Diagnosis Of Thyroid Tumors Research Articles

Towards improving the utility of fine‐needle aspiration biopsy for the diagnosis of thyroid tumours

Towards improving the utility of fine‐needle aspiration biopsy for the diagnosis of thyroid tumours

Genomic instability measurement in the diagnosis of thyroid neoplasms.

Clinically palpable thyroid nodules are present in approximately 10% of the population, although only 5% to 7% of these nodules harbor malignancy. Fine-needle aspiration has become one of the central tools in the diagnostic armamentarium of the surgeon/endocrinologist. There is, however, up to a 30% indeterminate diagnostic rate associated with this technique, resulting in unnecessary surgical interventions for patients harboring benign disease. A second issue of clinical importance is the unreliability of predicting outcomes based either on histologic findings alone or in combination with clinical staging. To address these diagnostic and clinical shortcomings, we have used measurement of genomic instability as a diagnostic and prognostic indicator for thyroid neoplasms. Genomic instability of thyroid tissue samples was determined by inter-(simple sequence repeat) PCR, microsatellite instability analysis, and fluorescence in situ hybridization (FISH) on thyroid neoplasms from 22 patients. Inter-(simple sequence repeat) PCR detected genomic instability with an index range 0% to 1.9% (mean, 0.56%) in patients with benign disease, whereas in patients with malignant histologic findings the values ranged from 0% to 6.6% (mean, 2.9%). This difference between benign and malignant values was statistically significant (p =.004). There was no demonstrable microsatellite instability or loss of heterozygosity for six markers examined in this group. Losses of chromosomes 17 and X in benign disease and gains of chromosomes 7, 12, 17, and X in Hurthle cell carcinoma were observed, although not at a significant rate. Genomic instability as measured by inter-(simple sequence repeat) PCR was significantly higher for malignant diseases compared with benign thyroid tissues, but no such association was seen with aneuploidy or microsatellite instability.

鑑別に苦慮した甲状舌管癌

We encountered a case of thyroglossal duct carcinoma with adenomatous goiter in the thyroid. In this case, 77-year-old male was referred our hospital exhibiting an anterior cervical tumor. Preoperative findings of this tumor showed a hard mass of 30×30×20mm in the midline of the neck at the level of the thyroid cartilage, and skin invasion. On preoperative examination, tuberculin reaction (+) can appear similar to necrotic lymphnodes on MRI, and it is necessary to differentially diagnose tuberculous lymphadenitis and metastatic lymphnodes. Frozen biopsy during the operation could not discriminate between thyroglossal duct carcinoma and metastatic lymphnodes but postoperative pathohistogic diagnosis was papillary carcinoma. After 5 weeks, total thyroidectomy was performed for the tumors in the thyroid, and the pathohistologic diagnosis of thyroid tumor was adenomatous goiter, suggesting primary thyroglossal duct carcinoma.

Radiologic assessment of metastases to the thyroid gland.

We reviewed the radiologic and clinical data in patients with metastatic disease to the thyroid gland and assessed the role of radiologic techniques in this disorder. The findings on US (n = 11), CT (n = 7), MRI (n = 6), palpation or US-guided fine needle aspiration (FNA) biopsy, and clinical records were reviewed in 11 cases of pathologically verified metastatic tumors of the thyroid gland. Five patients had palpable thyroid nodules and six had nonpalpable nodules discovered incidentally with imaging procedures. Three patients had no known malignancies at the time of diagnosis of thyroid tumors. Correct diagnosis was obtained in 10 of the 11 cases with FNA biopsy. Thyroid metastases were detected in all of the cases with US and MRI and six of the seven cases with CT. Thyroid metastases were solitary (n = 5) or multiple (n = 6), and about half of them measured <2 cm in diameter. These tumors typically had well defined margins and no calcification and sometimes had cystic portions. Multiple nodules within the same patient were radiologically quite similar to each other. On US, metastases appeared as hypoechoic or markedly hypoechoic areas without halo, on CT as low density areas, and on MRI as areas of varying signal intensities. Half of the metastases showed hypointensity on either T2-weighted images or gadolinium-enhanced T1-weighted images. The tumors involved lymph nodes in 10 cases and other remote organs in 5. Level I or II or parotid nodes were involved in six cases. These radiologic features may alert clinicians to a possibility of metastatic thyroid cancer. US combined with US-guided FNA biopsy is suitable for early diagnosis of metastases to the thyroid gland.

