We studied the records of 342 patients with papillary thyroid carcinoma out of a total of 728 thyroid cancer patients treated at the Medical School of Hannover (MHH) from 1972 through 1992. The comprehensive data-abstracting forms were designed, and the acquired information was coded, stored, maintained, and evaluated by the Clinical Cancer Registry of the MHH. A total of 160 patients (46.8%) initially had lymph node metastases (N1 status). The N status significantly influenced recurrence (p < 0.00001) and survival (p < 0.00001). Excluding other risk factors developed by univariate and multivariate analysis, such as high age (age > 45 years, p < 0.001), tumor invasion (T4 tumor, p < 0.005), and distant metastases (M1, p < 0.001), lymph node metastases remained an independent, highly significant prognostic marker for more aggressive papillary thyroid cancer. N1 status did not influence survival of patients with T4 tumor but did influence those with T1-T3 status (p < 0.001). The influence of N1 status remained significant in patients older (p < 0.001) and younger (p < 0.05) than 45 years of age. Systematic compartment-oriented dissection of lymph node metastases improved survival (p < 0.005, T1-T3) and recurrence (p < 0.00001, T1-T3) especially in patients with T1-T3 tumors. In conclusion, lymph node metastases with a significant incidence at a young age and male sex had a substantial effect on survival and recurrence especially in those with tumor status T1-T3. Systematic compartment-oriented dissection of the lymph node metastases results in better survival and a lower recurrence rate.

The susceptibility loci for the three multiple endocrine neoplasia (MEN) type 2 syndromes have been mapped to the region of chromosome 10q11.2 containing the RET proto-oncogene, which codes for a receptor tyrosine kinase. The majority of MEN 2A and familial medullary thyroid carcinoma results from missense mutations within one of five cysteine codons in the extracellular domain of the RET proto-oncogene. We now report a missense mutation, resulting in the substitution of a threonine for a methionine at codon 918 in the tyrosine kinase catalytic domain, in the germline of 26 of 28 apparently distinct families with MEN 2B. DNA from five of 13 apparently sporadic MTC and one of 12 apparently sporadic phaeochromocytomas harboured a similar mutation, but the corresponding germline DNA was wildtype in each case.

Lymph node metastases have been proven to be the main prognostic factor in medullary thyroid carcinoma (MTC). This retrospective study was undertaken to evaluate the efficiency of two surgical techniques of regional lymph node dissection with regard to the normalization of pentagastrin-stimulated serum calcitonin level and patient survival: selective lymphadenectomy, i.e., the excision of macroscopically or microscopically involved lymph nodes, versus a systematic lymphadenectomy performed by the new technique of a compartment-oriented microdissection. From 1970 to 1990, 82 patients with sporadic (n = 57) and hereditary (n = 25) MTC underwent a total of 142 operations including 63 selective lymphadenectomies and, since 1986, 35 systematic lymphadenectomies. The study revealed that in node-positive MTC the rate of interventions with a postoperative normalization of pentagastrin-stimulated serum calcitonin was higher after systematic lymphadenectomy (29.2%) than after selective lymphadenectomy (8.5%) (P < 0.01). The rate of patients undergoing repeat surgery due to a recurrence of MTC was 48% after selective lymphadenectomy and 10% after systematic lymphadenectomy. Survival was significantly better for patients after systematic versus selective lymphadenectomy (P < 0.005). This study thus emphasizes that systematic lymphadenectomy, using the technique of a compartment-oriented microdissection of cervicomediastinal lymph nodes, represents the preferred surgical treatment as well as the optimum technique in primary as well as secondary node-positive MTC.