Comparative Prognostic Analysis of the Tall Cell Subtype of Papillary Thyroid Carcinoma With the Conventional Subtype Following the WHO 2022 Revision: An Indian Cohort Study

TL;DR

This study compares the aggressive tall cell subtype of thyroid cancer with the conventional subtype in an Indian population to assess prognosis and the validity of new WHO criteria.

Contribution

The study evaluates the WHO 2022 criteria for tall cell PTC and suggests a less stringent threshold may better predict clinical outcomes.

Findings

PTC with tall cell features showed higher rates of extrathyroidal extension, advanced T stage, and distant metastasis compared to classical PTC.

A 30% cutoff for 2x tall cells was significantly associated with recurrence and mortality, even after multivariate adjustment.

The WHO 2022 definition using 3x tall cells did not significantly correlate with recurrence or mortality.

Abstract

​​​Introduction: Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with multiple subtypes and accounts for the majority of thyroid malignancies worldwide. The tall cell subtype (TC-PTC) is recognised for its aggressive behaviour, poorer prognosis, and higher likelihood of extrathyroidal extension and distant metastasis. This study aimed to evaluate the prognostic validity of the revised WHO 2022 criteria for TC-PTC (≥30% of cells at least three times as tall as wide with dense eosinophilic cytoplasm and distinct cell membranes), compare clinicopathological features and outcomes of PTCs with any tall cell features (PTC-TCF) with classical PTC (cPTC), and determine whether less stringent morphological thresholds better identify clinically aggressive tumours.

Methods: This retrospective comparative study was conducted in the Pathology Department of a tertiary care hospital in Kerala over four years (2015-2019) with a minimum five-year follow-up. Two groups were compared: PTC-TCF and cPTC, designated as cases and controls respectively. Based on distant metastasis proportions in TC-PTC and cPTC from an earlier study, with 95% confidence, 80% power, and a 1:4 ratio, the minimum required sample size was 66 cases and 264 controls (total of 330). Clinical and histopathological details were obtained from electronic medical records, and follow-up data from the institutional cancer registry. Archived H&E slides of cases with tall cell components were retrieved and reassessed for degree and percentage of tall cells. Statistical analysis was performed using IBM SPSS version 20.0 (IBM Corp., Armonk, NY, USA), with p < 0.05 considered statistically significant.

Results: Of the 330 cases studied, 66 (20%) showed tall cell features. Compared with cPTC, PTC-TCF cases demonstrated significantly higher rates of extrathyroidal extension (ETE) (p < 0.001), advanced pathological T stage (p < 0.001), distant metastasis at presentation (p = 0.005), recurrence (p < 0.001), and mortality (p = 0.020). On multivariate analysis adjusted for tumour size and nodal status, T2 (HR = 12.70, p < 0.001) and T3 (HR = 17.40, p < 0.001) stages retained independent statistical significance.

Tumour subtype (p < 0.001), tumour size (p = 0.043), modified American Thyroid Association (ATA) risk class (p = 0.006), proportion of cells with height twice as tall as width (2x) ≥ 30% (p = 0.003), T stage (p = 0.043), and M stage at presentation (p = 0.021) were found significant with respect to recurrence and death trends on univariate analysis. Categorising tumours using the WHO 2022 definition for tall cell subtype (≥ 30% of cells with height thrice as tall as width or 3x) did not yield significant correlation with recurrence or mortality rates (p = 0.197). After controlling for tumour focality, ETE, and lymphovascular invasion (LVI), presence of 2× tall cells in ≥ 30% retained significance (HR = 2.46, p = 0.048) with respect to prognostic outcomes on multivariate analysis.

Conclusion: In our study, the proportion of 2x tall cells with a cutoff of 30% showed statistical significance with respect to recurrence and mortality, which was retained even on multivariate analysis. This indicates that setting a criterion of 2x-3x tall cells for the diagnosis of tall cell PTC could better predict the prognosis.

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