archesi M

Papillary carcinoma of the thyroid: hepatocyte growth factor (HGF) stimulates tumor cells to release chemokines active in recruiting dendritic cells.

Tissue distribution of dendritic cells was investigated in eight cases of papillary carcinoma of the thyroid using immunohistochemistry. Most dendritic cells had an immature phenotype (CD1a++, CD11c+, CD40+, CD86-, HLA-DR-) and were located at the invasion edge of the tumor. This pattern of distribution was profoundly different from that of CD68+ macrophages, which were evenly distributed throughout the tumor. The ability of tumor cells to release chemotactic factors active on dendritic cells was investigated in primary cultures of the same cases of papillary carcinoma, and was compared to that of the corresponding normal thyroid cells obtained from the tumor-free contralateral lobe. Chemotactic activity of culture supernatants was tested against dendritic cells in a chemotaxis chamber. It was found that papillary carcinoma cells were active in releasing chemotactic activity, that hepatocyte growth factor (HGF; 100 ng/ml) or interleukin (IL)-1beta (10(3) U/ml) induced a fourfold increase in the amount of chemotactic activity released, and that normal thyroid cells obtained from the same patients were as effective as tumor cells. Characterization of chemokines at RNA level revealed that unstimulated cells contain large amounts of IL-8 and monocyte chemotactic protein (MCP)-1 RNAs, and that stimulation with HGF or IL-1beta induced RNAs for regulated upon activation normal T expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-3alpha, interferon-gamma-inducible protein 10 (IP-10), and, to a lesser extent, MIP-1alpha and MIP-1beta. The possibility that HGF/Met interaction has a biological role in vivo was investigated in serial sections of six tumors immunostained for CD1a+, Met protein, and HGF. It was found that all six tumors were intensely and diffusely positive for Met protein, that HGF staining was present in tumor cells of the advancing edge, and that HGF+/Met+ tumor cell nests were infiltrated by CD1a+ dendritic cells. The foregoing observations are consistent with the possibility that HGF stimulation of Met+ tumor cells is one of the molecular mechanisms involved in the recruitment of dendritic cells.

Hepatocyte growth factor (HGF) stimulates tumour invasiveness in papillary carcinoma of the thyroid

The present study has investigated the functional role of the Met receptor in primary cultures of 20 papillary carcinomas and of normal thyroid cells obtained from the same patients. Normal and tumour cells grew as adherent cells, formed a confluent monolayer after 10–20 days, had epithelial morphology, and were immunoreactive for cytokeratin, vimentin, and thyroglobulin. The potential effect of hepatocyte growth factor (HGF) on cell invasiveness was investigated in Boyden chambers, using a nucleopore filter coated with Matrigel as the barrier and HGF as the chemoattractant. Tumour cells of five out of seven cases of papillary carcinoma were more responsive to HGF than the corresponding normal cells in terms of the number of migrated cells per mm2. Involvement of the Met receptor in the HGF‐induced migratory response was suggested by the observation that the agonistic anti‐Met monoclonal antibody (MAb) DO‐24 was equally effective. HGF did not affect the proliferative activity of thyroid cells. Under the same experimental conditions, 10 per cent fetal bovine serum (FBS) induced a two‐fold increase in [3H]thymidine incorporation into normal cells and tumour cells. These findings are consistent with the possibility that HGF plays a crucial role in determining the invasiveness of tumour cells in papillary carcinoma of the thyroid. Copyright

