Basal cell carcinoma (BCC), a common tumour of epithelial origin, is locally invasive and has a low risk of metastasis, estimated to range from 0.028% to 0.1% (1). However, once BCC metastasizes to distant organs, the effective therapeutic options are limited, leading to poor patient outcome.Recent studies have shown that epithelial-mesenchymal transition (EMT) suppresses epithelial features, and induces mesenchymal traits to epithelial cells in several pathological conditions (2,3). Of note is that tumours of epithelial origin can express transcription factors Snail and Twistl, or the cell adhesion molecule N-cadherin as a mesenchymal marker. We have previously shown that N-cadherin is up-regulated in invasive tumours, but not in carcinoma in situ of extramammary Paget's disease, and that EMT is associated with distant organ metastasis, leading to poor patient survival (4,5). However, it remains unclear whether EMT plays a key role ir the development of highly invasive phenotype and potential metastasis in BCC. We report here the first case of morphoeic and metastatic BCC showing the induction of Twistl and the epithelial-to-mesenchymal conversion of cadherins in association with multiple organ métastases.
CASE REPORTA 51-year-old Japanese man presented with a 3-cm ulcerated nodule with peripheral focal pigmentation on the upper back ( Fig. la). A biopsy specimen disclosed the proliferation and invasion of epithelial strands with mesenchymal transition and rich stroma, indicating a diagnosis of morphoeic BCC (Fig. lb). The patient underwent a tumour resection, and the defect was reconstructed with the trapezius musculocutaneous flap. After 4 years of follow-up, a subcutaneous mass appeared in the patient's supraclavicular fossa. Under the histological diagnosis of metastatic BCC, the tumour was surgically resected with subsequent reconstruction using the pectoral major musculo-cutaneous nap, followed by a total of 60 Gy radiation to the local region. However, multiple foci of tumour metastasis were found in the left levator scapulae muscle and the pleura ofthe left lung by magnetic resonance imaging. The patient underwent systemic chemotherapy with a combination of cisplatin and doxorubicin. However, the therapeutic effect was minimal, and at the time of writing, the tumours were disseminated in the lung. Fig. 1. Clinical, roentgenological, and pathological features in metastatic basal cell carcinoma (BCC). (a) Clinical presentation of 3-cm ulcerated nodule on the upper back with peripheral, focal pigmentation, (b) Haematoxylin & eosin stains (x 400) ofthe cutaneous primary site show foci of basaloid tumour ceils on the superiorly and infiltrative tumour cells within the stroma. (c) Prominent Twistl expression was revealed in the nuclei of tumour cells (arrowheads) at the invasive front in the index case, (d) No Twist 1 expression was found in control representative nodular BCC by immunohistochemistry. Scale bars= 100 um (b); 30 \irri (c, d).To clarify the potential role of EMT in metastatic BCC, we investigated...