A 20-year-old man was admitted to our hospital because of fever and knee joint pain on March 20, 1986. Physical examination revealed generalized lymphadenopathy and hepatomegaly. White blood cell count was 32,800 microliters with 74.4% blast cells. Bone marrow was hypercellular with 93.6% blast cells. Blast cells were weakly positive for acid phosphatase and PAS stainings but were negative for peroxidase, sudan black B and esterase stainings. Cell surface marker analysis of blast cells disclosed that they were positive for anti-HLA-DR, CD19, CD24, CD33 and CD38, but were negative for CD10 and CD20. Cytoplasmic immunoglobulin of blast cells was negative and TdT activity by immunofluorescent method was positive. Chromosomal analysis of bone marrow samples revealed normal karyotype. Therefore, this case was diagnosed as having acute lymphoblastic leukemia (L2) and achieved complete remission with LVP therapy consisting of 1-asparaginase, vincristine and prednisolone. Gene analysis of blast cells disclosed germ-line configuration of both the immunoglobulin heavy chain gene and T cell receptor beta chain gene. We speculated that the phenotype of leukemic cells might precede the genotype in some cases of acute leukemia.

A 71-year old male was admitted to our hospital because of general malaise and fever. Peripheral blood showed Hb 8.1 g/dl, platelet 7.0 X 10(4)/microliters, and WBC 18.100/microliters with 64% leukemic cells. Bone marrow showed normocellularity with 73.4% leukemic cells. They were positive for peroxidase and alpha-naphthyl butyrate esterase stainings. Serum and urine lysozyme levels were elevated. He was diagnosed as having acute myelomonocytic leukemia (M 4 in FAB classification). Chromosome analysis of bone marrow cells showed 45, XY, -17, t (9; 17) (q22; p13) and double minute chromosomes (DMs) were observed in the 50 cells analyzed. A complete remission (CR) was obtained by DCMP regimen, but he relapsed as acute monocytic leukemia (M 5 b in FAB classification) and died 5 months after diagnosis. DMs appear to be rare in acute leukemia and the clinical and etiologic implications of DMs are discussed.

A 74-year-old man was admitted on November 1986 because of general fatigue. His peripheral blood showed pancytopenia without immature cells since December 1985. Hematological data showed RBC 150 X 10(4)/microliter, PLT 7,000/microliter, WBC 12,000/microliter with 93.6% leukemic cells. The bone marrow smear revealed NCC 14.5 x 10(4)/microliter with 76% leukemic cells. The leukemic cells were characterized by faint staining with peroxidase stain and strong positivity for CD 13 antigen determined with immunoperoxidase method and flow cytometric analysis. The chromosomal analysis of tumor cells represented as follows: 44, XY, -3, -4, -9, -20, 2q+, 6p-, 7q-, 12q+, +2 mar. Although remarkable reduction of leukemic cells in peripheral blood was obtained one month after initiation of 19-days intravenous continuous infusion of N4-behenoyl-1-beta-D-arabinofuranosylcytosine (BHAC), he suffered from severe systemic candida infection with severe leukopenia and died. Not only advanced age but also complex karyotypic abnormality would contribute to failure of treatment in this case. The significance of complex karyotypic abnormality in acute non-lymphocytic leukemia in discussed based on the current literature.

Chromosomal banding studies were performed on 13 patients with acute myeloid leukemia with maturation (M 2). Six patients revealed t (8;21) (q22;q22), five normal karyotype, and the remaining two +8 and inv (16) (p13 q22), respectively. Apparent pseudo-Pelger-Huët anomalies in mature neutrophils were observed in all the 6 patients with t (8;21), but in only one of the 5 patients with normal karyotype. Neutrophil alkaline phosphatase (NAP) score decreased in all but one in the former group while it increased in all the patients in the latter group. The former group had a median follow-up of 20.8 months or more, whereas the latter group had a median survival of 4.4 months or more. Accordingly, it was suggested that two major chromosome subgroups may be present among patients diagnosed as having M 2: one subgroup with t (8;21) and the other with normal karyotype. One patient with M 2 and inv (16) showed almost the same hematologic features as those observed in patients with acute myelomonocytic leukemia (M 4) and inv (16) except for a small population (6.8%) of monocytoid cells in the bone marrow.

