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To evaluate long-term survival and response to RAI treatment in patients with differentiated thyroid cancer (DTC) and 131Iodine-avid metastatic lung disease.A retrospective review of 639 DTC patients followed-up at the Hospital de Clínicas, Buenos Aires, Argentina, showed that 42 (6%) patients had lung metastasis, and 24 patients were included for analysis.Seventeen were women, and 7 were men (F:M=2.4:1). Eighteen patients (75%) had PTC, and 6 (25%) had FTC. The median age at diagnosis was older than 45 years in 50%, and the median follow-up was 13 years. Good response to treatment (GRT: no evidence of disease or biochemical persistence without structural correlate) was observed in 46% of patients (all with diffuse postdose radioiodine uptake and no structural images higher than 1 cm in diameter); and 21% patients died from disseminated lung metastasis. Overall survival at 5 and 10 years was 100% and 88.4%, respectively. The Cox proportional hazard ratio showed that extrathyroidal invasion, positive uptake of 18-FDG, and metachronous diagnosis of the lung metastasis were variables that significantly predicted death. Those patients who had a GRT did with a mean effective cumulative RAI dose of 457.3±29.7 mCi 131I (range, 300-600 mCi 131I).Lung metastasis showed a slow progression with a high long-term overall survival. The presence of synchronous lung metastasis, the absence of nodules larger than 1 cm, and the lack of uptake of FDG were predictive factors for an early response to treatment with RAI cumulative doses lower than 600 mCi 131I.

Papillary thyroid carcinoma is the most common type of thyroid malignancy. The diagnostic features of these tumors include characteristic nuclear cytology. However, many variants have been reported with different morphology and molecular profiles. Although the vast majority of papillary thyroid carcinomas have an excellent prognosis, some variants of papillary thyroid carcinoma can have a more aggressive course. With this increased attention to papillary thyroid carcinoma variants has come the need to sort out which variants are clinically important and should be recognized by practicing pathologists. The main objectives of this review article are to (1) summarize the gross and histopathologic features of papillary thyroid carcinoma; (2) provide an overview of the subtypes of papillary thyroid carcinoma and their prognosis; (3) discuss established and emerging data on the immunohistochemical findings that are helpful in differential diagnosis; and (4) summarize molecular findings and pathogenesis of these lesions.

In this study, we describe a case of papillary carcinoma in a 15-year-old girl who presented with a hyperfunctioning (hot) thyroid nodule and discuss it in the context of current management guidelines for patients with thyroid nodules. In adults, hot nodules rarely require cytologic or histologic evaluation, and hyperthyroidism is often treated with radioiodine (131I). However, in children and adolescents, the malignancy rate for nodules (both cold and hot) is higher and surgery is often necessary. Surgery may serve as a therapy, as well as a diagnostic tool, to treat hot nodules in children and adolescents.

Objective: To examine the prevalence of BRAF mutation among thyroid cancer histologic subtypes and determine the association of BRAF mutation with indicators of poor prognosis for papillary thyroid cancer and patient outcome. Background Data: The appropriate extent of surgical treatment, adjuvant therapy and follow-up monitoring for thyroid cancer remains controversial. Advances in the molecular biology of thyroid cancer have helped to identify candidate markers of disease aggressiveness. A commonly found genetic alternation is a point mutation in the BRAF oncogene (BRAF V600E), which is primarily found in papillary thyroid cancer and is associated with more aggressive disease. Methods: BRAF V600E mutation status was determined in 347 tumor samples from 314 patients with thyroid cancer (245 with conventional papillary thyroid cancer, 73 with follicular thyroid cancer, and 29 with the follicular variant of papillary thyroid cancer). Univariate and multivariate analyses were performed to determine the association of BRAF V600E with clinicopathologic factors and patient outcome. Results: The prevalence of BRAF V600E mutation was higher in conventional papillary thyroid cancer (51.0%) than in follicular variant of papillary thyroid cancer (24.1%) and follicular thyroid cancer (1.4%) (P < 0.0001). In patients with conventional papillary thyroid cancer, BRAF V600E mutation was associated with older age (P = 0.0381), lymph node metastasis (P = 0.0323), distant metastasis (P = 0.045), higher TNM stage (I and II vs. III and IV, P = 0.0389), and recurrent and persistent disease (P = 0.009) with a median follow-up time of 6.0 years. Multivariate analysis showed that BRAF V600E mutation [OR (95% CI) = 4.2 (1.2-14.6)] and lymph node metastasis [OR (95% CI) = 7.75 (2.1-28.5)] were independently associated with recurrent and persistent disease in patients with conventional papillary thyroid cancer. Conclusions: BRAF V600E mutation is primarily present in conventional papillary thyroid cancer. It is associated with an aggressive tumor phenotype and higher risk of recurrent and persistent disease in patients with conventional papillary thyroid cancer. Testing for this mutation may be useful for selecting initial therapy and for follow-up monitoring.

