Cytologic features of differentiated high-grade thyroid carcinoma: A multi-institutional study of 40 cases.

BACKGROUND: Differentiated high-grade thyroid carcinoma (DHGTC) is recently recognized by the World Health Organization (WHO) as a subgroup of thyroid carcinomas with high-grade features while retaining the architectural and/or cytologic features of well-differentiated follicular-cell-derived tumors. The cytomorphology of DHGTC is not well documented despite potential implications for patient triage and management. METHODS: The pathology archives of six institutions were searched for cases diagnosed on resection as "high-grade thyroid carcinoma" using WHO criteria. The fine-needle aspiration (FNA) cohort represents a 10-year period (2013-2023); all were reviewed to confirm DHGTC classification. The corresponding FNAs were assessed for 32 cytomorphologic features. RESULTS: Forty cases of DHGTC with prior FNA were identified. The mean patient age was 64.2 years. The average lesion size was 4.9 cm, and the majority demonstrated a TI-RADS score of 4 or 5 (95.2%). Three main high-grade subsets of DHGTC based on corresponding histology included papillary thyroid carcinoma (65%), follicular carcinoma (22.5%), and oncocytic carcinoma (12.5%). Over 97% of FNA cases were classified as Bethesda category IV or above. Approximately 25% of DHGTC showed cytologic features that included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, or necrosis (p < .05); 68% of DHGTC cases were associated with high-risk molecular alterations. TERT mutations occurred in 41%, of which 89% of these were associated with a second mutation, usually RAS or BRAF p.V600E. CONCLUSIONS: Cytology has a low sensitivity for DHGTC, although a subset of DHGTCs have cytologic features raising the possibility of a high-grade thyroid carcinoma. Other findings include high-risk molecular changes and clinicopathologic features such as older patient age and larger lesion size.

Thyroid nodules with DICER1 mutation or PTEN alteration: A comparative cytologic, clinical, and molecular study of 117 FNA cases.

BACKGROUND: DICER1 mutations and PTEN alterations are increasingly detected by thyroid fine-needle aspiration (FNA). Both are associated with nodular thyroid disease and cancer. The authors analyzed a large comparative thyroid FNA cohort with DICER1 mutation or PTEN alteration. METHODS: A total of 117 thyroid FNAs with DICER1 or PTEN alterations were retrieved from the databases of two academic medical institutions. Demographic, clinical, and radiologic data were collected; FNA slides were analyzed for 29 cytomorphologic features. RESULTS: Of 117 thyroid FNAs, 36 (30.8%) had DICER1 mutation and 81 (69.2%) showed PTEN alteration. The DICER1 cohort had 33 (91.7%) females and three (8.3%) males (mean, 40.9 years); 61.8% had multinodular disease. FNAs were classified as atypia of undetermined significance (AUS), 23 (63.9%); follicular neoplasm (FN), 12 (33.3%); and malignant, 1 (2.8%). The PTEN subgroup had 66 (81.5%) females and 15 (18.5%) males (mean, 55.2 years) with increased multinodular disease (93.8%, p = .0016). PTEN FNAs had greater cytologic diversity: non-diagnostic, 2 (2.5%); benign, 5 (6.2%); AUS, 44 (54.3%); FN, 24 (29.6%); and malignant, 6 (7.4%). Both DICER1 and PTEN cases showed a range of resected tumor subtypes. The DICER1 cohort included thyroblastoma, and the PTEN group included anaplastic carcinoma. The cytomorphology of DICER1 and PTEN cases showed overlapping features, especially microfollicular patterns. Minor cytomorphologic differences included papillary patterns in DICER1 (p = .039), and oncocytic changes (p < .0001) in PTEN. CONCLUSIONS: DICER1 and PTEN FNAs reveal many cytologic similarities. DICER1 patients are younger, and PTEN patients had multinodular disease. Awareness of these genetic cohorts can identify patients at risk for thyroid cancer.

Thyroblastoma: A DICER1-associated embryonal neoplasm and fine needle aspiration diagnostic criteria.

Thyroblastoma is a rare, aggressive embryonal thyroid neoplasm associated with DICER1 mutation. It usually presents as a rapidly growing thyroid mass diffusely infiltrating the thyroid lobes and extending into perithyroidal tissue. Most thyroblastomas were initially diagnosed as malignant teratoma or carcinosarcoma. The cytologic features of thyroblastoma have not been well documented. Here, we present the cytological findings of a case of thyroblastoma in a 19-year-old female with a dominant solid left thyroid nodule. A fine needle aspiration biopsy of the mass revealed a highly cellular aspirate composed of crowded, atypical, high nuclear to cytoplasmic ratio epithelial cells, arranged in a variety of architectural patterns including rosette-like microfollicular, solid, and morular. In addition, the background contains a minor population of atypical mesenchymal cells. The cytologic differential diagnosis of thyroblastoma includes primary thyroid neoplasms such as adenomatous nodule, follicular adenoma, follicular carcinoma, and poorly differentiated thyroid carcinoma as well as metastatic carcinoma.

Constitutive Cytomorphologic Features of Medullary Thyroid Carcinoma Using Different Staining Methods.

