Diagnosis Of Follicular Carcinoma Research Articles

The Role of Ultrasound in Thyroid Assessment

The recent prevalence of ultrasonography (US) has facilitated the early detection and qualitative evaluation of thyroid nodules. Furthermore, novel technical developments are extending the application range of US for other thyroid diseases. The use of US to differentiate between thyroid carcinoma and benign nodule, between a metastatic lymph node and a reactive node, between thyroid lymphoma and chronic thyroiditis, and between destruction-induced thyrotoxicosis and Graves’ disease is introduced. Classification systems for thyroid nodule have shown high diagnostic accuracy for thyroid carcinomas except follicular carcinoma. US diagnosis of lymph node metastasis showed high specificity but low sensitivity. Patients who were suspected of thyroid lymphoma based on US findings should undergo incisional biopsy or thyroidectomy for diagnosis of the histologic type if fine needle aspiration biopsy findings suggest lymphoma. Patients should be carefully followed even if they were diagnosed as negative based on cytologic findings. Measurement of thyroid blood flow is helpful for diagnosing destruction-induced thyrotoxicosis, such as painless thyroiditis, by distinguishing the lesion from Graves’ disease. Ultrasonography is useful for diagnosing various thyroid diseases, including thyroid carcinoma. The remaining issue to be resolved is the diagnosis of follicular carcinoma. Trials using novel techniques to differentiate these lesions are expected. Key words: ultrasound, thyroid assessment

Expression of claudin 1, 4 and 7 in thyroid neoplasms.

The distinction of thyroid carcinoma from benign thyroid neoplasm, as well as the subtyping of papillary carcinoma (PC) and follicular carcinoma (FC), may be performed histopathologically in the majority of cases. However, in certain cases, it is difficult to histopathologically distinguish between PC and FC, as well as follicular adenoma (FA), FC and the dominant nodule of multinodular goiter (MNG-DN). The present study aimed to determine the roles of the expression levels of the tight junction proteins claudin 1, 4 and 7 in the differential diagnosis of PC, FC, FA, MNG-DN, medullary carcinoma (MC) and anaplastic carcinoma (AC). The current study included 114 cases of histopathologically diagnosed thyroid neoplasia, which were distributed as follows: 29 FA, 18 MNG-DN, 47 PC, 10 FC, 5 MC and 5 AC. The expression levels of claudin 1, 4 and 7 were examined using immunohistochemical methods. The results revealed a significant difference in claudin 1 expression between malignant and benign thyroid neoplasms (P<0.001). Claudin 1 expression was not detected in any of the MNG-DN cases, and no significant difference in claudin 1 expression levels was identified between FA and FC (P=0.653). However, a statistically significant difference was observed between FC and PC (P<0.001). Claudin 4 expression did not differ between malignant and benign thyroid neoplasms, neither between MNG-DN, FA and FC, nor between FC and PC (P=0.068, P=0.502 and P=0.481, respectively). Claudin 7 exhibited positive immunohistochemical staining in 107 patients (94%); however, no significant difference in claudin 7 expression §levels was identified between malignant and benign thyroid neoplasms among MNG-DN, FA and FC (malignant, P=0.135; benign, P=0.470). Claudin 7 exhibited positive staining in all PC and FC cases. Therefore, claudin 1 expression levels may be useful in distinguishing cases of FC and PC with overlapping histopathological features, and provide a novel immunohistochemical marker for the subtyping of thyroid carcinoma.

Thyroid Frozen Section

A total of 704 cases of thyroid cancer were retrospectively reviewed (2005 to 2011) to assess the contribution of frozen section (FS) to preoperative fine-needle aspiration (FNA). There were 613 papillary carcinomas (87.1%), of which 237 were <1.0 cm. FNA was diagnostic or suspicious in 39.9% of micropapillary thyroid carcinomas and 75.8% of papillary carcinomas. FS was diagnostic in 52.3% and 76.6%, respectively. In no instance did the FS diagnosis change the procedure (total or near-total thyroidectomy). Neither FNA nor FS was diagnostically definitive in follicular neoplasms. A diagnosis of follicular carcinoma was made only after thorough histologic analysis. FS should have a less prominent role in the management of thyroid masses, especially in the context of total thyroidectomy for benign disease. FS may be more productively applied to the identification of metastatic lymph nodes or parathyroids in the surgical field.