To evaluate the clinical behaviour of adenocarcinoma of the uterine cervix, the nuclear DNA content was microspectrophotometrically measured. And the relationship between the DNA histogram and histologic features (the extension of the tumor, histologic differentiation, histologic type, and size of lesion) was examined. The results were as follows: (1) The incidence of aneuploidy in cases with carcinoma extending beyond the cervix (group A) was 58.5% (10/17), significantly more than the 11.8% (2/17) in cases with carcinoma confined to the cervix (group B). And the DNA content was distributed more widely in group A than in group B. (2) As the degree of histologic differentiation decreased, the incidence of aneuploidy became higher and DNA content was distributed more widely. (3) Concerning the histologic type and size of the lesion, no definite tendency was noted in the ploidy pattern or in the distribution of DNA content. In conclusion, it was thought that aneuploidy and the wide distribution of DNA content in cervical adenocarcinoma suggests that the carcinoma may have extended beyond the cervix.

Alteration of oncogene and loss of chromosomal heterozygosity are infrequent in human gastric carcinoma compared with those in other gastrointestinal carcinomas. Amplification of c-erbB-2 gene is observed in well differentiated adenocarcinoma, while sam gene is found in poorly differentiated adenocarcinoma or scirrhous carcinoma. sam gene, which was isolated from a gastric cancer cell line KATO-III by a DNA renaturation method, encodes tyrosine-specific protein kinase domain. A good correlation evidently exists between the synchronous expression of TGF alpha and ras p21 and biological malignancy of gastric carcinoma. c-myc and c-fos proteins are found not only in tumor cells but also in stromal cells including macrophages and fibroblast around the tumors. The prognosis of patients with c-myc p 62-positive stromal cells is significantly better than that of patient with p 62-negative stromal cells. Coamplification of the hst-1 gene and int-2 is observed in 50% of primary tumors and all metastatic tumors of esophageal carcinoma. PCR (polymerase chain reaction) technique seems to be useful for the detection of oncogene point mutation in human gastric carcinoma.

Described herein are two brothers with 21-hydroxylase deficiency (21-OHD) associated with adrenal tumors, and these possible mechanisms are discussed. A 34-year-old male was admitted on Jan. 9, 1984 because of an enlarged and tender left breast. Physical examination revealed short stature (152 cm, 76.5 kg), gynecomastia and shortening of metacarpal bone. His testes were small (2.6 X 1.6 X 1.9 cm). Urinary excretion of 17-OHCS was within normal range (5.9 mg/day), but those of 17-KS, 17-KGS and pregnanetriol were markedly increased (44.4, 110 and 22.6 mg/day, respectively). Plasma concentrations of progesterone and ACTH and urinary excretions of estrone, estradiol and estriol were also increased. Urinary excretions of 17-KS were decreased to 11.7 mg/day and 17-KGS to 22.3 mg/day after the ingestion of 2 mg/day dexamethasone for two days. The computed tomography and a scintigraphy with 131I-Adosterol revealed a tumor in the left adrenal gland, and the adrenal arteriography revealed a neovascularity and a tumor stain in the tumor. These data indicated that the patient was suffering from both 21-OHD and the left adrenal tumor. At this point, adenoma or adenocarcinoma of the adrenal gland was suspected. The left adrenal tumor (85 g) was resected on April 10, 1984, and the pathological diagnosis was adrenal adenoma. The patient's endocrinological abnormalities, however, did not improve after the operation. Urinary excretions of 17-KS and KGS were increased to 57.9 and 108.5 mg/day, respectively, in the patient's elder brother, and 63.3 and 127.9 mg/day, respectively, in his younger brother, indicating that they also had 21-OHD. Interestingly, an adrenal tumor was diagnosed by abdominal computed tomography in the elder brother who had the same HLA typing as the present case. The three brothers had 21-OHD, and two of them had both 21-OHD and adrenal tumor. To our knowledge, this is the first report documenting the co-existence of adrenal tumors in brothers with 21-OHD. This suggests that adenoma can be one of the complications of 21-OHD, probably due to the chronic stimulation by ACTH, and that a possible linkage to HLA may exist in such cases.

Analysis of DNA ploidy patterns was performed on 76 diffusely infiltrating carcinomas of the stomach and the results correlated with histologic findings and outcome. Twenty six cases were diploid (34%) and 50 cases were aneuploid. There was no correlation between DNA ploidy and histologic type, depth of invasion, lymphatic invasion, evidence of peritoneal dissemination or curability. In aneuploid tumors, incidence of vascular invasion was significantly higher than that in diploid tumors (p less than 0.05). In addition, the patients with aneuploid tumors had a poor prognosis than with diploid tumors. These results indicate that DNA ploidy patterns may possibly be a useful prognostic marker for diffusely infiltrating carcinomas of the stomach.

