Incidental unilateral and bilateral ductal carcinoma in situ encountered in the surgical management of young male gynecomastia

Abstract

BACKGROUND:

The increased risk for malignant tumors associated with male gynecomastia has been well established and many authors have reported cases of concurrent gynecomastia and ductal carcinoma in situ (DCIS) in the same breast. Synchronous bilateral breast cancer in association with gynecomastia is exceptionally rare. We aim to report and evaluate the management outcome of 5 cases of gynecomastia associated with DCIS (1 bilateral and 4 unilateral).

METHODS:

A retrospective database analysis of the surgical treatment outcome of 74 male patients who had gynecomastia was done. A bilateral subcutaneous nipple-preserving mastectomy approach was done to all. Histopathology reports were reviewed.

RESULTS:

74 patients diagnosed and treated for gynecomastia were included. The incidence rate of gynecomastia in our hospital male patients was 0.17%. The mean age was 22 years, range 17–29 years. Five (6.76%) patients were found in histopathology specimens to have DCIS, 1 patient (23 years old) had bilateral DCIS of low grade, 4 patients had unilateral positive involvement, 3 had right breast DCIS, and 1 had left breast DCIS, and all were of low-grade papillary subtype. The incidence of ductal carcinoma in situ among our series gynecomastia patients was 6.76%.

CONCLUSION:

We conclude that gynecomastia is a benign breast disease but recent reports had described malignant variants, mostly DCIS, including 5 young males in our series. Therefore, regardless of the age group, histopathological examination of the resected gynecomastia tissue should be carefully done in all patients. Further evidence-based studies are needed to investigate the optimum management of incidental DCIS in gynecomastia specimens.

Introduction

Male gynecomastia is a benign over-development of the male breast glandular tissue due to a disorder of the endocrine system in which there is an increase in estrogen influence and a decrease in testosterone effects that lead to an increase in the size of the breast tissue. However, pathological conditions, congenital and endocrine diseases, tumors, and drugs should be ruled out. The exact cause of gynecomastia is unknown in about 25% of cases. Most adolescent males have asymptomatic gynecomastia during puberty which is attributed to the influence of hormonal changes during puberty while the prevalence of symptomatic gynecomastia is reported to be much lower [1].

The prevalence of gynecomastia in men has increased in recent years as evident by published clinical reports, but the epidemiology of the disorder is still not fully understood. New cases of gynecomastia are common in three different age populations: newborns (60–90% of male babies and most cases resolve spontaneously), adolescents (50–70%), and men older than 50 years of age (24–65%). Senile gynecomastia was reported in men between the ages of fifty and eighty [2].

In the majority of cases, gynecomastia does not require treatment. In cases of idiopathic pubertal gynecomastia, reassurance and an explanation of the natural course of gynecomastia is usually sufficient [3]. In all ages, if a specific cause of the gynecomastia is diagnosed and treatment is initiated during the initial phase, the breast hypertrophy may regress. If gynecomastia persists for over a year, medical treatment will be unlikely to achieve regression, and surgery will be required if the patient wants a correction [4].

The distinctive feature of gynecomastia is an enlargement of the male breast which is rubbery or firm glandular subcutaneous tissue. It could be unilateral or bilateral in which patients could present with asymmetrical or unilateral findings. Milky nipple discharge is rarely reported, but could occur in patients affected by a prolactin secreting tumor [5]. Males who develop gynecomastia may experience anxiety and stress due to the concerns of breast cancer despite the very low reported incidence [6].

It is usually diagnosed by a detailed history and breast physical examination [7].

Mammography can differentiate true gynecomastia from a mass that requires tissue sampling to exclude malignancy, and it was found to be fairly accurate in distinguishing between malignant and benign male breast diseases and can substantially reduce the need for biopsies. The sensitivity and specificity of mammography for benign and malignant breast conditions exceed 90%; however, the positive predictive value for malignant conditions is low (55%) because of the low prevalence of malignancy in patients presenting with gynecomastia [8] (Fig. 1).

Surgical approaches to the treatment of gynecomastia include subcutaneous mastectomy, liposuction-assisted mastectomy, laser-assisted liposuction, and laser-lipolysis without liposuction. Complications of mastectomy may include hematoma, surgical wound infection, breast asymmetry, changes in sensation in the breast, necrosis of the areola or nipple, seroma, noticeable or painful scars, and contour deformities [9].

The traditional surgical treatment for gynecomastia is a sharp excision of the mammary gland through a semicircular incision on the edge of the areola. Cases with skin redundancy may be managed by various techniques; liposuction may be used as the only modality or used as an adjunct to the other surgical techniques [10].

The pathological examination is aimed primarily at detecting atypia, carcinoma in situ, or invasive breast cancer. The need for pathological examination in patients younger than 20 years without pathological findings is questionable [11].

