Malignant Neurinoma Research Articles

Analysis of Extended Resection of Limb Soft Tissue Leiomyosarcoma.

Leiomyosarcoma is an uncommon soft tissue sarcoma that composed of malignant mesenchymal cells with distinct features of the smooth muscle lineage. Typically affects the uterus and gastrointestinal tract, it can rarely be seen in large blood vessels, lymphatic and glandular duts, the mesentery, the omentum, retroperitoneum, and limbs. Occurrence is particularly rare in the limb region. Retrospective study based on patient records and postoperative pathological histological features. Four patients with limb leiomyosarcoma that were operated between 2016 and 2020 were included, three of them arising in the subcutis of the thigh region and one in cubitus. Extend resection with satisfactory outcomes is reported. Pathological examination showed that masses were composed of a fascicular arrangement of hyperchromatic spindle-shaped cells, characterized by the proliferation of epithelioid cells with eosinophilic cytoplasm for epithelioid leiomyosarcoma. Leiomyosarcomas that arise in the soft tissue, although rare, should be differentiated from other lesions, such as neurilemoma, neurofibroma, liomyoma,lipomyoma, synoviosarcoma, rhabdomyosarcoma, malignant fibrous histiotoma, and malignant neurinoma.

Laparoscopic splenectomy for inflammatory pseudotumor of the spleen.

We report two cases of inflammatory pseudotumor of the spleen treated by laparoscopic splenectomy. The first patient was a 61-year-old woman with a 3cm splenic tumor detected incidentally by ultrasonography. Computed tomography showed a well-demarcated splenic mass. She underwent hand-assisted laparoscopic splenectomy. The second patient was a 51-year-old man in whom a splenic tumor was found on follow-up computed tomography after resection of occipital malignant neurinoma. Ultrasound and magnetic resonance imaging confirmed a splenic tumor, which showed no uptake on 18F-fluorodeoxyglucose positron emission tomography. Laparoscopic splenectomy was performed. The histopathological diagnosis was inflammatory pseudotumor in both cases. Their postoperative course was uneventful, with a postoperative hospital stay of 11 and 8 days, respectively. Splenectomy is usually performed in patients with splenic tumors because imaging techniques cannot exclude malignancy. Laparoscopic splenectomy may be a useful option for patients with splenic tumors.

Spinal neurinomas: retrospective analysis and long-term outcome of 179 consecutively operated cases and review of the literature

Background We present a series of 179 spinal neurinomas consecutively observed at the Department of Neurosurgery at the University of Florence for a period of 30 years (between 1967 and 1997). We decided to limit the retrospective study to obtain at least 5 years of follow-up. Therefore, 20 additional neurinomas treated between 1997 and 2002 were excluded. Methods All the cases are evaluated under statistical, clinical, neuroradiological, and surgically technical profiles based on data from clinical records and from periodic check-ups after surgery. In particular, the results are analyzed on the basis of an accurate pre- and postsurgical evaluation using Karnofsky's scale and Kleklamp-Samii's scoring system. Results We treated 179 spinal neurinomas in 152 (93 male and 59 female) patients. The mean age was 44.3. In 33 cases the neurinoma was sited in the cervical tract, in 59 cases in the dorsal tract, and in 87 cases in the lumbo-sacral tract. Eleven patients harbored Recklinghausen's neurofibromatosis (7 NF1 and 4 NF2 of which 1 was intramedullary). In 123 cases the neurinoma was intradural, in 11 cases it was extradural, in 2 intra/extradural, in 9 it had a dumbbell form, and in 2 cases it was intramedullary; the remaining cases had neurofibromatosis. The most common presurgical symptom was segmental pain. Total removal of the lesion was possible in the first operation for 174 neurinomas. We encountered 3 cases of malignant neurinoma of which 1 was in NF2. The result of surgery was recovery in 108 cases; 2 patients with NF2 died, and local recurrence occurred even after total exeresis (excision) and radiotherapy in the cases of malignant neurinoma. Conclusions Schwannomas represent the most frequent tumor lesions of the spine with prevalence for the cervical-inferior tract and the dorso-lumbar passage. Intramedullary neurinomas are rarely observed. The total surgical removal of neurinomas is often an attainable goal, and clinical improvement is the common outcome with exception to malignant forms and NF2 neurofibromatosis. We describe a series of 179 treated schwannomas.

Trend of brain tumor incidence by histological subtypes in Japan: estimation from the Brain Tumor Registry of Japan, 1973-1993.

