Diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare but aggressive form of thyroid cancer that occurs more commonly in children than adults. Although thyroid cancer in children is usually treatable, this particular subtype behaves differently. The cancer often spreads beyond the thyroid gland into nearby tissues and lymph nodes, and many children require extensive surgery and radioactive iodine therapy. Despite these treatments, about half of patients have recurrent disease that requires repeated surgeries and additional radiation over their lifetime.

One major challenge in treating this disease is that some thyroid cancers can no longer absorb radioactive iodine, which is normally used to destroy remaining cancer cells after surgery. Our research suggests that these therapy-resistant cancer cells undergo a biological change called squamous transformation. When this transformation occurs, the cancer cells lose the cellular pump that helps them to take up radioactive iodine, making them resistant to this radiation treatment. Early detection of these cells may identify children at high risk for recurrence. Our work also identifies new therapies that might be effective for children with radiation-resistant disease. Research to understand squamous transformation may lead to improved therapy for many children with recurrent and aggressive thyroid cancers.