LAUSR

This month’s edition of the journal Cytopathology contains a series of articles describing various recent developments in thyroid FNA, very much a hot topic. The role of thyroid FNAC continues to evolve, driven by recent developments in thyroid tumour diagnosis, classification, prognostication and the introduction of new therapies including gene therapies. Recent changes include the recognition of poorly differentiated carcinoma of the thyroid as an intermediate prognostic lesion between well differentiated papillary thyroid carcinoma/follicular thyroid carcinoma and anaplastic thyroid carcinoma and the redesignation of encapsulated or circumscribed follicular variant of papillary thyroid carcinoma without capsular or vascular invasion (if other strict criteria are met) as non-invasive follicular thyroid neoplasm with papillary-like nuclear features NIFTP. As the latest World Health Organisation Classification of Tumours of Endocrine Organs states, ‘. . .by far the most controversial issue that has impacted the field in recent years has been the proposed introduction into the classification of well differentiated follicular tumours of a group of neoplasms (intermediate, borderline). . . that are morphologically and behaviourally intermediate between follicular adenoma and follicular carcinoma/follicular variant of papillary carcinoma’. As the histopathological diagnostic criteria change, cytological diagnostic thresholds are adapting to updated histopathological tumour classifications, one of the drivers for revision of the Bethesda System for Reporting Thyroid FNA Cytology and other international thyroid FNA reporting terminologies. The diagnostic dilemma of the indeterminate thyroid FNA is well known. Some papillary thyroid carcinomas on FNA show minimal nuclear atypia, a low cell yield or are cystic, and some benign lesions may show cytomorphological features that are atypical or suggestive of malignancy and these aspirates cannot be readily classified as either benign or malignant. These aspirates comprise approximately 25% or so of all FNAs, so-called indeterminate thyroid FNAs. Thyroid FNA is both a diagnostic test for thyroid carcinoma and a triage test for benign thyroid nodules. An accompanying review article discusses molecular techniques applicable to diagnosis of indeterminate thyroid FNA, tumour prognostication and therapy. Another article by Decaussin-Petrucci et al. discusses the routine application of BRAF, TERT promoter and HRAS/NRAS mutational analysis in thyroid FNA, demonstrating the value of BRAF V600E and TERT promoter mutations as specific tests for malignancy in a routine clinical practice setting using residual material from liquid-based thyroid FNA. Poorly differentiated thyroid carcinoma is a comparatively rare lesion and its diagnosis histologically can be challenging because of diagnostic overlap with other subtypes of thyroid carcinoma that may show diagnostically similar microscopic features, eg some solid variants of papillary thyroid carcinoma, follicular thyroid carcinoma with a solid growth pattern, anaplastic thyroid carcinoma or the possibility of a metastatic tumour to the thyroid. Insular or solid architecture, hypercellularity, high nuclear-cytoplasmic ratio and mitotic activity are features that may suggest a diagnosis of poorly differentiated thyroid carcinoma in thyroid FNA. As Saglietti et al. explain, of the 101 cases of poorly differentiated thyroid carcinoma reported in the literature only 27% were recognised preoperatively. The authors highlight the value of immunohistochemistry on slides or cell block material to distinguish poorly differentiated thyroid carcinoma from medullary thyroid carcinoma as poorly differentiated thyroid carcinoma is negative for tumour markers such as calcitonin and carcinoembryonic antigen and is usually positive for thyroglobulin and thyroid transcription factor 1, also the use of TERT promoter mutation which is found at relatively high (40%) frequency in poorly differentiated thyroid carcinoma with lower rates of mutation for TP53 and EIF1AX. Kakudo and colleagues have written an extensive review of approaches to thyroid FNA in Asia and of Asian cytology practice. Of particular interest to journal readers will be the discussion of thyroid carcinoma surveillance (no immediate surgery) for malignant thyroid nodules. While there are currently no randomised controlled trials of thyroid cancer surveillance strategies, the Japanese experience suggests that this approach can be workable. Questions remain as to whether surveillance is effective outside of very strict practicecontrolled settings with strict patient inclusion and exclusion criteria, high quality ultrasound, FNA cytology, and clinical follow-up although criteria have been developed and similar strategies for thyroid cancer surveillance have been proposed in North America.