Tumors of the thyroid gland: histologic and cytologic features--part 2.

Tumors of parafollicular cells and nonepithelial tumors occur less frequently than tumors derived from follicular cells. This review summarizes the histologic and cytologic features of these neoplasms and the nonneoplastic diseases that often have to be included in the differential diagnosis of thyroid tumors. Also, the role of fine-needle aspiration biopsy and frozen section interpretation in the diagnosis of thyroid nodules are discussed.

Preoperative diagnosis of medullary thyroid carcinoma by RT-PCR using RNA extracted from leftover cells within a needle used for fine needle aspiration biopsy.

Fine needle aspiration Biopsy (FNAB) is commonly used to diagnose thyroid tumors. In some clinical situations, however, accurate diagnosis requires a more objective method than cytological examination alone. Medullary thyroid carcinomas (MTC) derive from C cells in the thyroid and express some specific messenger RNAs (mRNA), such as those transcribed from the RET proto-oncogene, the calcitonin gene, and the gene for carcinoembryonic antigen (CEA), which usually do not exist in normal thyroid follicular cells or thyroid tumors of follicular epithelial descent. Recently, we established a new method for the molecular diagnosis of thyroid tumors without additional invasion to the patient by extracting RNA for RT-PCR from the leftover cells inside the needles used for fine needle aspiration biopsy (Aspiration Biopsy-Reverse Transcription-Polymerase Chain Reaction, ABRP). By applying the ABRP method to the detection of RET, calcitonin, and CEA mRNAs, an accurate molecular-based diagnosis for MTC maybe established as an adjunct to cytological diagnosis. In this study, 35 aspirates were obtained at the time of surgery from thyroid tumors, including 11 MTCs. The expression of these mRNAs in the leftover cells inside the needles used for the aspiration was then examined. Transcripts from all three genes were detected in the samples from all 11 MTCs, but none of these mRNAs were detected in the other tumors or normal thyroid tissues. Furthermore, MTC was preoperatively diagnosed in three patients by ABRP detection of these mRNAs, and these diagnoses were confirmed by subsequent cytological and histopathological analyses. Thus RT-PCR detection of RET, calcitonin, and CEA mRNAs in FNABs may be an efficient molecular adjunct for diagnosing MTC.

Diagnostic Applications of Immunohistochemistry to Thyroid Tumors.

Application of immunohistochemical methods has greatly contributed to diagnostic thyroid pathology, especially to the diagnosis of thyroid tumors. These techniques can demonstrate specific markers for follicular and C (parafollicular) cells and their tumors. Therefore, they facilitate defining the spectrum of thyroid tumors, and also are useful for the distinction between tumors of different histogenesis. In this paper, we reviewed thyroid specific proteins and compounds as immunohistochemical markers, i. e. thyroglobulin (TG), thyroxine (T4), triiodothyronine (T3), thyroperoxidase (TPO), TSH receptor (TSHR), Na/I symporter (NIS), thyroid transcription factor-1 (TTF-1), and calcitonin. In addition, we also reviewed intermediate filaments and other proteins having a considerable diagnostic value in thyroid tumor pathology.

Measurement of serum TSH in the investigation of patients presenting with thyroid enlargement.

