Case 1
An 8-year-old girl underwent biopsy and subsequent lumpectomy for a breast mass. Surgical pathology showed a gland-forming tumour with microcystic, solid and trabecular architecture. Tumour cells were vacuolated with Periodic Acid Schiff-positive (PAS+) intraluminal secretions. IHC for oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) were negative.
Haematoxylin and eosin (H&E) (Left Hand Panel) and Pan-TRK IHC (Right Hand Panel) of a Paediatric Patient with Secretory Carcinoma of the Breast
Antibody for IHC: clone EPR17341 available from Abcam, Cambridge, MA, USA(www.abcam.com)
The patient was treated with fluorouracil, doxorubicin, and cyclophosphamide. The tumour recurred a year later in the patient’s chest wall and distant metastases to the lung were subsequently detected.
NTRK gene fusion testing
Pan-TRK IHC showed positive cytoplasmic and nuclear expression in tumour cells.
TRK inhibitor treatment
The patient was treated with the TRK inhibitor larotrectinib and responded well to the drug.
Clinical interpretation and impact of NTRK gene fusion testing
This patient has clinical and pathologic findings consistent with secretory carcinoma of the breast [1]. While survival is very good for these cases, distant metastases have been reported.
The vast majority of cases of secretory carcinoma are characterised by ETV6-NTRK3 fusions [1]. ETV6-NTRK3 fusions have nuclear expression (in addition to cytoplasmic expression) of TRK protein by IHC in approximately 50% of cases.
The high likelihood of NTRK3 fusion in this case due to the tumour type involved, in addition to the confirmatory pan-TRK IHC, is sufficient evidence for the presence of an NTRK fusion.
References
- Tognon C, Knezevich SR, Huntsman D et al. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell 2002; 2: 367-376.