A Case of Malignant Transformation of Recurrent Respiratory Papillomatosis That Was Effectively Treated with Pembrolizumab.

[INTRODUCTION] Recurrent respiratory papillomatosis (RRP) is a benign tumor caused by the human papillomavirus that mainly occurs in the larynx; the tumor is known to show malignant transformation in a small percentage of cases. In this report, we describe a case of rapidly growing cervical metastasis due to malignant transformation of RRP that was successfully treated with pembrolizumab.

[CASE PRESENTATION] A 79-year-old man diagnosed as having laryngeal papilloma was referred to our department, and we resected the tumor by transoral laser microsurgery (TLM). Postoperative histopathology showed papillary lesions with mild cellular atypia, suggestive of papilloma. Six years later, the patient visited our hospital again with worsening hoarseness of the voice and an enlarged papillary lesion of the larynx. We performed a second TLM and postoperative histopathological examination revealed a papillary squamous cell carcinoma. In the early postoperative period, the patient developed a recurrence at the primary site and received radiotherapy (70 Gy). Three months after the completion of radiotherapy, a rapidly enlarging metastatic lymph node was observed in the right cervical region, and we performed neck dissection. Five months after the surgery, a rapidly enlarging mass appeared in the anterior cervical subcutaneous region, and the patient received palliative radiation. Since an immunohistochemical examination of a specimen obtained at the time of neck dissection showed high PD-L1 expression, with a combined positive score of 100, the patient was initiated on treatment with pembrolizumab 1 month later. Although the patient developed fever and a skin rash as adverse events, the tumor disappeared almost entirely within 3 weeks. Thereafter, we have observed no evidence of recurrence for over 1 year.

[CONCLUSION] The PD-1/PD-L1 pathway has been implicated in the tumorigenesis of RRP. This pathway may also play an important role in the malignant transformation of RRPs. Therefore, evaluation of tumor PD-L1 expression is recommended in these cases.