No abstract

The prevalence of H-RAS, K-RAS, and N-RAS gene mutations in thyroid tumors according to malignancy and histology is controversial. Differences in methodology and histological classifications may explain discrepant results. To address this issue, we first performed a pooled analysis of 269 mutations garnered from 39 previous studies. Mutations proved significantly less frequent when detected with direct sequencing than without (12.3% vs. 17%). The rate of mutation involving N-RAS exon 1 (N1) and K-RAS exon 2 (K2) was less than 1%. Mutations of codon 61 of N-RAS (N2) were significantly more frequent in follicular tumors (19%) than in papillary cancers (5%) and significantly more frequent in malignant (25%) than in benign (14%) tumors. H-RAS mutations in codons 12/13 (H1) were found in 2-3% of all types of tumors, but H-RAS mutations in codon 61 (H2) were observed in only 1.4% of tumors, and almost all of them were malignant. K-RAS mutations in exon 1 were found more often in papillary than follicular cancers (2.7% vs. 1.6%) and were sometimes correlated with special epidemiological circumstances. The second part of this study involved analysis of 80 follicular tumors from patients living in Marseille (France) and Kiev (Ukraine). We used direct sequencing after PCR amplification of exons 1 and 2 of the three RAS genes. Common and atypical adenomas were separated using strict cytological criteria. Mutations of H1-RAS were found in 12.5% of common adenomas and one follicular carcinoma (2.9%). Mutations of N2-RAS occurred in 23.3% and 17.6% of atypical adenomas and follicular carcinomas, respectively. These results confirm the predominance of N2-RAS mutations in thyroid follicular tumors and their correlation with malignancy. They support the implication of N2-RAS mutations in the malignant progression of thyroid follicular tumors and the assumption that some atypical adenomas are precursors of follicular carcinomas.

Endoscopic adrenalectomy is the procedure of choice for patients with small functioning adrenal tumors. For most surgeons invasive adrenal carcinoma is an absolute contraindication for laparoscopic adrenalectomy (LA). Whether LA should be proposed for large (> 6 cm), potentially malignant tumors is questionable. The aim of this study was to evaluate the risks and outcome of LA performed in our department in patients with tumors > 6 cm and potentially malignant. We performed a retrospective study of 216 patients who underwent 233 LAs in our department from 1994 to 2000. We selected 19 patients with a tumor > 6 cm and potentially malignant: 8 nonfunctional tumors, 4 cortisol-secreting tumors, 1 virilizing tumor, and 6 pheochromocytomas. In none of these patients did preoperative investigations demonstrated invasive carcinoma. The median tumor size was 70 mm. LA was performed by a transperitoneal flank approach. Conversion to open adrenalectomy was performed in two patients owing to intraoperative evidence of invasive carcinoma. The median operating time was 150 minutes (range 95-240 minutes). Capsular disruption occurred during the dissection of two pheochromocytomas. There was no postoperative morbidity. Six patients had an adrenocortical carcinoma on pathologic diagnosis: three of the eight nonfunctional tumors, one of the four cortisol-secreting tumors, and one virilizing tumor. One patient presented with liver metastases 6 months after surgery and died. The five other patients are disease-free with a follow-up ranging from 8 to 83 months. The 13 patients with benign lesions (6 cortical adenomas, 1 ganglioneuroma, 6 pheochromocytomas) are disease-free with a median follow-up of 47 months (range 10-81 months). In experienced hands LA can be proposed for large, potentially malignant tumors. Conversion to open adrenalectomy should be performed if local invasion is observed during surgery. At present the risk of intraabdominal recurrence is unknown.

The aim of our study was to assess the ability of routine calcitonin (CT) measurement to improve the preoperative diagnosis of medullary thyroid carcinoma (MTC) in nodular thyroid diseases. We systematically determined basal CT in 1167 patients before thyroid surgery and performed a pentagastrin (Pg) CT stimulation test in 121 of these patients whose basal CT level was normal. Sixteen MTC (1.37%) were found on histopathological examination of surgical specimens: 14 in the 34 patients (41.1%) with abnormal basal CT levels and 2 in the 1133 patients with normal basal CT levels (0.17%). An abnormal increase in Pg-stimulated CT was observed in 7 of the 121 patients tested and was related to microscopic MTC in 2 cases. Among 1167 thyroidectomized patients with nodular thyroid diseases, the prevalence of MTC was 1.37% and reached 41.1% when the basal CT level was abnormal (3% of the patients). CT evaluation detected MTC, whereas other procedures, such as fine needle aspiration cytology, failed, thus allowing early radical surgery. CT measurement should thus become a routine part of the diagnostic evaluation of nodular thyroid diseases.

