Diagnosis of occult thyroid carcinoma by thyroid ultrasonography with fine needle aspiration cytology

OBJECTIVE: To assess the role of ultrasonography and fine needle aspiration cytology (FNAC) in preoperative diagnosis of patients with occult thyroid carcinoma (OTC). STUDY DESIGN: Data on 768 thyroid carcinoma patients receiving primary treatment at Chang Gung Medical Center were retrospectively reviewed. Of these patients, 97 had OTC. To detect small thyroid nodules early and define the characteristics of clinically palpable nodules, thyroid ultrasonography with FNAC were performed on 67 histopathologically proven OTC patients. Analysis for diagnostic value was done for ultrasonography and FNAC. RESULTS: In the 67 patients receiving ultrasonography with FNAC, 23 were preoperatively diagnosed as having papillary thyroid carcinoma and 1 as having follicular carcinoma. The tumor size of these 24 preoperative FNAC-proven OTC was 0.81 +/- 0.23 cm (mean +/- SD). In the remaining patients, 10 presented pictures suspicious for malignancy, with a mean tumor size 0.63 +/- 0.24 cm, and 33 (49.3%) were diagnosed as having benign thyroid lesions in preoperative FNAC. The tumor size in these 33 lesions was 0.58 +/- 0.24 cm. Fifty-seven of the 67 OTC patients received frozen sections. Thirty-eight papillary thyroid carcinomas and four follicular carcinomas were correctly diagnosed on frozen sections. CONCLUSION: Although the rate is not high, high-resolution ultrasonography and FNAC is the best approach to preoperative diagnosis for OTC patients today.     

Hyperthyroidism and carcinoma of the thyroid gland

The incidence of thyroid carcinoma in hyperthyroidism varies considerably from as low as 0.3% to as high as 16.6% with a higher rate in toxic nodular goiters. Occult thyroid carcinoma (< 1.5 cm or microscopic foci) is the rule and only a few tumors are suspected preoperatively with ultrasonography or fine needle aspiration or 131 I scan. In 408 patients who underwent surgery for hyperthyroidism in our Surgery Department from January 1967 through December 1994 the incidence of thyroid carcinoma was 5.6% (23 cases). In detail, a neoplasm occurred in 5 cases of Graves' disease (specific incidence: 3.8%), in 13 cases of toxic nodular goiter (12.5%) and in 5 cases of hyperfunctioning adenomas (2.8%). 19 cancers were papillary (12 in toxic nodular goiter, 3 in Graves' disease, 4 in hyperfunctioning adenomas), three were follicular (1 in Graves' disease, 1 in toxic nodular goiter, 1 in hyperfunctioning adenomas) and 1 medullary in Graves' disease. A papillary carcinoma was diagnosed preoperatively on fine needle aspiration with ultrasonography in only two patients with Graves' disease and confirmed by postoperative histological examination on permanent section. We do not believe in the frozen-section examination intraoperatively because it's not diagnostical for follicular lesions and evaluates rarely capsular invasion. Twenty patients received total thyroidectomy and four of them also lymphoadenectomy. Three patients received emithyroidectomy: in two cases for occult papillary carcinoma and in the last case for local cancer invasion (T4N0M0). Twenty patients are alive and with no evidence of cancer recurrence. Mean follow-up is 59.6 months. Our retrospective study shows a progressive increase of the incidence of coexisting thyroid malignancy and hyperthyroidism especially in toxic nodular goiter, probably related to extended surgical indications. Our findings do confirm that, even in the presence of hyperthyroidism, all thyroid nodules require careful diagnostics for exclusion of malignancy.     

Solitary thyroid nodule in Khartoum

Ninety four patients with solitary and significantly dominant thyroid nodules were studied. Inadequate sampling was reported in 5 patients (5.9%). In the remaining 89 patients, 64 had simple goitre (72%), 12 follicular adenoma (13.5%), 12 were malignant nodules (6 follicular, 5 papillary and one anaplastic) (13.5%) and one patient had Hashimoto's thyroiditis. The incidence of malignancy in the clinically solitary nodules was 14% (10/70) compared to 10% (2/19) for the dominant nodules which increased to 16% (8/49) versus 10% (4/40) respectively after ultrasonography and histopathological confirmation of the nature of the gland. There is a low positive predictive value for follicular neoplasm with fine needle aspiration cytology (FNAC) (44%). This is due to the fact that reports of suspicious follicular pattern is agreed not to imply definite malignancy, however total lobectomy was done for those patients whereas terms like "not suspicious" and "highly suspicious" are considered to mean, benign and malignant respectively and in those latter groups the prediction was 100%. The study stresses the importance of FNAC techniques in reducing the surgical load with minimal false negative results, increasing the yield of carcinoma and projecting the importance of a significantly dominant nodule in endemic areas.     