We describe the histologic variants of papillary and follicular carcinomas associated with 109 spindle and giant cell carcinomas (SGCC) of the thyroid and determine the incidence of rhabdoid and thyroglobulin inclusions in these tumors. In addition, we searched for rhabdoid and thyroglobulin inclusions in 120 papillary carcinomas (PC) (all 15 variants included), 23 differentiated follicular carcinomas (DFC), (6 with insular pattern), 6 poorly differentiated follicular carcinomas (PDFC) and 34 follicular adenomas (FA). The following differentiated thyroid carcinomas coexisted with SGCC: 51 (46.8%) PC, (34 conventional type, 14 tall cell variant and 3 follicular variant), 6 (5.5%) DFC, 1 follicular carcinoma with insular pattern (0.9%), and 3 oncocytic carcinomas (2.8%). Eleven SGCC (10%) and 2 (33%) PDFC showed rhabdoid features, but lacked thyroglobulin inclusions. Thyroglobulin inclusions were found in 10 FA (29%), 8 (17%) follicular variants of PC and in 7 (30.4%) DFC. There were no rhabdoid inclusions in any of these differentiated thyroid tumors. Our findings support the hypothesis that most SGCC result from dedifferentiation or anaplastic transformation although the mechanisms that underlie this transformation remain unknown. The finding that only 1 (0.9%) SGCC was associated with follicular carcinoma with insular pattern contradicts the opinion that this tumor occupies an intermediate position between differentiated and anaplastic carcinomas. Rhabdoid features are markers of PDFC and SGCC while thyroglobulin inclusions are markers of FA and differentiated thyroid carcinomas with follicular phenotype.

PURPOSE Questions arise concerning the behavior and prognosis of the follicular variant of papillary thyroid carcinoma. PATIENTS AND METHODS Between 1990 and 2003, 92 patients with follicular variant of papillary carcinoma (group A) were enrolled in a long-term study and compared with control groups of follicular thyroid carcinoma (group B, 40 cases) and pure papillary thyroid carcinoma (group C, 99 subjects). RESULTS Gender (female/male), age, and follow-up duration (years, mean ± standard error) in groups B, A, and C were 36/4, 43 ± 3, 11 ± 1.1; 79/13, 46 ± 2, 9.5 ± 0.7; and 82/17, 44 ± 1, 10 ± 0.6, respectively. At the time of diagnosis, the rates of extensive extra thyroidal local spread, bilateral lesions, and vascular invasion were higher in group A than in group C. The rate of metastasis tumors was higher in group A than in group C and was comparable in groups A and B. Complete remission was reported in 95% of group B patients, 98% of group C individuals, and in only 77% of group A subjects. Persistent stable lesions and progressive disease rates in groups B, A, and C were 2.5% and 2.5%, 15% and 8%, and 0% and 2%, respectively. The survival rates at the end of the study were 100% in all cohorts, but the cumulative dose of administered radioiodine in group A was higher than in group C and was comparable to that given in group B. Metastases dedifferentiation was observed only in the group A (three patients). DISCUSSION Follicular variant of papillary thyroid carcinoma may be more aggressive than previously considered and should be clearly distinguished from the two other forms of well-differentiated thyroid carcinoma.

