Mary Moschovi

Midline Carcinoma of Children and Young Adults With NUT Rearrangement

PURPOSE A balanced chromosomal translocation, t(15;19), resulting in the BRD4-NUT oncogene, has been identified in a lethal carcinoma of young people, a disease described primarily in case reports. We sought to amass a more definitive series of tumors with NUT and/or BRD4 gene rearrangements and to determine distinct clinicopathologic features. PATIENTS AND METHODS Carcinomas (N = 98) in young individuals (median age, 32.5 years) were screened for NUT and BRD4 rearrangements using dual-color fluorescence in situ hybridization. Four published carcinomas with BRD4 and NUT rearrangements were also evaluated. Immunophenotypic analyses were performed. RESULTS Eleven tumors had NUT gene rearrangements, including eight with BRD4-NUT fusions and three with novel rearrangements, which were designated as NUT variant. All NUT-rearranged carcinomas (NRCs) arose from midline epithelial structures, including the first example arising below the diaphragm. Patients were young (median age, 17.6 years). Squamous differentiation (seen in 82% of NRCs) was particularly striking in NUT-variant cases. In this first description of NUT-variant carcinomas, the average survival (96 weeks, n = 3) was longer than for BRD4-NUT carcinomas (28 weeks, n = 8). Strong CD34 expression was found in six of 11 NRCs but in zero of 45 NUT wild-type carcinomas. CONCLUSION NRCs arise from midline structures in young people, and NRCs with BRD4-NUT are highly lethal, despite intensive therapies. NUT-variant carcinomas might have a less fulminant clinical course than those with BRD4-NUT fusions. CD34 expression is characteristic in NRCs and, therefore, holds promise as a diagnostic test for this distinctive clinicopathologic entity.

Ki-1 Lymphoma with Cardiac Involvement at Initial Presentation

Anaplastic large cell lymphoma is a rare malignancy in childhood. We describe the case of a 6-year-old boy with Ki-1 lymphoma of the thymus who presented with an endocardiac mass. The first histologic analysis suggested a high-grade undifferentiated sarcoma, but reevaluation and immunohistochemistry confirmed the CD30+ lymphoid derivation of the process. The patient was given chemotherapy and 24 months later he remains in complete remission. It is noted that echocardiography was repeated many times to detect heart lesion.

Could cisplatin as a front-line treatment in childhood non-Hodgkin's lymphoma be a promising therapy?

Non-Hodgkins lymphomas (NHL) were often erroneously diagnosed as other malignancies and treated accordingly. In this study cisplatin combined with vincristine, cyclophosphamide, and Adriamycin was used incidentally as a front-line treatment in seven children with NHL, because the initial histologic diagnosis was that of a sarcoma. After reevaluation three patients had Ki-1 anaplastic large cell lymphoma of T-cell origin, two abdominal B-cell diffuse high-grade NHL, one mediastinal diffuse large B-cell lymphoma, and one B-cell lymphoma in the stomach. They received at least two courses of cisplatin combined regimen and continued with other protocols for NHL. All patients showed an extremely good response from the first course of therapy and the masses vanished completely. They were followed up for a mean time of 29.5 months and are all in complete remission. The data indicate that cisplatin is active against NHL and might be a promising alternative front-line therapy.

GENE (p53, c-myc, bcl-2, fas, bax, mdr-1) REGULATION OF CHEMOTHERAPY - INDUCED APOPTOSIS DURING THE TREATMENT OF ACUTE LEUKEMIAS

GENE (p53, c-myc, bcl-2, fas, bax, mdr-1) REGULATION OF CHEMOTHERAPY - INDUCED APOPTOSIS DURING THE TREATMENT OF ACUTE LEUKEMIAS

STUDY OF MINIMAL RESIDUAL DISEASE (MRD) IN B-CELL LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA OF CHILDHOOD WITH THE USE OF THE SPECIFIC IMMUNOGLOBULIN VARIABLE HEAVY CHAIN FAMILY (VH) OLIGONUCLEOTIDES 87

STUDY OF MINIMAL RESIDUAL DISEASE (MRD) IN B-CELL LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA OF CHILDHOOD WITH THE USE OF THE SPECIFIC IMMUNOGLOBULIN VARIABLE HEAVY CHAIN FAMILY (VH) OLIGONUCLEOTIDES 87

Activity of 5-formyl tetrahydrofolate cyclodehydrase and 5,10-methenyl tetrahydrofolate cyclohydrolase in primary brain tumors in children

The activity of the enzymes 5-formyl tetrahydrofolate cyclodehydrase and 5,10-methenyl tetrahydrofolate cyclohydrolase has been studied cytochemically in childrens primary brain tumors. These enzymes play a significant role in purine biosynthesis. Thirty children, aged 1-12 years, were studied, 12 with medulloblastoma, 14 with glioma grade I-IV, and 4 with ependymoma. The activity of the enzymes was apparent as cytoplasmic granules that sometimes overlie the nucleus of the tumor cells. This coincidence showed that different types of brain tumors exhibit different degrees of enzymic activity, which in some cases correlated positively with the malignant potential of the tumor. Approximately one third of the cases were negative for any activity of these enzymes. The intensity of the staining of 5,10-methenyl tetrahydrofolate cyclohydrolase activity was actually higher than that of 5-formyl tetrahydrofolate cyctodehydrase. The clinical or prognostic significance of these findings remains to be clarified, but we believe that cylochemistry provides a sensitive technique for the detection, localization, and description of these enzymes in brain tumor cells. A clear understanding of the mode of action of these enzymes may contribute to devising novel therapeutic strategies.