A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see commetns

BACKGROUND: The National Cancer Data Base (NCDB) represents a national electronic registry system now capturing nearly 60% of incident cancers in the U. S. In combination with other Commission on Cancer programs, the NCDB offers a working example of voluntary, accurate, cost-effective "outcomes management" on a both a local and national scale. In addition, it is of particular value in capturing clinical information concerning rare cancers, such as those of the thyroid. METHODS: For the accession years 1985-1995, NCDB captured demographic, patterns-of-care, stage, treatment, and outcome information for a convenience sample of 53,856 thyroid carcinoma cases (1% of total NCDB cases). This article focuses on overall 10-year relative survival and American Joint Committee on Cancer (AJCC) (3rd/4th edition) stage-stratified 5-year relative survival for each histologic type of thyroid carcinoma. Care patterns also are discussed. RESULTS: The 10-year overall relative survival rates for U. S. patients with papillary, follicular, Hürthle cell, medullary, and undifferentiated/anaplastic carcinoma was 93%, 85%, 76%, 75%, and 14%, respectively. For papillary and follicular neoplasms, current AJCC staging failed to discriminate between patients with Stage I and II disease at 5 years. Total thyroidectomy +/- lymph node sampling/dissection represented the dominant method of surgical treatment rendered to patients with papillary and follicular neoplasms. Approximately 38% of such patients receive adjuvant iodine-131 ablation/therapy. At 5 years, variation in surgical treatment (i.e., lobectomy vs. more extensive surgery) failed to translate into compelling differences in survival for any subgroup with papillary or follicular carcinoma, but longer follow-up is required to evaluate this. NCDB data appeared to validate the AMES prognostic system, as applied to papillary cases. Younger age appeared to influence prognosis favorably for all thyroid neoplasms, including medullary and undifferentiated/anaplastic carcinoma. NCDB data also revealed that unusual patients diagnosed with undifferentiated/anaplastic carcinoma before age of 45 years have better survival. CONCLUSIONS: The NCDB system permits analysis of care patterns and survival for large numbers of contemporaneous U. S. patients with relatively rare neoplasms, such as thyroid carcinoma. In this context, it represents an unsurpassed clinical tool for analyzing care, evaluating prognostic models, generating new hypotheses, and overcoming the volume-related drawbacks inherent in the study of such neoplasms. [See editorial on pages 2434-6, this issue.]     

Aberrant tau phosphorylation and neurite retraction during NGF deprivation in PC12 cells

OBJECTIVE: To investigate the final results of cases with preoperative diagnoses of thyroid follicular neoplasms by fine needle aspiration cytology (FNAC). STUDY DESIGN: A retrospective review of 6,499 patients who received thyroid ultrasonography with FNAC at Chang Gung Memorial Hospital. Among 6,499 patients, 209 (3.2%) were diagnosed by FNAC as having follicular neoplasms, of which 84 received surgical treatment. Eighty-two of the 84 cases had a frozen section prepared during the operation. RESULTS: Thyroid malignancy was confirmed histopathologically in 164 cases. Among 84 thyroid follicular neoplasm patients, 21 cases were diagnosed as malignant tumors, including papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and Hürthle's cell carcinoma. Ultrasonography on these 21 patients revealed that 16 cases (76.2%) had low echo density in the thyroid nodule. The percentage was statistically significantly different from that in benign cases, 23.8% (P < .05). A higher incidence of malignancy was found in males, but the data did not reach statistical significance (P = .0586). CONCLUSION: Most of the follicular neoplasms revealed by FNAC were benign lesions. Low echo density on ultrasonography and male sex carried a higher risk of malignancy.     