We examined the expressions of both c-myc and MDR1 in four samples isolated from a CML-bc patient in series during the clinical course. A 46-year-old man was diagnosed as chronic phase of CML in june 1985. In February 1987, the diagnosis of blastic transformation was made because of marked increase of blastic cells. He was initially treated with vincristine (V) and prednisolone (P) successfully. However, the effect of VP therapy was gradually attenuated, so that combined chemotherapies including anthracyclines were started. After the treatments of several courses, tumor cells acquired the refractory to both vincristine and adriamycin . He died in January, 1988. Northern blot hybridization studies revealed no expression of MDR1 mRNAs. However, the expression of c-myc was increased in the latest sample. These findings suggest that the expression of c-myc mRNA in tumor cells of this case reflects one characteristic of clinically refractory states to chemotherapies.

A 12-year-old boy with Philadelphia chromosome positive acute lymphoblastic leukemia received bone marrow transplantation (BMT) from an HLA identical sibling during the second remission. The diagnosis was made at the age of nine. Laboratory examination on admission revealed remarkable leukocytosis (92,000/microliters) with 93% lymphoblasts in the peripheral blood. Blastic cells were FAB L1 common ALL. Chromosomal study on both peripheral blood and bone marrow cells showed that lymphoblasts had an abnormal karyotype of 47, XY, inv (9), t(9; 22), +17. One month later he achieved remission by induction therapy consisting of vincristine, L-asparaginase, doxorubicin, and prednisolone. He was given intrathecal injection of methotrexate and cranial irradiation of 24 Gy for CNS prophylaxis. The cells with Philadelphia chromosome disappeared during remission. Hematological relapse occurred twenty one months later after first remission on April, 1986. He received re-induction therapy including L-Asp VDP, and high-doses of cyclophosphamide, methotrexate and araC. He obtained karyotypic remission on October 1986. Subsequently, bone marrow transplantation was performed following high-dose araC, CY and TBI as preconditioning on December 18, 1986. Methotrexate and cyclosporin A were given intravenously to prevent GVHD. On day 14, karyotypic conversion was detected, suggesting the successful bone marrow grafting. Acute GVHD appeared on day 25, and was treated with prednisolone and cyclosporin A. Prednisolone was tapered by day 80. On day 91, cyclosporin A was discontinued because herpes zoster occurred. Acyclovir was effective, but skin GVHD reappeared. With low-dose prednisolone, skin GVHD improved. Sicca syndrome soon appeared and was followed by chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

We report a 25 year-old male of CML, who repeated lymphoid blast crises twice and finally experienced a myelomonocytic blast crisis. In the first and the second crises, after 2 years of chronic phase, the blasts were only weakly positive or negative for terminal deoxynucleotidyl transferase. Based on other morphological features of the blasts, however, lymphoid blast crisis was strongly suspected. Actually, he responded well to the vincristine and prednisolone therapy. In the third crisis, the blasts showed myelomonocytic features. He did not respond to the same regimen, and died of intracranial infiltration during daunorubicin and cytosine arabinoside therapy after one year from the first crisis. Chromosomal analysis showed the karyotypes of 46, XY, t(9:22) (q34:q11) in the chronic phase, 45, XY, -7, -9, +der(9) t(7;9) (q11;p11), t(9:22) (q34:q11) in the lymphoid blast crisis, and 46, XY, t(9:22) (q34:q11), t(11:17) (q23:q25) in the myelomonocytic blast crisis.

Using flow cytometry, basic experiments and clinical trials to investigate DNA aneuploidy were performed. The site of the peak in the DNA histogram was found to be unstable in the flow cytometric assay. However, relatively stable DNA indices can be obtained if only internal standards, such as human lymphocytes, etc., are added to the samples, thus results in a more precise detection of aneuploidy. In 11 cases of head and neck tumors, DNA aneuploidy was observed in six out of seven cases that were histopathologically diagnosed as being malignant tumors, showing a correlation with the pathological studies as a whole. Further clinical studies may prove that the present method can be useful for the pathological, supplementary diagnostic and prognostic evaluations.