HPV-positive cervical squamous cell carcinoma metastasis to the breast,mimicking primary tumor

In a patient diagnosed with breast squamous cell carcinoma, the presence of metaplastic breast carcinoma with squamous differentiation, or a primary breast SCC, must be considered. However, in the presence of previous cervical neoplasia, a third hypothesis of metastatic cervical neoplasia may be considered.

The evaluation for the presence of HPV in the breast lesion does not make the diagnosis based on the characteristic of the lesion. In patients with breast cancer and cervical intraepithelial neoplasia [6] or invasive cervical cancer [7], HPV is present in breast lesions in up to half of the cases. In general, the presence of HPV in breast cancer ranges from 20.9% to 23% [8] and the literature discuss the possible association of HPV in breast cancer carcinogenesis [7]. Pure and metaplastic breast SCC are rare entities, and generally have a basal expression, with the expression of genomic HPV being observed in 14% of patients [9].

By immunohistochemistry, p16 expression is associated with high-grade lesions and the presence of invasive disease to the cervix, also suggesting previous HPV[10,11] infection, and p63 expression for metaplastic breast carcinoma [3]. On the other hand, high p16 expression was observed in approximately 40.1% of breast tumors [12], not being specific to the cervix. P16 and HPV are usually present in invasive lesions of the cervix, but their positivity in the breast does not exclude metastatic origin.

Negativity for mammaglobin and GCDFP-15 suggests the non-mammary origin of the tumor [13], in spite of the focal expression of GATA-3. Due to the question regarding the origin of SCC, immunohistochemistry was performed using p63, SOX10 and RE/RP/Her2 (Table 1). If it were primary of the breast, it would be triple negative, a condition associated with SCC. However, negativity for p63 suggested absence of primary breast squamous cell carcinoma or metaplastic carcinoma. Negativity for SOX10 may be present in breast cancer, but its absence also occurs in the presence of metastatic squamous cell carcinoma disease. Thus, negativity for SOX10 [14], the expression of p16 and the hybridization to HPV 16, associated with a past of cervical cancer, strengthen the hypothesis of metastatic disease of the cervix.

In the immunohistochemical evaluation of squamous cell neoplasia in the breast (Table 1), it is suggested to consider the assessment of markers p63, SOX10 and p16, a fact that, in this case, confirmed the metastatic origin of the lesion, something not previously demonstrated in the literature.