Cytological spectrum of diseases in goiter in Kadapa, a semiurban city in southern part of India – A 2-year retrospective study

Background: Thyroid gland produces thyroid hormone, thyroxine. Goiter is an indefinite term applied to the enlargement of thyroid gland. The normal thyroid gland in non-goitrous state weighs 25–35 g. Thyroid gland disorders are common endocrine disorders in the world. Aims and Objectives: This is a retrospective study done to know the age and gender distribution of goiter and various pathological conditions in goiter. This study showed that the incidence is common in 3rd–5th decade of life and nodular and colloid goiter are the common causes of goiter followed by follicular adenoma and papillary carcinoma. Materials and Methods: The data were collected from cytology registers of Pathology Department of FIMS Hospital, Image Diagnostics and Seetha Diagnostics, Kadapa, during the 2-year period from January 2021 to December 2022. The data collected as above were systematically analyzed and reviewed for age and sex distribution, clinical presentation, and cytological diagnosis. Results: Majority of the patients were female accounting for 324 cases (94.18%) and 20 patients (5.81%) were male. The maximum incidence is in young females between 31 and 40 years age group (24.70%) followed by 41–50 years age group (23.83%) and then in 21–30 years age group (22.38%). All together, the overall maximum incidence is seen in females between 21 and 50 years age group (70.91%). The most common pathological disease is nodular goiter followed by colloid nodule, both being iodine deficiency goiters. Conclusion: The study showed the thyroid disorders are more common in females. The non-neoplastic lesions constitute the predominant cause for goiter followed by benign neoplasms and then malignant neoplasms.

Histopathological analysis of thyroid lesions: an institutional experience

Background: Diseases of thyroid are one of the most common endocrine disorders affecting general population which range from non-neoplastic to neoplastic lesions. The incidence and pattern of thyroid lesions depend on various factors which include sex, age, ethnic and geographical patterns. Majority of thyroid lesions are non-neoplastic only <5% are malignant. The aim of the present study was to determine the frequency and histomorphological pattern of thyroidectomy specimens and their relationship with age and sex of the patient.Methods: This retrospective study was conducted in the department of pathology, Govt. Medical College, Alappuzha for a period of 2 years. The study included 620 thyroidectomy specimens received in the Department of Pathology. All the biopsy reports were reviewed, and different lesions were categorised according to age and gender distribution. The data was analysed by standard statistical methods.Results: The commonest of the non-neoplastic lesions was nodular colloid goiter followed by lymphocytic thyroiditis, Hashimoto thyroiditis Nodular hyperplasia and thyroglossal cyst. Most common malignant lesion in this study is papillary carcinoma and benign lesion is follicular adenoma. Age group of patients ranged from 6 ½ to 84 years. The study showed a female predominance of 88.38%.Conclusions: Thyroid disorders are commonly encountered endocrine diseases. The study showed a female predominance. Peak age of incidence of thyroid lesions was between 40 and 50 years. Most common lesion was follicular adenoma and most common malignant lesion was papillary carcinoma.Histopathological examination is the mainstay for definite diagnosis and management of thyroid neoplasms.

