In a 22-year old man plasma calcitonin was normal in the basal state but elevated to 2.6 ng/ml after stimulation with calcium and pentagastrin. Two other family members had had bilateral pheochromocytoma accompanied by medullary carcinoma of the thyroid in one case and by adenomas of the parathyroid glands in the other. The literature of Sipple's syndrome, the value of calcitonin assay and the grounds for screening in affected families are reviewed. Surgery (total thyroidectomy) confirmed the clinical suspicion of C-cell hyperplasia and medullary microcarcinoma of the thyroid gland. Hyperplasia of the parathyroid glands was also found.

Chromosome instability syndromes are defined by either an increase of chromosomal breakage or by an increase of sister chromatid exchange number, or by an increase of the two. Bloom's syndrome, Ataxia telangiectasia, Fanconi's Anemia are the main components of this group. The incidence of cancers or malignant blood diseases is high. The finding of DNA repair abnormalities in some of them and their high sensitivity to particular mutagenic agents makes those syndromes an interesting model for oncogenesis.

The term preleukemia may be used to refer to patients with acquired chronic cytopenias (refractory anemia with an excess of blast cells, refractory sideroblastic idiopathic anemia, or others idiopathic refractory cytopenias) who develop acute myeloid leukemia (AML) months or years later. In these syndromes, an abnormal bone marrow karyotype is found in about 50% cases, like in de novo AML. These abnormalities are similar to those observed in AML (mostly +8, -7, -5 or 5q-). The translocations t(8;21) and t(15;17) are never observed in preleukemia. Correlations exist between hematological data and cytogenetic features namely, in the 5q- syndrome. Thus in preleukemia the cytogenetic analysis is a valuable diagnostic method. At the present time, the prognostic value of the bone marrow karyotype is not clearly established but in single chromosome deletions (5q-, 20q-) the acute transformation is rare or delayed. At the opposite, evolution of the karyotype is generally regarded as a progression to high malignancy.

Detectable karyotypic changes have been observed in more than 50% of the patients with ALL, distinct nonrandom chromosome abnormalities have been found. Some of these can be correlated with particular parameters such as age, morphology of the blasts, lymphocyte surface markers, prognosis. Karyotype is an important independent prognostic factor in ALL, even when other well-known risk factors are considered but an abnormal clone is not always associated with a poor prognosis. Burkitt leukemia and lymphomas have been shown to present characteristic and specific translocations t(8;14) and variants t(2;8) and t(8;22). It appears that the structural change of chromosome no 8 involving band q24 is a consistent chromosome feature in these malignancies, and that this peculiar region on chromosome no 8 probably plays an important biological role in the development of these malignant proliferations. The association of cytogenetic and molecular biology techniques would allow in the near future a better understanding of the genesis and significance of chromosome anomalies in malignant blood diseases.

A review of the literature upon 102 cases with cytogenetic study of preleukemic states (Prel.) and/or acute secondary leukemia (ASL) following chemotherapy and/or radiotherapy treatment has been made. The karyotype was almost always abnormal (91%) of cases). There was a predominance of hypodiploidy with abnormalities including chromosome number 5 (-5 ou 5q-) and/or number 7 (7- or 7q-) (chromosomes studied with banding). The abnormalities were present in preleukemia state. The pattern of the acute secondary leukemia was particularly different from that acute leukemia de novo: high frequency of preleukemia state, ANLL type of leukemia, very bad prognosis, importance of cytogenetic abnormalities. There was a great interest in the study of the karyotype for the previous detection in ASL: this allowed their discovery as soon as the preleukemia state.