Thyroid Follicular Carcinoma: Sonographic Features of 50 Cases

The purpose of our study was to retrospectively evaluate sonography of thyroid follicular neoplasms for features that would aid in distinguishing follicular carcinoma from follicular adenoma and for any imaging features that distinguish the Hürthle-cell variant of follicular carcinoma from classic follicular carcinoma. The study cohort consisted of patients with the diagnosis of follicular carcinoma and patients with the diagnosis of follicular adenoma. Fifty patients (25 men and 25 women; median age, 59.5 years) with a diagnosis of follicular carcinoma (27 with classic follicular carcinoma, 22 with Hürthle-cell variant of follicular carcinoma, and one insular variant) in a 6-year period were included. Fifty-two control patients (10 men and 42 women; median age, 46.5 years) were selected from a random sampling of all cases of follicular adenoma during the same time period. Sonograms were reviewed in consensus by four radiologists for various features. All study patients and control patients underwent surgical resection and pathologic analysis of their thyroid follicular neoplasm. The chi-square or Fisher's exact test was used for categorical variables; the Wilcoxon's rank sum test was used for continuous variables. Hypoechoic appearance (82% of follicular carcinoma patients vs 50% of follicular adenoma patients; p<0.005; odds ratio [OR]), 0.5; 95% CI, 0.3-0.7), absence of halo (64% of follicular carcinoma patients vs 42% of follicular adenoma patients; p<0.05; OR, 0.4; 95% CI, 0.2-0.9), absence of cystic change (90% of follicular carcinoma patients vs 69% of follicular adenoma patients; p<0.05; OR, 0.2; 95% CI, 0.1-0.7), greater patient age (median age of 59.5 years for follicular carcinoma patients vs 46.5 years for follicular adenoma patients; p<0.05), size of the tumor (median size of 11.75 mL for follicular carcinoma patients vs 5.95 mL for follicular adenoma patients; p<0.05), and male sex (50% of follicular carcinoma patients vs 19.2% of follicular adenoma patients; p<0.005; OR, 3.7; 95% CI, 1.6-8.9) were more frequently associated with follicular thyroid cancer than with benign adenoma. No significant difference in the prevalence of refractive shadowing, echotexture, visible invasion, lymph node enlargement, adjacent nonfollicular suspicious lesions, vascularity subtype, and calcifications was observed between the two groups. Within the follicular carcinoma subgroup, homogeneous or predominantly homogeneous echotexture (67% of classic follicular carcinoma patients vs 36% of Hürthle-cell variant of follicular carcinoma patients; p<0.05; OR, 3.5; 95% CI, 1.1-11.4) and the presence of calcifications (22% of classic follicular carcinoma patients vs 4% of Hürthle-cell variant of follicular carcinoma patients [multivariate analysis including age]; p < 0.05; OR, 22.9; 95% CI, 2.0-261.9) were associated with classic follicular carcinoma. Greater patient age (median age of 53 years for classic follicular carcinoma patients vs 64.5 years for Hürthle-cell variant of follicular carcinoma patients; p<0.05) was associated with Hürthle-cell variant follicular carcinoma. There was no association between tumor volume, sex, sonographic halo, refractive shadowing, echogenicity, visible invasion, lymph node enlargement, adjacent nonfollicular suspicious lesions, vascularity subtype, and cystic change between the subgroups of follicular carcinoma. The sonographic features of follicular adenoma and follicular carcinoma are very similar, but larger lesion size, lack of a sonographic halo, hypoechoic appearance, and absence of cystic change favored a follicular carcinoma diagnosis. Increased patient age and male sex are associated with malignancy. Within the follicular carcinoma subgroup, Hürthle-cell variant of follicular carcinoma is more often seen in older patients with nodules having a heterogeneous appearance and lacking internal calcifications.