CD56 expression in benign and malignant thyroid lesions

@#Introduction: Thyroid cancer is the most common endocrine malignancy with more than 95% originating from follicular epithelial cells. Diagnostic dilemma may arise in occasional cases such as when an encapsulated nodule with a follicular growth pattern exhibits clear nuclei with grooves making it difficult to distinguish a follicular adenoma from encapsulated follicular variant papillary thyroid carcinoma. This study aimed to evaluate the diagnostic utility of an immunohistochemical marker, CD56, to distinguish between benign and malignant thyroid lesions. Materials and Methods: We retrospectively studied CD56 expression in 54 benign and 54 malignant thyroid lesions using archival formalin fixed paraffin-embedded tissue blocks for the study period from January 2010 to December 2015, diagnosed in a tertiary hospital. Results: CD56 was expressed in 52/54 (96.3%) of benign specimens and only 24/54 (44.4%) of malignant ones. The malignant specimens comprised 31 (57.4%) papillary thyroid carcinomas (PTC), 11 (20.3%) follicular carcinomas (FC), seven (13%) medullary thyroid carcinomas (MC), one (1.9%) poorly differentiated carcinoma (PC) and four (7.4%) anaplastic carcinomas (AC). CD56 was not expressed in 28/31 (90.3%) of the PTCs, 1/11 (9.1%) FCs, 1/4 (25%) of ACs while all MCs and the PD were positive. The benign group comprised nodular hyperplasias (29/54), lymphocytic thyroiditis (10/54), follicular adenomas (FA) (14/54) and one hyalinising trabecular tumour. CD56 was expressed in all the benign cases except one FA and one nodular hyperplasia. Thirteen of the 14 FAs were CD56 positive. The difference in expression between benign and malignant tumours was statistically significant as the p value was <0.01. Conclusion: CD56 is a potentially good immunohistochemical marker for differentiating papillary thyroid carcinoma from other benign follicular lesions of the thyroid especially in differentiating follicular variant PTC from FA in equivocal cases.

A study on the clinical manifestations and the incidence of benign and malignant tumors in a solitary thyroid nodule.

Tumors are either benign or malignant. The thyroid nodule, which is usually a clinical manifestation of most of the thyroid disorders, is one among them which has been the subject of controversies with divergent opinions and views. Clinical presentation of thyroid nodules varies widely ranging from solitary nodules to benign and malignant tumors. Thyroid nodules accounts up to 8% of the adult population having palpable nodules. However studies on its incidence in the population residing near seacoast are limited. Hence, the present study is carried in an aim to evaluate the clinico-pathological correlation of solitary thyroid nodule and the incidence of malignancy in the population residing at sea coast. The study is conducted in the Narayana Medical College & Hospital (NMCH), which is situated within 10-15 km radius of the seacoast in Nellore district of Andhra Pradesh, India. In this study, 73 subjects were selected who presented with thyroid swelling which was clinically confirmed as solitary thyroid nodule. Out of 73 cases, 12 cases (16.5%) were found to have malignant lesions with remaining 61 cases (83.5%) being benign lesions. The incidence of malignancy among solitary thyroid nodule subjects is up to 16.5% in the population residing near seacoast. Thus the present study warrants people to consult surgeons for early diagnosis and adequate treatment without being passive as most of these swellings are asymptomatic for long duration.

Expression of Kiss-1, Ki-67 and VEGF-C in papillary thyroid carcinoma and its stereological determination / 军事医学

Objective To explore the expression and significance of Kiss-1, Ki-67 and VEGF-C in papillary thyroid carcinoma(PTC) and thyroid follicular adenoma (FA).Methods Forty-four cases of PTC and twelve cases of FA paraffin-embedded tissues were used .Immunohistochemical staining and microscopic image analysis technique were used to analyze the expression of Kiss-1, Ki-67 and VEGF-C.Results The integrated optical density (IOD) of Kiss-1, and VEGF-C in the PTC groups was 475.56 ±126.02 and 805.29 ±226.05,respectively.The proliferation index of Ki-67 protein was (3.36 ±1.11) %and the difference between the PTC and FA groups was statistically significant (P<0.05).The IOD of the above two indices was 408.12 ±124.05 and 912.63 ±108.12 in the PTC with lymph node metastasis group , respectively, while the proliferation index of Ki -67 protein was (3.93 ±0.92) % and the difference vs the group without lymph node metastasis was significant ( P <0.05 ) .In the PTC with capsular infiltration group the IOD of above two was 425.58 ±87.38 and 891.37 ±149.36, the proliferation index of Ki -67 protein was (3.79 ±1.09) %and the difference with PTC group without capsular infiltrtion was statistically significant (P<0.05).Linear correlation analysis showed that Ki-67 and VEGF-C were with positively correlated in PTC and FA tissues (P<0.05),while Kiss-1 and Ki-67, VEGF-C were with negatively correlated in PTC and FA tissues (P<0.05).Conclusion Kiss-1, Ki-67 and VEGF-C can facilitate the differential diagnosis of PTC and FA , serving as prognostic indicators in patients with PTC .

