The Multifaceted Profile of Thyroid Disease in the Background of DICER1 Germline and Somatic Mutations: Then, Now and Future Perspectives

DICER1 protein is a member of the ribonuclease (RNAse) III family with a key role in the biogenesis of microRNAs (miRNA) and in microRNA processing, potentially affecting gene regulation at the post-transcriptional level. The role of DICER1 and its relevance to thyroid cellular processes and tumorigenesis have only recently been explored, following the acknowledgement that DICER1 germline and somatic changes can contribute not only to non-toxic multinodule goiter (MNG) lesions detected in individuals of affected families but also to a series of childhood tumours, including thyroid neoplasms, which can be identified from early infancy up until the decade of 40s. In a context of DICER1 germline gene mutation, thyroid lesions have recently been given importance, and they may represent either an index event within a syndromic context or the isolated event that may trigger a deeper and broader genomic analysis screening of individuals and their relatives, thereby preventing the consequences of a late diagnosis of malignancy. Within the syndromic context MNG is typically the most observed lesion. On the other hand, in a DICER1 somatic mutation context, malignant tumours are more common. In this review we describe the role of DICER protein, the genomic events that affect the DICER1 gene and their link to tumorigenesis as well as the frequency and pattern of benign and malignant thyroid lesions and the regulation of DICER1 within the thyroidal environment.

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

The Correlation of age and gender with prevalence of histopathological patterns of thyroid diseases among Iraqi patients

Objectives: The aim of this study was to investigate the prevalence of histopathological patterns of thyroid lesions and their relation to age and gender in patients underwent total or near total and partial thyroidectomy. Methods: 430 biopsy blocks examined for patients who had undergone total or near total and partial thyroidectomy for both non-neoplastic and neoplastic thyroid lesions, between January 2018 to December 2020 at Surgical Department, Medical city, Baghdad, Iraq. Results: Out of 430 thyroidectomy specimens, 275 (64%) cases of non-neoplastic lesions, and 155 (36%) cases of neoplastic lesions were present. There were 63 males and 367 females with a male to female ratio of 1:5.6. The age ranged in males from 12 to 83 years with a mean age of 47.5 years and the age ranged in females from 10-68 years with a mean age of 39 years. In non-neoplastic lesions, the predominant lesion was the nodular hyperplasia with 233 (84.7%) cases followed by Hashimoto thyroiditis with 24 (8.7%) . In neoplastic lesions, papillary carcinoma was the commonest lesion with 98 (63.2%) cases followed by follicular carcinoma with 11 (7%) cases. Conclusion : Nodular colloid goiter was the most common non –neoplastic lesion with female predominance . Papillary carcinoma was the most frequent thyroid cancer accounting for 84.4% of thyroid cancers. with micropapillary variant making 44.89 % with most cases occurring in the third and forth decade.There appears to be a slightly increased trend of papillary carcinoma diagnosis. The present study highlights the necessity for time to time assessment of neoplastic lesions in young and middle-aged female for initial detection.

A Study on Cytomorphological and Histopathological Correlation of Head and Neck Lesions in a Tertiary Care Centre, Bhubaneswar, Odisha

BACKGROUND The head and neck region is an anatomic site having lymph nodes, nerves, veins, arteries, muscles, mucosal epithelium to salivary glands, thyroid, and a host of developmental tissues. Any of these tissues can become pathological, resulting in a mass. Fine needle aspiration cytology (FNAC) is regarded as a reliable method of investigation in diagnosis of head and neck lesions. However, histopathology is the gold standard of diagnosis. The purpose of this study was to assess the frequency of head and neck tumours according to the sites of their occurrence and to find out the correlation of cytopathological findings by FNAC and histopathological findings by biopsy. METHODS This prospective study undertaken from June 2012 to June 2014 in the Department of Pathology, IMS and SUM Hospital, Bhubaneswar, a tertiary care center. All the patients attending different outdoor of IMS & SUM Hospital, Bhubaneswar with head & neck lesions referred for FNAC were included in the study. The results of FNAC were compared with that of histopathological findings by tissue biopsy. Data collected was entered in MS Excel and analysed using the same software. Descriptive statistical measures like frequency and percentage. Data was presented in tabular form. RESULTS The commonest site of lesion was in the lymph node followed by thyroid gland. There was preponderance of female sex in thyroid lesions whereas males were commonest in other sites. The accuracy in cyto-histopathology correlation between benign and malignant lesion was 96.36 % and 88.89 % respectively and was most corroborated in the thyroid lesions (50.6 %). CONCLUSIONS Cyto-histo correlation of head and neck lesions provides an important, quick, excellent, and sensitive diagnostic tool to exclude non-neoplastic lesions from neoplastic lesions. KEYWORDS Head and Neck Lesions, FNAC, Histopathology

Correlation between Ultrasonography and Fine Needle Aspiration Cytology (FNAC) Findings in Patients with Thyroid Lesions

Background:Thyroid nodules are common presentation in patients having thyroid disorders. There is approximately 4-5% incidence of clinically apparent thyroid lesions in general populations.Thyroid nodules are about four times more common in females than in males. The present study aims to diagnose the thyroid lesions and evaluate to relation and diagnostic test of ultrasonography (USG) and Fine Needle Aspiration Cytology (FNAC) report. To determine the sensitivity of ultrasonography in detecting thyroid lesions.Method:This was hospital based prospective study carried in 94 patients who came to radiology department for USG neck, after clinical examination frommedicine, surgery and ENT department.Those patients with thyroid lesions were followed and advised for USG guided FNAC of thyroid swelling. The patients who were advised for FNAC, and gave consent for procedure were included in the study. The USG guided FNAC was done and wasfurther evaluated by pathologist. Results:Out of 94 cases, 85 were benign nodules and 9 were malignant nodules by USG which were further confirmed by FNAC with results of 87 benign and 7 malignant.The USG diagnosed the benign thyroid nodule with sensitivity of 96.55% and specificity of 85.71%, positive predictive value 98.82%, negative predictive value 66.67%, accuracy 95.74%. The result revealed that there is a strong relation between diagnoses of benign thyroid lesions by USG and final diagnosis by FNAC (P=0.001).Conclusion:High resolution grey scale imaging features can differentiate benign and malignant lesions. USG is very helpful for FNAC, characterization of nodules and provides differential diagnosis in those patients affecting with thyroid disorders.