Analysis of small lung nodules diagnosed by open lung or thoracoscopic biopsy

We examined clinicopathologic findings in 86 cases with peripheral lung nodules less than 30 mm in size diagnosed by open lung or video-assisted thoracoscopic surgery (VATS) biopsy. Biopsies were conducted because of the new appearance or enlargement of nodules as evidenced in a comparison with retrospective chest films in 47 patients, X-ray findings of malignancy suspicion without retrospective films in 13, enlargement of nodules after the administration of antituberculosis agents in 9, and a past history of malignancy in 17. Mean tumor size was 18.1 mm in primary lung cancer (n = 29), 16.2 mm in metastatic lung cancer (n = 13), 16.3 mm in tuberculosis (n = 18), 15.3 mm in nonspecific inflammation (n = 12), 16.7 mm in benign lung tumors (n = 7), 7.5 mm in intrapulmonary lymph node (n = 2), and 19.4 mm in others (n = 5). Among primary lung cancers with a clear N-factor, the percentage of T1N0M0 cancers was up to 72%. No significant difference was observed in either of the reasons for these biopsies and the size of nodules among diseases. To detect early lung cancer and increase the rate of cure, small pulmonary nodules that could be hardly diagnosed using bronchoscopic or needle aspiration biopsy should be diagnosed positively using VATS biopsy.     

Comparison of intraoperative cytology with frozen sections in the diagnosis of thyroid lesions

We retrospectively studied the usefulness of intraoperative cytology (IOC) and frozen section (FS) in the rapid diagnosis of 68 thyroid lesions. In 14 cases of papillary thyroid carcinoma, IOC correctly diagnosed 13 cases, while FS correctly diagnosed 11 cases. There was no significant difference in sensitivities, and both methods had similar specificities. In 21 cases of colloid nodule, IOC was slightly more sensitive than FS; IOC correctly diagnosed 16 cases, while FS correctly diagnosed 15 cases. However, the specificity of IOC was only 71%, but was 98% for FS. Of 17 follicular adenomas, FS diagnosed 16 as follicular neoplasms and misdiagnosed only 1 as a colloid nodule. By contrast, IOC misdiagnosed 9 follicular adenomas as colloid nodules, most of which were macrofollicular variants with abundant colloid. Of 11 follicular carcinomas, FS diagnosed all as follicular neoplasms, while IOC misdiagnosed 3 as colloid nodules. While IOC is not as accurate as FS in the diagnosis of colloid nodules and follicular neoplasms, it is highly sensitive and specific in the diagnoses of papillary carcinoma and performance of the technique is rapid and easy. In an intraoperative setting, IOC is a useful adjunct to FS in screening thyroid nodules for the presence of papillary carcinoma.     

Significance of nondiagnostic fine-needle aspiration of the thyroid

BACKGROUND: Fine-needle aspiration biopsy (FNAB) has been shown to be rapid and cost effective in the evaluation of thyroid nodules. The significance of nondiagnostic (unsatisfactory) FNAB is uncertain, however. METHODS: We reviewed 345 consecutive thyroid FNABs and identified 59 patients with initially unsatisfactory specimens. These patients had follow-up to determine whether their thyroid nodules proved to be malignant. RESULTS: Three patients (5.1%) were found to have organ-confined papillary carcinoma of the thyroid, the largest tumor mass measuring 1.2 cm. Six patients (10.2%) had benign adenomas. CONCLUSIONS: In most cases of initially nondiagnostic FNAB of a thyroid nodule, neoplasia is not found subsequently. A minority of cases may still harbor malignancy. None of our patients in whom repeated FNA was either nondiagnostic or suggestive of benign disease were ultimately found to have a malignancy.     