Chromosome anomalies, structural and/or numerical changes are present in about 50% of acute non lymphoid leukemia (ANLL). They are non-random: chromosome 8, 7, 5 and 11 being more frequently involved. Correlations between chromosomal anomalies and type of proliferation have been established: translocation t (8;21) and acute myeloblastic leukemia M2; translocation t (15;17) and acute promyelocytic leukemia M3; structural anomalies of chromosome 11 long arm and acute monoblastic leukemia M5. A relationship between prognosis and leukemic karyotype has been found. Median survival is generally longer in patients with normal karyotypes. Future studies may correlate chromosome anomalies and metabolic changes with the help of progress in gene mapping. A better knowledge will provide not only a better therapy but also a better understanding of the leukemic process.

Chromosome banding techniques have been useful to define abnormal chromosomes in acute leukemia. The comparison between cases reported from different centers has been possible only with the acceptance of a universal system of classification and nomenclature for acute leukemia as well as for chromosomal rearrangements. Chromosomes abnormalities in acute leukemia are found in about 50 per cent of patients. They appear to be non random. Clinical, morphologic and cytogenetic findings have been correlated. Diagnosis and prognosis significance of chromosome abnormalities is of importance. The problem of normal or so called normal cells in 50 per cent of acute leukemia is set.

The chromosomal involvement in the development of malignancy in chronic myeloid leukemia is not a random event. A second Ph1, a trisomy 8, an isochromosome 17q, a trisomy 17 are the main abnormalities. These aberrations use to occur as a karyotypic evolution, either simple or complicated. An extra-medullary development of blastic transformation was demonstrated by chromosomal analysis. It is difficult to demonstrate a correlation between chromosomal abnormalities and clinical evolution in the acute phase of chronic myeloid leukemia.

A review on the association between acute leukemias (AL) and constitutional chromosome abnormalities (CCA) is presented. AL, myeloblastic or lymphoblastic according to age are 16 to 20 times more frequent in Down Syndrome (DS) children than in non DS children. The incidence of acquired chromosome abnormalities is similar in leukemic cells of DS and non DS patients but the type of anomalies, in the leukemic myeloblastic cells of DS, are different: hyperdiploidy, excess of C, F and G. Gain of chromosomes 8, 19 and 22 would characterize leukemic myeloblasts in an early stage of differentiation. Recent data on transient leukemoid reactions show that a 21 in DS appears to be predisposing factor in the development of AL. Association between AL and other balanced or unbalanced CCA appears until now to be fortuitous.

This report concerns the history of a portugesian family including one case of MEN II a (female, born 1932, presenting medullary carcinoma of the thyroid--MCT--, hyperparathyroidism and suspected pheochomocytoma), and three others with MCT alone or in association with pheochromocytoma. The diagnosis of MCT has been made possible investigating six members of the kindred by use of IR - calcitonin measurements and pentagastrin injection. This provocative screening test is also of interest to follow operated patients.

Characteristics and cytogenetic markers of 36 human malignant cell lines were studied. Structural abnormalities of chromosomes 1, 2, 3, 6, 7, 9, 11, 12 and 22 were the most frequent. Relative polysomy for chromosome 3, 7, 16, 19, 20, 22 and monosomy for chromosome 9 were observed. Each cell line contained structural and/or numerical abnormalities of chromosome 7, but structural abnormalities of this chromosome were only observed in cell lines derived from metastases; while only polysomy of chromosome 7 was observed in cell lines derived from primaries or local recurrences.

Two cases of acute leukemia in patients with breast cancer are reported. In the first patient, erythroleukemia occurred three years after breast cancer was treated by mastectomy, followed by local radiotherapy ; complementary chemotherapy (melphalan) has been given for twenty-six months. The second patient had onset of acute lymphoblastic leukemia four months after breast cancer was treated by surgery only. This patient subsequently has complete remission. Both patients died shortly after onset of leukemia. In the first patient, bone marrow cytogenetic studies evidenced major abnormalities at an early stage of the disease, with abnormal mitoses in all the cells, whereas, in the second patient, only minor abnormalities were found. A review of previously published cases of breast cancer with acute leukemia was done. Our findings suggest that the association of leukemia with breast cancer may result from therapy is some cases (secondary induced acute leukemias) while in others it may occur spontaneously.