Unilateral nipple discharge in a man without a palpable mass diagnosed as breast cancer

Abstract

A 69-year-old man without a family history of breast cancer presented to his primary care physician with a 1-year history of clear, unilateral nipple discharge (ND) without an associated palpable breast mass. His laboratory findings were significant for hyperprolactinaemia at 28 ng/mL. Diagnostic work up including mammography, ultrasound and core needle biopsy ultimately revealed a ductal carcinoma in situ and a rare papillary variant of invasive ductal carcinoma. The patient was referred to a multidisciplinary oncology team and underwent a right total mastectomy followed by adjuvant hormonal therapy. The patient made a good postoperative recovery and remains without evidence of recurrence 6 months from surgery. Male breast cancer is rare, but its incidence is increasing. Male breast cancer presenting as ND without a palpable mass is uncommon. Early recognition of breast symptoms in men can lead to earlier diagnoses and improved outcomes.

Background

Male breast cancer (MBC) is rare, constituting less than 1% of all breast cancers.¹ The most common presenting symptom of MBC is a palpable breast mass, while less common symptoms include nipple discharge (ND), nipple bleeding, nipple retraction, nipple ulceration and/or pain.² This case highlights an uncommon situation in which breast cancer was diagnosed in a man who presented to his primary care physician with the sole complaint of unilateral ND without a palpable breast mass or any other abnormal breast findings. Breast symptoms in men, although uncommon and often overlooked, can be indicative of an underlying breast malignancy.

Case presentation

A 69-year-old African-American man presented to his primary care physician with 1 year of clear, intermittent, right-sided ND. The discharge was initially reported to be bloody but was serous by the time he was evaluated. The patient also noted more recent onset of nipple swelling and pain. His medical history was significant for hypertension, type 2 diabetes mellitus, obesity and erectile dysfunction. Vitamin D, hydrochlorothiazide, lisinopril, metoprolol, nifedipine, ranitidine and sildenafil. The patient had a brother diagnosed with colon cancer at the age of 52 years, a sister diagnosed with colon cancer at the age of 62 years, another sister diagnosed with pancreatic cancer at the age of 68 years and his mother was diagnosed with lung cancer at the age of 84 years. There was no family history of breast or ovarian cancer. The patient had a smoking history of 8.75 pack-year and quit 12 years prior to presentation. He drinks 2.4 oz of alcohol per week. He denied a history of drug use and is currently retired. On physical examination, there was no palpable breast mass, breast asymmetry, skin changes, breast tenderness, ND or axillary lymphadenopathy.

Investigations

Initial laboratory data revealed a normal white blood cell count of 7100 cells/µL, haemoglobin of 13.6 g/dL, creatinine of 1.02 mg/dL, sodium of 144 mEq/L, potassium of 4.4 mEq/L, calcium of 10 mg/dL, total bilirubin of 0.3 mg/dL and an elevated prolactin of 28.9 ng/mL (reference range: 4.0–15.2 ng/mL). On follow-up, right breast mammography showed a 5-mm asymmetry near the nipple (figure 1A). A right breast ultrasound showed a 6-mm mostly cystic mass with a 3-mm eccentric mass with mixed echogenicity (BIRADS 4), raising concern of an intraductal mass behind the right nipple (figure 1B). A subsequent ultrasound-guided biopsy revealed atypical ductal hyperplasia, intraductal papilloma and duct ectasia on histopathological analysis. The patient was then referred for an excisional biopsy of the right breast mass. The first sample was taken from breast tissue and revealed ductal carcinoma in situ (DCIS) grade II with cribriform and solid architectural patterns. The second sample was taken from behind the right nipple and showed papillary carcinoma grade II (figure 2). Both of the carcinomas were strongly oestrogen and progesterone positive (ER+/PR+). The patient was referred for genetic screening given his strong family history of cancer. A STAT 9-gene breast cancer panel (screens for BRCA1/2, PTEN, TP53, ATM, CHEK2, PALB2, CDH1 and STK11) was unremarkable. A multigene panel for 47 genes (Invitae Common Hereditary Cancers Panel, Invitae Breast Cancer STAT Panel, ATM gene and CHEK2 gene) also revealed no deleterious mutations.

Figure 1.

Imaging of the right breast mass. (A) Mammogram of right breast showing 0.5 cm asymmetry just medial to the nipple. (B) Ultrasound of right breast demonstrating 0.6×0.4 cm cystic mass with 0.3 cm eccentric mass with mixed echogenicity.

Figure 2.

Papillary carcinoma of breast. Photomicrograph showing neoplastic cells growing on a delicate fibrovascular stroma (black arrow) in an arborising pattern.

Treatment

The patient was referred to a multidisciplinary oncology team that included a breast surgeon, medical oncologist, radiation oncologist and geneticist. The National Comprehensive Cancer Network guidelines for breast cancer were followed throughout the patient’s management. The patient underwent an excisional biopsy of the right breast mass. A formal diagnosis of stage 0 right DCIS with tumour, node, metastases (TNM) classification, pTisNxcM0, was made. However, since the posterior and superior surgical margins were determined to be inadequate (1 mm each), further surgery to obtain wider surgical margins was recommended with the option of either a central lumpectomy followed by radiation or a right total mastectomy. Following discussion of risks and benefits of both procedures with his breast surgeon, the patient opted to undergo a right total mastectomy, which was completed 4 weeks later and included a right axillary sentinel lymph node biopsy. There was no evidence of tumour spread to the lymph nodes and the revised staging was pTisN0cM0. Since both breast lesions were strongly ER+/PR+, he was eventually placed on adjuvant hormonal therapy with tamoxifen, 20 mg once daily.