Role of pro-angiogenic marker galectin-3 in follicular neoplasms of thyroid.

The role of pro-angiogenic marker galectin-3 (GAL-3) was examined in differential diagnosis of follicular neoplasms of thyroid into histological subsets of follicular adenoma (FA), follicular carcinoma (FC) and follicular variant of papillary thyroid carcinoma (FVPTC). The study included 22 cases from January 2006 to June 2011 comprising of FA (n = 12), FC (n = 3) and FVPTC (n = 7). Immunohistochemical evaluation of GAL-3 was performed on representative histologic sections from the resected thyroid specimens. The proportion of stained cells and intensity of staining in tumor blood vessels were evaluated. GAL-3 expression showed that angiogenesis was prominent in malignancy (FC and FVPTC) and negative in non-neoplastic thyroid parenchyma and benign condition (FA). GAL-3 expression was found to differentiate benign from malignant follicular neoplasms. Focal and diffuse positivity for GAL-3 was found to be associated with FC and FVPTC respectively, thus GAL-3 can be used as a immunohistochemical marker in the differential diagnosis of follicular neoplasms of thyroid based on the type of expression. Limitation of this study was relatively less number of cases studied; however, this data need to be corroborated in larger cohort.

Problems in Diagnosis and Management of Follicular Neoplasm / 대한갑상선학회지

Thyroid follicular adenoma and hyperplastic adenomatoid nodule may show overlapping cytologic pattern with thyroid follicular carcinoma and follicular variant of thyroid papillary carcinoma. Fine-needle aspiration cytology (FNAC) has limited role in differential diagnosis of those lesions showing high cellularity and absence of colloid. Those lesions are conventionally termed 'follicular neoplasm'. As diagnostic hallmarks of follicular carcinoma (vascular- and capsular invasion) cannot be detected by cytology, verification by histology after surgery is mandatory. However, only 20% of patients with thyroid nodules diagnosed cytologically as 'follicular neoplasm' are finally diagnosed as carcinoma after surgery. Therefore, there have been many trials to differentiate follicular adenoma (FA) from follicular carcinoma (FTC) in preoperative setting. Among those trials are 1) cell morphometry analysis by computer graphics, analysis of telomerase expression level, quantitation of specific protein markers, or intensive cytological analysis using FNAC specimens, 2) ultrasonographic evaluation, dynamic MRI, or MR spectroscopy for thyroid nodules and 3) gene expression profile analysis for thyroid nodules by microarray technique, all showing limited success or limitations hampering clinical application. Similarly, intra-operative frozen section analysis of thyroid nodule had been known to be of no diagnostic utility in a prospective, randomized trial. Current management strategy for 'follicular neoplasm' is initial surgery for diagnostic purpose to get pathologic diagnosis. If the nodule is diagnosed finally as FTC, completion thyroidectomy with or without radioactive iodine therapy is recommended in most cases. Minimally invasive FTC (without vascular invasion) is known to have excellent prognosis in most cases, so traditionally those patients had undergone unilateral operation without completion thyroidectomy. But, there had been reported cases showing distant metastasis and/or recurrence in patients with 'minimally invasive FTC'. One of problems in diagnosis of 'minimally invasive FTC' is lack of international standardization for pathologic diagnosis. Optimal surgical extent for cases with FTC is not known yet. It might have been due to lack of risk stratification of patients which is unique to FTC (not well differentiated thyroid cancer as a whole), lack of biomarker predicting prognosis of FTC, and lack of controlled trial for management of patients with FTC. In near future, application of molecular diagnostic markers is expected to improve our management strategy for thyroid nodules diagnosed as 'follicular neoplasm', if molecular pathogenesis of FA and of FTC are comprehensively understood.