The morphologic distinction between papillary and follicular neoplasms of the thyroid gland can be difficult, especially on small biopsy specimens or in fine-needle aspirations. To determine whether immunohistochemistry could help in achieving the correct diagnosis, we characterized the staining pattern for a series of papillary and follicular neoplasms of the thyroid gland. A pilot study was performed using a panel of antibodies, including high-molecular-weight keratin (HMWK, 34 beta E12), cytokeratin (CK) 5/6, CK7, CK13, CK14, CK20, AE1/AE3, CAM5.2, involucrin, and villin. Of these antibodies, involucrin and HMWK showed strong differential staining between follicular and papillary neoplasms. HMWK stained 91% of papillary carcinomas, including follicular variants, with a median of 53% positive cells, and involucrin stained 72.5% of papillary neoplasms with a median of 45% positive cells. HMWK stained only 20% of follicular neoplasms, whereas involucrin stained 29% of cases. Papillary neoplasms showed strong, although patchy, staining with HMWK and involucrin, whereas those follicular neoplasms that did have staining showed a weak, diffuse pattern of staining. We believe that HMWK, and involucrin to a lesser degree, could be useful in differentiating papillary from follicular neoplasms, especially for cytologic cell block material or for cases in which the architectural pattern is follicular.

Background: We sought to evaluate the predictive value of preoperative fine-needle aspiration (FNA) on surgical decision making by evaluating the final pathologic diagnosis and comparing it to the preoperative diagnosis. Further, we wished to calculate the predictive accuracy of each of several types of preoperative FNA diagnosis. Study Design: A retrospective chart review of 151 thyroid resections between July 1990 and April 1996 at the University of Virginia was undertaken. The mean age was 45 years (range, 11 to 85 years). Preoperative laboratory values, presenting symptoms, imaging studies, and predictive values of preoperative FNA and intraoperative frozen section were analyzed. Results: Symptomatology was poorly predictive of a benign versus malignant postoperative final pathologic diagnosis. Sensitivity, specificity, and accuracy of frozen section versus FNA was 86% versus 86%; 99% versus 93%, and 96% versus 92%, respectively, if the reading "cancer" or "suspicious" were predicted as positive for malignancy and "benign" or "follicular" were predicted as negative for malignancy. If only the reading "cancer" was predicted as positive for malignancy and only "benign" was predicted as negative for malignancy, sensitivity and specificity for FNA were 100% and 96%, respectively, and 100% and 99%, respectively, for frozen section. Forty-nine "follicular" lesions obtained by preoperative FNA resulted in 46 benign diagnoses after surgical resection. Conclusions: The use of preoperative FNA is a powerful diagnostic tool in the hands of skilled pathologists. There is increasing evidence that intraoperative frozen section adds little to intraoperative decision making in patients diagnosed with thyroid cancer by preoperative FNA. Less definitive interpretations decrease the sensitivity, specificity, and accuracy of the FNA diagnosis.

SUMMARY BACKGROUND DATA: The extent of primary thyroidectomy for differentiated thyroid cancer is controversial. There are strong proponents for total thyroidectomy based on its presumed and theoretical disease control benefits. In contrast, there are equally strong advocates of less aggressive thyroidectomy with its lower hazard of parathyroid and recurrent nerve injury. The authors have addressed whether total thyroidectomy has a survival benefit justifying its use in patients with high-risk primary cancer. The major risk factors include age and the following the pathologic determinants follicular histology, vascular invasion, and extracapsular extension. MATERIALS AND METHODS: The clinical pathologic, therapeutic, prognostic, and outcome data were reviewed in 347 patients with well-differentiated thyroid cancer. Seventy-five percent were women, 216 patients were in the younger age group (low-risk) (21-50 years), 103 were in the intermediate-risk group (51-70 years), and 28 were in the high-risk group (>70 years). Included in the high-risk pathologic category were 158 patients who had follicular histology (55), extracapsular extension (107), or vascular invasion (119). Total thyroidectomy was performed in 56 patients, near or subtotal thyroidectomy in 47 patients and lobectomy in 55 patients. The 10-year disease specific survival in the overall patient group was 82% in patients with total thyroidectomy, 78% in patients with subtotal thyroidectomy, and 89% in patients with lobectomy (p = 0.30). There was no significant survival difference according to extent of thyroidectomy in the intermediate or high-risk groups either by age or in patients who had high-risk pathologic feature. CONCLUSIONS: Total thyroidectomy in high-risk patients with differentiated thyroid cancer (containing follicular histology, vascular invasion, or extracapsular extension) showed no benefit over partial thyroidectomy. This suggests that the general use of total thyroidectomy is not indicated, except in highly selected patients.

