A deep learning-based algorithm for tall cell detection in papillary thyroid carcinoma

Abstract

Introduction: According to the World Health Organization, the tall cell variant (TCV) is an aggressive subtype of papillary thyroid carcinoma (PTC) comprising at least 30% epithelial cells two to three times as tall as they are wide. In practice, applying this definition is difficult causing substantial interobserver variability. We aimed to train a deep learning algorithm to detect and quantify the proportion of tall cells (TCs) in PTC.

Methods: We trained the deep learning algorithm using supervised learning, testing it on an independent dataset, and further validating it on an independent set of 90 PTC samples from patients treated at the Hospital District of Helsinki and Uusimaa between 2003 and 2013. We compared the algorithm-based TC percentage to the independent scoring by a human investigator and how those scorings associated with disease outcomes. Additionally, we assessed the TC score in 71 local and distant tumor relapse samples from patients with aggressive disease.

Results: In the test set, the deep learning algorithm detected TCs with a sensitivity of 93.7% and a specificity of 94.5%, whereas the sensitivity fell to 90.9% and specificity to 94.1% for non-TC areas. In the validation set, the deep learning algorithm TC scores correlated with a diminished relapse-free survival using cutoff points of 10% (p = 0.044), 20% (p < 0.01), and 30% (p = 0.036). The visually assessed TC score did not statistically significantly predict survival at any of the analyzed cutoff points. We observed no statistically significant difference in the TC score between primary tumors and relapse tumors determined by the deep learning algorithm or visually.

Conclusions: We present a novel deep learning-based algorithm to detect tall cells, showing that a high deep learning-based TC score represents a statistically significant predictor of less favorable relapse-free survival in PTC.

Fig 1. CONSORT flow diagram of the datasets used in the study.

Papillary thyroid carcinoma is abbreviated as PTC.

Fig 2. The convolutional neural network model consisted of two algorithms.

a) A segmentation algorithm detects the tumor tissue (blue), which is fed as an input to a b) tall cell (TC) segmentation algorithm trained to detect TC epithelial regions (red) as well as non-TC epithelial regions (green). Finally, the TC score of the total epithelial area was calculated.

Fig 3

a) A zoomed-out view of a papillary thyroid carcinoma tissue sample in which the results of the deep learning (DL) algorithm’s first layer are shown (blue). From the registered carcinoma area, the DL algorithm then registers the carcinoma epithelium as either b) tall cell (TC) (red) or c) non-TC area (green). The DL algorithm determines the percentage of the epithelium covered by TCs, that is, the TC score.

Fig 4. Kaplan–Meier curves for relapse-free survival (RFS) among patients with papillary thyroid cancer according to three tall cell percentage thresholds: 10%, 20%, and 30% based on visual assessment (a–c) and using the algorithmic assessment (d–f).

In the figure, tall cell is abbreviated as TC.

Fig 5. Kaplan–Meier curves for relapse-free survival (RFS) among patients with papillary thyroid cancer according to tall cell percentage thresholds: <10%, 10–29%, and ≥30% based on a) visual assessment and b) algorithmic assessment.

In the figure, tall cell is abbreviated as TC.