Pembrolizumab in a Patient With a Metastatic CASTLE Tumor of the Parotid

Abstract

Carcinoma showing thymus-like elements (CASTLE) is a rare tumor, most commonly found in the thyroid gland. Here we report a case of CASTLE tumor localized to the parotid gland, recognized in retrospect after a late manifestation of symptomatic pleural carcinomatosis. The original tumor in the parotid gland was treated by surgery followed by radiotherapy. Ten years later, a metastatic disease with recurrent pleural effusions occurred. Pleural carcinomatosis was strongly positive for CD5, CD117, and p63 as was the original tumor of the parotid, which allowed the diagnosis of a CASTLE tumor. Additionally, the pleural tumor expressed high levels of programmed death ligand 1 (PD-L1), and the patient underwent treatment with the monoclonal PD-L1 inhibitor pembrolizumab achieving a partial remission. To the best of our knowledge, this is the first patient with a metastatic CASTLE tumor treated with a PD-L1 inhibitor.

Carcinoma Showing Thymus-Like Differentiation (CASTLE) Arising in the Sublingual Gland

“…The patient was free of disease 1 year after the end of treatment. 5 The second case has been recently described by Lorenz et al 6 in a 79-year-old woman hospitalized for progressive dyspnea and pleural carcinomatosis; 11 years earlier, the patient had been treated for undifferentiated carcinoma of the right parotid gland by total parotidectomy, selective neck dissection (levels II-IV), and adjuvant RT. Both histological examination of pleural metastases and the review of the primary parotid tumor was consistent with CASTLE.…”

“…24 Rare patients had been described having a fatal and rapid evolution, with metastatic disease involving lungs, brain, liver, and pleura. 6,22,25,26 Optimal treatment modalities for CASTLE have not been settled due to its rarity. Radical surgery, consisting of the removal of the primary tumor along with possible lymph node metastases, is considered the treatment of choice.…”

“…20 Only 2 cases of CASTLE have been reported to occur in major salivary glands. 5,6 One occurred in the parotid gland in a 55-year-old woman treated by total parotidectomy and ipsilateral selective neck dissection; the tumor was staged as pT1 N1 M0 and thereafter surgery was followed by adjuvant RT. The patient was free of disease 1 year after the end of treatment.…”

“…4 Two cases involving the parotid gland have been recently reported, and one of them was properly classified as CASTLE several years after the initial diagnosis in the setting of metastatic disease, thus highlighting the difficulty of histological recognition of this entity, especially when presenting in unusual sites. 5,6 In this case report, we describe a hitherto unreported CASTLE arising in the sublingual gland; also, we summarize the findings of the 2 cases of major salivary gland CASTLE that have not been reported until now.…”

Genomic variation associated with carcinoma showing thymus‐like elements (CASTLE) in thyroid gland

“…With the development of immunotherapy, immune checkpoint inhibitors have proven to be effective in some solid tumors. Lorenz et al 28 reported a patient with parotid CASTLE tumor and pleural metastasis who achieved partial remission after treatment with the PD‐1 inhibitor pembrolizumab. In our study, case 2 developed lung metastasis 2 years after the initial treatment and received platinum‐based combined chemotherapy followed by the PD‐1 inhibitor immunotherapy for 1 year.…”