Patients with gynecomastia have a favorable prognosis. These patients present with two main concerns: ruling out breast cancer and cosmetic correction. The first concern is adequately addressed by following the appropriate diagnostic evaluation. Breast cancer is rare in males, representing less than 1% of all cases of breast cancer; only 1% of mammograms in men reveal breast cancer. Therefore, the decision to treat and the choice of treatment should be based on the degree to which this condition has affected the quality of life and mental health of patients and on their desire for cosmetic correction [12].

The increased risk for malignant tumors with gynecomastia has previously been described in some case-control studies. It has been claimed that gynecomastia is more common among men who later develop testicular cancer and breast cancer. Sometimes the treatment of malignancies may be the cause for gynecomastia, such as estrogen treatment in prostate carcinoma and cytostatic treatment in various malignancies. In a cohort study, Olsson et al. [13] found that there is a significantly increased risk of testicular cancer and squamous cell carcinoma of the skin in men who have been operated on for gynecomastia.

Male ductal carcinoma in situ (DCIS) is rare and usually presents as a palpable mass or bloody nipple discharge on the affected side. It has been reported in conjunction with gynecomastia in the same breast, and many authors have reported cases of concurrent gynecomastia and DCIS in the same breast, in male patients. Synchronous bilateral breast cancer in association with gynecomastia is exceptionally rare [14–19].

In this paper, we aim to report and evaluate the management outcome of 5 cases of gynecomastia associated with DCIS (1 bilateral and 4 unilateral).

Materials and methods

A retrospective database analysis of the surgical treatment outcome of 74 Saudi Arabian patients affected with gynecomastia between January 2003 and December 2012 was done. All patients were referred to the general surgery outpatient clinic in a public health general hospitals in Medina, Saudi Arabia.

All patients were reviewed by a detailed history and physical examination.

The preoperative workup, selection of patients, surgical procedures, and follow-up were carried out by the same surgical team. All patients had the same preoperative workup (complete blood count, coagulation profile, blood chemistry, sex hormones test, chest x-ray, electrocardiogram, bilateral breast ultrasound, fine needle aspiration). Patients who presented with large breasts, 67 (90.5%), had mammography done. The surgical procedure and postoperative care were carefully discussed with the patients, and all patients were admitted to the surgical floor one day before surgery, and discharged on the second postoperative day.

The procedure was done under general anesthesia, supine position, a bilateral subcutaneous nipple-preserving mastectomy approach was done to all patients. A drain was used in all patients and was removed when collecting less than 50 ml per day. The skin incision was closed in a cosmetic subcuticular pattern in all patients. All patients were given cefazolin prophylactic antibiotic.

The computerized database medical records were reviewed and analyzed for preoperative factors such as age, duration of the disease, and postoperative factors like wound infection, wound scar, the histopathology report of the specimen. The collected data was recorded on a computerized database file, and statistical analysis was performed using the Statistical Package for Social Science (SPSS) program (Release 22).

Results

74 Saudi Arabian patients affected by gynecomastia were included. At the same period, the overall total number of male patients treated in our hospital for various diseases was 42,827. The incidence rate of gynecomastia in our hospital male patients was 0.17%. The mean age was 22 years, range 17–29 years.

All patients, 74 (100%), presented with asymptomatic bilateral gynecomastia. No pain, nipple discharge, or abnormal mass was recorded. Social embarrassment was the main reason for seeking surgical treatment. The mean duration of the disease was 4.3 years, range (2–7) years.

A positive family history of benign breast disease (gynecomastia, fibroadenoma) was recorded in 28 (37.84%) patients. A positive family history of breast cancer was recorded in 11 (14.86%) patients including the 5 patients proved to have DCIS.

39 (52.7%) of our patients were obese. No other predisposing factors were recorded for any patient. No co-morbid systemic diseases were recorded.

Analysis of the patients data for the possible etiology of gynecomastia did not point to a specific etiologic factor, even sex hormones analysis was normal in all the study population, so we had to label the etiology in all the patients (100%) as idiopathic.

All patients had a bilateral subcutaneous nipple-preserving mastectomy performed. The mean operative time was 75 ± 5 minutes, and the mean estimated blood loss was 22 ± 7  mL . No intraoperative complications were recorded. Postoperative analysis showed that in 54 (73%) patients, drains were removed on the first postoperative day, and in 20 (27%) on the second postoperative day. Six (8.1%) patients had wound infection treated with antibiotics and wound irrigation, and four (5.4%) patients developed hypertrophic wound scar. The mortality rate was (0%).

69 (93.24%) male patients had histopathological features of gynecomastia on final histopathology. 5 (6.76%) male patients were found in histopathology specimens to have DCIS on top of gynecomastia:

1 patient (23 years old) had bilateral DCIS of lowgrade papillary subtype.