Our objective was to evaluate 18 F-FDG PET uptake in patients with nonmetastatic and metastatic chromaffin-derived tumors. Methods: Twenty-eight consecutive unrelated patients with chromaffin tumors, including 9 patients with genetically determined disease, were studied. A combination of preoperative imaging work-up, surgical findings, and pathologic analyses was used to classify the patients into 2 groups: those with nonmetastatic disease (presumed benign, n 5 18) and those with metastatic tumors (n 5 10). 18 F-FDG PET was performed in all cases. Visual and quantitative analyses were individually graded for each tumor. Somatic mutations of the succinate dehydrogenase subunits B and D and Von-Hippel Lindau genes were also evaluated in 6 benign sporadic tumor samples. Results: All but 2 patients showed significantly increased 18 F-FDG uptake on visual analysis. The maximum standardized uptake value (SUVmax) ranged from 1.9 to 42 (mean 6 SD, 8.2 6 9.7; median, 4.6) in nonmetastatic tumors and 2.3 to 29.3 (mean 6 SD, 9.7 6 8.4; median, 7.4) in metastatic tumors. No statistical difference was observed between the groups (P 5 0.44), but succinate dehydrogenase-related tumors were notable in being the most 18 F-FDG-avid tumors (SUVmax, 42, 29.3,21,17, and 5.3). Succinate dehydrogenase and Von-Hippel Lindau-related tumors had a significantly higher SUVmax than did neurofibromatosis type 1 and multiple endocrine neoplasia type 2A syndrome-related tumors (P 5 0.02). 18 F-FDG PET was superior to 131 I-metaiodobenzylguanidine in all metastatic patients but one. By contrast, 18 F-FDG PET underestimated the extent of the disease, compared with 6-18 F-fluorodopa PET, in 5 patients with metastatic pheochromocytoma. However, succinate dehydrogenase mutations (germline and somatic) and functional dedifferentiation do not adequately explain 18 F-FDG uptake since most tumors were highly avid for 18 F-FDG. Conclusion: 18 F-FDG PET positivity is almost a constant feature of pheochromocytomas and paragangliomas. It may be considered a molecular signature of such tumors, although which aspect of the plethora of molecular changes associated with dedifferentiation, germline genetic defects, or the adaptive response to hypoxia is responsible for this characteristic requires further elucidation.

Postoperative haematoma may have a multifactorial aetiology. Numerous manoeuvres and surgical haemostatic agents may be employed to minimise the risk of haematoma formation but are no substitute for meticulous haemostasis. In the event of haematoma formation, early surgical re-intervention is strongly advocated with due care given to at risk structures.

PCs are rare but should be included within the differential diagnosis of a neck lump. True PCs are non-functional. Pathological and immunohistochemical findings are suggestive of a branchial origin. Fine-needle aspiration may be curative and is diagnostic due to the characteristic appearance of the fluid and high PTH levels on assay.

Measuring serum calcitonin (CT) in patients with thyroid diseases allows preoperative diagnoses of sporadic medullary thyroid carcinoma (MTC) and C-cell hyperplasia (CCH). The aim of this prospective study was to distinguish biochemically between CCH and MTC. Basal CT (bCT) was determined in 7276 consecutive patients referred for thyroid disease. Patients with recurrent, persistent, or familial MTC were excluded. When bCT was > 10 pg/ml a pentagastrin-stimulated CT (sCT) assay was performed. Patients were routinely operated on when bCT > 30 pg/ml or sCT > 100 pg/ml or when other indications for surgery were present. An extensive search for CCH or microscopic MTC was conducted by immunochemistry. Pathologic findings were correlated with the bCT and sCT values. In this study 66 patients were included. No morphologic alterations of C-cells were observed in 5 patients; 16 patients presented with CCH and 45 with MTC. Statistical analysis revealed a correlation of sCT and overall bCT with tumor size and staging (p < 0.001). Considering cutoff values for bCT of > 30 pg/ml and for sCT of > 200 pg/ml, the positive predictive value of the test to detect MTC was 100% and the negative predictive value 63%. No patients with MTC at stage 2 to 4 had bCT < 30 pg/ml or sCT < 200 pg/ml. A bCT value of > 30 pg/ml or sCT > 200 pg/ml (or both) is highly predictive of MTC, requiring total thyroidectomy with lymph node dissection. Values of bCT < 30 pg/ml and sCT < 200 pg/ml do not distinguish between CCH and MTC at stage 1. In this case total thyroidectomy at least is recommended, and the role of nodal dissection might be discussed.