In order to estimate the risk of primary brain tumor (PBT), we attempted to estimate the national incidence rates of PBT by histological subtypes using the Brain Tumor Registry of Japan (BTR). The number of deaths due to PBT in a certain year is the sum of the deaths among patients diagnosed in different years. Registered cases in the BTR represent incident cases of PBT in the whole country multiplied by a cover rate. The cover rate is defined as the proportions of PBT cases that the Registry counts in relation to all the cases in the country in a given year. If the survival experience among the registered cases represents the survival experience of all cases, then the rate of registered deaths represents all deaths due to PBT in Japan. By this logic, we estimated the cover rates and incidence rates from 1973 to 1993 using the BTR and National Vital Statistics data. Our estimates showed three patterns of time trends: (1) a gradual linear increasing trend before the 1980s followed by a plateau (total PBT, gliomas, meningioma, and hemangioblastoma), (2) a trend with a step-up increase in the 1980s followed by a plateau (germ cell tumor and pituitary tumor), and (3) a linear increasing trend throughout the observation period with no plateau (malignant lymphoma and neurinoma). Furthermore, obvious sex differences in time trends were observed in rates of meningioma, germ cell tumor, and pituitary tumor. The results of this study demonstrated several distinctive patterns in time trends, which give us insight into the possible etiologies of brain tumors. Further epidemiological study is needed to elucidate these findings.

Cauda equina tumors: a French multicenter retrospective review of 231 adult cases and review of the literature.

Large series of cauda equina tumors in adults are seldom reported. This French series retrospectively reviews 231 cases collected for the congress of the Societe Francaise de Neurochirurgie in 1996. The authors first analyze this series and then discuss the pertinent literature. Schwannoma was the most frequent benign tumor in this series, followed by ependymoma. Very few malignant tumors were recorded; these were usually malignant neurinomas nearly always in neurofibromatosis patients. Some other rare tumors were also recorded, including paragangliomas. This series confirms the importance of the pretherapeutic neurological status in functional prognosis. All schwannomas can be cured, while ependymomas and paragangliomas may recur after a very long delay. Surgery must be as complete as possible, since adjuvant therapies are proven to have little efficacy. This type of tumor requires very long follow-up. Prognosis is good for hemangioblastomas. Sphincter dysfunctions carries a poor prognosis and may appear after primary surgery, more often after treatment of recurrences.

長管骨転移性骨腫ように対する骨接合術（セメント併用）の経験

In recent years, surgical treatments have been applied to cases with intense pain due to bone metastases of a malignant tumor and to those with pathological bone fractures. In the present study, we examined the postoperative result of cases in which osteosyn thesis combined with bone cement was performed in our department for metastatic bone tumors, aiming at improvement in QOL. Subjects were three men and one woman with the mean age of 66 years, with metasttic bone tumors in long cavity bones for which osteosynthesis combined with bone cement was performed. The observation period varied from 2 months to 13 months with a mean of 5 months. The regions were the femur in two cases, tibia in one and humerus in one, and the primary foci were renal carcinoma in two, bladder cancer in one and malignant neurinoma in one. During surgery, the metastatic focus was curetted and the bone fixed with a plate or an intermedullary rod and reinforced bone cement. In regard to QOL, pain was relieved in all cases and the patients recovered to the ADL level before appearance of symptoms. In the aspect of surgical indication, this technique had little surgical invasion with satisfactory short-term postoperative results leading to a marked improvement in QOL.

AgNOR Content and PCNA Expression in Transplanted Malignant Neurinoma in Rats

Malignant neurinomas can be induced in BD IX rats by transplacental application of ethylnitroso-urea during pregnancy. Tumors develop in the offspring in trigeminal and spinal nerves and can be easily transplanted upon rats of the same strain. During the first passages a considerable shortening of subsequent induction periods takes place. Concurrently, silver stained Nucleolar Organizer Regions (AgNORs) increase in number and other measured AgNOR parameters change in a similar way. The number of cells that express the proliferation marker PCNA equally becomes more frequent during the first subcutaneously transplanted generations. There is high correlation between AgNOR parameters, number of PCNA expressing cells, induction times and passage. It is concluded that the first generations of the transplantation model of these tumors can be used to test the validity of proliferation indicators. Our results show further that AgNORs in fact belong to the group of markers of proliferation.

