SUN-391 - Durable Disease Control of Anaplastic Thyroid Carcinoma with Pembrolizumab

Background: Anaplastic thyroid carcinoma (ATC) is rare but causes a disproportionate share of thyroid cancer deaths. Immune checkpoint inhibition has demonstrated emerging activity in ATC. Durable responses in BRAF-wild-type disease remain incompletely characterized.

Case: An 85-year-old male undergoing PET imaging for prostate cancer was found to have incidental intense uptake in the right thyroid lobe. Ultrasound demonstrated a 7.1-cm right thyroid nodule, and fine-needle aspiration was suspicious for papillary thyroid carcinoma (Bethesda V). He underwent total thyroidectomy with level VI lymph node dissection. Pathology demonstrated anaplastic thyroid carcinoma (major component) arising in association with follicular-variant papillary thyroid carcinoma (6.0 cm), with focal vascular invasion ( < 4 vessels), lymphatic invasion, and positive anterolateral and posterior margins; gross extrathyroidal extension was not identified. One of two level VI lymph nodes contained isolated tumor cells by immunohistochemistry (pT3aN1a; AJCC stage IVB).

Results: Initial post-operative PET/CT demonstrated FDG-avid thyroidectomy-bed disease with cervical and supraclavicular lymph nodes, bilateral pulmonary metastases, and adrenal uptake suspicious for metastases. Molecular profiling was BRAF V600E-negative and fusion-negative, with NRAS Q61R, PIK3CA M1043V, TP53 R248Q, and APC and PIK3R1 deletions. Tumor PD-L1 immunohistochemistry demonstrated diffuse expression with a tumor proportion score of 100%. The patient received multimodal therapy including IMRT and pembrolizumab, achieving marked regression of pulmonary metastases and durable disease control over three years. On I-123 whole-body scan with SPECT/CT (3/2024), uptake was confined to the thyroidectomy bed (left > right) without nodal or distant radioiodine-avid disease; ultrasound (5/2024) demonstrated heterogeneous bed tissue and two 3-mm indeterminate nodes.

Conclusion: This case demonstrates sustained multi-year disease control of metastatic, BRAF-wild-type ATC with NRAS/PI3K/TP53 alterations treated with PD-1 inhibition.

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