Thyroid Ultrasonography

The recent prevalence of ultrasonography (US) has facilitated the early detection and qualitative evaluation of thyroid nodules. Furthermore, novel technical developments are extending the application range of US for other thyroid diseases. The use of US to differentiate between thyroid carcinoma and benign nodule, between a metastatic lymph node and a reactive node, between thyroid lymphoma and chronic thyroiditis, and between destruction-induced thyrotoxicosis and Graves' disease is introduced. Classification systems for thyroid nodule have shown high diagnostic accuracy for thyroid carcinomas except follicular carcinoma. US diagnosis of lymph node metastasis showed high specificity but low sensitivity. Patients who were suspected of thyroid lymphoma based on US findings should undergo incisional biopsy or thyroidectomy for diagnosis of the histologic type if fine-needle aspiration biopsy findings suggest lymphoma. Patients should be carefully followed even if they were diagnosed as negative based on cytologic findings. Measurement of thyroid blood flow is helpful for diagnosing destruction-induced thyrotoxicosis, such as painless thyroiditis, by distinguishing the lesion from Graves' disease. Ultrasonography is useful for diagnosing various thyroid diseases, including thyroid carcinoma. The remaining issue to be resolved is the diagnosis of follicular carcinoma. Trials using novel techniques to differentiate these lesions are expected.

Vascular and Capsular Pseudoinvasion in Thyroid Neoplasms

The diagnosis of follicular carcinoma of the thyroid requires the identification of capsular and/or vascular invasion, with the exception of distant metastases. However, several artifacts may mimic both vascular and capsular invasion. This article presents two cases of pseudo invasion in encapsulated follicular neoplasms. Their differentiation from true vascular and capsular invasion is discussed and the criteria for true invasion are reviewed.

Follicular neoplasm of the thyroid—vanishing cytologic diagnosis?

The significance of making a diagnosis of follicular neoplasm on fine needle aspiration (FNA) biopsy remains a controversial issue, considering that the diagnosis of follicular carcinoma is based on histological criteria and the significantly decreasing incidence of follicular carcinoma in the general population. On FNA the main differential diagnoses of follicular neoplasm includes follicular variant of papillary carcinoma (FVPC), follicular adenoma, follicular carcinoma and benign solitary nodule occurring in a goiter. Several studies have looked at immunohistochemical and molecular markers to distinguish benign from malignant lesions but none of them have proved to be infallible. Although, FVPC is a distinct entity from the follicular neoplasm group, it is not always possible to separate it from the other follicular lesions because of overlapping cytologic features and often-sporadic presence of nuclear features, follicular variant of papillary carcinoma remains the main pitfall in a diagnosis of follicular neoplasm. Since a significant number of cases that are malignant on follow-up are usually FVPC, consequently, follicular neoplasm is an essential diagnostic consideration on FNA. In addition, follicular carcinoma, despite a decreasing incidence continues to be a real entity. Therefore, it is essential that follicular neoplasm continue to be part of our diagnostic repertoire.

Computerized nuclear morphometry in thyroid follicular neoplasms

Differential diagnosis of follicular adenoma (FA) and follicular carcinoma (FC) of the thyroid can be challenging in the routine practice of surgical pathology because the diagnosis of FC is strictly defined and identification depends on the presence of invasion of the capsule or blood vessels. These features may be equivocally presented in the histological sections and interpreted subjectively by different pathologists, so an objective approach to solve this problem is essential. Computerized morphometry is a scientific tool to evaluate cellular changes and it can enhance the interpretation of morphological features by the transformation of pathological changes in cells to a qualitative form. The present study investigated the diagnostic role of objective computerized nuclear morphometry in follicular neoplasms. Thirty-six cases of thyroid FC and 36 cases of FA from patients who were matched by age and sex were studied. Four nuclear parameters were selected and analyzed: mean nuclear area, mean nuclear perimeter, largest to smallest diameter ratio of the nuclei, and coefficient of variation of the nuclear area. The results indicate that all the chosen nuclear variables were significantly correlated with the FA and FC studied. In conclusion, computerized nuclear morphometry can be considered a helpful ancillary tool for differential diagnosis of FA and FC.