4 patients had unilateral positive involvement, 3 had right breast DCIS, and 1 had left breast DCIS, all were of low-grade papillary subtype.

The incidence of ductal carcinoma in situ among our series gynecomastia patients was 6.76%. All 5 patients had positive family history of breast cancer (4 maternal and 3 grand maternal). The age at presentation of the 5 patients was recorded as follows: 17, 19, 20, 21, and 23.

Patients with DCIS

17 years old male, had left breast papillary DCIS, positive maternal and grand maternal history of breast cancer (both are dead), tested (ER) and (PR) positive, tested (HER2) negative.

19 years old male, had right breast papillary DCIS, positive maternal history of breast cancer (mother is dead), tested (ER) and (PR) positive, tested (HER2) negative.

20 years old male, had right breast papillary DCIS, positive grand maternal history of breast cancer (grandmother is dead), tested (ER) and (PR) positive, tested (HER2) negative.

21 years old male, had right breast papillary DCIS, positive maternal history of breast cancer (mother is dead), tested (ER) and (PR) positive, tested (HER2) negative.

23 years old male, had bilateral breast papillary DCIS, positive maternal and grand maternal history of breast cancer (both are dead), tested (ER) and (PR) positive, tested (HER2) positive (Table 1) (Fig. 2).

With a follow-up time of 2 years, none (0%) of the 5 patients developed recurrent, or metastatic disease evident by biopsy of the nipple areola area of both breasts done to all 5 patients 1 year postoperatively, breast and axillary ultrasound, and computerized tomography scan (CT scan for lymph nodes and systemic metastasis) 2 years postoperatively.

Discussion

Despite that gynecomastia is the most common pathology of the male breast, only a few patients will actually seek a surgical treatment in which the psychosocial influence or the painful feature is the main reason. Because of the unavailability of sufficient clinical reports, it is difficult to estimate the number of patients with gynecomastia who eventually undergo surgical excesion [20]. All our 74 patients requested surgical excision for social reasons, and none had a fear of malignant potentials. In fact, 63 (85.14%) had no idea at all about male breast cancer.

Liposuction was reported to be effective if the breast enlargement is mainly composed of adipose tissue and the overlying skin is fairly taut. Subcutaneous mastectomy is indicated for the removal of glandular tissue and redundant skin (visible inframammary skinfolds) and pain relief [21]. Our approach was a nipple sparing subcutaneous mastectomy in all patients, and no asymmetry or skin redundancy was recorded during postoperative follow-up.

The well-established complications of the surgical treatment of gynecomastia include hematoma, seroma, wound infection, skin sensory changes, pain, breast asymmetry, skin redundancy, and scarring, with the most common complication reported is a poor cosmetic outcome, although the final results of surgery may not be apparent for a year [21]. In our series, the use of surgical drains eliminated hematoma and seroma complications in all patients, though, it might have had contributed to the (8.1%) wound infection recorded. Only 4 (5.4%) patients developed hypertrophic wound scar.

Three types of gynecomastia have been described: nodular, dendritic, and diffuse glandular in which each type represents a different degree of ductal and stromal proliferation. The nodular and dendritic forms correspond to the florid and fibrous stages of proliferation, respectively, whereas the diffuse glandular type corresponds to epithelial proliferation and is often linked to the use of exogenous hormones [22]. In our series, reevaluation of the histopathology specimens showed that only 13 (17.6%) had a diffuse glandular type. The rest were all of the nodular types.

The classical feature of ultrasound examination is a subareolar hypoechoic mass, which may have typical nodular features and a long axis that is parallel to the skin (nodular gynecomastia), or it may be triangular with extensions that radiate into the subareolar fat (dendritic gynecomastia), or it may resemble a female breast (diffuse gynecomastia). The color-Doppler evaluation reveals moderate, harmonious intralesional vascularization [23] (Fig. 3).

Gynecomastia has been hypothesized to be associated with male breast cancer, but no increased risk has been found. Coexistence of the two conditions has only occasionally been identified. Even rarer are cases of DCIS with gynecomastia, especially in the young adult population. To date, only 7 cases of DCIS in the setting of gynecomastia have been described in patients 25 years old or younger [24]. In our series, all 5 patients who had DCIS were below 25 years old (17, 19, 20, 21, 23).

Male breast cancer is uncommon, but, the incidence has increased (to 1.08 in 100,000 in 1998 from 0.86 in 100,000 in 1973) [25]. Positive testing of the human epidermal growth factor receptor 2 (HER2), a negative prognostic factor in women is found less often in men [26]. Men were reported to be more frequently (ER) and (PR) positive, which could indicate an increased proliferative activity [27]. During 20 years of surgical practice in our local community, we encountered only one case of male breast cancer (in 2003 – 29 years old male), which was incidentally found after biopsy for bloody nipple discharge following football trauma to the chest wall.