Significance of Expression of Cell Cycle Related Proteins and Apoptosis Related Proteins in Follicular Adenoma and Follicular Carcinoma of Thyroid

PURPOSE: To explore the role of cell cycle regulators and apoptosis regulators in carcinogenesis of thyroid, the expression of cell cycle related proteins (cyclin D1, Ki-67) and apoptosis related proteins (survivin, caspase 3, bcl-2, p53) were investigated in follicular adenoma and follicular carcinoma of thyroid. METHODS: The following formalin-fixed paraffin embedded surgical specimens were immunohistochemically stained by avidin-biotin complex method for cyclin D1, Ki-67, survivin, caspase 3, bcl-2, p53; 15 cases of follicular adenoma (FA), 31 cases of minimally invasive follicular carcinoma (MIFC) and 12 cases of widely invasive follicular carcinoma (WIFC). RESULTS: The overexpression of six gene products in follicular neoplasms of thyroid was noted in varying frequency. Among them, increased Ki-67, caspase 3 index and overexpression of bcl-2 were noted in statistically significant, widely invasive follicular carcinoma than that of follicular adenoma and minimally invasive follicular carcinoma. CONCLUSION: These results suggest that the overexpression of Ki-67, caspase 3, bcl-2 appear to play an important role during follicular carcinogenesis of thyroid. In addition, the overexpression of these proteins is related to the differentiation of MIFC and WIFC. However, further molecular genetic studies are required to determine the interrelationships between the expression of cell cycle related proteins and apoptosis related proteins.

Cytologic Features of Folliculars Adenoma and Follicular Carcinoma of the Thyroid: A Study on the Likelihood of Cytologic Diagnosis by Fine Needle Aspiration Cytology / 대한세포병리학회지

Fine-needle aspiration cytology (FNAC) cannot differentiate follicular adenoma from follicular carcinoma since this distinction can only be based on the presence of capsular or vascular invasion, and this cannot be detected on a cytologic smear. The goal of this study was to define the diagnostic cytologic findings of follicular neoplasm and the possibility of diagnosing follicular neoplasm by performing FNAC. The cases of histologically diagnosed follicular adenoma and follicular carcinoma on the thyroidectomy specimens were retrieved. Among them, the cases with preoperative FNAC that was done within 3 months of the operation were finally selected. Then we reviewed the FNAC and histologic slides of 19 cases: 9 follicular adenomas and 10 follicular carcinomas. Our results suggest that for cases of follicular neoplasm, the aspirates show high or abundant cellularity, frequent follicle formation and occasional cellular atypism of the follicular cells. However, the atypism is more pronounced and more frequently noticed in the cases of follicular carcinoma, which reveals more higher anisocytosis (7/10, 70%), nuclear pleomorphism (9/10, 90%), coarse clumping of chromatin (8/10, 80%) and cellular overlapping (8/10, 80%).

Clinical Manifestation and Differential Diagnosis of Thyroid Follicular Neoplasm / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: A preoperative differential diagnosis between follicular adenoma and follicular carcinoma of thyroid is very difficult, and the standard basis for distinction is the presence of capsular and/or vascular invasion. In this study, we analyzed the findings of preoperative tests and clinical features to facilitate the differential diagnosis and treatment of the follicular neoplasm. SUBJECTS AND METHOD: A retrospective review of medical records was carried out on 104 patients who had undergone thyroid surgery and had been diagnosed with thyroid follicular adenoma or carcinoma from 1995 through 2004. The final pathologic diagnosis was compared to the various clinical data including the result of fine needle aspiration cytology (FNAC) and ultrasonographic findings. RESULTS: Of total 104 cases, 82 were follicular adenoma and 22 were follicular carcinoma. The incidence of carcinoma was significantly higher in male than in female. The result of FNAC were divided into 6 cytodiagnostic groups, namely, inadequate, colloid nodule without atypia, colloid nodule with atypia, follicular neoplasm without atypia, follicular neoplasm with atypia, or highly suspicious malignancy. The incidence of carcinoma was significantly higher in the groups with atypia such as colloid nodule with atypia, follicular neoplasm with atypia, and highly suspicious malignancy than in the groups without atypia. The incidence of follicular carcinoma was significantly higher in ill-defined marginal cases. Calcification on ultrasonography also indicated the possibility of malignancy. CONCLUSION: The incidence of follicular carcinoma was significantly high in male patients, atypia in FNAC, and ill-defined margin and calcification on ultrasonography.

