Secretory carcinoma is a very rare type of breast carcinoma. Lamovec and Bracko [18
] reported 4 cases of SC in a retrospective series of 7038 breast carcinoma cases, and Botta et al [19
] found one case of SC among 3000 breast carcinoma cases.
The age at presentation varies from 3 to 87 years with a median age of 25 years [1
]. The male-female ratio is approximately 1:6 [20
]. The case presented herein is extremely unusual as SC, particularly metastatic SC, has rarely been reported in males. Literature search identified only 16 other cases of SC in males. Our case was older than the average age reported for secretory carcinoma in males which is 17 years. Only the case reported by Kuwabara was older than our case (66 years) [22
]. Table summarizes the main clinical features of the cases of SC reported in males.
Data on 17 males with Secretory Breast Cancer
SC's can demonstrate several histological patterns including, solid, microcystic, and ductal, with many tumors containing all three patterns [24
]. The tumor cells are polygonal with granular eosinophilic cytoplasm. Atypia is minimal or absent and mitotic activity is low [20
]. A typical finding is the presence of intracellular and extracellular secretions [7
]. This secretory material is periodic acid-Schiff and alcian blue positive [24
]. In this tumor there was no expression of steroid receptors or HER2. A recent study has reported than only 4 and 2 out of 13 cases expressed the estrogen and progesterone receptor respectively and only two were HER2 positive [26
]. In the current case, the tumor had the t(12;15) ETV6-NTRK3 fusion gene (Fig. ).
The most frequent clinical presentation is of an asymptomatic mobile mass, which is usually subareolar. The tumor size varies from 1 cm to 16 cm with an average diameter of 3 cm. [7
]. Our patient had a mass of 7 cm × 5 cm. As the patient reported that the lesion had been present for at least 10 years, it had behaved in a slow growing, indolent fashion. This is supported by other reported cases [20
]. In this regard, Biallo et al., have reported a MIB1 labeling index of 11.4% (range: <1 to 34%) [26
Surgery is considered the primary treatment of secretory carcinoma, however, due to scarcity of reported cases no published guidelines for surgical management exist. There are however, many cases reported of patients who had suffered a local recurrence, therefore mastectomy appears to be a sound surgical choice [1
]. There are no data however on conservative treatment but this option could be explored particularly in cases where breast development has not yet occurred. In regard to the management of the axilla, the overall incidence of axillary lymph node infiltration is around 30% in children and adults regardless of gender [21
], hence axillary lymph node dissection is advocated by some authors for tumors ≥2 cm [7
]. Nevertheless, sentinel node biopsy, may be useful for secretory carcinomas. A recent report on a 9-year-old girl treated with simple mastectomy and axillary sentinel lymph node biopsy shows that this is feasible [27
Postoperative radiotherapy [19
] and adjuvant chemotherapy [7
] have been used on at least two occasions. There is at present insufficient evidence to recommend either approach in the management of secretory carcinoma.
Local recurrence after a long disease-free interval has been described in numerous cases; [1
] however these occurred in patients that underwent conservative surgery. This is the second case reported with chest wall recurrence after mastectomy. In the other case the patient was treated with wide local excision and she is alive at 11-month follow-up. In contrast, our case also presented distant recurrence [12
Distant metastases from secretory carcinoma are extremely rare with only four cases reported [20
]. Our case is the fifth case who developed distant metastases, this, despite having only two positive lymph nodes at resection. Another recently reported patient remained disease free at a follow-up of 13 months despite having 12 out of 14 positive nodes and not having received adjuvant chemotherapy [23
There are several reported cases of patients with secretory breast carcinoma with distant metastases who were treated with either single agent or combination chemotherapy without success. Among the drugs reported are 5-FU, vindesine, mitomycin and prednisone, adriamycin, epirubicin, cyclophosphamide, carboplatin, and even newer active agents such as docetaxel. These data clearly show that this neoplasm is not chemosensitive, as all of the patients treated with chemotherapy showed disease progression while on treatment [7
] and [29
]. In our case, despite using UFT alone and with concomitant radiotherapy there was no response. These observations are in contrast with reports on the high chemosensitivity to common agents (vincristine, cyclophosphamide, adriamycin, dactinomycin and ifosfamide) for congenital fibrosarcomas and mesoblastic nephromas, two other neoplasms associated with the translocation ETV6-NTRK3 [30
]. This suggests that secretory breast carcinoma, due perhaps to its slow growing behavior, acquires additional genetic alterations than ultimately confer chemoresistance. It will be very useful to establish cancer cell lines from this tumor type to study whether the chemoresistance is a general phenomenon or drug specific.