Surgical management of non-small-cell lung cancer with ipsilateral mediastinal node metastasis (N2 disease)

Between 1979 and 1989, 876 patients with non-small-cell lung carcinoma were referred to our unit for surgical treatment. One hundred forty-six patients were judged not suitable for surgical treatment on clinical, radiologic, or bronchoscopic findings. Cervical mediastinoscopy or anterior mediastinotomy (or both) showed that 151 patients had mediastinal involvement by invasion or metastases into the ipsilateral (N2 disease) or contralateral (N3 disease) superior mediastinal lymph nodes and were therefore deemed inoperable. Except for one patient who had involvement of a single nodal station at mediastinoscopy, all other patients (n = 578) undergoing thoracotomy were thought, on the basis of computed tomographic scan or mediastinal exploration (or both) not to have N2 disease. Despite our efforts to avoid surgery on patients with N2 disease, at thoracotomy routine mediastinal node dissection disclosed that 149 patients had unsuspected N2 disease. Resection was possible in 130 (87.3%) by pneumonectomy (n = 72), bilobectomy (n = 7), lobectomy (n = 49), or lesser resection (n = 2). In three patients the resection was incomplete (2.3%), but in 127 a complete resection was performed (85%). Histologic examination in these 149 patients showed that 72 tumors were squamous cell carcinoma, 54 adenocarcinoma, 14 large-cell carcinoma, and 9 of mixed type. Eight patients died in the hospital after thoracotomy. Adjuvant therapy was not used after complete resection. Complete follow-up was obtained in 134 patients and the mean follow-up period was 27.25 months (1 to 116 months). The actuarial 5-year survival for those having complete resection was 20.1%. There was a statistically significant difference favoring long-term survival in those patients with squamous cell carcinoma (p < 0.01) and those in whom only one nodal station was involved (p < 0.05). Neither the extent of resection nor the involvement of any specific nodal station influenced long-term survival. Despite rigorous preoperative investigations, routine mediastinal node dissection demonstrated mediastinal node metastasis for the first time at thoracotomy in 26% of our patients. We believe resection is justified in these patients, who have already necessarily incurred the morbidity and mortality of thoracotomy, so long as complete resection is possible.     

Immunohistological differentiation of benign thyroid follicular cell tumors from malignant ones: usefulness of anti-peroxidase and JT-95 antibodies

An immunohistological investigation using anti-thyroid peroxidase (PO) and JT-95 (JT) antibodies was conducted on surgical specimens of papillary carcinoma (n = 12), follicular carcinoma (n = 8), follicular adenoma with prominent papillary structure (n = 12), follicular adenoma (n = 8) and adenomatous goiter (n = 8). In benign lesions, follicle-forming and papillae-forming epithelia showed positive staining with anti-PO antibody. In 26 of 28 benign lesions, PO-positive areas covered 50% or more of the cut surface area of the lesions. However in carcinomas, PO-positive areas were non-existent (13/20) or only focal (7/20) and the papillae did not stain. The incidence of JT-positive cases was higher in papillary carcinomas (12/12) than in other lesions (13/36). JT-positive areas were much wider than PO-positive areas in papillary carcinomas, whereas in benign lesions, PO-positive areas were wider than or at least roughly equal to, JT-positive areas. Follicular carcinomas did not stain or stained only focally with these antibodies. In conclusion, these two antibodies seem useful in differentiating benign from malignant follicular cell tumors.     

Amygdalar volume and emotional memory in Alzheimer's disease

The cytologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) can be difficult owing to the paucity of nuclear changes of papillary carcinoma and overlapping features with other follicular-derived lesions. We report our fine-needle aspiration (FNA) experience with 17 histologically proved cases of FVPTC with a preceding FNA. All cases showed increased cellularity and a background of moderate to abundant thin watery colloid with variable amounts of thick eosinophilic colloid. The cells were arranged mainly in monolayer sheets and syncytial fragments; occasional microfollicle formation with abundant fine eosinophilic cytoplasm was seen. Nuclear enlargement was a consistent finding in all cases. Only 5 cases showed prominent nuclear features of papillary carcinoma. Histologic examination showed encapsulated follicular-patterned nodules with multifocal random distribution of nuclear features of papillary carcinoma that were more pronounced in the subcapsular locations of the lesions. This morphologic heterogeneity explains the variability seen in FNA specimens of FVPTC and may result in false-negative diagnoses. We believe that these findings should be considered when interpreting follicular lesions; suspicion of an FVPTC should be conveyed in the cytopathology report, which may prompt intraoperative assessment to avoid a second surgical intervention for completion thyroidectomy.     

