Clonal evolution from trisomy into tetrasomy of chromosome 8 associated with the development of acute myeloid leukemia from myelodysplastic syndrome.

Tetrasomy 8, though rare, is usually associated with trisomy 8, a far more common chromosomal abnormality in acute myeloid leukemia (AML). Yet the clonal relationship between trisomy 8 and tetrasomy 8 in the cases with these chromosomal abnormalities has been unclear. Here, we report a case of a 17-year-old male, diagnosed as having a myelodysplastic syndrome (MDS). Chromosome analysis showed the presence of trisomy 8. Five years later, he developed overt AML exhibiting tetrasomy 8 only. After chemotherapy, the blast cells in the bone marrow decreased to 3.4%, and the karyotype showed trisomy 8 alone. Fluorescence in situ hybridization using a probe specific for chromosome 8 showed that the percentages of cells exhibiting 2/ 3 /4 signals were 7.8/89.2/2.0 at the MDS stage, 20.5/36.1/41.0 when overt AML developed and 24.0/72.1/2.4 after chemotherapy. These results suggested that tetrasomy 8 is derived from the AML clone, possibly evolved from the MDS clone with trisomy 8. To our knowledge, this is the first detailed case report of clonal evolution from trisomy 8 into tetrasomy 8 associated with the development of AML from MDS.

Influence of p53 mutation on pathological grade, but not prognosis of non-Hodgkin's lymphoma.

Mutations in the p53 gene were detected in 27 of the 107 (25%) cases of non-Hodgkin's lymphoma (NHL), examined by assaying the transcriptional activity of p53 in yeast. A relatively high mutation rate of p53 was observed in B-cell intermediate-grade NHL and in T-cell high-grade immunoblastic NHL, in contrast to the relatively low mutation rate observed in other pathological classifications. However, retrospective analyses of all 76 cases revealed that the survival profile and therapeutic responses were very similar in NHL patients bearing lymphomas with a mutant p53 or with the wild-type p53 even within the subclasses characterized by frequent p53 mutation. In patients with high-intermediate grade tumors, the median survival period was 24 months in mutated p53 cases and 14 months in wild-type cases. Complete remission (CR) was observed in 9 of the 17 patients (53%) with mutated forms of p53 and 18 of the 35 patients (51%) with wild-type p53 genes. Our analyses of NHL patients revealed that the presence of p53 mutations may influence pathological grades of NHL, but did not strongly correlate with poor prognosis or reduced chemo/radiosensitivity in NHL. Hence, mutations of p53 do not serve as a prognostic, or chemo/radiosensitivity marker in NHL.

Reassessment of non-hodgkins's lymphoma with a "nodular" growth variant: a clinicopathologic study of follicular, mantle cell and marginal zone lymphomas prospectively diagnosed with multiparameter analyses.

Although three subtypes of non-Hodgkin's lymphoma (NHL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), are now well recognized as independent categories, their biological behavior has not been fully compared. One of the reasons for this may be that subclassification by histological examination alone is often difficult since they all have a common variant of a "nodular" growth pattern and occasionally show similar cytological morphology. Recently, we reviewed patients with FL, MCL and MZL, who were prospectively diagnosed, using multiparameter analyses with unfixed fresh biopsy materials. Of 407 NHL patients, 101 (24.8%) belonged to these three categories and 80 could be followed; FL (n=27), MCL (n=27) and MZL (n=26). Twenty eight cases with diffuse large B-cell (DL-B) lineage lymphoma were selected as control at random. The frequency of the MCL patients with performance status (PS) 2 to 4 (41%) was significantly higher than MZL patients (4%) [P< 0.001]. The 3 year survival rate with FL, MCL, MZL and DL-B was 71.5%, 57.4%, 93.3% and 53.1%, respectively. The survival rate for MZL was significantly better than both FL (p = 0.048) and MCL (p = 0.0085). Significant differences were also found in the overall survival rates among the four risk groups as defined by the International Index [I2](low, low-intermediate, high-intermediate and high; 97.4%, 79.6%, 39.4% and 18.2%, respectively). A multivariate analysis revealed that the International Index may be a significant predictor for short survival (p=0.0001) in the patients with FL, MCL or MZL. These results suggest that MZL shows an apparently better prognosis than FL and MCL and is found to be a prognostically independent category. In contrast, the clinical outcome in MCL is the worst among the three subtypes and was closer to that of DL-B. The International Index can be applied to a wide spectrum of NHL, including MCL, MZL and FL, to and can predict prognosis in these cases.

A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review of the literature.

We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity.

[A case report of volatile solvent psychosis].

A case (male, 27 years old) with chronic thinner intoxication, whose mental condition was reexamined in accord with a court order, is reported. He had been sniffing thinner from age 12 to 27. Since the age of 17, he experienced visual and auditory hallucinations without sniffing thinner. He had no family history of schizophrenia. The psychiatric examination revealed that he had positive symptoms of schizophrenia, especially the first rank symptoms, such as auditory hallucinations (i.e. voices commenting and voices arguing), experience of influence (withdrawal of thought, thought insertion and influence of thought) and delusional perception, but did not show negative symptoms (i.e. blunting thought). Furthermore, he could maintain good emotional contact with others. Hallucinations, which appeared in acute intoxication with thinner, were second rank symptoms, different from those observed in the sober period when he was not under the influence of the thinner. Judging from above facts it was difficult to diagnose this case as schizophrenia or the flashback phenomenon of thinner dependence. Although the disease concept of volatile solvent psychosis has not been clearly established, this case may suggest that the first rank symptoms are important manifestations of volatile solvent psychosis.

[An inquiry into the factors affecting the complaints of subjective symptoms in VDT operators].

In a study of VDT workers the relationship between 1) their general life condition and working environment and 2) their eye, shoulder, neck, arm, waist and back complaints and their psychological symptoms was investigated. The subjects of the study were (147 workers whose age ranged from 18 to 39 years, and who had used VDT for a monthly average of more than 40 h. The results were as follows: 1) For most of the symptoms, a tendency was observed for females to complain more than males and for younger workers to complain more than the older workers. Neck, shoulder, arm, waist and back complaints were more common than psychological symptoms. These physical complaints appeared to be the most common among VDT workers. 2) The occurrence of eye-related symptoms is related to items directly affecting sight. This reaffirms the importance of illumination for the visual system. 3) This investigation showed that a relatively good VDT working environment was secured for the subjects of the present study. It is important that consideration be given to labor management such as provision of rest period and supervision.