Medullary carcinoma of the thyroid is always linked to a high basal level of calcitonin or to an abnormal increase of the hormone after stimulation: this is generally the case in incipient tumoral metastases and in sub-clinical familial cases. Moreover, a normal stimulation test does not allow to eliminate the probability of a tumoral heredity and it is often difficult to discriminate between sporadic and familial cases or normal and high risk subjects during familial screening. So, in the absence of established rules of follow-up, repetitive stimulation tests will be often necessary as well as an extensive investigation of members of the families.

Within 2 years, two sisters, aged 23 and 33, were operated on for a craniopharyngioma. With regard to this exceptional feature, relation between neuroectodermal affections and craniopharyngiomas is discussed, and genetic determination of the occurrence of those tumors is evoked.

During a study of 80 subjects from the same family, 47 persons underwent clinical examination and blood sampling for carcinoembryonic antigen and thyrocalcitonin. A preliminary investigation had shown that two members of the family had histologically confirmed amyloid stroma MTC, 2 others had probable malignant disease, 3 children died of intestinal obstruction in the neonatal period, and a fourth child operated for megacolon when 3 days old was the descendant of 2 subjects with probable thyroid carcinoma. Three years later, the study was updated and concentrated on the patients with the highest risk of developing malignant disease. The diagnosis was confirmed in one patient considered to have probable MTC. One case of malignant disease was discovered in a child considered to be normal 6 years previously. Three other patients, considered to be normal 6 years before had very probable MTC. These results indicated that familial investigations including plasma calcitonin measurements after pentagastrin stimulation, are valuable when amyloid stroma MTC is diagnosed in one member of the family. This test should be repeated periodically. The surgical indications in patients with abnormal responses should take into consideration the psychological context.

The preoperative diagnosis of medullary thyroid carcinoma (MTC) can be made by measuring serum calcitonin levels (CT). If the patient has a thyroid nodule--sporadic or familial MTC--the serum CT will be raised but in the familial form of the disease, the diagnosis should be made at a much earlier, subclinical stage when surgery can be curative: this is possible when raised hormone levels are observed after stimulation tests. However, as this form of cancer sometimes presents late, repeated stimulation tests are necessary, with all the difficulties that it implies, in all patients with normal hormone levels in whom it is impossible to exclude tumoral heredity, whether they belong to a family with a case of sporadic MTC or to a healthy branch of a family affected by heredity.

Familial polyposis and more particularly Gardner's syndrome is a difficult affection to treat in children, due to the risk of degeneration of polyps. Two factors are accepted by all authors as being of major importance: the need for early treatment to avoid degeneration; the advantage of maximum mucosal excision to avoid repeated follow up examinations and removal of further polyps from the remaining rectum. Three cases of familial polyposis and Gardner's syndrome were treated by either total colectomy and rectal mucosectomy (2 cases) or a partial Reifferscheid procedure (1 case). Two problems related to prognosis appear to be solved by this procedure: the need to operate on a child lacking clinical symptoms, and to obtain valid continence with a minimum of suveillance after surgery.

Five bidirectional selective breedings have been carried out in mice for quantitative antibody responses to various natural immunogens. Appropriate crosses between the five "high responder" lines and between the five "low responder" lines resulting from these selections, were performed to obtain balanced hybrid populations. These populations were further selected for antibody production on the basis of multiple responses i.e., responses to all the antigens used in the previous separate selections. The result was a marked amplification of the interline divergence. The low line in particular has a profound deficiency for both primary and secondary responses. Moreover a high incidence of lymphomas was observed among these low responder mice (up to 42%).

Chromosome 1 long arm abnormalities (translocations, partial of complete trisomies) are non-randomly but inconstantly associated with specific translocations involving chromosomes 8, and 2, 14 or 22 in Burkitt's lymphomas and leukemias. All nine Burkitt's lymphoma cell lines not associated with Epstein-Barr virus (EBV) were shown to exhibit a chromosome 1 long arm abnormality and were present in only 3 out of 18 EBV positive cell lines. Bands 1q23 - 1q24 were involved in EBV-negative cell lines. It was thus hypothesised that genetic information resembling that included in viral genome exists on chromosome 1 long arm. This hypothesis implies new possible aspects of relationship between Burkitt's cell line proliferation and EBV.

An heritable multiple intestinal adenocarcinoma was observed in the offspring of an outcross between a male (or female) parent originating from our C57 Black/6M strain and his female (or male) mating counterpart originating from an experimental subline of the same strain, propagated following multigeneration exposure of the male parent to low level tritium, as drinking water (10 microCi/ml) for 35 days prior to mating.