(1) Background: Accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to a spectrum of cytomorphologic features. However, there is a scarcity of studies describing the cytomorphologic features as seen on fine-needle aspiration (FNA) smears prepared using different staining methods. (2) Methods: We performed a retrospective study on MTC cases with available FNA slides from 13 hospitals distributed across 8 Asia-Pacific countries. The differences in the constitutive cytomorphologic features of MTC with each cytopreparatory method were recorded. A comparative analysis of cytologic characteristics was carried out with appropriate statistical tests. (3) Results: Of a total of 167 MTC samples retrospectively recruited, 148 (88.6%) were interpreted as MTC/suspicious for MTC (S-MTC). The staining methods used were Papanicolaou, hematoxylin-eosin, and Romanowsky stains. Seven out of the eleven cytologic criteria can be readily recognized by all three cytopreparatory methods: high cellularity, cellular pleomorphism, plasmacytoid cells, round cells, dyshesive cells, salt-and-pepper chromatin, and binucleation or multinucleation. An accurate diagnosis was achieved in 125 (84.5%) of the 148 samples whose FNAs exhibited five or more atypical features. Conclusions: The present work is the first study on MTC to compare the morphological differences among the cytologic staining techniques. We investigated the constitutive features and the reliability of diagnostic parameters. A feasible scoring system based upon cytomorphologic data alone is proposed to achieve a high degree of diagnostic accuracy.

Cytologic diagnosis of medullary thyroid carcinoma in the Asia-Pacific region.

BACKGROUND: The accurate preoperative identification of medullary thyroid carcinoma (MTC) is challenging due to the rarity of tumor and variable cytologic appearance. The Asian experience with diagnosing MTC by fine-needle aspiration (FNA) was scarcely reported. METHODS: Cases of MTC with available FNA slides were enrolled from 13 hospitals representing 8 Asia-Pacific countries. Clinicopathological information, including sample preparation technique, staining method, original cytologic diagnosis and review diagnosis were collected. RESULTS: Of a total of 145 MTC cases retrospectively recruited, 99 (68.3%) were initially interpreted as MTC/suspicious for MTC (S-MTC). The distribution of original FNA diagnostic categories was not associated with the staining method or sample preparation technique. The staining methods used were Papanicolaou, hematoxylin-eosin and Romanowsky stains. Liquid-based cytology (LBC) was used only in three countries. After reviewing all cases, the diagnostic rate of MTC/S-MTC increased to 91.7% (133/145). Cases with initially unrecognized MTC had either marked pleomorphism or cytology mimicking papillary carcinoma or follicular neoplasm. Although LBC provided certain benefits, there was no significant difference in diagnostic accuracy between conventional smear and LBC. Immunocytochemistry was available in 38 cases (26.2%), all of which were correctly recognized as MTC. CONCLUSION: Our report summarizes how MTC is handled in contemporary Asian thyroid FNA practice. Although the detection rate of MTC by cytology alone is less satisfactory, integration with ancillary tests could achieve an excellent performance. The recognition of constitutive cytomorphologic features is needed for each cytopreparatory method, which may result in a lower threshold to initiate further workup for MTC.

Application of the Bethesda System for Reporting Thyroid Cytopathology in the Pediatric Population.

OBJECTIVES: We aimed to provide the Asian experience with the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) in pediatric thyroid nodules. METHODS: Consecutive thyroid fine-needle aspirates (patient age, ≤18 years) were retrospectively collected from 7 tertiary centers in 5 Asian countries. RESULTS: Of 194,364 thyroid aspirates, 0.6% were pediatric cases (mean age, 15.0 years). Among 827 nodules with accessible follow-up, the resection rate and risk of malignancy (ROM) were 36.3% and 59.0%, respectively. Malignant nodules (n = 179) accounted for 59.7% of resected nodules and 21.6% of all thyroid nodules with available follow-up. Compared with the published adult series, pediatric nodules had a higher resection rate and ROM, particularly in the indeterminate categories. CONCLUSIONS: Our study demonstrates that Asian pediatric thyroid nodules had higher ROM than those from adults. The prototypic outputs of TBSRTC may need to be adjusted in the pediatric population.

Current Status of Thyroid Fine-Needle Aspiration Practice in Thailand.

Thyroid carcinoma is one of the leading malignancies in Thailand increasingly prevalent in the female population. Fine-needle aspiration (FNA) cytology is a widely used diagnostic tool for evaluation of thyroid nodules and thyroid cancer. Thyroid FNA is a routine procedure universally performed in Thai hospitals by a variety of clinical specialists. Manual guidance is the first-line choice complemented by ultrasound assistance in selected cases. Despite national guidelines recommendations, the diagnostic criteria and terminology of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was slowly adopted in the local settings. Currently, the Bethesda system is actively promoted by the local professional societies as a uniform reporting system. Experience with thyroid FNA has been rarely reported to date-only a handful of publications are available in local journals. Our review, in addition to presenting various aspects of thyroid FNA in Thailand, established for the first time national references for a certain statistical outputs of TBSRTC based on the original multi-institutional cohort. The risk of malignancy in 2,017 operated thyroid nodules collected from three tertiary thyroid cancer centers was 21.7%, 14.7%, 35.9%, 44.4%, 76.7%, and 92.6% for categories I to VI, respectively. The malignancy risk in several diagnostic categories (II to IV) was higher than the risk estimated by TBSRTC and recent meta-analysis studies. We endorse the use of uniform terminology of the Bethesda system in Thailand, which will help facilitate communication among diverse medical professionals involved in the management of patients with thyroid nodules, to share local experience with the international audience.