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Clinicopathological features and outcomes of multifocal versus unifocal papillary thyroid carcinoma a retrospective cohort study (143957)

Keshi Maheswaran 1 , Spinder Samra 2 , Lucy Mauviel 1 , Louis Britten-Jones 1 , Gideon Sandler 3 , Christian Girgis 1 4 , Albert Kim 1 4
  1. Sydney Medical School, Faculty of Medicine and Health, University of Sydney , Sydney , NSW, Australia
  2. Pathology, Institute of Clinical Pathology and Medical Research, Sydney, NSW, Australia
  3. Department of Head and Neck Surgery, Westmead Hospital, Westmead, NSW, Australia
  4. Department of Endocrinology, Westmead Hospital, Westmead, NSW , Australia

The 2025 American Thyroid Association (ATA) guidelines incorporate multifocality, laterality, and tumour focus size into papillary thyroid carcinoma (PTC) risk stratification (1). However, their prognostic significance remains uncertain (2-5). This study evaluated associations between multifocality, clinicopathological characteristics, and clinical outcomes.

This retrospective cohort study included patients with PTC who underwent surgical management at Westmead Hospital between 2016-2025. Patients were classified as having unifocal or multifocal disease, with further stratification by microcarcinoma status and laterality. Data collected included clinicopathological features and treatment outcomes within a 2-year follow-up period, including radioactive iodine (RAI) use, additional surgery, biochemical response and recurrence as defined by the 2025 ATA guidelines (Table 1). Categorical variables were analysed using chi-square tests with Cramer’s V for effect size, and continuous variables were analysed using independent samples t-tests.

Among 241 patients, 111 had unifocal and 130 had multifocal PTC. Mean age was similar between groups (46.4±15.4 vs 46.5±16.0 years, p=0.955). A lower proportion of female patients had multifocal disease (66.9% vs 78.4%, p=0.048) and multifocal disease was associated with larger cumulative tumour size (32.9±24.9 vs 22.2±14.6, p<0.001). No other significant differences were observed between unifocal and multifocal cohorts in aggressive pathological features or treatment outcomes. Microcarcinoma was more prevalent in the multifocal cohort (80.8% vs 15.3%, p<0.001). Multifocal tumours with macroscopic foci demonstrated greater cumulative tumour size, increased margin involvement (41.7% vs 17.5%, p=0.010), and more advanced staging (p=0.020) but there were no significant differences in treatment or outcomes.  Bilateral multifocal disease had greater cumulative tumour size than unilateral multifocal disease (p<0.001), although differences in recurrence were not statistically significant.

Multifocal PTC is heterogeneous and was not associated with worse outcomes in this cohort. Tumour characteristics and laterality identified distinct pathological patterns warranting further investigation with multivariable and longer-term outcome analyses.

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