A rare case of hyperthyroidism in the presence of a functioning bone metastasis secondary to an occult thyroid cancer is reported. A 59-year-old woman's pelvic bone metastasis was much too extensive and hypervascular to permit resection. An I-131 scan showed striking activity in the pelvic metastasis, which reflected ectopic excessive production of thyroid hormone by a functioning metastatic thyroid carcinoma. After total thyroidectomy, the patient received I-131 ablation and transcutaneous intra-arterial embolization therapy but her metastasis progressively enlarged. Microscopically, concomitant follicular and papillary cancer was found in close proximity to the thyroid. The patient now has vertebral metastases, and her hyperthyroid state still requires methymazole to prevent thyrotoxicosis.

Ras mutations have been found in thyroid lesions. Different studies have shown different frequencies of mutations among benign and malignant lesions. The presence of point mutations in codons 12 and 13 of the c-K-ras, c-H-ras, and N-ras genes was studied in 58 thyroid lesions (10 nodular goiters, 10 follicular adenomas, and 15 papillary, 10 follicular, and 13 anaplastic carcinomas). DNA was extracted from formalin-fixed paraffin-embedded tissue, and target sequences were amplified in vitro by the polymerase chain reaction. Mutations were detected by the presence of restriction-fragment-length polymorphisms either occurring naturally or introduced artificially by the use of mutant primers. No characterization of the mutations was performed. Results were correlated with clini-copathologic features and patient follow-up. One goiter showed a mutation at codon 13, c-K-ras. All follicular adenomas, including three hyalinizing trabecular adenomas, were negative. Four papillary carcinomas presented mutations (one at codon 13, c-K-ras; three at codon 12, N-ras). Two follicular carcinomas showed mutations at codon 12, N-ras. Five anaplastic carcinomas showed mutations (two at codon 12 and two at codon 13, c-K-ras; one at codon 12, N-ras). In summary, the results confirm that ras oncogenes play a role in thyroid tumorigenesis, probably at an early step. Ras mutations appear not to be related to prognosis.

Ectopic thyroid tissue with no orthotopic gland is extremely rare; malign transformation of ectopic thyroid is also an uncommon event, and rarer is the follicular variant of papillary carcinoma. In this clinical report, a case with submandibular ectopic thyroid without orthotropic thyroid gland is presented. Treatment was a complete resection of tumor, and histologic findings reveal follicular variant of papillary carcinoma. The patient had an uneventful postoperative recovery, and a substitution treatment with thyroxine was maintained. Physicians should be aware of the possibility that a lingual, submandibular, or lateral neck swelling could be an ectopic thyroid gland. This entity poses specific diagnostic and therapeutic difficulties, and definitive diagnosis is histologic. Computed tomographic scan, radioactive scan, and ultrasonography are necessary in revealing the presence of normal thyroid gland. Recommended treatment is primarily surgical, sometimes associated with radioiodine I 131 therapy and a substitution treatment with thyroxine.

1-123 scintigraphy showed unilateral lactation and tetrofosmin scintigraphy showed the virtual disappearance of the right lower limb in a 43-year-old woman who had had polio.