Clinical-Pathological and Molecular Evaluation of 451 NIFTP Patients from a Single Referral Center

Background: Non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were introduced in thyroid pathology in 2016. NIFTPs are a group of follicular neoplasm with an indolent behaviour. In this study, we gathered a large retrospective cohort of NIFTPs and compared those presenting as solitary lesions and NIFTPs found in multifocal setting. Methods: A retrospective search of NIFTPs was performed, and the clinico-pathological features were recorded. For a subgroup of patients, pre-surgical ultrasound (US) evaluation, cytological diagnosis, and molecular analysis were available. Results: We collected 451 NIFTPs; 254 (56.3%) were truly solitary tumours, while 197 coexisted with one or more NIFTP/cancer. Contrasting unifocal and multifocal settings, NIFTPs size was the only significantly different parameter. Preoperatively, NIFTP nodules mostly showed low-risk US characteristics, indeterminate cytology and a RAS-like molecular profile. Conclusion: NIFTPs often coexist with collateral thyroid tumours. However, no clinical-pathological differences can be observed between solitary and “multifocal” NIFTPs. Despite the well-established clinical indolence of NIFTP, a careful monitoring of the contralateral lobe should not be excluded.

Rate and Clinical Predictors of Malignancy in Thyroid Nodules with Indeterminate Cytology

Background: Fine needle aspiration cytology (FNAC) cannot differentiate between benign and malignant conditions in cytologically indeterminate thyroid lesions. Therefore, a minimum of diagnostic lobectomy is required for definitive diagnosis. The objective of this study is to identify the rate of malignancy and clinical features that may possibly predict malignancy in patients with these lesions, in Ethiopian hospitals. Methods: This was a retrospective review of the medical records of patients who underwent surgery for cytologically indeterminate thyroid lesions in three referral hospitals between September 2015 and September 2020. Results: Of 85 patients with indeterminate cytology findings, 56 (63.5%) were follicular, and 29 (34.1%) were reported to be hurthle cell neoplasms. Follicular lesions of undetermined significance (FLUS) and suspicious for follicular neoplasm were each reported in single cases (1.7%). Malignant disease was diagnosed in 19 (22.4%) of patients. A follicular variant of papillary cancer was detected in 7 (11.5%) patients. Hard nodule consistency was reported in 9 of 11 malignant lesions and 5 of 66 benign lesions. In multivariate binary logistic regression, hard nodule consistency was found to be associated with malignancy (P = 0.012, AOR = 7.28 (1.5, 34.54) 95% CI ). The ill-defined surface of a nodule was found to be associated with malignancy though the association was not statistically significant (P = 0.088, AOR = 0.162 (0.020, 1.313) 95% CI. Ultrasound evaluation of thyroid nodule was performed only in 41 (47.7%) of patients. Conclusion: The rate of malignancy in thyroid nodules with indeterminate cytology was 22.4%. The risk of malignancy was higher in patients with hard thyroid nodule consistency and ill-defined surface. Despite the established benefits of ultrasound for the evaluation of thyroid nodules, the current practice of its use in our setup is suboptimal. Keywords: Follicular; hurthle cell; indeterminate cytology; predictors of malignancy

Contemporary Management of Thyroid Nodules

Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Significance of RAS Mutations in Thyroid Benign Nodules and Non-Medullary Thyroid Cancer

Thyroid nodules are detected in up to 60% of people by ultrasound examination. Most of them are benign nodules requiring only follow up, while about 4% are carcinomas and require surgery. Malignant nodules can be diagnosed by the fine-needle aspiration cytology (FNAC), which however yields an indeterminate result in about 30% of the cases. Testing for RAS mutations has been proposed to refine indeterminate cytology. However, the new entity of non-invasive follicular thyroid neoplasm, considered as having a benign evolution and frequently carrying RAS mutations, is expected to lower the specificity of this mutation. The aggressive behavior of thyroid cancer with RAS mutations, initially reported, has been overturned by the recent finding of the cooperative role of TERT mutations. Although some animal models support the carcinogenic role of RAS mutations in the thyroid, evidence that adenomas harboring these mutations evolve in carcinomas is lacking. Their poor specificity and sensitivity make the clinical impact of RAS mutations on the management of thyroid nodules with indeterminate cytology unsatisfactory. Evidence suggests that RAS mutation-positive benign nodules demand a conservative treatment. To have a clinical impact, RAS mutations in thyroid malignancies need not to be considered alone but rather together with other genetic abnormalities in a more general context.

Could Negative Tc-99m-Methoxyisobutylisonitrile (MIBI) Scintigraphy Obviate the Need for Surgery for Bethesda III and IV Thyroid Nodules?

In about 20% of all cases, the fine needle aspiration cytology (FNAC) results are equivocal, delivering the two common categories of indeterminate cytology, Bethesda III and IV. The observed rates of malignancy vary widely among institutions, with the urgent need for a more precise risk stratification. 99mcTc methoxyisobutylisonitrile scintigraphy (MIBI) is less expensive than molecular testing and has been shown to have a high negative predictive value. For this reason, the results of MIBI scintigraphy in adult patients with indeterminate FNAC were collected, and correlated with the final pathology reports of surgical specimens. Patients receiving FNAC, MIBI scintigraphy and surgery for sonographic suspicious hypofunctional thyroid nodules between 2015 and 2019 at the University Hospital of Cologne, Germany were identified. Sensitivity, specificity, positive predictive and negative predictive value of MIBI scintigraphy were calculated. Seventy-eight patients with sonographic suspicious hypofunctional thyroid nodules underwent surgery after interdisciplinary case discussion of both FNAC and MIBI results. In 49 (62.5%) cases, FNAC consisted of Bethesda III and IV results. In 39 (79.6%) of these cases, MIBI scintigraphy resulted in mismatch and intermediary results, but in only 4 (10.2%) of these cases was a carcinoma diagnosed. The negative predictive value of MIBI scintigraphy was 90–100%, respectively. Relying on the negative predictive value of MIBI match results might have obviated the need for surgery in 20.4% cases; one papillary microcarcinoma, however, would have been missed. MIBI scintigraphy has an underused potential for improving the diagnostic precision of hypofunctional thyroid nodules.