Inherited interstitial deletion of chromosomes 5p and 16q without apparent phenotypic effect: further confirmation.

We describe two families in which an inherited interstitial deletion is present without apparent associated phenotypic abnormalities. The first deletion was discovered in a 19-year-old male with a previously diagnosed peroxisomal disorder. High-resolution chromosome analysis was interpreted as 46,XY,del(5)(p14.1p14.3). The patient's phenotypically normal mother had the same interstitial deletion. Chromosome 5p14 deletion has been reported in a three-generation family without phenotypic anomalies. We hypothesize that the affected son's phenotype may be coincidental or represent unmasking of an autosomal recessive peroxisomal disorder in the deleted region. The second interstitial deletion was detected by amniocentesis for advanced maternal age. High-resolution chromosome analysis was interpreted as 46,XX,del(16)(q13q22). The same deletion was found in the healthy mother and a normal brother. The pregnancy was carried to term and resulted in the birth of a normal girl. We report these cases as further evidence that rare, unbalanced deletion of specific chromosomal regions may result in no phenotypic effect. Consequences may result from expression of an autosomal recessive disorder on the homologous chromosome. Identification of such deletions is especially important for prenatal diagnosis and genetic counselling.

Borderline malignant serous tumors of the ovary maintained on extracellular matrix: evidence for clonal evolution and invasive potential.

Four cases of advanced stage (II or III) and one case of early stage (IC) borderline malignant serous cystadenocarcinomas of the ovary were maintained on culture dishes coated with an extracellular matrix (ECM) produced by bovine corneal endothelial cells. Cells harvested for chromosomal analysis after 2-3 days showed diploid or near-diploid modalities in all cases. Banded chromosome studies in two cases revealed nonrandom clonal abnormalities with trisomy 2, 7, and 12 in seven of 13 metaphases. No structural abnormalities were noted. These cytogenetic findings differ from those found in malignant serous tumors of the ovary. In addition, borderline tumor cells digested the ECM in all cases and formed a cribiform pattern within a few days of primary culture. This study suggests clonal progression from early to advanced stages of borderline malignant serous tumors; readily distinguishable from overtly malignant serous tumors of the ovary. Ability of tumor cells derived from both primary tumors and metastatic implants to digest the ECM implies the possibility that borderline serous tumors have invasive potential.

Ewing's sarcoma of the scapula with metastases to the lung and eye.

A small, round cell tumor of the left scapula was found in a 3-month-old female Caucasian child. The histology was consistent with Ewing's sarcoma. Subsequently, a solitary pulmonary metastasis was excised. Thirty-one months after diagnosis, the child presented with leukokoria and a solitary pleural metastasis. The histology of both was identical to that of the original scapular tumor. G-banded karyotypes of the pulmonary metastasis and the ocular tumor revealed the presence of a balanced translocation, 46,XX, t(11;22)(q24;q12), which supported the original diagnosis of Ewing's sarcoma.

Acute nonlymphocytic leukemia in a glue sniffer.

A 17-year-old white male with a past history of chronic inhalational abuse of plastic glue was referred to our institution for sore throat, cervical adenopathy, and an abnormal peripheral blood smear. A diagnosis of acute myelomonocytic leukemia was made and abnormalities in cytogenetic studies were demonstrated. Specific inquiry regarding this form of drug exposure should be pursued when searching for possible etiologies of malignant disease.

Adverse effects of aneuploidy on the outcome of remission induction therapy for acute nonlymphocytic leukaemia: analysis of types of treatment failure.

Cytogenetic studies were carried out on bone marrow specimens obtained from 98 patients with acute nonlymphocytic leukaemia. Patients were treated with cytosine arabinoside and an anthracycline antibiotic. The remission rate for patients in whom only normal metaphases were detected (NN patients) was 69% while the remission rates were 50% and 40% respectively for patients in whom both normal and abnormal metaphases were seen (NA patients) and for those in whom only abnormal metaphases were noted (AA patients). Analysis of remission induction failure types suggests that the differences in outcome were related to a tendency for patients with aneuploid leukaemia to be more likely to have drug resistant disease and to the lesser ability of NA and AA patients to survive and receive a second course of therapy if the first course failed to induce a complete remission.

"Masked" philadelphia chromosome (Ph1) due to an unusual translocation.

The case of a 58-year-old white female with Philadelphia (Ph1)-positive chronic myelocytic leukemia (CML) and a "masked" Ph1 chromosome is described. The Ph1 was due to a translocation involving chromosomes #12 and #22, in which most of the long arm of #12 had been translocated to the deleted #22 (Ph1). The necessity of performing banding analysis in those cases of CML where a Ph1 is not readily apparent is stressed and the literature on"masked" Ph1 chromosomes is briefly summarized.

Benign prostatic hyperplasia in an XX man.

A sixty-nine-year-old white phenotypic male who was being investigated for a myeloproliferative disorder, was found to have an XX karyotype in all cells examined in bone marrow, lymphocytes, and skin fibroblast cultures. Despite essentially no testosterone in the plasma, he also suffered from severe prostatic hyperplasia, a finding not reported previously in patients with this genotype. While endocrine studies showed normal follicle-stimulating hormone, the luteinizing hormone level was twice the upper limit of normal and estrogens were in the normal female range. Except for complete absence of Leydig cells, testicular histology resembled that usually found in Klinefelter syndrome. The patient died of the combined effects of the myeloproliferative disease and urinary tract obstruction. The mechanism of occurrence of the sex chromosome anomaly as well as the cause and implication of the unusual finding of prostatic hyperplasia are discussed.

Non-disjunction of an unusual X chromosome.

Because of multiple abnormalities in her children, a young mother was investigated and shown to have a 47,XXX chromosome constitution. Additional C group chromosomes without visible centromeric constrictions were found in a number of cells from the peripheral blood, and using C and Q banding techniques these chromosomes were identified as X chromosomes. Analysis of the banding karyotypes of 300 cells revealed that the acentric X chromosomes had the ability to replicate and that this replication was associated with non-disjunction leading to aneuploid cells. Even though cultured skin cells did not have acentric or extra chromosomes in addition to the triple-X, examination of buccal mucosa cells for the presence of X-bodies suggested that the phenomenon of non-disjunction was present in the epithelial cells of the patient. In addition to the X without a visible centromeric constriction, either acentric D or E chromosomes were found. The data suggest that a functional defect in the cells per se is responsible for the appearance of the acentric chromosomes.

Chromosomal damage in human leukocytes induced by lysergic acid diethylamide.

Addition of lysergic acid diethylamide to cultured human leukocytes resulted in a marked increase of chromosomal abnormalities. The distribution of chromosome breaks deviated significantly from random, with an accumulation of aberrations in chromosome No. 1. Cytogenetic investigation of a patient extensively treated with this drug over a 4-year period for paranoid schizophrenia showed a similar increase in chromosomal damage.