Role of ultrasound-guided fine-needle aspiration biopsy in evaluation of nonpalpable thyroid nodules

To determine the role of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the evaluation of incidentally diagnosed nonpalpable thyroid nodules (NP-TN), we compared the diagnostic yield of US-FNAB in NP-TN larger than 10 mm in diameter, with palpation-guided (P-FNAB) in palpable thyroid nodules (P-TN) in the same hospital setting. Of 108 consecutive patients with NP-TN (female/male: 97/11, age: 55.2 +/- 14.3, mean +/- SD), malignancy was identified in 8 patients (7 with thyroid papillary carcinoma, 4 of which had extrathyroidal spread, and 1 patient had metastasis of pulmonary adenocarcinoma). Male gender was associated with higher prevalence of malignancy (p = 0.09) while calcification and/or cystic degeneration of the nodule did not predict the cytological findings. Malignancy was identified in 16 of 151 consecutive patients with P-TN (female/male: 139/12, age: 44.1 +/- 9.5, mean +/- SD) indicating a similar rate of malignancy in both NP-TN and P-TN. In the P-TN group thyroid cancer was more common in males (p = 0.007), and the US properties of the nodule did not predict its cytological diagnosis. In conclusion, because similar rates of cancer are detected by FNAB in both NP-TN and P-TN, an FNAB is recommended for NP-TN larger than 10 mm.     

Clinical significance of clonality in thyroid nodules

BACKGROUND: Many different neoplastic and hyperplastic thyroid diseases present with clinically apparent thyroid nodules. Clonality analysis indicates whether a nodule arises from the polyclonal proliferation of a group of cells or forms a clone from a genetically altered cell and thus provides objective information on the origin of the thyroid nodules. Clonality was studied in thyroid nodules using the polymerase chain reaction (PCR) assay in the X-linked human androgen receptor (HUMARA) gene by random X chromosome inactivation in women. METHODS: DNA samples were obtained from 28 nodules in 21 women. All nodules and non-tumour thyroid tissues were fractioned selectively under a cryostat. Genomic DNA was isolated and digested with HhaI. PCR amplification of the HUMARA locus was performed using PCR mixtures containing [alpha-32P]2'-deoxycytidine 5'-triphosphate. The PCR products were analysed by denaturing gel electrophoresis. RESULTS: The HUMARA alleles were heterogeneous in 18 of 21 patients. Among the 23 nodules from 18 patients, all of the eight papillary thyroid carcinomas were monoclonal. Two solitary nodules from follicular adenomas were monoclonal. Of the 13 follicular nodules from nodular goitres, ten were polyclonal and three were monoclonal. The monoclonal follicular nodules were larger in size (3.5 versus 2.0 cm, P< 0.05) and had a tendency towards more cystic changes than polyclonal nodules. CONCLUSION: PCR-based clonality study of thyroid nodules may help to distinguish hyperplastic from neoplastic nodules.     

Efficacy of sonographically guided biopsy of thyroid masses and cervical lymph nodes

OBJECTIVE: We performed a prospective study in 96 patients to determine accuracy of sonographically guided fine-needle aspiration biopsy of thyroid masses and cervical lymph nodes. MATERIALS AND METHODS: Real-time sonography was used to guide biopsy of 112 cervical masses in 96 patients (71 patients with impalpable masses, 16 with failed unguided attempts, patient's or physician's preference in nine). The diameters of all masses were less than 3 cm, with a mean of 1.5 cm and a median of 1.5 cm. Twenty-nine masses measured 1 cm or less in diameter, 60 masses between 1.1 and 2.0 cm, and 23 masses between 2.1 and 3.0 cm. Cervical masses that were sampled by biopsy included 75 thyroid masses and 37 lymph nodes. RESULTS: Diagnostic specimens were obtained in 102 (91%) of 112 masses sampled. Sixty-eight (91%) of 75 biopsies of thyroid tissue and 34 (92%) of 37 biopsies of lymph nodes were diagnostic. Nondiagnostic thyroid biopsies included four of complex cysts and three of solid nodules. Sonographic follow-up (1 year) revealed no change or decrease in size of those seven lesions. Sixty of 68 diagnostic thyroid biopsies showed benign processes: 42 macrofollicular adenomas, six colloid adenomas, five microfollicular adenomas, four probable cases of thyroiditis, and three hemorrhagic cysts. The remaining eight diagnostic thyroid biopsies showed malignant processes: seven papillary carcinomas and one metastatic small-cell carcinoma. Of 34 diagnostic biopsies of lymph nodes, 26 showed malignant processes and eight showed benign processes. Surgery in the three patients with nondiagnostic biopsies of lymph nodes revealed two recurrent medullary cancers and one benign node. CONCLUSION: Sonographically guided fine-needle aspiration biopsy of neck masses has a high sensitivity (91%) and should be routinely used to evaluate indeterminate masses in the neck.     

