Neuropeptide Y in neuroblastoma: increased concentration in metastasis, release during surgery, and characterization of plasma and tumor extracts.

Five children with neural crest tumors (two ganglioneuromas, one ganglioneuroblastoma, and two neuroblastomas) were investigated regarding neuropeptide Y-like immunoreactivity (NPY-LI) in tumor tissue and plasma at diagnosis and during surgery. Radioimmunoassay of extracted plasma revealed higher NPY-LI at diagnosis of neuroblastoma (640 and 230 pmol/L resp) than ganglioneuroblastoma or ganglioneuroma (74, 45, and 26 pmol/L resp). During surgery of neuroblastoma plasma NPY-LI increased two- to four-fold while no peroperative increase was seen in the other children. NPY-LI was considerably higher in neuroblastoma tissue (220 pmol/g and 144 pmol/g) than in ganglioneuroblastoma (40.2 pmol/g), ganglioneuroma (0.6 and 4.4 pmol/g), or healthy adrenal tissue (5.5 pmol/g). The highest NPY-LI concentration was found in neuroblastoma metastasis, 3,091 pmol/g. Gel-permeation chromatography of a neuroblastoma tumor showed that a majority of NPY-LI was representing intact NPY (NPY 1-36) while metastasis and plasma from the same child mainly contained smaller immunoreactive fragments. High concentrations of systemic NPY in neuroblastoma patients are of tumoral origin. Plasma levels of NPY and its fragments can be useful in diagnosing and monitoring neuroblastoma, and for early detection of relapse or metastatic disease. A possible involvement of NPY in neuroblastoma tumor growth and spread deserves further investigation.

Ganglioneuroblastoma with disseminated bone marrow infiltration in an adult.

Ganglioneuroblastoma is an extremely rare neoplasm of adults. We present a case of adrenal ganglioneuroblastoma in a 47-year-old female with disseminated bone marrow involvement. Bone marrow involvement was the major manifestation which determined the mortality of this patient. This case suggests that the diagnosis of bone marrow involvement should be carefully considered even in adult-onset ganglioneuroblastoma.

Bilateral testicular neuroblastoma. Scintigraphic depiction and therapy with I-131 MIBG.

The authors describe a 29-year-old man who had a 16-year history of neuroblastoma and uncommon manifestations. At age 13, he was diagnosed with stage III retroperitoneal ganglioneuroblastoma that was resected. Ten years later, bilateral testicular enlargement and a pelvic mass from infiltration of the neuroblastoma became palpable. Metastatic involvement was depicted with MIBG, a radiotracer that concentrates in tissues of the sympathetic nervous system. Using I-131 MIBG, the tumors were treated with therapeutic doses of radiation and a partial response was obtained. This case is unique because of the massive degree of bilateral testicular infiltration and its occurrence as a late manifestation of neuroblastoma in early adulthood.

Unusual intramandibular neural tumor.

Neural tumors within the jaw bones are exceptional. We present the histologic observation of a central mandibular tumor of neural origin. Immunohistochemistry confirmed the neural nature of the tumor, which had features of a schwannoma (neurilemmoma) together with ganglion cells as seen in ganglioneuroma. Moreover, the association with an intracranial tumor, possibly a meningioma, is emphasized.

[The place of 99mTc-MDP skeletal scintigraphy in neuroblastoma. Is a new assessment necessary?]. / Stellenwert der 99mTc-MDP-Skelettszintigraphie beim Neuroblastom. Ist eine Neubewertung nötig?

The present study compares the reliability of MIBG and MDP bone scans in detecting bone metastases of neuroblastoma. Out of 57 patients, 23 had both 99mTc-MDP and 123I/131I-MIBG scans within a 2-week period. In 10 patients at primary diagnosis there was an underestimation of skeletal involvement by MIBG in 1/5, in 13 patients at follow-up in 3/9; 99mTc-MDP scans were able to visualize skeletal involvement in all those cases. There was only one false positive MDP scan. These results suggest that MIBG alone may fail to visualize skeletal involvement of neuroblastoma and should therefore be complemented by additional 99mTc-MDP scintigraphy.

Polysomy of chromosome 7 is associated with amplification and overexpression of the EGF-receptor gene in a human carcinoma cell line derived from a brain metastasis.