The rare DCIS has been reported to account for 5–7% of male breast cancer [19]. The papillary form of DCIS is the most common, but all subtypes that were reported in females could also occur in males [22]. A pure DCIS was reported to occur in about 5% of the cases which could be because the pathology is often associated with invasive cancer elsewhere [22]. DCIS is more common in women, accounting for 20% of breast cancer cases [23]. Of all DCIS, male and female patients, about 30–50% would eventually develop invasive cancer in the subsequent 10–20 years, and so the actual prevalence in the general population may be higher [24]. The causes of DCIS in men are not well established because men lack the terminal duct lobular unit (TDLU) in which DCIS originates in women, so, it was hypothesized that DCIS in men originates from the duct epithelium [22].

Although bilateral gynecomastia is more common, there is no evidence that either unilateral or bilateral disease increases the risk of male breast cancer. However, rapid growth in one breast necessitates consideration of diagnoses beyond gynecomastia and should be further investigated. Hyperthyroidism, liver cirrhosis, testicular tumor, and obesity are independent risk factors and may confound the association with gynecomastia [18]. 39 (52.7%) of our patients were obese, but none of the 5 patients who had DCIS were obese. No other predisposing factors were recorded for any patient.

The majority of male breast cancers are of the ductal subtype that usually present late, with about 40% are in stage III or IV disease [22]. In the reported cases, men were less likely to be diagnosed in the early stages, but diagnosis at the non-invasive stage has increased which could be due to the improved awareness of male breast cancer. Many factors that increase the risk of male breast cancer have been recognized and include high estrogen levels, positive family history, BRCA 2 gene, hyperprolactinemia, Klinefelter’s syndrome, and history of prior radiation [28,29]. Until today, no increased breast cancer risk associated with gynecomastia in males has been established [30–34].

The rare incidence of DCIS and the presence of concurrent gynecomastia can frequently result in misdiagnoses. The prognosis in male DCIS is uncertain. It may be worse than it is in women, but this suggestion is disputed because of small sample sizes [23]. At 8 years of follow-up in women, the frequency of ipsilateral tumors is 13% with lumpectomy and breast irradiation; morality is 1.6% [26]. Cutuli et al. observed 4 recurrences in the follow-up of 31 male DCIS patients: 3 after lumpectomy, and 1 after modified radical mastectomy [16]. Among all cases of male breast cancer, 0.7% will suffer contralateral disease with a standardized incidence ratio of 30 overall and 110 for patients younger than 50 years of age at onset. Treatment of male DCIS does not have an established benchmark; it is guided by experiences reported in the literature [28,29].

Mammography for male breast cancer has a reported sensitivity of 92% and specificity of 91% [30]. Mammography was positive for gynecomastia in 67 (90.5%) of our patients population, the rest 7 patients had so small breast tissue to be compressed (Fig. 1).

Calcifications are less frequently associated with male breast cancer than female breast cancer. Malignant calcifications in the male breast often have a more benign appearance and can be more scattered or round [14,31]. In our series, none of the patients had recorded evidence of calcification neither on mammogram nor on the ultrasound studies.

Management of male breast cancer is largely based on studies that deal with female breast cancer. Typical treatment for males with DCIS is total mastectomy without axillary node dissection [14,21]. In a series of 31 cases of pure DCIS in men by Cutuli et al., 19 cases underwent axillary node dissection, with all sampled lymph nodes negative [16]. Recurrence of male DCIS following total mastectomy has yet to be described. In the same series only four recurrences were reported, none of which were in patients treated with total mastectomy. No further adjuvant therapy is necessary, and prognosis for DCIS in males is excellent [24]. Males DCIS, like that of females, is reported to have a good prognosis [32]. In our series, despite short follow-up period of 2 years, zero (0%) of the 5 patients developed recurrent, or metastatic disease, evident by biopsy of nipple areola area of both breasts done to all 5 patients 1 year postoperative, ultrasound and CT scan 2 years postoperative.

The principle of the nipple areola complex preservation in breast cancer surgery is mostly due to the patient wish for a cosmetic result. The current literature is suggesting low recurrence rates after nipple-sparing mastectomy (NSM) which resulted in its wide acceptance as a prophylactic procedure. However, the therapeutic NSM is still debatable due to factors like the reported rates of nipple involvement are 0–58%, the size of the primary tumor, multicentricity, and lymph node positivity [34]. In our series, nipple sparing was done to all patients, and biopsy after 1 year was negative in all 5 patients.

Conclusion

We conclude that gynecomastia is a benign breast disease but recent reports had described malignant variants, mostly DCIS, including 5 young males in our series. Therefore, regardless of the age group, histopathological examination of the resected gynecomastia tissue should be carefully done in all patients. Further evidence-based studies are needed to investigate the optimum management of incidental DCIS in gynecomastia specimens.