneous tissue with no disturbances. B) echotexture, slight increase in vascularization. B) Right breast ultrasound revealing a tumor of uniform Percutaneous biopsy; histopathology report: unspe- echotexture with fat predominance. cific chronic mastitis. nant tumors, it is important that the radiologist In our study population we found mostly benign should be familiar with the spectrum of diseases disease, where gynecomastia was the most com- and imaging manifestations in order to establish mon diagnosis. The most frequently reported timely diagnosis. During our study, we were able malignancy was invasive ductal adenocarcino- to see variable diseases of the male breast and ma, consistent with literature reports and studies their wide distribution in different age groups, conducted in other hospitals. knowing that the disease may be present from very early stages in life all the way to old age. Regarding reason for consultation we found In order to conduct and draw conclusions from a agreement with the world literature. It is impor- breast study, the BI-RADS report system must be tant to keep the clinical history of patients in considered, which makes no distinction between mind with the goal of helping the radiologist to genders. When our patients were classified using suspect a likely diagnosis. this system, the most common category was BI-

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A B C

Figure 5. Invasive ductal adenocarcinoma. BI-RADS-5 category. 86-year-old male referred because of CT scan finding. A) CT scan with IV contrast, axial view: tumor in right subcutaneous tissue of the anterior chest with important contrast enhancement. B) Mammogram, MLO view of the right breast, retroareolar area: dense tumor with spiculated border associated with low density microcalcifications. In the upper quadrant another lesion with similar features. C) Right breast ultrasound, retroareolar area: heterogenous tumor, predominantly hypoechoic with irregular borders and microlobulations in the lower outline, with echogenic halo. With color Doppler there is increased intranodular and peripheral vascularization. It is associated with nipple retraction.

Table 2. Laterality of lesions

Laterality Right Left Both

Number 37% (n=17) 37% (n=17) 26% (n=12) of lesions

Table 3. BI-RADS category

BI-RADS category 1 2 3 4 5

Total number of 0 36 1 2 1 patients (90%) (2.5%) (5%) (2.5%)

accounts for the greatest incidence of cases. Is Figure 6. Epidermal inclusion cyst. BI-RADS-2 ca- spite that malignant disease of the male breast tegory. 29-year-old male with palpable nodes in the right breast dating 3 days. Breast ultrasound: ovoid is not common, it is important to keep in mind epidermal lymph node, circumscribed, hypoechoic, the different clinical and imaging manifestations with diffuse increase of the adjacent fat, suggesting that may suggest this disease in order to provide association with inflammatory process. patients with timely and integral treatment.

RADS 2, with benign findings and no probability It is very important to know about the different of a malignant lesion. radiological appearances of the different dis- eases that may involve the male breast, as well CONCLUSION as to learn to use diagnostic tools properly. The initial study must be a mammography; however, Benign breast disease is the most common one ultrasound must be recognized as a powerful in patients of the male gender; gynecomastia modality (together with mammography) to dif-

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