A Case of Follicular Adenoma Occurring in Congenital Goiter due to Dyshormogensis / 대한소아내분비학회지

Follicular adenoma is a benign encapsulated tumor with evidence of follicular cell differentiation. It is the most common thyroid neoplasm, usually solitary and has a well-defined fibrous capsule. We experienced a case of follicular adenoma occurring in congenital goiter and reported with the brief review of related literature

The Clinical Utility of HBME - 1 Immunostaining in the Diagnosis of Follicular Carcinoma of Thyroid / 대한내분비학회지

BACKGROUND: Currently, in follicular lesion of aspirates of thyroid, pathologic evaluation of surgical specimen is the only diagnostic method whether the patient had follicular thyroid malignancy or not. The aim of this study is the evaluation of the clinical utility of HBME-1 immunostaining in the diagnosis of follicular thyroid malignancy in surgical specimen, and to establish the diagnostic guideline of HBME-1 immunostaining. METHODS: From 1994 to Sep. 1999, the 72 paraffin embedded tissue, which was already diagnosed as thyroid follicular carcinoma or adenoma through the pathologic evaluation of surgical specimen, were studied. Among 72 specimens, the 29 follicular carcinoma were included, and the others were follicular adenoma. The specimens were stained with HBME-1 monoclonal antibody by standard avidin-biotin peroxidase complex methods. One limited pathologist had read the findings of the immunostaining with a basis such as percent of tumor area. These percentage were divided to 4 grade as follows: 1) Grade 0: negative stained, 2) Grade 1: stained area or = 60%. After we had set a basis of follicular carcinoma as more than Grade 2, defined the clinical utility of HBME-1 immunostaining. The clinical utility was based that the concordance rate between pathologic diagnosis and the findings of immunostaining was more than 80% in both groups. RESULTS: 1) There was significant difference between two groups in intensity of cellular staining (p=0.04, x2). But, there might not be helpful to rule out follicular carcinoma of thyroid from adenoma in fine-needle aspirates. 2) In both groups, the percent of stained area of tumor was very diverse from 0% to 100%, and was statistically significant different (p=0.007). 3) Because the only 5 cases of normal tissue in both groups were stained weakly, the HBME-1 immunostaining was like to specific reaction with tumor tissue in both groups. 4) When we had set a basis of follicular thyroid carcinoma as more than Grade 2 (> or = 30%), the concordance rate between pathologic diagnosis and the findings of immuno- staining was 69.7% in follicular adenoma, 65.5% in follicular carcinoma, respectively. CONCLUSION: The HBME-1 immunostaining may not be help to differentiate follicular carcinoma from adenoma.

SPARC Expression in Thyroid Follicular Adenomas and Carcinomas

SPARC, secreted protein acidic and rich in cysteine, is a extracellular matrix-associated protein implicated in the modulation of cell adhesion, migration, cell cycle regulation, and angiogenesis. SPARC is expressed in fibrocytes and endothelial cells involved in tissue repair and invasive malignant tumors in the gastrointestinal tract, breast, lung, kidney, adrenal cortex, ovary, and brain. This study was aimed to characterize the different expression of SPARC in the thyroid follicular adenomas and follicular carcinomas. Immunohistochemical staining was performed in paraffin-embedded tissues of 25 follicular adenomas and 15 follicular carcinomas of the thyroid gland. Immunohistochemically, SPARC was not expressed in the 19 follicular adenoma and 2 follicular carcinoma but highly expressed in the 6 follicular adenoma and 13 follicular carcinoma. These findings suggest that SPARC is a potential diagnostic marker of follicular carcinoma and is helpful to distinguish follicular carcinoma from follicular adenoma without vascular or capsular invasion.

