Rare distant metastases to pancreas, liver, and lung as initial presentation of mixed tall cell and columnar cell variants of papillary thyroid cancer

Abstract

Summary The most common sites of distant metastases of papillary thyroid carcinoma (PTC) are lung and bone. Widespread distant metastases of PTC are rare and associated with poor overall prognosis. Metastases to sites such as liver and pancreas are extremely rare, and literature is sparse on overall survival. In this report, we present a 57-year-old man whose initial presentation of PTC was with pancreatic, liver, and lung metastases, and subsequently developed metastases to bone and brain. He underwent a total thyroidectomy, neck dissection, and tracheal resection. Pathology revealed a predominant columnar cell variant PTC with focal areas of tall cell variant, and genomic sequencing showed both PIK3CA and BRAF gene mutations. Radioactive iodine ablation with I-131 did not show any uptake in metastatic sites and he had progression of the metastases within 6 months. Therefore, therapy with lenvatinib was initiated for radioactive iodine refractory disease. Our patient has tolerated the lenvatinib well, and all his sites of metastases decreased in size. His liver and pancreatic lesions took longer to respond but showed response 6 months after initiation of lenvatinib, and he remains on full dose lenvatinib 18 months into treatment. Learning points Papillary thyroid carcinoma (PTC) usually metastasizes to lung and bone but can rarely occur in many other sites. Patients with distant metastases have significantly worse long-term prognosis. Lenvatinib can be an effective treatment of radioactive iodine refractory PTC with rare sites of distant metastases. Lenvatinib can be an effective treatment of PTC with BRAF V600E and PIK3CA mutation.

Targeting Tumor Microenvironment Akt Signaling Represents a Potential Therapeutic Strategy for Aggressive Thyroid Cancer

“…In addition to the BRAF mutation, poorly differentiated (PDTCs) and anaplastic thyroid cancers (ATCs) often have other genetic and/or non-genetic alterations that can lead to the activation of certain signaling pathways involved in cancer cell growth and tumor progression. Activations of such signaling in cancer cells often cause unresponsiveness to treatments commonly used for thyroid cancer, including radiation and chemotherapy [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Currently, the success of targeted therapeutic strategies for advanced thyroid cancers is still limited [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”