Sensitivity and Specificity of Diagnostic Biomarkers in Thyroid Diseases: From circulating chemistry to molecular cytogenetics.

Abstract

OBJECTIVES: This study aims to understand the role of auto antibodies in the structural derangement of thyroid tissue and to identify the specific immune marker for diagnosing the thyroid lesions. Hence the objectives of this research work were to know the significance of FT3, FT4, TSH, anti TPO antibody, anti thyroglobulin antibody in various thyroid lesions, to study immune marker expression of HBME-1 and Galectin 3 in the resected thyroid specimen, to correlate between serum markers and tissue immune markers in the thyroid lesions and to know commonest mutation of RET proto-oncogene in thyroid specimens in familial thyroid malignancies METHODOLOGY: This was a two year prospective study carried out from 2015 to 2016 at Dept. of pathology, BLDE (Deemed to be University), Shri B M Patil Medical College, Hospital & Research Centre, Vijayapura. The study group included out patients and in patients with thyroid abnormality. All cases referred to cytology section were included and individuals on hormone therapy or antithyroid drugs as treatment were excluded from the study. So total of 165cases were studied during this period. Thyroid function test (serum TSH, Free T4 and Free T3), anti TPO and anti TG antibodies were measured from the preferable early morning 5ml venous drawn blood sample. Fine needle aspiration was performed in all cases. Histopathology correlation of cases was done of resected thyroid tissue and immune markers HBME1 and Galectin 3 was done where ever required. Ret oncogene mutational study was carried out on few prophylactic thyroidectomy specimens which accounted to 14cases. RESULTS: Total of 165 cases of thyroid swellings were studied and observed females preponderance with 81% and male 19% distribution respectively. Commonest age group affected was 3rd and 4th decade. Youngest patient was 12yrs old and oldest 72years. Thyroid hormones assay were within normal range of all individuals. Anti thyroperoxidase (Anti TPO) and anti-thyroglobulin (Anti-TG) levels were significantly raised in autoimmune thyroiditis and in few cases of papillary carcinoma. All 165 cases were subjected for Fine Needle aspiration cytology and diagnoses were categorized according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). 24cases were non diagnostic(excluded from the study), 83cases categorised as II, 32cases as categorised III, 16cases as cat IV, 9 cases belonged to cat v and 15 cases were categorised in cat VI. Seventy one cases (71 cases) had histopathological correlation. Commonest histopathological diagnosis was colloid goitre (21cases), 16 cases showed chronic thyroiditis (Lymphocytic thyroiditis 11 cases, Granulomatous thyroiditis 3cases and Graves’ disease 2 cases), 10 cases of follicular adenoma and 24 cases were thyroid malignancy. Papillary carcinoma was commonest malignancy with 15 cases, 4 cases of follicular carcinoma, 2 cases of medullary carcinoma and 2 cases of metastatic carcinoma (both were squamous cell carcinoma metastasis). One rare case of mucoepidermoid carcinoma was diagnosed. CONCLUSION: Anti TPO is significantly raised in chronic thyroiditis and papillary carcinoma. The Bethesda system of Reporting Thyroid Cytology (TBSRTC) is strongly recommended for thyroid cytopathology.HBME 1 and Galectin 3 have high specificity and sensitivity in diagnosing thyroid malignancies. C634R was commonest exon seen in Ret oncogene mutations.