In otherwise euthyroid patients presenting with thyroid enlargement, reduction in serum thyrotrophin (TSH) concentrations measured in a sensitive assay may be a marker of thyroid autonomy and may therefore indicate a benign underlying pathology. We investigated prospectively a cohort of 467 subjects presenting consecutively to our thyroid clinic with nodular or diffuse enlargement of the thyroid. Subjects were divided into those with normal (0.4-5.5 mU/l), low but detectable (0.1-0.39 mU/l) or undetectable (< 0.1 mU/l) serum TSH concentrations. The final pathological diagnosis was defined by fine-needle aspiration cytology and clinical follow-up of at least 2 years or by fine-needle aspiration cytology and histology following surgical treatment. Serum TSH concentrations below normal were found in 75 patients (16.1%), those with low serum TSH results having higher mean free T4 concentrations, were older and were more likely to be female. In those with undetectable serum TSH, no patient had a diagnosis of thyroid neoplasia and in those with low but detectable TSH, thyroid neoplasms were diagnosed in two patients (3.4%). In those with normal serum TSH, 12.0% had a final diagnosis of thyroid neoplasm (p = 0.013). Overall, thyroid malignancy was found in one patient (1.3%) of those with a serum TSH measurement below the normal range and 6.9% of those with normal serum TSH (p < 0.06). Reduction in serum TSH at presentation may identify a group which requires less intensive investigation and follow-up than those without biochemical evidence of thyroid autonomy.

Renal Cell Carcinoma Metastatic to the Thyroid Gland: A Comparative Molecular Study Between the Primary and the Metastatic Tumor.

A case of renal cell carcinoma metastatic to the thyroid gland is presented. The thyroid tumor showed typical features: clear cells arranged in nests with a prominent sinusoidal vascular pattern. The histologic appearance was identical to the renal tumor removed 6 yr before. A comparative molecular study between the primary and the metastatic tumor showed a common profile with a loss of heterozygosity at identical loci on chromosome 3, which provided further support to the metastatic nature of the thyroid tumor. However, the frequent existence of allele losses on chromosome 3p in both renal cell carcinomas and primary thyroid follicular carcinomas rest some force from such a molecular approach to the differential diagnosis of thyroid tumors that contain a predominant population of clear cells.

CD57 (Leu-7) expression is helpful in diagnosis of the follicular variant of papillary thyroid carcinoma.

CD57 (HNK-1) is a oligosaccharide antigen that is expressed by cells of several lineages. It is present on multipotential neuroepithelial cells during embryogenesis, and tumours of epithelial, neuroectodermal and nerve sheath origin also express CD57. Its role in the diagnosis of thyroid tumours is controversial. We have studied CD57 expression by immunohistochemistry to determine its utility in the classification of thyroid follicular lesions. Study material included 114 normal thyroid sections, 77 benign thyroid lesions (29 colloid nodules, 22 follicular adenomas, 20 cases of Hashimoto's thyroiditis and 6 of Grave's disease) and 83 thyroid carcinomas, including 31 follicular variants of papillary carcinoma. We observed CD57 positivity in 95% of thyroid carcinomas, 27% of follicular adenomas and 10% of colloid nodules. It was not expressed in the normal thyroid. CD57 expression in thyroid carcinomas was significantly different from that in normal and benign thyroid lesions (P < 0.0001). The follicular variant of papillary thyroid carcinoma also showed significantly higher CD57 expression than colloid nodules (P < 0.0009) or follicular adenomas (P < 0.0009). No significant difference was seen between colloid nodules and follicular adenomas. We conclude that CD57 immunohistochemistry is valuable in the classification of thyroid follicular lesions into benign and malignant groups and is also helpful in the diagnosis of the follicular variant of papillary thyroid carcinoma.

術前Ｔ１Ｎ０と診断した甲状腺分化癌 治療法の検討

Since we use fine-needle aspiration cytology under ultrasonographic imaging for the diagnosis of thyroid tumors, we can easily detect small thyroid cancers.However, there is a question whether to operate on the small well-differentiated thyroid cancers or not, because the majority of the thyroid cancer have a good prognosis.Therefore, we studied 95 patients with pre-operative T1NO thyroid cancer who had been treated in our department from 1986 to 1996. 35 patients of the 95 had positive nodes (38.9%), 21 had intrathyroidal metastases (22.1%) ; and 7 had extra-thyroidal invasions (7.4%) . Two patients out of these 7 showed an invasion of the trachea that might have had an influence on survival.We feel that surgical treatment is indicated for small thyroid cancer based on.