Outcome and follow-up

The patient did reasonably well postoperatively. He presented twice (2 months and 3 months after surgery) with swelling and pain at the mastectomy site—on both occasions, he was diagnosed with a haematoma in the surgical bed and had successful resolution of symptoms with aspiration and drainage. Tamoxifen was discontinued at 3 months after surgery due to intolerable side effects, including malaise and headache. The patient continued to have guideline-based postoperative surveillance. There was no clinical evidence of recurrence based on symptoms and physical examination (including clinical breast examination) 6 months following his surgery.

Discussion

Our case represents two infrequent forms of MBC that presented as unilateral, clear ND without a palpable mass on physical examination. Our patient did not have a family history of breast cancer (recognised in 15%–20% of MBC cases),² making this case even more unique. DCIS and papillary carcinoma present in as few as 0.1% and 0.02% of all breast cancer cases, respectively.³ In one study, DCIS in men presented as ND (bloody type) in 40% of cases.⁴ Although there is sparse data on papillary carcinoma, different case reports recognise ND as an important symptom prompting evaluation.^{5 6}

ND presenting as the chief complaint in MBC is uncommon. It presents in 1%–12% of cases, as compared with an underlying breast mass presenting in as much as 97% of cases (table 1).² Our patient went about 80 weeks without a clinically evident mass on palpation. According to Morrogh and King, the typical timing from initial presentation of ND to mass formation is an average of 16 weeks.⁷ ND is significant because it is strongly associated with MBC. As much as 22%–57% of men with ND were found to have some form of cancer, compared with 1%–16% in women.^{7 8} The discharge associated with MBC is often bloody, pink, serous, or clear, while white or milky discharge is more likely to be benign.⁷ The prognosis for men is largely based on stage and axillary node involvement. The 5-year overall survival in order from stage 1 to stage 4 is 87%, 74%, 57% and 16%, respectively.³ Black race appears to be associated with a higher incidence rate and worse outcome in comparison to white race. According to Surveillance, Epidemiology, and End Results (SEER) registry data, the incidence rate of MBC per 100 000 individuals in blacks is 1.8 versus 1.2 in whites and the 5-year survival rates in blacks is 73% versus 86% in whites.⁹ While the risk of death from MBC in black men was higher than in white men, these changes were found to be negligible after controlling for income and access to healthcare.¹⁰ It was once believed that men with breast cancer have overall lower survival than women. However, once staging and other factors (eg, age at diagnosis and male life expectancy) are adjusted, the prognosis for men with breast cancer is similar to women.³ It has been established, however, that at the time of diagnosis, men are more likely to have lymph node (42% vs 33%; p<0.0001) and distant metastasis (4% vs 3%, p<0.0001) as well as a higher grade on histology. As compared with 10% of women, 17%–20% of men have stage 3 or 4 disease. This has been variously hypothesised to be secondary to a lack of awareness that breast cancer can develop in men and the lack of routine screening. Qualitative studies have shown a remarkable reluctance on the part of men to discuss breast symptoms.^{11 12} Factors often cited are the traditional conceptualisation of the breast as a feminine organ and of breast cancer as a female disease coupled with the lack of knowledge that men can develop breast cancer.¹³ This was seen in our patient who reported his symptoms to his physician about 6 months after onset, noting a sense of embarrassment related to breast symptoms.

Table 1.

Presenting signs and symptoms of MBC²

Presenting symptom	Frequency, %
Breast mass	50–97
Nipple retraction	10–51
Local pain	4–20
Nipple ulceration	4–17
Nipple bleeding	2–9
ND	1–12
None	1–2

MBC, male breast cancer; ND, nipple discharge.

Another important barrier to optimal management in MBC is the singular lack of quality research into MBC as evidenced by the fact that there have been no randomised controlled trials related to MBC in the last 50 years. MBC continues to be treated per guidelines established for female breast cancer.¹⁴ International cooperative research consortiums aiming to pool prospective data on MBC represent a positive step in this direction and can likely improve gender-specific knowledge on MBC, as related to hormonal and genetic profile, treatment response and the psychosocial aspect of care. It is important for physicians to engage with and validate breast-related symptoms in men. Given the lack of routine screening recommendations, maintaining a high degree of clinical suspicion for breast cancer, especially in high risk patients, can result in early diagnosis and potentially improved outcomes.

In conclusion, we discuss a case of DCIS and papillary carcinoma that presented as ND without a palpable mass. ND has a greater association with breast cancer in men than women. Recognising the importance of this symptom can result in early diagnoses of MBC and improve patient outcomes.

Learning points.

• Breast symptoms in men should always warrant a thorough evaluation.

• Male breast cancer (MBC) may present as nipple discharge without a palpable mass.

• Early recognition of symptoms leading to the diagnosis of MBC can improve eventual outcomes.