High Rate of Recurrence After Lobectomy for Solitary Thyroid Nodule

OBJECTIVE To evaluate the long-term outcome of patients treated by lobectomy for solitary thyroid nodule. DESIGN Retrospective study. SETTING University hospital. PATIENTS 83 patients admitted with a clinical diagnosis of solitary thyroid nodule. INTERVENTIONS Preoperative ultrasonography showed a solitary nodule in 32 patients and this finding was confirmed intraoperatively in 24 cases (77%). 59 patients with multinodular goitres were treated by total thyroidectomy and 24 with solitary nodule by lobectomy. MAIN OUTCOME MEASURES Postoperative complications and freedom from nodule recurrence and/or parenchymal irregularity. RESULTS One patient after lobectomy and 3 after total thyroidectomy developed temporary recurrent laryngeal nerve injury. Postoperative temporary hypoparathyroidism occurred in 13 patients (22%) after total thyroidectomy and in no patient after lobectomy (p = 0.02). Neither permanent recurrent laryngeal nerve injury nor permanent hypoparathyroidism occurred after either procedure. Among patients who underwent lobectomy, 6 had an adenoma and 18 had a nodular hyperplasia. At 4-year follow-up, the freedom rate from any thyroid nodule recurrence or parenchymal irregularity was 44.7%, and the freedom rate from nodular recurrence was 74%. Men tended to have a 4-year freedom rate from nodular relapse poorer than women (48% vs. 87%. p = 0.07). Nodular recurrence occurred in one patient operated on for an adenoma, and all the other recurrences occurred in patients with nodular hyperplasia. CONCLUSIONS The mid-term freedom rate from thyroid nodule recurrence or parenchymal irregularity after lobectomy for solitary nodule of the thyroid is unsatisfactory. This observation calls for a better evaluation of long-term results after lobectomy for this condition and identification of risk factors predictive of recurrence. This would enable a more appropriate preoperative selection of patients undergoing lobectomy, indicating total thyroidectomy for those patients with solitary nodule at high risk of recurrence.

Facial nerve function after parotidectomy for neoplasms with deep localization.

PurposeTo determine whether the deep location of a parotid gland neoplasm is specific risk factor for facial nerve paralysis after parotidectomy.MethodsWe retrospectively reviewed 88 patients, including 59 with a benign superficial neoplasm of the parotid treated by superficial parotidectomy (group 1); 5 with a benign deep neoplasm treated by total parotidectomy (group 2); 20 with a malignant superficial neoplasm treated by total parotidectomy (group 3); and 4 with a malignant deep neoplasm treated by total parotidectomy (group 4).ResultsTemporary facial nerve paralysis developed in 10.3%, 20%, 10%, and 50% of groups, 1, 2, 3, and 4, respectively. Permanent facial nerve paralysis developed in 0%, 0%, 10% and 50% of groups 1, 2, 3, and 4, respectively.ConclusionThe risk factor associated with nerve damage resulting from surgery for parotid neoplasms were malignancy and deep localization. However, the deep location of a benign tumor was not a major risk factor for permanent paralysis.

Incidental Parathyroid Adenomas with Normocalcemia Discovered During Thyroid Operations: Report of Three Cases

Abstract We report three cases of parathyroid adenoma incidentally discovered during a total thyroidectomy. No patients showed any clinical or chemical features that led us to suspect a hyperparathyroidism condition before operation, but a macroscopically enlarged parathyroid was discovered during the dissection and it was removed in all three cases. All patients had a single adenoma confirmed by a histological analysis. Calcemia decreased after operation in every case but only one patient needed temporary adjunctive therapy. No permanent hypoparathyroidism or recurrent hyperparathyroidism was observed. We recommend that any enlarged parathyroid discovered during neck surgery should thus be removed in order to avoid the risks of future surgical procedures due to successive bouts of clinical hyperparathyroidism.

Thyroid Teratoma in a Six-Year-Old Boy

553 A6-YEAR-OLD BOY WAS ADMITTED to the Pediatric Endocrinology Unit because 2 months prior his mother noted a mass in the thyroid region. The clinical history was uneventful. At physical examination, the right lobe of the thyroid was enlarged and firm, not painful, and rose with swallowing. Thyroid function was normal (free thyroxine [FT4], 1.4 ng/dL; normal range, 0.78–1.84), thyrotropin (TSH) 2.1 IU/mL (normal range, 0.2–5) and thyroid antibodies were undetectable. Calcitonin was in the normal range 6.6 pg/mL (normal range, 15). At ultrasound, the right lobe was mostly occupied by a solid nodule of 38 23 17 mm, with marked and dishomogeneous hypoecogenicity. Multiple calcifications were also detectable (Fig 1). Color Doppler ultrasound showed perinodular and intranodular vascularity. Two fine-needle biopsies were performed (the second one under general anesthesia); both were nondiagnostic, showing no thyreocites. Total thyroidectomy was performed because of the suspicion of a carcinoma during surgery. At histological examination a mature thyroid teratoma was found (Fig. 2), presenting with mature neural tissue (positive at immunohistochemistry for glial fibrillary acid protein [GFAP], neurofilaments [NF], synaptophisin [SYN], protein S100, chromogranin A), mixed with respiratory epithelium, gastrointestinal glands, mucosal glands, connective tissue mixed with thyroid tissue. At 2-year follow-up the child remains healthy.