Chromosome numbers and DNA-content in intra-cerebrally transplanted experimental gliomas

Serially transplanted experimental tumors of the central and peripheral nervous system can be used as models to investigate open questions in human neurooncology. Altered susceptibility of higher passages to chemotherapy might be correlated with chromosome number and DNA-content variations which would be partly expressed as changes in proliferation behaviour. Karyotypes therefore were analysed in the 73rd to 90th generations of transplanted experimental gliomas. Wide variation of chromosome number was observed; 2 major types of distribution occurred, the one presenting with, the other without stemlines. Large chromosomes # 1 and # 4 were often monosomic, while small chromosomes of ## 8 to 20 were increased up to the fivefold. Lines with prominent and few markers were observed. On the whole, cells of the proliferating pool of the tumor had to be considered as hypotetraploid. Comparison of chromosome numbers and DNA content gave good correlation; differences between the 2 were explained by the fact that only the number of chromosomes was taken into account, regardless of whether small or large chromosomes were lacking or in excess. When intracerebrally transplanted tumors had been previously treated by administration of BCNU, the DNA content was altered, indicating an increased share of diploid cells in the proliferation pool. Results are at variance with earlier findings in tissue cultures of directly induced malignant gliomas and neurinomas in rats. The findings in transplanted tumors can be interpreted as a result of increased malignancy in transplantation tumors, documented by rapid growth in the animal and dedifferentiated histologic morphology.

Organ-specific carcinogenicity of N-methyl-N-nitrosourea in F344 and ACI/N rats.

Male and female F344 rats were continuously administered N-methyl-N-nitrosourea (MNU) in their drinking water at concentrations of 200 or 100 ppm, and both sexes of ACI/N rats were given MNU at a concentration of 200 ppm. By the 42nd week of the experiment, high incidences of brain/spinal cord tumors were observed in both strains of rats. Histologically, many of them were astrocytomas or anaplastic astrocytomas. In addition, malignant neurinomas were also detected in the spinal nerve roots and trigeminal nerves, although their incidences were rather low. There was no difference in the type and incidence of these neurogenic tumors between the two strains of rats. Tumors of the tongue and esophagus were mainly observed in the high-dose group of F344 rats and those of the glandular stomach were observed in the low-dose group of F344 rats. In ACI/N rats, tumors of the heart and renal pelvis were detected. The organ-specific carcinogenicity of MNU in these two strains of rats was compared with that of MNU in Donryu rats. It was demonstrated that organ specificity of MNU given orally was influenced not only by the strain of rats but also by the dose level.

Immunity to transplantable nitrosourea-induced neurogenic tumors. I. Potentiation of tumor immunity with Corynebacterium parvum.

Various injection schedules of C. parvum and tumor cells of the nitrosourea-induced malignant neurinoma, TR-481, were used to induce tumor immunity in syngeneic CDF rats. Although subcutaneous injection of the poorly immunogenic TR-481 cells alone or with C. parvum caused retardation of growth of 2 x 10(5) TR-481 cells injected 1-3 weeks later, no significant difference in tumor size or incidence was obtained, as judged by tumor growth at 8 weeks. In contrast, injection of TR-481 with C. parvum into C. parvum-presensitized rats caused a more significant degree of tumor immunity with complete inhibition of the challenge tumor growth in 17-33% of the animals. Repeated subcutaneous injection of gamma-irradiated TR-481 tumor cells mixed with C. parvum also proved effective, resulting in absence of tumor growth in 40% of the rats. Tumor immunity was specific, since growth of an unrelated tumor was unaffected. It is suggested that local immunological reactivity to C. parvum in the immunizing tumor promotes development of specific tumor immunity.

Short-term tissue culture observations of experimental primary and transplanted nervous system tumors.

Tumors of the central and peripheral nervous system were induced in BD-IX rats and transplanted serially. Both primary and transplanted tumors in different generations were cytologically analyzed, using primary explants in vitro. Four hundred and thirty single tumors were examined in vitro over th period 1969 to 1977, using the following methods: conventional aniline staining, special silver impregnation, supravital observation of cells by phase contrast microscopy, locomotion studies with time-lapse cinematography, and ultrastructural analysis from transmission and scanning electron microscopy. Cells grown in vitro were subdivided into the following groups, according to their morphology: (1) Apolar cells: Round cells only observed in rare tumors of the nasal cavity and sporadically in transplanted neurinomas; they are thought to represent cells from the reticular variant of neurinoma in the latter. (2) Bipolar cells occurred in two forms: As bipolar fibroblasts and as slender bipolar cells observed in explants of malignant neurinomas. The latter cells grow in parallel arrangements; their tentative interpretation as Schwann cells is consistent with their description in human neurilemomas. (3) Semipolar cells with one clear-cut edge and a broad ruffled membrane opposite. They are described as fibroblasts in the course of locomotion. (4) Multipolar cells, observed in several forms in primary and transplanted gliomas exclusively. Variants with long processes were seen in the first passages of intracerebrally transplanted tumors only; in later generations, all cells had short branching processes and little cytoplasm. Conclusions concerning the cytologic derivation of experimental tumors are discussed.