甲状腺腫ようの術前検査

Fifty patients were treated surgically and postoperative pathological diagnoses were obtained for thyroid tumors resected in our clinic between January 1, 1987 and April 31, 1989. These patients underwent a variety of preoperative examinations (CT, MRI, thallium scintigraphy (T1), and fine needle aspiration (FNA)) by retrospective study. The diagnostic accuracy of these preoperative examination methods showed echo (specificity 80.0%, sensitivity 70.6%), CT (75.0%, 69.2%), MRI (75.0%, 70.0%), T1 (82.4%, 80.4%), and FNA (80.0%, 70.6%). Thirty one patients treated surgically, underwent both echo examination and FNA as routine preoperative examinations, in addition to postoperative pathological diagnosis. In these patients, validity showed positive rate 87.5%, and negative rate 73.3%. These results indicated that echo and FNA as preoperative routine examination methods for the diagnosis of thyroid tumors, showed high diagnostic accuracy, and the potential to reduce both the physical and economic shares of patients.

MAGNETIC RESONANCE IMAGING OF THYROID TUMORS

Recently magnetic resonance imaging (MRI) has been increasingly employed for diagnosis of thyroid tumors, however, the value has not been established as yet. In this study MRI pictures of tumorous lesions of the thyroid in patiens, who were operated on after MRI and definitely diagnosed based on pathological examination, were examined. Subjects were 149 lesions, inluding 46 papillary carcinomas, 7 follicular carcinomas, 39 follicular adenomas, 13 adenomatous goiters and 14 cysts. All lesions were evaluated with T1-weighted, T2-weighted and Proton-weighted images. Consequently, following conclusions were obtained. 1. Cysts had no pseudocapsule and appeared as high intensity on T1 and T2-weight images. 2. Most of follicular adenomas had intact pseudo capsule and homo-genous contents. 3. Most papillary carcinomas less than 1cm in diameter did not visualized. The carcinomas more than 1cm in diameter had partial pseudo capsule and heterogenous contents. 4. Follicular carcinomas were similar to follicular adenoma in MRI. 5. It was difficult to distinguish benign from malignant tumors, only with signal intensity in all pulse sequences.

Molecular genetics of human thyroid neoplasms.

Cancers are thought to develop as a result of sequential mutations of genes important in the control of cellular growth. Recently investigators identified a number of genetic defects that affect oncogenes and tumor-suppressor genes and that provide insight into the biology of benign and malignant thyroid neoplasms. Future implications for thyroid tumor diagnosis and prognosis are considered in this chapter.

Measurement characteristics of stereological and histochemical methods in the diagnosis of thyroid tumours.

Seventy-two female mice of BALB/c strain were divided into three control and three perchlorate groups. The perchlorate groups drank 1.2% sodium perchlorate solution. After 8 or 32 weeks of the 46-week experiment one control and one perchlorate group were totally irradiated with 0.8 Gy on 5 consecutive days. Ten normal thyroid glands, 10 with hypertrophy and hyperplasia, 8 follicular adenomas and 10 follicular carcinomas were histologically and stereologically analysed. The results showed significant differences in the average nuclear volume (p < 0.05) and in the average number of the silver-stained nucleolar organiser regions (AgNORs) per nucleus (p < 0.005) between the follicular adenomas and the follicular carcinomas. The method of counting Ag-NORs per nucleus was more valid, more accurate and more economical than the method of measuring the average nuclear volume.

甲状腺腫ように対する穿刺吸引細胞診の検討

甲状腺腫ように対する穿刺吸引細胞診の検討

Supportive role of image analysis and DNA ploidy pattern in the diagnosis of thyroid tumors.

