Role of Cytomorphometry and BRAFV600E Immunocytochemistry With a Cytologic Diagnosis "Suspicious for Papillary Thyroid Carcinoma"

Thyroid nodules (TNs) are a common finding, detected by ultrasound in about 70% of healthy individuals, with women being four times more affected. While most TNs are benign, the primary clinical goal is to exclude malignancy, which occurs in 4-6.5% of cases. Risk factors for TNs include age, gender, iodine imbalance, family history, and radiation exposure. Thyroid cancer incidence has risen due to improved diagnostic methods such as ultrasound, FNAC, CT, MRI, and PET scans. Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy (90%), followed by follicular, Hurthle cell, medullary, and anaplastic carcinomas. Most thyroid cancers have an excellent prognosis, with a 5-year survival rate of 98.6%. FNAC is the gold standard for diagnosing TNs, and the Bethesda system (TBSRTC) categorizes cytology results into six groups with varying malignancy risks. The "suspicious for malignancy" category (74% risk) includes mostly suspicious papillary thyroid carcinoma (SPTC), but false positives occur, especially in cases of Hashimoto's thyroiditis. SPTC diagnosis can be challenging, leading to potential overtreatment. To improve diagnostic accuracy, additional techniques like detailed ultrasonographic criteria, intraoperative frozen section, and molecular marker testing are used. Cytomorphometric analysis has been explored for distinguishing benign from malignant thyroid lesions, assessing nuclear size, shape, and chromatin patterns. Most studies have focused on histological sections, but applying morphometry to cytology could enhance automated and accurate diagnoses. Molecular studies reveal that PTCs primarily arise from MAPK pathway mutations, with BRAFV600E being the most common (60%). This mutation is strongly associated with aggressive tumor behavior and recurrence. BRAFV600E testing combined with FNAC significantly improves diagnostic accuracy, increasing sensitivity from 76.71% (mutation testing alone) to 96.62% when combined with cytology. This integration has reduced false-negative PTC diagnoses and facilitated targeted therapies.

Sex

All

Inclusion Criteria:

* Only Papanicolaou (PAP) and Hematoxylin \& Eosin (H\&E) stained FNAC smears diagnosed as suspicious for papillary thyroid carcinoma will be included in the study.
* Only FNAC smears with well-preserved nuclear morphology will be included in the study.
* Smears with histopathological slides.

Exclusion Criteria:

* FNAC smears lacking histopathological confirmation.
* Smears with extensive nuclear overlap and poor morphology.
* Smears obscured by inflammation, blood, or mucoid material.
* Smears exhibiting cellular degenerative changes or drying artifacts.
* Any patient with missing data.

• BACKGROUNDZhu Y, Ren W, Song Y, Fan Z, Wang Q, Jin H, Guo Y, Bai Y. Cytomorphologic features as predictors of aggressiveness in patients with pT1 papillary thyroid carcinoma: a retrospective study of associations with clinicopathological parameters in 226 fine-needle aspirates. Gland Surg. 2021 Jan;10(1):319-327. doi: 10.21037/gs-20-618. PMID 33633988
• BACKGROUNDTamhane S, Gharib H. Thyroid nodule update on diagnosis and management. Clin Diabetes Endocrinol. 2016 Oct 3;2:17. doi: 10.1186/s40842-016-0035-7. eCollection 2016. PMID 28702251
• BACKGROUNDPriya SS, Sundaram S. Morphology to morphometry in cytological evaluation of thyroid lesions. J Cytol. 2011 Jul;28(3):98-102. doi: 10.4103/0970-9371.83462. PMID 21897541
• BACKGROUNDParker KG, White MG, Cipriani NA. Comparison of Molecular Methods and BRAF Immunohistochemistry (VE1 Clone) for the Detection of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis. Head Neck Pathol. 2020 Dec;14(4):1067-1079. doi: 10.1007/s12105-020-01166-8. Epub 2020 May 1. PMID 32358715
• BACKGROUNDMohorea I, Socea B, Carap AC, Serban D, Ceausu Z, Ceausu M. Morphometric study in thyroid tumors. Exp Ther Med. 2023 Sep 6;26(4):497. doi: 10.3892/etm.2023.12196. eCollection 2023 Oct. PMID 37745041
• BACKGROUNDMahajan A, Lin X, Nayar R. Thyroid Bethesda reporting category, 'suspicious for papillary thyroid carcinoma', pitfalls and clues to optimize the use of this category. Cytopathology. 2013 Apr;24(2):85-91. doi: 10.1111/j.1365-2303.2012.00966.x. Epub 2012 Feb 22. PMID 22356185
• BACKGROUNDLeiker AJ, Yen TW, Cheung K, Evans DB, Wang TS. Cost analysis of thyroid lobectomy and intraoperative frozen section versus total thyroidectomy in patients with a cytologic diagnosis of "suspicious for papillary thyroid cancer". Surgery. 2013 Dec;154(6):1307-13; discussion 1313-4. doi: 10.1016/j.surg.2013.06.031.