Papillary and follicular thyroid carcinoma metastatic to the skin: a case report and review of the literature

Cutaneous metastases from thyroid cancers are rare. We report the case of an otherwise asymptomatic 81-year-old woman with an enlarging scalp lesion. Her solitary skin metastasis was the presenting feature of thyroid carcinoma. Routine histopathology of the lesion was notable for an atypical clear cell neoplasm. Immunohistochemistry was positive for thyroglobulin. Subsequent resection of the thyroid gland identified separate foci (< 1 cm) for both papillary and follicular carcinoma. Although such immunohistochemical staining has been used previously, it has never been reported to provide the definitive diagnosis for a solitary cutaneous metastasis from the thyroid. Previous tumors had anatomic features in a clinical context that permitted identification by routine light microscopy. Clear cell features found in the follicular focus of carcinoma in the thyroid suggest that it is the primary. A worldwide literature review reveals that follicular carcinoma has a greater preponderance than papillary carcinoma for cutaneous metastasis and that the majority of skin metastases from either papillary or follicular thyroid cancer are localized to the head and neck.     

Determination of skeletal age using the Oxford Score in children with epiphyseolysis of the femur head

Differentiated thyroid carcinoma often has a favourable prognosis. However, there is no unanimity about the surgical procedure used. In this analysis we evaluated the surgical complications of 178 patients operated on for differentiated thyroid carcinoma during a 12-year period. 110 of the patients were operated in one session and 68 in two. Total thyroidectomy was performed in 106 patients and ipsilateral lobectomy together with contralateral subtotal resection in 72 patients. Tumour was bilateral or multicentric in 59 patients (33%). Hypoparathyroidism occurred in eight patients (4%), without differences between total thyroidectomies and lobectomy plus subtotal resections. Hypoparathyroidism tended to be more common after completion resection than after completion thyroidectomy (4/28 vs 1/40; P = 0.08). Accidental injury to the recurrent laryngeal nerve occurred in one patient (0.6%) during a contralateral resection. During a median follow-up of 4.5 years, tumour recurrence was detected in 22 patients (12%). In papillary carcinoma it was more common in patients who had underwent lobectomy plus contralateral resection than after total thyroidectomy (11/60 vs 3/88; P < 0.01). However, the median follow-up times were unequal. In conclusion, total thyroidectomy and even completion thyroidectomy is as safe as less radical lobectomy together with contralateral resection. Thus, total thyroidectomy should be offered to all patients with differentiated thyroid carcinoma until there is a reliable method to recommend for those patients who can be treated with less radical procedures.     

Combination of radioiodine (131I) and probe-guided surgery for persistent or recurrent thyroid carcinoma

To improve the completeness of surgical excision of persistent or recurrent differentiated thyroid carcinoma, the following protocol was used for the treatment of 54 patients with functioning lymph node metastases: administration of 3.7 gigabecquerels (100 mCi) 131I; total body scintigraphy (TBS) on day 4; surgery on day 5, using an intraoperative probe (Gammed 2, Eurorad); and postoperative TBS with the remaining 131I activity on day 7. The 54 patients (35 women and 19 men presenting 47 papillary carcinomas, 2 well differentiated follicular carcinomas, and 5 poorly differentiated follicular carcinomas) had already undergone surgery for differentiated thyroid carcinoma: total thyroidectomy (51 patients) or lobectomy with isthmusectomy (3 patients), with lymph node dissection in 33. One to 7 131I treatments were performed before inclusion. Preoperative 131I-TBS with a high dose of 131I allowed accurate localization of previously suspected neoplastic foci and detection of yet unknown foci in 56%; it was the most sensitive tool for localizing neoplastic foci. The use of an intraoperative probe was considered decisive in 20 patients, as neoplastic foci were found inside sclerosis due to previous surgery (n = 9), at unusual sites behind vessels or in the mediastinum (n = 10), or both (n = 1). In 26 patients, it facilitated the preoperative detection of foci with 131I uptake already depicted at preoperative 131I-TBS. In all 46 patients, the completeness of excision was demonstrated by both the probe and the postoperative 131I-TBS and was confirmed during follow-up. Of note, lymph node metastases undetected by 131I-TBS or by the probe were found in 14 patients at histological examination. This clearly shows that en block dissection is the only recommended procedure. In four patients, no neoplastic foci were found and in four patients, uptake was either due to the thymus (in two) or to the salivary glands (in two).     