Expression of Human Telomerase Reverse Transcriptase in Thyroid Follicular Neoplasms: An Immunohistochemical Study

Differential diagnosis of follicular adenoma (FA) and follicular carcinoma (FC) of the thyroid can be difficult in the routine practice of surgical pathology because the diagnosis of FC is strictly defined and determined by the presence of capsular and/or vascular invasion by the tumor. These features may be equivocal in the histologic sections. On the other hand, telomerase is expressed in many human cancers and is thought to contribute to their immortality. Human telomerase reverse transcriptase (hTERT) is the major determinant of human telomerase activity, and its expression is suggestive of capacity for unlimited replication. This case-control study examined the expression of hTERT using immunohistochemistry in 36 thyroid FC and 36 FA from patients who were matched by age and sex. The aim was to investigate the value of immunohistochemical staining for hTERT in the differential diagnosis of follicular neoplasms. The results revealed 23 cases of FC and 14 cases of FA that showed high expression of hTERT, with moderate to strong immunoreactivity. The remaining cases showed weak or negative staining. The difference between FA and FC was statistically significant (p < 0.05). In conclusion, immunohistochemical staining for hTERT can be considered an ancillary marker for differential diagnosis of FA and FC.

Skull Metastasis From Thyroid Follicular Carcinoma With Difficult Diagnosis of the Primary Lesion-Case Report-

A 57-year-old male patient presented with an immobile ellipsoid mass of 6-cm diameter in the right occipitoparietal region. Cranial computed tomography showed the mass with dense contrast enhancement causing bone destruction. After embolization of the mass, total resection was performed. Histological examination showed the mass had a capsule, with no invasion of the dura mater or dermis, and the follicles of various sizes covered with mono-lined thyrocytes were full of colloid. Immunohistochemical examination showed positive staining for thyroglobulin. Postoperatively, levels of thyroid hormones were normal, and thyroid ultrasonography and technetium-99m scintigraphy showed no abnormalities. Fine needle aspiration biopsy performed at various locations of the thyroid gland revealed no atypical thyroid cells. Whole body technetium-99m scintigraphy found no abnormal bone involvement. The histological evidence was suggestive of follicular carcinoma metastasis. Surgical treatment was planned for the thyroid gland, but the patient did not consent. Two years later, the patient presented with the pain and sensitivity in the sacrum, the right iliac wing, and the right caput femoris. Computed tomography revealed lytic lesions in these areas. Bone metastases were identified. Whole body scintigraphy showed increased activity in these regions, but the cranium and all other tissues were normal. The patient underwent total thyroidectomy under a diagnosis of follicular carcinoma. The present case of a lytic skull lesion associated with normal thyroid tissue on admission but finally treated as follicular thyroid cancer emphasizes the difficulty in histological discrimination of follicular carcinoma from normal thyroid tissue.

I-123 Uptake by Intrathoracic Stomach

A 40-year-old man who had a total thyroidectomy 3 years earlier for follicular carcinoma of the thyroid received 100 mCi 1-131 for ablation. Follow-up 1-123 total-body scan showed successful thyroid gland ablation, but also showed persistent stomach activity in the esophageal bed. The patient had resection of esophageal cancer and the stomach was reconstructed in the esophageal bed 7 years prior to the diagnosis of follicular carcinoma. These findings demonstrate well-documented physiologic uptake in the gastric mucosa, which can lead to misinterpretations.

Clinico‐pathologic prediction of malignancy of thyroid follicular lesion with FNAC‐A multivariate analysis

Background: Patients suffering thyroid nodules with the diagnosis of follicular lesion on FNAC normally undergo thyroidectomy as the diagnosis of follicular carcinoma can only be ascertained by histopatholoigc examination. We undertake this study to examine the likelihood of various preoperative clinicopathologic parameters to predict malignancy.Methods: All the patients presented with thyroid nodules with follicular lesion diagnosed by FNAC were retrospectively evaluated if they have undergone thyroidectomy. The final histopathologic diagnoses were the gold standard. The clincopathologic parameters studied encompassed: gender, age, previous thyroidectomy, enlarging nodule, nodule size, presence of symptom, incidental finding, presentation duration, presence of Hurthle cell, cytological atypia and colloid content. The statistical analysis was carried out by SSPS 11.0 software. P‐value &lt;*Τ*0.05 was considered statistically significant.Results: A total of 354 thyroidectomies have been carried out from January 1998 to December 2003. Sixty‐seven patients satisfied the inclusion criteria. The mean age was 51.3 ± 15.4 years old. There were only eight male patients. The final histopathologic results were: hyperplastic nodule (n = 32), follicular or Hurthle cell adenoma (n = 22), follicular carcinoma (n = 3), Hurthle cell carcinoma (n = 3), papillary carcinoma (n = 4), medullary carcinoma (n = 1) and two cases of Hashimotos thyroiditis. On univariate analysis, nodule enlargement and cytological atypia were found to be significant predictors of malignancy. (Table) However, only the nodule enlargement remained significant on multivariate analysis. (P=0.048) Sex (M vs F) NS Age (&lt;50 vs &gt;/50 year) NS Previous thyroid surgery (Yes vs No) NS Enlarging nodule (Yes vs No) P=0.024 Nodule size (&lt;3 vs &gt;/=3 cm) NS Symptoms (Yes vs No) NS Incidental finding (Yes vs No) NS Presentation duration (&lt;2 vs &gt;/=2 year) NS Hurthle cell (Yes vs No) NS Cytological atypia (Yes vs No) P=0.046 Colloid content (Yes vs scanty/nil) NS Conclusion: Enlargement of thyroid nodules with follicular lesion diagnosed by FNAC significantly associate with malignancy. This category of patients should receive early thyroidectomy.

The value of frozen section in intraoperative surgical management of thyroid follicular carcinoma.

Preoperative and intraoperative diagnosis of follicular carcinoma (FC), resulting in one-stage surgical treatment of follicular thyroid tumors, is an important issue in thyroid surgery. In the 10-year period there were 4158 operations performed on thyroid gland. There were 1559 patients with follicular tumors, 70 (4.4%) of them having FC. We analyzed the groups of patients with FC determined on frozen section (FS) and permanent section (PS) according to duration of clinical symptoms, ultrasound (US) examination, tumor size, patient gender and age, intensity of invasion, localization, and multiple or solitary occurrence of tumor. FC was diagnosed in 39 (55.7%) patients on frozen section (FS). Among the encapsulated (minimal invasion) carcinomas, the FS was accurate in 19 of 33 (57.6%) FC and in 5 of 15 (27.8%) Hürthle cell carcinomas (HCC); among extensively invasive carcinoma in 11 of 14 (78.6%) FC and in 4 of 5 (80.0%) HCC. FC was significantly more common in men (p <.001) and in the right lobe (p <.05). We did not find statistically significant differences concerning duration of symptoms, US examination, tumor size, patient age, and multiple or solitary occurrence of the tumor between the patients with FC diagnosed on FS and the patients with FC diagnosed on PS. The intraoperative diagnosis of FC is difficult. Although the percentage of false-negative results was relatively high (44.3%), there were no false-positive results. This means that the second operation was avoided in 55.7% of the patients, and no unnecessary thyroidectomies were performed. FS biopsy is an important method in surgery of follicular tumors. Improved technical support and the ability to analyze a greater number of slides will increase the accuracy of the method.