The authors give the approach managing for medullary thyroid carcinoma in families afflicted by the multiple endocrine tumor syndromes, as defined by "G. E. T. C." (Groupe d'Etude des Tumeurs à Calcitonine), French Group based in Paris, 1983. Diagnosis of MEN II a usually follows investigations in a family of an adult patient found, at thyroid surgery, to have a MTC. Age related probability of development of hereditary MCT is stated. Investigations of the family must be most careful if the index patient is found to have medullary carcinoma on the both sides of the thyroid gland, and/or pheochromocytoma. Sequential monitoring (by means of blood calcitonin measurements following IV infusion of pentagastrin) of family members at risk between 5-35, allows diagnosis of C-cell hyperplasia and treatment of tumor in his earliest stages--MEN II b is usually recognizable in infancy or early childhood by clinical markers (mucosal neuromata, Marfanlike habitus and abnormalities of myenteric plexus). Report of patients in whom MTC was manifest as early as 18 months of age and metastasized at 2 years, require subjects at risk should be screened by CT immunoassay as soon as feasible and repeated annually until 35 years, and every 5 years after 35. The diagnosis of subjects at risk within a family is made easy by recognition of aforesaid clinical features and some more precocious abnormalities = disturbed intradermal histamine reaction and thickened corneal nerve fibers.

When the alert ophthalmologist found visible corneal nerves on a clear stroma, he must remind about the multiple endocrine neoplasia syndrome (M.E.N.-2b) and look for the medullary carcinoma of thyroid and the pheochromocytomas. Recognition of these ocular lesions as components of the syndrome is of the utmost importance because prompt identification of individuals affected by multiple endocrine neoplasia type 2 b facilitates early treatment of associated medullary thyroid carcinomas and pheochromocytomas. These endocrine neoplasias must be carefully searched by endocrine means. We present for the first time, in our knowledge, one family with M.E.N.-2b syndrome without endocrine neoplasias at this moment. We think it can be one minor presentation. We call this form "familial multiple mucosal neuromas".

Multiple Endocrine Neoplasia type 2b (MEN 2b) is a rare syndrome. The principal features are: medullary thyroid carcinoma (MTC), dysmorphism, a ganglioneuromatosis and pheochromocytomas. Eight cases of MEN 2b have been observed at the Institute Gustave Roussy, between 1968 and 1983. Seven involved children under 15 years of age. Eight had a bilateral MTC; six had dysmorphism; six had mucosal tongue neuromas. Six were troubled with visceral ganglioneuromatosis of whom two had intestinal obstruction and one urinary chronic retention. One patient had pheochromocytoma with hypertension. From this experience and other data it appears that: the dysmorphism is frequently poorly interpreted; the visceral ganglioneuromatosis is an early and severe feature; it is important to examine the patient for pheochromocytoma; the MTC must be detected by calcitonin dosage after stimulation, and requires total thyroidectomy; familial screening must be done. To improve the poor prognosis of MEN 2b, early diagnosis and aggressive treatment are necessary.

Medullary thyroid carcinoma is diagnosed with difficulty and at an advanced stage as a consequence of its rarity and its relatively recent knowledge. Therefore, the extent of the disease is already important at the therapeutic stage and the chance of cure is poor. One hundred and thirty four cases treated in the Gustave Roussy Institut (Villejuif) and the Jean Godinot Institut (Reims) between 1942 and 1983 have been studied retrospectively. One hundred and seventeen of them diagnosed after 1960 have been analyzed. We have pointed out the clinical features which should lead to diagnosis and with present means should assure it with the minimum of delay. We have outlined the multiple endocrine neoplasia syndromes IIa and IIb and repeated the necessity of clinical and biological familial screening, 11 per cent of cases are inherited.

Invasive squamous cell carcinomas of the uterine cervix from 12 untreated patients were examined for the presence of human papillomavirus (HPV) genomes and for the state of the oncogenes c-myc and c-Ha-ras. Blot hybridization experiments have demonstrated the presence of the genome of HPV type 16 (HPV 16) in six tumors and that of the genomes of HPV types weakly related to HPV 16 or HPV 18 in five others. In the nine tumors corresponding to advanced stages of the disease (stages 3 and 4) there was a 3-30 fold amplification of c-myc and/or c-Ha-ras. A concomitant amplification of both oncogenes was found in eight cancers. In only one of the three tumors confined to the cervix (stage 1), the oncogene c-Ha-ras was weakly amplified. Neither HPV DNA sequences, nor oncogene amplification were detected in the leukocytes of five patients. Thus, it seems likely that specific HPV types play a role in the development of carcinomas of the uterine cervix, and that cellular oncogenes, activated through an amplification process, are involved in at least some steps of tumor progression.