Papillary thyroid carcinomas are the most common endocrine cancer and are usually associated with good survival. However, some variants of papillary thyroid carcinomas may behave more aggressively than classic papillary thyroid carcinomas. The tall cell variant of papillary thyroid carcinoma is the most common aggressive variant of papillary thyroid carcinoma. The aggressive behavior has been ascribed to the histologic subtype and/or to the clinicopathologic features, an issue that remains controversial. The columnar variant of papillary thyroid carcinoma can be aggressive, particularly in older patients, with larger tumors showing a diffusely infiltrative growth pattern and extrathyroidal extension. A papillary thyroid carcinoma is designated as solid/trabecular variant when all or nearly all of a tumor not belonging to any of the other variants has a solid, trabecular, or nested (insular) appearance. This tumor must be distinguished from poorly differentiated thyroid carcinoma which has the same growth pattern but lacks nuclear features of papillary thyroid carcinoma and may show tumor necrosis and high mitotic activity. New to the fourth edition of the WHO Classification of Tumours of Endocrine Organs, the hobnail variant of papillary thyroid carcinoma is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. All of these variants are histologically unique and important to recognize due to their aggressive behavior.

Aggressive Variants of Papillary Thyroid Carcinoma: Hobnail, Tall Cell, Columnar, and Solid

This article reviews the small percentage of thyroid tumours that are not classified as classic papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma. It includes subtypes of papillary thyroid carcinoma, including, tall-cell, hobnail/micropapillary, columnar cell, diffuse sclerosing and solid variants. Poorly differentiated carcinoma, high-grade carcinoma and anaplastic thyroid carcinoma are reviewed. Also discussed are entities that are unusual but need to be recognized as primary thyroid neoplasms, i.e. mucoepidermoid carcinoma, sclerosing mucoepidermoid carcinoma with eosinophilia, and mammary analogue secretory carcinoma/secretory carcinoma. The pathological features and prognostic factors are described; a brief review of molecular correlates of these neoplasms is included.

Special types of thyroid carcinoma.

Kennichi Kakudo, Andrey Bychkov, Yanhua Bai, Yaqiong Li, Zhiyan Liu and Chan Kwon Jung Faculty of Medicine, Department of Pathology and Laboratory Medicine, Nara Hospital, Kindai University, Ikomacity, Japan, Department of Pathology, Kameda Medical Center, Kawagoe, Chiba, Japan, Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China, Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong, China, Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Shandong, China, and Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea

https://onlinelibrary.wiley.com/doi/pdf/10.1111/pin.12737

The new 4th edition World Health Organization classification for thyroid tumors, Asian perspectives

Papillary thyroid carcinoma is the most common thyroid malignancy and it is usually associated with a good prognosis. However, recurrence, metastases, and cancer death may occur in 10 to 15% of patients with more aggressive types of papillary thyroid carcinoma, such as tall cell, columnar cell, solid variant, or the more recently described hobnail variant of papillary thyroid carcinoma. Papillary thyroid carcinoma with a prominent hobnail pattern is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. The hobnail variant of papillary thyroid carcinoma shows prominent hobnail features, which have also been referred to as micropapillary. The typical hobnail/micropapillary morphological features show loss of cellular polarity/cohesiveness and support an epithelial-mesenchymal transition as a possible mechanism of metastasis. BRAF p.V600E is the most common mutation in papillary thyroid carcinoma, including the hobnail variant; recent and continuing studies are focused on defining other molecular anomalies that may be useful for prognostic stratification and may provide therapeutic targets.

Hobnail Variant of Papillary Thyroid Carcinoma: a Literature Review

This review summarises molecular pathological techniques applicable to thyroid FNA. The molecular pathology of thyroid tumours is now fairly well understood. Molecular methods may be used as a rule-in test for diagnosis of malignancy in thyroid nodules, eg BRAF V600E point mutation, use of a seven-gene mutational panel (BRAF V600E, RAS genes, RET/PTC or PAX8/PPARG rearrangement), or as a comprehensive multigene next-generation sequencing panel, eg ThyroSeq v2. Molecular methods can also be applied as rule-out tests for malignancy in thyroid nodules, eg Afirma or ThyroSeq v2 or as markers of prognosis, eg TERT promoter mutation or other gene mutations including BRAF V600E, TP53 and AKT1, and as tests for newly defined tumour entities such as non-invasive follicular thyroid neoplasm with papillary like nuclei, or as a molecular marker(s) for targeted therapies. This review describes practical examples of molecular techniques as applied to thyroid FNA in routine clinical practice and the value of molecular diagnostics in thyroid FNA. It describes the range of molecular abnormalities identified in thyroid nodules and thyroid cancers with some practical applications of molecular methods to diagnosis and prognosis of thyroid nodules and thyroid cancer.

/pdf/molecular-pathology-and-thyroid-fna-4bq528c9v7.pdf

Molecular pathology and thyroid FNA.

// Lianghong Teng 1, 2 , Wanglong Deng 3 , Junliang Lu 1 , Jing Zhang 1 , Xinyu Ren 1 , Huanli Duan 1 , Shannon Chuai 3 , Feidie Duan 3 , Wei Gao 2 , Tao Lu 1 , Huanwen Wu 1 , Zhiyong Liang 1 1 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China 2 Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing, China 3 Burning Rock Biotech Co. Ltd., Guangzhou, China Correspondence to: Zhiyong Liang, email: liangzhiyong1220@yahoo.com Huanwen Wu, email: whw14093@163.com Keywords: papillary thyroid carcinoma, hobnail variant, next-generation sequencing, molecular features, TERT promoter mutation Received: December 06, 2016     Accepted: January 24, 2017     Published: February 28, 2017 ABSTRACT Background: As a rare but aggressive papillary thyroid carcinoma (PTC) variant, the genetic changes of hobnail variant of PTC (HVPTC) are still unclear. Results: The prevalence of HVPTC was 1.69% (18/1062) of all PTC diagnosed in our cohort. 73 samples from 55 patients (17 HVPTC, 26 CPTC, 7 PDTC and 5 ATC) were successfully analyzed using targeted NGS with an 18-gene panel. Thirty-seven mutation variant types were identified among 11 genes. BRAF V600E mutation was the most common mutation, which is present in almost all HVPTC samples (16/17, 94%), most CPTC samples (20/26, 77%), and none of the ATC and PDTC samples. TERT promoter mutation (C228T) was identified in 2 ATC and one HVPTC patient. RAS and TP53 mutation are almost exclusively present among ATC and PDTC samples although TP53 mutation was also observed in 3 HVPTC patients. Six different GNAS mutations were identified among 8 CPTC patients (31%) and none of the HVPTC patients. The only patient who died of disease progression harbored concomitant TERT C228T mutation, BRAF V600E mutation and TP53 mutation. Methods: HVPTC cases were identified from a group of 1062 consecutive surgical specimens diagnosed as PTC between 2000 and 2010. Targeted next-generation sequencing (NGS) was applied to investigate the mutation spectrum of HVPTC, compared to classical PTC (CPTC), poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC). Conclusion: As an aggressive variant of PTC, HVPTC has relatively specific molecular features, which is somewhat different from both CPTC and ATC/PDTC and may underlie its relatively aggressive behavior.

Hobnail variant of papillary thyroid carcinoma: molecular profiling and comparison to classical papillary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma.

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Hobnail variant of papillary thyroid carcinoma: molecular profiling and comparison to classical papillary thyroid carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma.