Outcome of a dog undergoing definitive-intent intensity-modulated radiation therapy for an intranasal ganglioneuroma.

An 11-year-old intact male Shiloh Shepherd was presented for evaluation of epistaxis, decreased nasal airflow, and destructive caudal nasal lesion identified using CT. Histopathologic evaluation of the nasal mass was consistent with a ganglioneuroma. The dog was treated with 10 × 4.2 Gy using IMRT technique. Post radiation therapy (RT), improvement in clinical signs were noted. Tumor progressed in size based on CT evaluation at 49 days, 3, and 6 months post-treatment. A grade 2 oral mucositis was the only RT side effect noted. Radiation therapy as described above was completed without evidence of high-grade radiation toxicities and has potential to improve clinical signs but failed to induce tumor response.

An urban legend: Malignant transformation caused by radiotherapy in patients with presacral ganglioneuroma. The necessity and first-time administration of radiotherapy. Case report and literature review.

Ganglioneuromas (GNs) are well-differentiated, rare benign tumors of neural crest origin and are, for the most part, considered to be the benign equivalent of neuroblastomas. There are very few cases of GN reported to be at presacral location in the literature. The standard form of treatment is the total surgical excision. However, total resection of GN is not always possible depending on the neuron, from which it originates, and its localization. Moreover, adjuvant radiotherapy (RT) or chemotherapy is not recommended even though patients are still symptomatic after subtotal resection. This view is based on the urban legend that it undergoes a malignant transformation although it is a benign tumor. Moreover, there are no data indicating that the GN cases reported in the literature have undergone RT. Therefore, articles about the suspicion that GN may undergo spontaneous or malignant transformation after RT are absolutely controversial. Based on our case, we present here, we believe that we will explain the valid necessity of application of RT that we administered for the first time and that with the clarification of this controversial topic, a significant gap will be closed in the literature.

Malignant peripheral nerve sheath tumors arising from ganglioneuromas.

Two typical malignant peripheral nerve sheath tumors (PNST) arising in preexisting ganglioneuromas are described. To the best of our knowledge, this association of tumors has not been reported in detail previously. Neither patient had the stigmata nor family history of Von Recklinghausen's neurofibromatosis. In both cases, the ganglioneuromas evolved from more primitive neuroectodermal tumors (one neuroblastoma, one ganglioneuroblastoma) and both patients developed their malignant PNST at previously irradiated sites. Both patients died within 2 years of the diagnosis of their malignant PNST. The origin of these malignant PNSTs from Schwann cells is supported by an ultrastructural analysis of 27 neuroblastomas, ganglioneuroblastomas, and ganglioneuromas.

Clonal variation of DNA repair in a human glioma cell line.

Clonal heterogeneity in response to ionizing radiation was found for a human glioma cell line, IN859. We have investigated the most sensitive clone, the most resistant clone and the parent line for differences in DNA repair fidelity using the method of plasmid reconstitution. Significant differences in repair fidelity were found between the two clones, and between the sensitive clone and the parent line. The resistant clone and the parent line showed the greater repair fidelity. A comparison of two different restriction enzymes, which cleave the plasmid with blunt or cohesive-ended double-strand breaks, did not reveal differences in repair fidelity. Equal numbers of plasmids were integrated in each cell line, but the sensitive clone showed a higher frequency of misrepair of cleaved plasmid. Misrepair was characterized by partial or complete loss of sequence at the site of plasmid cleavage. We conclude that the radiosensitive clone exhibits increased misrepair.

The effect of patient motion on dose uncertainty in charged particle irradiation for lesions encircling the brain stem or spinal cord.

A specialized charged-particle radiotherapy technique developed at Lawrence Berkeley Laboratory (LBL) is applied to patients with lesions abutting or surrounding the spinal cord or brain stem. This technique divides the target into two parts, one partially surrounding the critical structure (brain stem or spinal cord) and a second excluding the critical structure and abutting the first portion of the target. Compensators are used to conform the dose distribution to the distal surface of the target. This technique represents a novel approach in treating unresectable or residual tumors surrounding the spinal cord or brain stem. Since the placement of the patient with respect to beam-shaping devices is critical for divided-target treatments, a method for calculating dose distributions reflecting random patient motion is proposed, and the effects of random patient motion are studied for two divided-target patient examples. Dose-volume histograms and a normal-tissue complication probability model are used in this analysis. For the patients considered in this study, the normal-tissue-complication probability model predicts that random patient motion less than or equal to 0.2 cm is tolerable in terms of spinal cord complications.

Gangliocytoma masquerading as a prolactinoma. Case report.