Neoplastic and preneoplastic lesions in rats after oral administration of a single dose of N-nitrosomorpholine (author's transl)

The administration of a single oral dose of 320 mg/kg body wt. N-nitrosomorpholine (NNM) to 62 Sprague-dawley rats resulted in neoplastic and preneoplastic changes in different organs, especially in liver and kidney. After a lag period of 4 weeks, nearly all experimental animals developed preneoplastic (clear cell, acidophilic, basophilic, mixed cell) foci of the liver parenchyma. Sporadically, small neoplastic nodules were found in the liver as early as 4 weeks after the beginning of the experiment. After a lag period of 1--2 years, 4 of 13 rats showed multiple neoplastic hepatic nodules and one animal a hepatocellular carcinoma. The bile ductules of some animals responded to the carcinogen by forming mucous cholangiofibroses and cystic cholangiomas. After long lag periods, large cholangiofibromas were found in two experimental animals. One or two years after application of the carcinogen, many animals developed epithelial (clear cell, acidophilic, chromophobic, basophilic, oncocytic) kidney tumors, often cystic. Pathologically changed (clear cell, chromophobic, basophilic, oncocytic) tubules are regarded as precursors of the epithelial tumors. The latered tubules appear for the first time at about half a year after application of the carcinogen. Apart from multiple cysts of the liver and kidneys some pancreatic cysts developed in two animals. In addition, two mesenchymal kidney tumors, one malignant neurinoma, two subcutaneous fibromas, one fibroadenoma, and one squamous cell carcinoma of the skin were observed.

Gross vascularization of experimentally induced transplanted tumors of the central and peripheral nervous system

Subcutaneously and intracerebrally transplanted neurinomas as well as intracerebrally grafted gliomas, both derived from primary tumors with resorptive carcinogens were investigated after injection of micropaque by conventional histologic methods and by postmortem X-ray analysis. Growth pattern and vasculature were similar in subcutaneously and intracerebrally transplanted malignant neurinomas. The most common feature was a parallel arrangement of vessels as shown by microradiography and vessel free zones. In intracerebrally grafted glioma, the growth of tumors was confined to or starting from the ventricular system. Sinusoidal vessels, capillary proliferations and proliferation of vessel wall were found. The outstanding feature was the occurrence of extravascular contrast deposits, thus indicating the vulnerability of tumor vessels and frequency of hemorrhages into these tumors.

Effect of levamisole on malignant experimental neurinoma grown subcutaneously in a young rat: brief communication.

Levamisole, a drug that stimulates the immunologic defenses of the host, was tested on the experimental malignant neurinoma grown subcutaneously in young female inbred CDF rats in 3-month trial. The drug resulted in prevention of tumor growth in 80% of the treated animals, whereas tumors grew in 100% of the controls. After discontinuation of the drug, none of the animals in the treated group showed evidence of tumor growth upon clinical and pathologic examination 1 month after drug treatment was terminated. Treated animals failed to show any side effects related to levamisole upon clinical and pathologic examination.

