Secretory carcinoma arising from axillary accessory breast: A rare presentation

Dear Editor,

Secretory carcinoma (SC) of the breast is a rare subtype of breast cancer with an indolent clinical course and a favourable prognosis.¹ In this article, we describe a patient with SC arising from the axillary accessory breast as an atypical presentation of this disease, confirmed by the presence of neurotrophic tyrosine receptor kinase 3 (NTRK3) fusion genes.

A 61-year-old woman presented with a 7-month history of an asymptomatic subcutaneous nodule in her left axilla. She had a history of hypertension, controlled with regular anti-hypertensive medications, but no other chronic diseases or malignancies. Regular screening mammograms did not reveal any suspicious lesions. There was no family history of inherited disease. On examination, a 1.5 cm x 1.5 cm mobile, rubbery subcutaneous nodule was noted in her left axilla [Figure 1a]. Biopsy of the lesion revealed a nodule composed of neoplastic cuboidal epithelial cells in a microcystic and papillary-cystic pattern, adjacent to non-neoplastic accessory breast tissue in the deep subcutaneous layer [Figure 1b]. The cells exhibited monotonous nuclei, eosinophilic cytoplasm, distinct nucleoli, and prominent intracellular and extracellular secretory materials [Figure 1c]. Immunohistochemically, the tumour cells were diffusely positive for S100, cytokeratin 5/6 (CK5/6), GATA-binding protein 3 (GATA3), and pan-tropomyosin receptor kinase (pan-TRK) [Figure 1d], while estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) staining were negative. Further image investigation revealed no evidence of malignancy in the breasts, lymph nodes, and salivary glands. The presence of the ETV6-NTRK3 gene fusion was confirmed by next-generation sequencing (NGS), which was preferred over fluorescence in situ hybridization (FISH) or reverse transcription polymerase chain reaction (RT-PCR) for research purposes and broader coverage of potential therapeutic targets. A diagnosis of SC arising from the accessory breast was made based on clinic-pathological correlation. Wide excision with a 1 cm safety margin was performed, and a regional lymph node survey showed no involvement. The patient remains free of recurrence or metastasis 1 year after the surgery.

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Figure 1:

A 1.5 cm x 1.5 cm mobile, rubbery subcutaneous nodule in the left axilla, as indicated by the black dotted circle.

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Figure 1b:

A subcutaneous nodule composed of neoplastic cuboidal epithelial cells in a microcystic and papillary-cystic pattern (black arrowhead), adjacent to non-neoplastic accessory breast tissue (black arrow), (Haematoxylin and eosin, 1x).

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Figure 1c:

The cells exhibited monotonous nuclei, eosinophilic cytoplasm, distinct nucleoli, and prominent intracellular and extracellular secretory materials, (Haematoxylin and eosin, 10x).

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Figure 1d:

The neoplastic cells were positive for Pan-TRK stained pathology image at 10x.

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SC of the breast is a rare subtype of breast carcinoma, accounting for only 0.15% of all breast cancers.² Clinically, it mostly presents as an indolent subcutaneous nodule on the breast. Pathologically, SC is characterised by neoplastic cells exhibiting intracellular and extracellular secretory materials, forming cribriform, papillary-cystic, lobulated, and/or microcystic patterns. Mild dysplasia may be observed, but necrosis and active cell proliferation are less evident compared to basal-like breast cancer. Immunohistochemically, SC expresses S100, Immunohistochemically, SC expresses S100, GATA3, SRY-box transcription factor 10 (SOX10), mammaglobin, mucin-4 (MUC4), and pan-TRK and is usually negative for ER, PR, and HER2. Studies have shown that these carcinomas develop due to t(12,15) ETV6-NTRK3 gene translocation, which can be identified using FISH, RT-PCR, or NGS.³ The pathological differential diagnoses of SC have been summarised in Table 1.⁴

SC is not anatomically restricted in its distribution and may occur in the breast (including the accessory breast), salivary glands, and skin appendage glands, as all these structures consist of ectodermally derived exocrine secretory units.³ When SC occurs in the axilla, the main differential diagnoses include SC arising from accessory breast, primary cutaneous secretory carcinoma (PCSC), metastatic breast SC, and metastatic salivary SC. Histology and immunohistochemistry alone cannot reliably distinguish primary axillary SC from metastatic SC of breast or salivary origin. Therefore, imaging studies are essential to rule out metastasis. SC arising from accessory breast can be differentiated from PCSC by the presence of adjacent accessory breast tissue and tumour involvement in the deep dermal-subcutaneous layer. Table 2 summarises the clinical characteristics, pathological findings, status of pan-TRK staining, status of ETV6-NTRK3 gene fusion, treatment, and clinical outcomes of reported SC from accessory breast and PCSC of the axilla.^2,3,5-10 To our knowledge, this is the third reported case of SC arising from the axillary accessory breast and the first to utilise NGS analysis for the detection of the ETV6-NTRK3 gene fusion in establishing the diagnosis.^2,5 Notably, ETV6-NTRK3 gene translocation is not exclusive to a specific origin site, emphasising the importance of clinico-pathological correlation for accurate diagnosis.

In conclusion, we report a rare case of SC of the accessory breast. The diagnosis was supported by distinctive histological features, the presence of adjacent accessory breast tissue, detection of ETV6-NTRK3 gene fusion, and exclusion of primary tumours in the breast and salivary glands. Awareness of this rare disease should prompt clinicians to accurately diagnose and plan appropriate treatment, as well as understand the disease’s prognosis.