CD10 expression is useful in the diagnosis of follicular carcinoma and follicular variant of papillary thyroid carcinoma.

CD10/neutral endopeptidase 24.11(NEP) is a membrane-bound zinc metalloproteinase the expression of which represents a useful tool in the classification and diagnosis of malignant leukemia and lymphoma. Recently, CD10 has been found to be expressed in nonhematopoietic tissues and various types of neoplasms. In this study, we examined CD10 immunostaining in paraffin sections of 70 distinct lesions to investigate whether CD10 is a useful diagnostic marker for thyroid neoplasms. CD10 was not detected in normal thyroid tissue, benign lesions (15 follicular lesions and 15 adenomatous goiters), and pure papillary carcinomas except for follicular variants. In contrast, CD10 was expressed in 8 of 10 (80%) follicular carcinomas and 7 of 9 (77%) follicular variant of papillary thyroid carcinomas. This appears to be the first report on the expression of this member of a newly identified gene family in thyroid tumors. In conclusion, immunohistochemistry of CD10 in paraffin sections is valuable in the classification of thyroid follicular lesions into benign and malignant groups and in the diagnosis of follicular variant of papillary thyroid carcinoma.

Histopathological and immunohistochemical features of thyroid carcinoma

Thyroid-specific malignant tumors are derived from follicle cells (papillary and follicular carcinoma), and from parafollicular, calcitonin-producing C-cells (medullary carcinoma). The main criterion for diagnosis of papillary carcinoma is the occurrence of ground glass, hypochromic nuclei, often associated with papillae as the prominent pattern of the tumor, and psammoma bodies. The diagnosis of follicular carcinoma is based on the true infiltration of the venous vessels outside the tumor capsule and the fungus-like infiltration through the tumor capsule into the surrounding parenchyma. Anaplastic carcinoma is mostly detected by the pathologist by fine-needle aspiration biopsy, or tumor reduction specimen. Medullary thyroid carcinoma is typically composed of solid nests and infiltrating formations of polygonal or spindle-shaped cells and amyloid deposits within the stroma of the tumor. Two main discriminatory immunohistochemical markers for tumors with follicular and parafollicular origin are thyroglobulin and calcitonin, respectively. Thyroglobulin is present in more than 95% of papillary and follicular carcinomas, whereas anaplastic thyroid carcinomas are mostly immunonegative for thyroglobulin. Medullary carcinoma is characteristically positive for calcitonin, pan-neuroendocrine markers, and often numerous peptides.

Role of frozen section, sex, age and tumour size in differentiating follicular adenoma from carcinoma: a meta-analysis

Abstract Background Frozen section (FS) has been the mainstay of intraoperative decision-making in thyroid neoplasms for many years. However, since the widespread use of preoperative fine-needle aspiration, the need for FS in patients with follicular neoplasms (FNs) has been debated. Preoperative features may be better at distinguishing follicular carcinoma (FC) from adenoma (FA). One reason why these issues are unresolved is because clinical studies are often too small to reach statistical significance. The purpose of this study was to combine modern trials and use the technique of meta-analysis to determine the efficacy of FS and the role of sex, age and tumour size in patients with FNs. Methods Inclusion criteria were published and unpublished studies between 1990 and 1999 inclusive, in which patients had a permanent pathology (PP) diagnosis of FA or FC (including Hurthle cell tumours) and underwent FS or had clinical features recorded. A pooled sample of the combined data was analysed for the prognostic variables and outcomes. P &amp;lt; 0·05 was considered significant. Results Nineteen studies were included. FS was evaluated in 11 studies (n = 2204). FS matched PP in 82 per cent of patients and was considered helpful. FS was indeterminate in 13 per cent of cases and was considered unhelpful. FS was detrimental in 4 per cent of patients. In 27 per cent of FCs, FS reported FA (false negative) and in 1 per cent of FAs, FS reported FC (false positive). Overall, FS had an 87 per cent sensitivity, 48 per cent specificity, 92 per cent positive predictive value, 35 per cent negative predictive value and 82 per cent accuracy. Clinical features were examined in ten studies (n = 1980). Nine studies (n = 1780) reported sex; 20 per cent of patients were male. A disproportionately high percentage of patients with FC were male (28 per cent) compared with female (P &amp;lt; 0·001). Two studies (n = 548) reported age; 36 per cent of patients were over 50 years old. A disproportionately high percentage of patients with FC were aged over 50 years (52 per cent) compared with those younger than 50 years (P &amp;lt; 0·001). Six studies (n = 1620) reported tumour size; 19 per cent of FNs were larger than 3–5 cm. A disproportionately high percentage of FCs were larger than 3–5 cm (33 per cent) compared with smaller lesions (P &amp;lt; 0·001). Conclusion FS is able to differentiate FC from FA in over 80 per cent of patients. It has a false-positive rate of less than 1 per cent and therefore may be trusted most when it reports a FC. In cases in which FS reports FA, male sex, age greater than 50 years and tumour size larger than 3–5 cm can be used as indicators that a FN will be a FC.