HISTOPATHOLOGICAL STUDIES OF NERVOUS SYSTEM TUMORS IN RATS INDUCED BY TRANSPLACENTAL ADMINISTRATION OF METHYLNITROSOUREA

1. When 50 mg/kg of Methylnitrosourea was transplacentally inoculated to Donryu rats, 110 out of their 116 offsprings survived more than 163 days, and in 60 of these 110 were observed 93 tumors in total.2. The sites of the tumors were as follows : Two in the brain, 2 in the spinal cord, 16 in cranial nerves, 22 in spinal nerve root, 23 in peripheral nerves, and 28 in extraneural organs.Nerve tumors totally 61, accounting for 65.6% of the total, that was a majority.3. The nerve tumors histologically showed the picture of neurinoma or malignant neurinoma. Electron microscopical observation of some of these nerve tumor revealed that constituent cells contained axis cylinders and that the surface of the cell membrane was covered with basement membrane-like homogeneous substance. Thus they presented the traits of Schwann cells.4. Four tumors formed in the cerebrospinal substances histologically showed monotonous cell structure, and 2 of them presented the picture of oligodendroglioma and the other 2 that of ependymoma-like.5. Twenty four tumors, including 18 nerve tumors, were Subcutaneously transplanted into rats of the same strain. Twelve nerve tumors and 3 other tumors were transplacentable.6. Out of 28 tumors, formed outside the nervous system, 18 were found in the Kidney, 4 in the mammary gland, 2 in the peritoneal cavity, and 2 in the bone. The renal tumors grossly appeared to be cystic tumor, and presented a histological picture of nephroblastoma-like.7. Cerebellar hypoplasia and disorder in cerebellar cell structure were observed in many cases. In addition, dental dysplasia and cicatrization in renal parenchyma suggested the cytotoxic effect of MNU.8. Comparison between intravenous and transplacental MNU administrations revealed that in both cases cranial, spinal and peripheral nervous tissue were involved by tumors, but that there was difference in target organs of cancer in the viscera.

Experimentally induced malignant neurinomas as transplantable tumors. Morphology and in vitro behaviour.

Malignant neurinomas, induced by ENU in rats, were transplanted on homologous hosts. One tumor originating from a spinal nerve root was followed through about sixteen serial subtransplantations. The growth characteristics of the grafted tumor, its morphologyin vivo andin vitro after explantation as well as its karyotype were described. Possible conclusions concerning the use of transplanted neurogenic tumors in experimental neurooncology as well as their tissue origin were discussed.

Biological characteristics of peripheral nerve tumors induced with ethylnitrosourea.

Nervous system tumors were induced in the offspring of BD-IX (inbred) and CFE (non-inbred) rats by transplacental administration of ethylnitrosourea. Tumors of the peripheral nervous system (PNS) were obtained in approximately 80% of all animals, and tumors of the central nervous system (CNS) in 16%. Although several peripheral nerves were sites of tumor formation, the trigeminal nerve was the most frequent nerve affected. In male CFE rats, 70% of all PNS tumors affected the trigeminal nerve. The incidence of trigeminal nerve tumors in female BD-IX rats was only 33% of PNS tumors. Light and electron microscopy showed that the PNS tumors are made-up of Schwann cells, and behave like malignant tumors. The tumors began as a proliferation of recognizable Schwann cells, later they lost their basement lamina, destroyed the nerve tissue and invaded neighboring structures, but did not metastasize. Like their human counterparts, they showed “dense” and “loose” areas. In both of these, Schwann cells were recognized as the tumor cells. Trigeminal nerve tumors were transplanted fromin vitro cultured cells or directly from transplanted fresh tumor fragments to isologous rats (BD-IX). Subcutaneous. intraperitoneal and intracerebral transplants were done. The morphology and behavior of the transplanted tumors were similar to the original malignant neurinomas.

Tumours of the peripheral and central nervous system induced in BD-rats by prenatal application of methyl methanesulfonate

The intravenous injection of methyl methanesulfonate ( 20–68 mg/kg) in BD IX rats on the 15th and 21st day of gestation led to the development of malignant neurogenic tumours in approximately 20% of the offspring. Two tumours were located in the cerebral hemispheres (classified as oligodendroglioma and mixed glioma) and six tumours (malignant neurinomas) originated from the peripheral nervous system. The average postnatal survival time of animals with neurogenic tumours was 292 days. No neurogenic tumours were found in the offspring of pregnant females treated with methyl methanesulfonate on the 9th day of gestation.

Morphology of transplacentally induced neurogenic tumors in Syrian hamsters

Pregnant Syrian hamsters were given 30 mg/kg ethylnitrosurea on the 15th day of pregnancy. Among 29 newborn animals, 22 could be grown up, 14 of which developed malignant tumors. Besides tumors of the trigeminal nerve which appeared first, particularly tumors of peripheral nerves were observed. In addition one nephroblastoma and one melanoma of the subcutis were induced. There were no tumors of the brain and spinal cord. The peripheral nervous tumors showed intensive regressive changes. In general, these tumors can be classified within the group of “malignant neurinomas”.

Malignant neurinomas of peripheral nerves.

Malignant neurinomas of peripheral nerves.