Diffuse sclerosing variant (DSV) of papillary thyroid carcinomais a rare form of thyroid cancer that demonstrates more aggressive histopathology than classical papillary thyroid carcinoma (c-PTC); however, if this leads to worse survival is debated. Many DSVs are driven by fusion events which are of recent clinical importance due to the advent of targeted RET inhibitors. A systematic search and meta-analysis of the literature was performed to compare outcomes of disease-specific mortality (DSM), metastatic and recurrent disease and the incidence of fusion events between DSV and c-PTC to July 2022. The Newcastle–Ottawa Quality Assessment studies was used to assess quality. An odds ratio (OR) was utilised to measure outcomes with 95% CIs. The Preferred Reporting Items for Systematic Reviews and Meta-analysis guideline was followed. Seventeen studies were included with 874 DSV patients compared to 76,013 c-PTC patients. DSV patients had worse DSM (OR=2.50, 95% CI 1.39–4.51) and presented with a higher rate of metastatic lymph nodes (OR = 5.85, 95% CI 2.73–12.53) and more distant metastases (OR = 3.83, 95% CI 2.17–6.77). DSV patients had higher odds of recurrent disease (OR = 3.23, 95% CI 2.00–5.23) and overall distant metastasis (OR = 2.70, 95% CI 1.74–4.17). Rates of RET fusion alterations for DSV ranged from 25 to 83%. DSV has a worse prognosis than c-PTC with higher rates of recurrent disease and distant metastasis. The high prevalence of RET fusions offers the potential to improve outcomes for patients with DSV.
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