S-100 protein is a differentiation marker in thyroid carcinoma of follicular cell origin: an immunohistochemical study

S-100 protein, a dimer of S-100 alpha and S-100 beta subunits (S-100 alpha and S-100 beta), is widely distributed in human tissue, and several papers describing S-100 protein expression in follicular cells of the thyroid have been published. In the present study, 105 cases of thyroid carcinoma (of which 96 were papillary, four follicular, two undifferentiated, and three medullary) were analyzed immunohistochemically for the expression of S-100 protein, S-100 alpha, S-100 beta, and thyroglobulin. In papillary carcinoma, 188 lesions were studied and classified into well differentiated types (56 papillary, 45 follicular) and poorly differentiated types (41 trabecular, four solid, eight squamoid, three tall, and one insular), because the histological structure of each tumor was heterogeneous. The percentage of lesions which expressed positively for S-100 protein and S-100 alpha, respectively, according to type were: papillary, 96 and 99%; follicular, 96 and 100%; trabecular, 95 and 100%; solid, 50 and 50%; squamoid, 50 and 75%; and tall, 33 and 100%. The insular type was negative for both. For papillary carcinoma, well differentiated lesions showed stronger S-100 alpha expression than poorly differentiated lesions. S-100 alpha expression was weaker in follicular and undifferentiated carcinoma than in papillary carcinoma. Medullary carcinoma also expressed S-100 alpha. S-100 beta was positive in lesions that expressed S-100 alpha strongly. Expression of S-100 protein and S-100 alpha protein correlated with thyroglobulin synthesis in the follicular cells. It was concluded that S-100 protein, mainly S-100 alpha, exists in thyroid follicular cells, that it exists in higher quantity in most of the well differentiated lesions but in lower quantity in poorly differentiated or undifferentiated lesions, and that S-100 protein, especially S-100 alpha, is a differentiation marker in carcinoma of thyroid follicular cell origin.     

TWIST gene mutation in a patient with radial aplasia and craniosynostosis: further evidence for heterogeneity of Baller-Gerold syndrome

BACKGROUND: The optimal management of high-grade dysplasia in patients with Barrett's esophagus is controversial. The aim of this study was to assess the prevalence of unsuspected carcinoma at esophagectomy in patients with Barrett's esophagus with high-grade dysplasia after endoscopic surveillance with jumbo biopsy forceps compared with standard biopsy forceps. METHODS: Twelve patients with high-grade dysplasia in Barrett's esophagus without gross or microscopic evidence of carcinoma underwent esophagectomy after preoperative endoscopy with 4-quadrant jumbo biopsies at 2-cm intervals. The findings in this group were compared with those in a group of patients with Barrett's esophagus who underwent esophagectomy for high-grade dysplasia after biopsies obtained at 2-cm intervals with standard biopsy forceps. RESULTS: Unsuspected cancer was found in 4 of 12 (33%) patients in the jumbo biopsy group compared with 6 of 16 (38%) in the standard biopsy group (p = NS). All 6 cancers in the standard biopsy group were intramucosal, whereas 2 were intramucosal and 2 were submucosal in the jumbo biopsy group. No patients in either group had lymph node metastases. CONCLUSIONS: Unsuspected cancer is found frequently in patients with Barrett's esophagus who are undergoing esophagectomy for high-grade dysplasia despite the use of a rigorous jumbo biopsy protocol. Esophageal resection is still indicated in appropriately selected patients with high-grade dysplasia until better markers of cancer risk are available.