To evaluate the supportive role of image cytometry and DNA ploidy pattern in the diagnosis of thyroid tumors, a preliminary study was performed on fine needle aspirates of 30 cases. Of these, 10 cases each were of colloid goiter, follicular neoplasm, and papillary carcinoma. The nuclear area and DNA value of 50 cells in each case were measured. The mean nuclear area in colloid goiter (69.50 + 12.62 sq.microns) was significantly lower than the mean nuclear area in a follicular neoplasm (88.71 + 15.51 sq.microns) (P less than 0.05). Similar differences between the mean nuclear area in colloid goiter and papillary carcinoma (124.0 + 12.27 sq microns) was also highly significant (P less than 0.001). The results obtained by image cytometry were compared with estimated DNA ploidy pattern of follicular cells from the same cases. All colloid goiter had mean nuclear area below 100 sq.microns with diploid DNA value. However, papillary carcinoma showed aneuploid DNA pattern in eight cases (80.0%), but mean nuclear area was above 100 sq.microns. A diagnostically useful finding obtained in two of the 10 cases of follicular neoplasm was the association of aneuploid DNA pattern with mean nuclear area of the follicular cells above 100 sq.microns indicating a high probability of carcinoma and thus demanding an urgent open biopsy. These cases were readily distinguished from other cases of the same category showing diploid DNA pattern and mean nuclear area of follicular cells below 100 sq.microns.

Expression of dipeptidyl aminopeptidase IV activity in thyroid carcinoma

Dipeptidyl aminopeptidase IV activity staining was performed in various thyroid tissues to evaluate this enzyme activity as a thyroid tumor marker. A total of 195 thyroid tissues were tested for their enzyme activity expression. All papillary and follicular carcinomas, 40 cases and 3 cases, respectively, showed enzyme activity, although two other carcinomas, one medullary and one anaplastic, were not stained. Follicular adenoma expressed enzyme activity in 4 of 26 cases. Fifty-two cases with adenomatous goiter, 54 with Graves' disease and 13 with chronic thyroiditis were judged to be negative. Five normal thyroids expressed no activity except for occasional positive staining of capillary endothelia. These data suggest that dipeptidyl aminopeptidase IV activity staining is very useful for pathological diagnosis of thyroid tumors.

Fine needle aspiration cytology in thyroid disorders

Fine needle aspiration biopsy (FNAB) has radically changed the management of patients with thyroid disorders in recent years. It has been shown to be a more sensitive and more specific diagnostic procedure than any other single parameter which includes clinical examination, imaging techniques and laboratory Investigations. If used as the initial diagnostic test in the evaluation of thyroid disorders, it has been shown to be extremely cost effective, eliminating or streamlining the need for other investigative procedures. The main value of this safe and rapid procedure is as a screening method for the diagnosis of thyroid neoplasms. Cytomorphology differentiates the malignant nodules and those showing atypical patterns requiring surgical removal from the benign lesions which can be followed up with periodic FNAB. Diagnostic surgical biopsies can be eliminated in up to 50% of patients and patient management and extent of surgery can be more effectively planned. Fine needle aspiration cytology can also determine whether patients with hypo- or hyperthyroidism have underlying thyroiditis. Lymphoid cell sub-types can be catergorised using immunocytochemical studies on the aspirated material. Similarly, DNA studies performed on such samples for thyroid malignancies may provide useful prognostic information.

Fine-needle aspiration cytodiagnosis of the "cold" thyroid nodule.

The results of 1886 fine-needle cytoaspirations of solid, palpable thyroid nodules, "cold" on scintiscanning, performed between 1 January 1978 and 31 December 1986, were analyzed. In total 36 diagnoses of malignancy were made (1.9%). The results of cytologic and histologic examinations were compared in 114 cases to verify the diagnostic accuracy of this method; there was agreement in 98 cases and discordance in 16 consisting of 13 false negatives (11.4%) and 3 false positives (2.6%). The sensitivity was 77.9%, specificity 94.5%, positive predictive value 93.8%, negative predictive value 80% and test efficiency 86%. These values are in the range of those reported in the literature and confirm the validity of fine-needle aspiration cytology in the preoperative diagnosis of thyroid neoplasms.