Cytopathology and AgNOR counts in fine-needle aspiration cytology smears of thyroid lesions.

The object of the present work is to study the cytomorphological features and the value of silver colloidal staining method in distinguishing the non-neoplastic, benign, and malignant neoplasm in fine-needle aspiration cytology (FNAC) smears of thyroid nodules. One hundred forty histologically confirmed aspirated samples of thyroid lesions were studied and classified cytologically. These smears were stained for AgNOR counts. The number and location of AgNOR dots as well as clusters in nuclei were studied by two different observers independently. Lower AgNOR counts were recorded in cases of thyroiditis (1.375 +/- 0.414), whereas follicular carcinoma had a higher number of AgNOR counts (5.04 +/- 0.52). The clusters of AgNOR dots were centrally located in colloid goitre, but no cluster arrangement was observed in cases of carcinomas. Increased nuclear size, nucleoli, and chromocentres were helpful in the diagnosis of follicular carcinoma. AgNOR counting cannot be reliably used on an individual case basis to differentiate adenoma from carcinoma. Therefore, AgNOR study in thyroid lesions can be used as an additional diagnostic method with cytomorphological features to differentiate benign and malignant follicular neoplasms.

Well differentiated follicular neoplasms of the thyroid: reproducibility and validity of a 'decision tree' classification based on nucleolar and karyometric features.

This study was conducted on fine-needle aspirates of well differentiated follicular neoplasms of the thyroid. A 'decision tree' classification based on the percentage of nucleolated nuclei, percentage of nuclei with two or more nucleoli and mean major nuclear diameter was adopted. We observed that the reproducibility and the validity of the follicular adenoma vs follicular carcinoma discrimination are greater than in the subjective evaluation. Moreover, similar classification results were obtained when measurements were performed either with a fully automated image analysis system or with semiautomatic or manual instrumentation. As for reproducibility of the inter-instrument comparisons, the k statistic values ranged from 0.85 to 1.00 (mean value 0.90, that is, an 'almost perfect' degree of agreement); in the subjective evaluations, the inter-observer comparisons showed values ranging from 0.20 to 0.56 (mean value 0.37, that is, 'fair'). In the decision tree classification, feature value thresholds were selected in order to have specificity of 100% and the predictive value of a positive result (carcinoma) of 100%; accuracy was 87% (range 86-89%), sensitivity 74% (71-79%), the predictive value of a negative result (adenoma) 79% (78-82%). In the subjective evaluation the values were as follows: accuracy 67% (64-71%), sensitivity 57% (50-64%), specificity 77% (71-79%), predictive value of a negative result (adenoma) 64% (61-69%), predictive value of a positive result (carcinoma) 71% (67-75%). The conclusion is that, by using a routine microscope equipped with a micrometer, the preoperative diagnosis of follicular carcinoma from smears can be formulated with a high degree of certainty.