The authors describe the case of a 36-year-old man who presented with bitemporal hemianopsia and a serum prolactin concentration of 1440 ng/ml. Magnetic resonance imaging of the pituitary revealed a presumed macroadenoma with suprasellar and temporal lobe extension. Although the patient's prolactin level was lowered to 55 ng/ml by bromocriptine therapy, no tumor shrinkage occurred. Fourteen months later, progression of visual field defects necessitated transsphenoidal resection, which was incomplete. Immunocytochemical analysis of the biopsy tissue was positive for prolactin and, in view of the clinical picture, more detailed analysis was not performed. External-beam radiotherapy was given 2 years later because of enlargement of residual tumor. Subsequently, despite a fall in the serum prolactin concentration to less than 20 ng/ml in response to the course of bromocriptine, the mass displayed further extension into the temporal lobe. Nine years after the patient's initial presentation, he underwent transfrontal craniotomy for sudden deterioration in visual acuity caused by hemorrhage into the mass. No adenohypophyseal tissue was identified in the resected tissue. The mass was composed of dysplastic neurons that were strongly immunoreactive for synaptophysin and neurofilament (indicating neural differentiation) and prolactin. Review of the original biopsy specimen indicated that the prolactin-positive cells had striking neuronal morphological characteristics. The final diagnosis in this case is prolactin-secreting gangliocytoma. Although exceedingly rare, this disease must be added to the differential diagnosis in cases of "prolactinoma" when bromocriptine therapy is followed by a marked decline in serum prolactin that is not accompanied by significant tumor shrinkage. Furthermore, in such instances, consideration should be given to "obtaining a biopsy sample prior to electing for radiotherapy.

Intraoperative irradiation: a new technique in pediatric oncology.

Adverse effects on normal tissue are the principal limiting factor in the use of radiation therapy. Maturing tissues are most susceptible to these side effects, so high-dose applications can be a particularly difficult challenge in children. Intraoperative radiation therapy (IORT) enables the radiation oncologist to displace or shield dose-limiting organs or structures. These first two cases of children treated with IORT suggest that IORT, used alone or in conjunction with external beam irradiation, may be useful in the pediatric age group.

Prognostic factors in neuroblastic tumors.

Data of 101 patients with neuroblastic tumors from 1950 to1974 at The Johns Hopkins Hospital have been abstracted onto specially designed summary sheets, and subjected to multifactorial analysis. One-third of the 21 benign ganglioneuromas showed evidence for spontaneous maturation. The overall cure rate among the malignant tumors was 39%. Cures were higher with an extraabdominal primary, with more mature histologic differentiation, and if excision, even partial, was carried out. Neither radiotherapy nor evolving modalities of chemotherapy appear to have had benefit over this 25-yr period. An age at diagnosis less than 2 yr, and a less extensive clinical stage both were independent predictors of survival. The apparent effects of a favorable site of tumor origin, or more mature histologic differentiation were not of major impact in and of themselves, but correlated better with clinical stage. Two prognostic schemata, based on stage plus age, and stage plus histologic differentiation plus age respectively, proved to be 95% accurate in our experience. With more extensive evaluation and experience, either or both may be helpful in the management of malignant neuroblastic tumors, and assessment of therapeutic regimens.

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.

Radiation-induced leiomyosarcoma of the great vessels presenting as superior vena cava syndrome.

A patient with a pleomorphic intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presented clinically with a superior vena cava syndrome. A latent period of 29 years elapsed between receiving orthovoltage radiation to the neck and right side of chest to treat recurrent ganglioneuroblastoma, and the appearance of a leiomyosarcoma and subsequent recurrences. The patient underwent partial resection of the tumor, received adjunct chemotherapy, and was shown to be free of disease by clinical tests and by magnetic resonance imaging (MRI) 17 months after completion of chemotherapy. The criteria for the diagnosis of radiation-induced sarcomas are reviewed in relation to the present case. The critical role of magnetic resonance imaging in both the diagnosis and continued follow-up of the patient is described. This would appear to be the first reported case of radiation-induced intravascular leiomyosarcoma of the great vessels of the neck and mediastinum presenting as a superior vena cava syndrome.

The role of surgery, radio- and chemotherapy in the treatment of neuroblastoma and ganglioneuroblastoma.

Personal experiences with biochemical assessments of the urinary catecholamine metabolite excretion in 460 patients with neuroblastoma and 55 patients with ganglioneuroblastoma, as well as prognostic factors and selected data characterizing the role of surgery, radio- and chemotherapy in the treatment of neuroblastoma are reviewed. Recommendations regarding optimal combinations of the 3 treatment modalities are made, taking into account age and stage.

Stage II neuroblastoma--does adjuvant irradiation contribute to cure?

Twenty-one children with Stage II neuroblastoma diagnosed between 1973 and 1983 were analyzed retrospectively. Median age at diagnosis was eleven months (1 week to 153 months). Primary tumor was above the diaphragm in 67% and below the diaphragm in 33%. All patients underwent surgical resection and pathologic diagnosis was neuroblastoma in 76% and ganglioneuroblastoma in 24%. Regional lymph nodes were positive in three of eleven patients sampled. Sixty-seven percent had gross residual disease, and thirty-three percent had microscopic residual disease. Seventeen patients received postoperative irradiation and none has relapsed (median follow-up 57 months). Four patients received surgery alone (median follow-up 24 months); one local relapse occurred in this group and was subsequently treated with irradiation. All patients are alive and disease free, with a median length of follow-up of 55 months. Radiation dosage was 1000-1800 rad in patients less than 12 months of age, and 1800-3000 rad in those greater than 12 months of age at diagnosis. The high disease-free survival rate in both groups of patients, but especially in the group receiving adjuvant irradiation, emphasizes the need for a controlled, prospective study to determine which Stage II neuroblastoma patients, if any, would be benefitted by postoperative irradiation.

Scoliosis associated with ganglioneuroblastoma: a case report with 17-year follow-up.

We describe the case of a 12-year-old boy with scoliosis due to a malignant ganglioneuroblastoma. He had a successful outcome, as was noted by 17-year follow-up of tumor resection and spinal fusion.