Allelotyping and Comparative Genomin Hybridization Studies in Papillary Thyroid Carcinomas and Follicular Adenomas / 대한내분비학회지

BACKGROUND: In our previous study, the prevalence of the known causes of thyroid tumorigenesis was relatively rare in Korean population, suggesting genetic and environmental differences exist. Screening of genetic alteration in papillary thyroid carcinoma(PTC) and follicular adenoma(FA) in whole genomic scale was needed prior to search on individual genes of possible causes. METHODS: Ten cases of PTC without ret/PTC-I, -2, -3 rearrangement and 5 cases of follicular adenoma were included in the study of microsatellite marker allelotyping. Sixty two microsatellite markers available, were chosen to cover the known sites of loss of heterozygosity(LOH) involved in thyroid tumors, tumor suppressor genes and terminal portion of each chromosomes. PCR was performed on tumor DNA and leukocytes DNA from each patient with MDE gel electrophoresis to detect LOH. Same specitnens as above, 3 case of normal thyroid tissues and NPA, ARO cell lines were included in the study of comparative genomic hybridization(CGH). Tumor and control DNAs were hybridized to metaphase chromosome with differential stainings with fluorescein and rhoda-mine-dUTP. Obtained results were analyzed by multicolor fluorescence computer assisted image analyzer. RESULTS: In allelotyping, LOH were detected in 5 cases of PTC, 2 cases on D10S1435, 1 case each on D2S1780, DSS1099, D11S1986, D16S539, 1 case of PTC revealed LOH on DSS1099, D11S1986. In FA, LOH were detected in 3 cases on D1S534, D1S226, Dl 1S907, D22S683, DXS9807. In CGH, Xp addition was noticed in 1 case of PTC, 12q and 10p addition was noticed in 1 case each, 16q deletion and 17q addition in 1 case of FA. CONCLUSION: No hot spot of LOH was noticed in microsatellite marker allelotyping, neither of common chromosomal change in CGH study suggesting unbalanced translocation or gene amplification more than 5-10 Mb may be involved in the genetic alteration of PTC and FA.

Demonstration of TCM-9 Monoclonal Antibody in Follicular Neoplasm of Thyroid / 대한세포병리학회지

Monoclonal antibody(TCM-9) against human thyroid cancers have been studied by screening with human thyroid cancers, normal and benign thyroid tissue, and normal human serum protein. A monoclonal antibody(TCM-9) that is known to have strong specificity for human thyroid cancer but not for Graves' disease, adenoma or normal thyroid does not bind to native or mature human thyroglobulin(Tg). We used to TCM-9 antibody by immunohistochemical staining on 5 follicular cancer, 2 follicular adenoma, 1 follicular neoplasm with suspicious invasion, 2 papillary cancer to ascer- tain being of help in differentiation between follicular carcinoma and adenoma. Reactivity of TCM-9 was observed in follicular carcinoma and papillary carcinoma but not observed in follicular adenoma. Thus TCM-9 is a novel monoclonal antibody against the thyroid cancer.

Thyroglobulin Synthesis of Oxyphilic Cells in Various Types of Neoplastic and Autoimmune Thyroid Diseases

To determine the content of thyroglobulin in oxyphilic cells of the thyroid, which have been considered as non-thyroglobulin producing cells, the degree of stainability of the various oxyphilic cells for thyroglobulin was compared with that of non-oxyphilic follicular cells in either same or different lesion. A total of 13 oxyphilic lesions, including three follicular adenomas containing oxyphilic cell nodules, four pure oxyphilic cell adenomas, and six Hashimoto's thyroiditis were compared with 16 of non-oxyphilic lesions such as, seven follicular adenomas, four chronic lymphocytic thyroiditis, and five Graves' disease. Many oxyphilic cells stained positively for thyroglobulin regardless of their morphologic variation, but less intensely than the usual follicular cells in follicular adenomas, chronic lymphocytic thyroiditis, and Graves' disease. The stainability of oxyphilic cells for thyroglogulin did not show any significant correlation with morphologic features, whereas in follicular adenomas, the non-oxyphilic follicular cells forming microfollicles stained less strongly for thyroglobulin than the same cells lining large mature follicles in a reproducible way. With above findings, we concluded that oxyphilic cells maintain the functional activity in terms of thyroglobulin synthesis, although the content of the thyroglobulin is less than that of non-oxyphilic colloid forming follicular cells.