The Potential Diagnostic Utility of TROP-2 & C-Kit in Thyroid Neoplasms

Background: Thyroid nodules are common finding, only 5% of nodules are malignant and the vast majority is non-neoplastic lesions or benign neoplasms. Thyroid cancer incidence is increasing faster than any other cancer types, thus representing one of the most common and clinically worrying malignant tumors of the endocrine system. Trophoblast antigen 2 (TROP2) is a transmembrane receptor glycoprotein encoded by the tumor-associated calcium signal transducer 2(Tacstd2) gene, which is located on chromosome 1p32. Although the biological function of TROP2 is unclear, accumulating evidence has demonstrated that its expression is elevated in various malignant tissues, whereas in human normal tissues relatively low or no TROP2 expression is observed. C-Kit is a type III receptor tyrosine kinase. C-Kit expression and signaling have been well characterized in several tumors, including gastrointestinal stromal tumors (GISTs). However, few studies have investigated c-Kit in the thyroid gland or in thyroid malignancies. The aim of this study was to investigate the diagnostic utility of TROP-2 on a large set of neoplastic thyroid lesions & to investigate the utility of TROP-2 & c-Kit markers to distinguish between benign and malignant thyroid neoplasms on Paraffin blocks. Methods: Immunohistochemistry for TROP2 and c-Kit was carried out on 85 different thyroid lesions (40 benign, 7 borderline and 38 malignant). Results: Malignant thyroid lesions were found to have negative expression of c-Kit in contrast to 80% of benign thyroid neoplasms. TROP2 was strong positive in 87.5% of papillary thyroid carcinomas (PTC), but there was no TROP2 expression in benign thyroid neoplasms, non-invasive follicular thyroid neoplasm with papillary like nuclear features, follicular carcinoma, anaplastic and poorly differentiated thyroid carcinoma. Conclusions: TROP2 is a good diagnostic tool for PTCs to differentiate between PTCs & other lesions with papillary like nuclear features as NIFTP, c-Kit is a good diagnostic tool for follicular adenoma & to differentiate between follicular adenoma & follicular carcinoma.

High-performance sonographical multimodal imaging of non cystic thyroid lesions: Chances of the preoperative diagnostics in relation to histopathology

AIM: To improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance ultrasound techniques: optimized B-mode morphology, elastography, Color-Coded Doppler-Sonography (CCDS) and contrast enhanced ultrasound (CEUS) MATERIALS AND METHODS: In 33 cases solid, non-cystic thyroid lesions were rated as TIRADS 3 and up from conventional B-mode examinations. Additional high resolution Power Doppler including HR- and Glazing-Flow as optimized macrovascularization techniques, shear wave elastography and CEUS were performed on these patients by one experienced examiner. For CEUS a bolus of 1–2.4 ml Sulfurhexafluorid microbubbles (SonoVue®, Bracco, Milan, Italy) was injected into a cubital vein and then the distribution kinetics of the contrast agent were documented from the early arterial phase (10 to 15 seconds after injection) to the late venous phase (5 minutes after injection). Postoperative histopathology was the diagnostic gold standard as it provides the most reliable proof. RESULTS: 33 patients (13 males, 20 females; age 29 –77 years; mean 55 years; SD 13 years) were included in this study. 28 of them had benign regressive thyroid nodules, 3 had adenomas and 4 were diagnosed with carcinomas (3 were histologically identified as papillary thyroid carcinomas, one as a medullary thyroid carcinoma). The volume of the thyroid gland ranged from 6.6 to 401.3 cm2 (mean 72.6±92.0 cm2). The adenomas diameters ranged from 9 to 40 mm (mean 22±16 mm) and the carcinoma diameters ranged from 19 to 33 mm (mean 26±6 mm). The 3 adenomas had different echogenicities: One was completely echofree, one was hypoechoic and one isoechoic. The 4 carcinomas however were equally characterized as hypoechoic and echofree. Two of three adenomas and all of the carcinomas showed an incomplete or diffuse margin. Micro-calcifications were found in one adenoma and in every carcinoma. However, no micro-calcifications were observed in cases of benign regressive nodules. Performing shear-wave elastography the adenomas showed lower values than the carcinomas: The tissue velocity of the adenomas ranged from 2.86 m/s to 3.85 m/s (mean 3.32±0.5 m/s) and in carcinomas from 3.89 m/s to 5.66 m/s (mean 4.18±0.3 m/s). Marginal hypervascularization was detected in two adenomas after applying CCDS. One adenoma was hypovascularized. The four carcinomas showed an irregular extreme hypervascularization along their margins as well as an irregular central normo- or hypervascularization in CCDS. The additional HR-Flow helped reducing artefacts. In CEUS the dynamic capillary microvascularization of all carcinomas was very irregular with early enhancement and followed by partial or complete wash-out. In CEUS two adenomas had no wash-out and the other one showed a partial wash-out. CONCLUSION: Using modern multimodal imaging offers new possibilities for the differentiation between benign and malignant thyroid lesions. It is a very important diagnostic tool in addition to the B-Mode TIRADS classification and eases the decision between TIRADS 3, 4 and 5. However, additional multicenter studies are required for more detailed evaluations.