Overexpression of the EGF-receptor gene is associated with the malignant nature of some tumors. We have recently reported the establishment of a human carcinoma cell line (T-CAR1), derived from a brain metastasis, that had 7 million EGF receptors per cell and was growth inhibited by EGF. The present study was carried out in order to further characterize the EGF-receptor protein in T-CAR1 cells, and to see if the overexpression of the EGF-receptor gene in these cells was associated with abnormalities at the genomic level. We have compared the T-CAR1 cells with the human glioblastoma cell line T-MG1, which has 135,000 EGF-receptors and is growth stimulated by EGF. The MW of the EGF receptors in T-CAR1 cells and T-MG1 cells was estimated to be 170 kDa, equal to the normal EGF-receptor. However, in T-CAR1 cells an additional protein reacted with the monoclonal antibody directed against the internal domain of the EGF receptor. The levels of EGF receptor-related RNAs in T-CAR1 cells and T-MG1 cells reflected the number of EGF receptors in these cell lines. The EGF-receptor gene was amplified ten-fold in T-CAR1 cells, while it was not amplified in T-MG1 cells. No restriction fragment length polymorphism of DNA digested with various restriction enzymes was seen in either of the cell lines. Chromosomal analysis of T-CAR1 cells showed polysomy of chromosome 7 and marker chromosomes derived partly from chromosome 7. Thus, in the T-CAR1 cell line it was an association between polysomy of chromosome 7 and EGF-receptor gene amplification.

Clinical manifestations of ganglioneuroma.

Ganglioneuroma may occur spontaneously or after therapy for neuroblastoma. This lesion may be metastatic or unresectable in the primary site. The rarity of this situation and lack of understanding of the biology of this benign condition may lead to extensive, potentially life-threatening attempts at surgical resection or the futile use of chemotherapy or radiotherapy to try to cause regression or control growth. The authors present here several cases which demonstrate the multiple presentations of ganglioneuroma and the potential problems which may arise in their management.

Extraosseous uptake of technetium-99m MDP in secondary deposits of neuroblastoma.

Extraosseous uptake of radiophosphate compounds i well recognized in primary neural crest tumors. In a review of 32 cases of neuroblastoma presenting over a three-year period at Children's Hospital of Philadelphia, nine patients were noted to have secondary lesions in eleven different sites accumulating radiotracer. The extraosseous uptake in metastases included: ascites, liver, lung, anterior mediastinum, and posterior mediastinum. These cases are reported to emphasize the ability of bone imaging to detect the presence of extraosseous soft tissue metastases and primary lesions.

Neuroblastoma: the Joint Center for Radiation Therapy/Dana-Farber Cancer Institute/Children's Hospital experience.

The treatment results for 118 patients with neuroblastoma seen at the Joint Center for Radiation Therapy/Dana-Farber Cancer Institute/Children's Hospital from 1970 to 1980 were analyzed. Patients were treated with a combination of surgery, radiation therapy, and chemotherapy depending on stage and age. Disease-free survival was excellent in all patient groups except those over one year of age with stage IV disease, a group for which currently available therapy cures only a small proportion of patients. Patients with stage III disease and older patients with stage II disease did extremely well (survival of 81% and 89%, respectively) and may have benefited from intensive treatment with all three modalities. Survival for infants (under one year) with stage IV neuroblastoma (90%) has clearly improved with intensive combination chemotherapy. With combination approaches and newer, more effective systemic regimens, a real impact on survival appears to have been made in the last decade. Better approaches will be necessary to cure more than an occasional older patient with stage IV disease.

Improved prognosis for infants with stage IV neuroblastoma.

From 1970 to 1982 11 infants with Evans stage IV neuroblastoma who were 11 months of age or less at diagnosis were treated. All but one were treated with intensive multiagent chemotherapy; eight had attempted surgical resection; only one received radiotherapy to the primary tumor. Ten of the 11 infants remain free of disease from 2 1/2 to 13 years (median, four years). Multiagent chemotherapy has clearly improved the outcome for infants with stage IV neuroblastoma.

Ganglioneuroma presenting with differentiated skeletal metastases. Report of a case.

The authors report the case of a child with retroperitoneal ganglioneuroma and cytodifferentiated skeletal metastases. The primary tumor was surgically resected, and the child is alive and well 2 years later without additional therapy. This rarely documented phenomenon can be explained by spontaneous cytomaturation within both primary and metastatic tumor.