J Pathol Transl Med.  2024 Nov;58(6):299-309. 10.4132/jptm.2024.07.25.

Diagnostic challenges in the assessment of thyroid neoplasms using nuclear features and vascular and capsular invasion: a multi-center interobserver agreement study

• Harahap AS
• Mutmainnah M
• Ham MF
• Khoirunnisa D
• Assadyk AH
• Cangara H
• Asri A
• Retnani DP
• Quzwain F
• Agustina H
• Istiadi H
• Windarti I
• Murti K
• Takbir M
• Mahastuti NM
• Kurniasari N
• Anggorowati N
• Abineno P
• Setyorini YP
• Kakudo K

• KMID: 2560671
• DOI: http://doi.org/10.4132/jptm.2024.07.25

Abstract

Background
The diagnosis of thyroid neoplasms necessitates the identification of distinct histological features. Various education/hospital centers located in cities across Indonesia likely result in discordances among pathologists when diagnosing thyroid neoplasms.
Methods
This study examined the concordance among Indonesian pathologists in assessing nuclear features and capsular and vascular invasion of thyroid tumors. Fifteen pathologists from different centers independently assessed the same 14 digital slides of thyroid tumor specimens. All the specimens were thyroid neoplasms with known BRAFV600E and RAS mutational status, from a single center. We evaluated the pre- and post-training agreement using the Fleiss kappa. The significance of the training was evaluated using a paired T-test.
Results
Baseline agreement on nuclear features was slight to fair based on a 3-point scoring system (k = 0.14 to 0.28) and poor to fair based on an eight-point system (k = –0.02 to 0.24). Agreements on vascular (κ = 0.35) and capsular invasion (κ = 0.27) were fair, whereas the estimated molecular type showed substantial agreement (κ = 0.74). Following the training, agreement using the eight-point system significantly improved (p = 0.001).
Conclusions
The level of concordance among Indonesian pathologists in diagnosing thyroid neoplasm was relatively poor. Consensus in pathology assessment requires ongoing collaboration and education to refine diagnostic criteria.

Keyword

Thyroid neoplasms; Observer variation; Papillary thyroid cancer

Figure

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  Fig. 1. The geographical distribution of participating pathologists. Each main island of Indonesia had at least one participating pathologist, with the largest number coming from Java and Sumatra.

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  Fig. 2. (A) The assessment of the microscopic appearance of this NRASQ61R-mutated case led to the most significant interobserver disagreement when using a three-point scoring system, primarily due to the ambiguous nature of the nuclear features. (B) The assessment of this HRASQ61R mutated-case led to the strongest interobserver agreement when assessed using a three-point system. Most pathologists assigned a total nuclear score of 1 for this case. (C) A BRAFV600E-mutated papillary thyroid carcinoma case showing marked nuclear alterations such as nuclear crowding, an irregular nuclear membrane, chromatin clearing, and nuclear grooves, with most pathologists agreeing on a total score of 3. (D) All pathologists noted vascular invasion (arrow). (E) This case demonstrated the greatest level of interobserver disagreement regarding capsular invasion, with some pathologists indicating "no" and others indicating "equivocal" (arrow).

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  Fig. 3. Box plots of total nuclear scores using the three-point scoring system (A) and the eight-point scoring system (B). As shown by the vertical axis, the total nuclear score after training was lower and showed a narrower range compared to the first round. Using the eight-point score system, there was a significant difference between the level of agreement in the first and second rounds (p = .001). aThe p-value is obtained from the mean calculation of Kappa value using a paired T-test.

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  Fig. 4. Comparative analysis of the average sum of nuclear scores provided by 15 pathologists across two rounds when using the three-point scoring system (A) and eight-point scoring system (B).

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  Fig. 5. Comparison of kappa values for nuclear features between endocrine and non-endocrine experts in the first round. PTC, papillary thyroid carcinoma.

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  Fig. 6. Comparison of kappa values for nuclear features between endocrine and non-endocrine experts in the second round. PTC, papillary thyroid carcinoma.

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Reference

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