Two children with stage III, IV sacrococcygeal yolk sac carcinoma were treated with cisplatin (CDDP), vinblastine (VBL), and bleomycin (BLM)(PVB therapy). One patient was a 1-year-6-month-old female having pulmonary and liver meatatasis, the other was a 1-year-9-month-old female with bilateral inguinal lymph node metastasis. In both, the blood levels of α-fetoprotein markedly decreased after 3 or 4 cycles of this therapy, and the tumors were resected.As maintenance therapy, the first patient received CDDP and adriamycin (ADM), and the second received CDDP+VBL because CDDP was considered to be the most effectie drug in this therapy, and from our experience in the treatment of advanced neuroblastoma, CDDP can be used up to a total dose of 1000 mg/m2 if attention is given to renal and auditory function, although VAC therapy and pulse VAC therapy had been used in some studies. The patients now have no evidence of disease.These results suggest that PVB therapy followed by active maintenance therapy with CDDP, ADM and VBL may be very effective for sacrococcygeal yolk sac carcinoma in children.
We have investigated the relationship between the expression of bcl-2 and myc family genes in primary human neuroblastoma (NB) tumors and cell lines. Of 20 NB tumors examined, bcl-2 transcripts were expressed at variable levels in 16 tumors of all clinical stages. Of the 2 tumors with N-myc amplification, one expressed bcl-2 at a high level, whereas the other did so at a low level. In contrast, all NB tumors showed the expression of c-myc and/or N-myc transcripts. Similarly, of 9 NB cell lines with N-myc amplification examined, 6 expressed bcl-2 at high levels, whereas the other 3 expressed it at barely detectable levels. The 3 cell lines without N-myc amplification also expressed bcl-2 protein at high levels. All NB cell lines tested expressed either c-myc or N-myc protein. These data suggest that in NB, there is no significant association between bcl-2 expression and advanced tumor stages or N-myc amplification. The data also show that bcl-2 expression does not always coincide with myc expression in NB, suggesting that bcl-2-independent mechanisms may exist in the bcl-2-negative NB tumor cells in order to suppress the cell death promoting action of high myc expression.
Two extraskeletal myxoid chondrosarcomas with a solid soft tissue mass occurred on the right upper arm of a 4-year-old boy and on the chest wall of a 1-year-old boy. Microscopically, both tumors were characterized by lobular configuration and were sparsely cellular with a background of myxoid matrix. The cells were small and round, and appeared undifferentiated, sometimes with a narrow eosinophilic cytoplasm. They grew in nests or strands and sometimes in a single file. They were strongly positive for S-100 protein and vimentin. Ultrastructural features suggested that the cells had a poorly differentiated mesenchymal nature with chondrocytic differentiation. These are the sixth and seventh reported cases of extraskeletal myxoid chondrosarcoma occurring in children. There are definite differences between this tumor with immature features and the extraskeletal myxoid chondrosarcoma in adults. Problems of differential diagnoses from other small round cell sarcomas also are discussed.
The superoxide-generating activity of blood monocytes from patients with hepatic cirrhosis was studied by the rapid and sensitive method using cytochalasin E and wheat germ agglutinin as triggering agents. The initial rates of superoxide generation by the patients' monocytes were 0.110 +/- 0.072 n mol/min/10(5) cells (mean +/- SD, n = 22) after sequential treatment with cytochalasin E and wheat germ agglutinin, while those of controls were 0.305 +/- 0.123 n mol/min/10(5) cells (mean +/- SD, n = 33) (P less than 0.001). The activity correlated inversely with indocyanine green retention rates; the regression line was Y = 0.220-0.0028 X (Y; superoxide-generating activity, n mol/min/10(5) cells, X; indocyanine green retention rate, per cent), whose test of significance of the regression coefficient was 0.010 less than P less than 0.025. The presence of ascites, a decreased in the number of white blood cells, and increased serum total bilirubin, also inversely correlated with the superoxide-generating activity. These show that in cirrhotic patient, the superoxide-generating activity of blood monocyte, which may reflect NAD(P)H oxidase activity, is impaired in proportion as the grade of hepatic cirrhosis increases.
We have examined expression of the smg p25A (a ras p21-like GTP-binding protein) gene in neural crest-derived tumor cell lines and neuroblastoma tissues. The human neuroblastoma cell lines GOTO, IMR-32, NB-1, and SK-N-SH expressed the 1.6-kilobase smg-25A mRNA. SH-SY5Y and SH-IN, variant cell lines with a neuronal phenotype derived from SK-N-SH, expressed much more smg-25A mRNA than did SH-EP1, a variant line with an epithelium-like phenotype also derived from SK-N-SH. The primitive neuroectodermal tumor cell lines SK-N-MC and KU-SN and the Ewing's sarcoma cell lines RD-ES and SK-ES expressed the smg-25A mRNA to a much smaller extent than did neuroblastoma cell lines. Of 15 human neuroblastoma specimens tested, 13 expressed the smg-25A mRNA to various extents. When the relative ratio of the smg-25A mRNA level to the glyceraldehyde-3-phosphate dehydrogenase mRNA level was compared among neuroblastoma tumor tissues, the value was significantly higher in tumors histologically diagnosed as ganglioneuroblastoma. The smg-25A mRNA was not detected in the tissues of Hodgkin's lymphoma, Wilms' tumor, Ewing's sarcoma, or undifferentiated sarcoma of the liver. These results suggest that the smg-25A mRNA level is closely related to the neuronal differentiation state of tumors derived from the neural crest.
We examined 52 children with advanced neuroblastoma who were diagnosed and treated during the past 7 years, and investigated the correlation between the degree of lymph node (LN) metastasis and the prognosis of neuroblastoma. In 8 of the 52 patients, distant LN metastasis was confumed both radio-graphically and histologically. The urinary homovanillic acid (HVA) level was markedly elevated in these patients, and it was higher than that in patients with regional LN metastasis (P <.05). The urinary vanillylmandelic acid (VMA) level and the VMA/HVA ratio were not significantly different between patients with regional and distant LN metastasis. None of the four examined patients with distant LN metastasis showed N-myc amplification of neuroblastoma tumors. An analysis of the survival rate in each patient group classified according to the degree of LN metastasis showed that the prognosis of the patients without LN mehtasis or with distant LN metastasis tended to be better than that of patients with regional LN metastasis. Our results indicate that patients with distant LN metastasis may belong to a subclass with different biological features and a better prognosis than those of other groups.
A congenital primitive neuroectodermal tumor associated with epithelial and glial elements is described. This soft-tissue tumor present on the right temple of a newborn boy consisted mainly of small round cells of the primitive neuroepithelial type, occasionally forming rosettes. The other components were focal glandular structures producing mucin, and aggregates of epithelioid cells bearing clear cytoplasm, both being distributed throughout the entire tumor. Additional glandular and clear cell components were strongly positive for various epithelial markers, such as carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin. Epithelioid cells were also positive for neuron-specific enolase and S100 protein. Glial differentiation was evidenced in some of the epithelioid cells by localization of cytoplasmic glial fibrillary acidic protein. These findings suggest that this tumor derives from a remnant of a neural crest, and the possibility of a special type of peripheral primitive neuroectodermal tumor is considered.
