Early malignant transformation of a petroclival meningothelial meningioma

Although some authors have reported the malignant transformation of meningiomas, there has been no previous report describing that a meningothelial meningioma transformed into an atypical meningioma within 1 year. This report documents a 57-year-old woman who presented with right hearing disturbance. Magnetic resonance imaging revealed a right petroclival meningioma. The tumor was subtotally removed and was diagnosed to be a meningothelial meningioma. Seven months after surgery, a recurrence of the tumor was confirmed. The diagnosis of this recurrent tumor was an atypical meningioma. The MIB-1 index and the percent of p53 protein-positive cells in the primary tumor were 4.6% and 35.4%, respectively, whereas those of the recurrent tumor were 34.7% and 33.1%, respectively. A chromosomal DNA copy number loss was observed on 1p, 6q, 10, 14q, and −22q detected in both the primary and the recurrent tumors. These results suggest that the present case had a potentially malignant tumor in the early stage, although it had the histological features of benign meningiomas. An evaluation of the MIB-1 index, as well as the expression of p53 and chromosomal aberrations, may be useful for predicting the malignant transformation of meningiomas.     

Transition from meningeal melanocytoma to primary cerebral melanoma. Case report

The authors describe the first case of an intracranial transition of a melanocytoma into a primary malignant melanoma within a short time. A 37-year-old woman presented with progressive brainstem syndrome due to a tumor, originally diagnosed and treated 12 years earlier, that extended from the petroclival area to the anterior craniocervical junction. The histological workup following subtotal tumor resection of the initial tumor had revealed the typical features of a fibrous melanocytic meningioma without increased proliferation. Ten years after the patient had completed treatment for the melanocytic meningioma, control neuroimaging demonstrated growth of the residual tumor with compression of the brainstem. Another neurosurgical intervention revealed a dark tumor of hard consistency. At this time immunohistochemical examinations demonstrated melanocytic features (expression of vimentin, S100 protein, and melan A) of the lesion with focally increased proliferation (5% of Ki-67-positive cells) but no higher mitotic activity. Clinical signs of deterioration along with imaging-confirmed tumor progression precipitated another operation within 7 months. A neuropathological examination revealed epithelial and anaplastic changes and indicated that the MIB-1 indices were greater than 25%. Pleomorphic changes and a focal high mitotic activity led to the diagnosis of a primary cerebral malignant melanoma. The patient's later clinical course consisted of a rapid diffuse meningeal spread of the lesion throughout the entire brain and spine. Despite whole-brain and stereotactic radiation therapy as well as chemotherapy, the patient died 4 months after the last neuropathological diagnosis. Although grossly resembling a meningioma, melanocytomas lack the former's histological and immunohistochemical features. The biological behavior of a melanocytoma is variable and recurrence may happen after subtotal resection, but intracranial transition into a malignant melanoma has not been observed previously.     

Major venous sinus resection in the surgical treatment of recurrent aggressive dural based tumors

BACKGROUND: Despite gross total resection, aggressive dural based tumors invading major venous sinuses have high recurrence rates with poor long-term survivability. Options for aggressive surgical management of dural sinus invasion may be limited by the inherently high risk of morbidity and mortality. METHODS: Between July 1996 and July 2002, 5 cases of recurrent aggressive dural based tumors were operated on. Gross total resection had been previously performed in 4 cases, and near total resection in 1 case. Tumor pathology included 2 malignant meningiomas, 1 hemangiopericytoma, 1 atypical meningioma, and 1 benign meningioma with atypical features. All tumors recurred within 3 to 47 months and occluded a major venous sinus (four superior sagittal and one dominant right transverse sinus). Gross total resection of tumor and involved venous sinus was accomplished in each case. RESULTS: Three patients had no signs of clinical or radiographic recurrence at 10, 18, and 53 months of follow up. One patient who developed a fatal pulmonary embolism 10 months postoperatively had evidence of tumor progression on autopsy. One patient had tumor recurrence at 10 months, but is alive at 38 months and receiving adjunctive therapy. CONCLUSION: For aggressive dural based tumors that recur with invasion of a major venous sinus, radical resection of tumor and occluded sinus can be performed safely and may improve long-term survival.     

Pulmonary and mediastinal glomus tumors--report of five cases including a pulmonary glomangiosarcoma: a clinicopathologic study with literature review

Pulmonary and mediastinal glomus tumors are rare lesions, with four previously reported primary pulmonary cases and three mediastinal cases. The authors report one mediastinal glomus tumor, a locally infiltrative type, and four pulmonary glomus tumors, including the first case of primary pulmonary glomangiosarcoma. These tumors show a variety of clinical and pathologic differences from the more common cutaneous variety, including later age at presentation, larger size, and more frequent atypical/malignant features. Mediastinal and pulmonary glomus tumors both have an average patient age at presentation of 45 years. However, compared with their pulmonary counterparts, mediastinal glomus tumors are less common, more often symptomatic, and are larger (average size, 5.4 cm). Additionally, mediastinal glomus tumors more often demonstrate malignant or atypical features. Pulmonary glomus tumors average 3.3 cm in greatest dimension, with the majority measuring less than 2.5 cm. The pulmonary glomangiosarcoma presented was large, measuring 9.5 cm, and showed increased mitotic count (9 mitoses/10 high-power fields), necrosis, cytologic atypia, and was associated with disseminated disease. Regardless of clinical symptoms, histologic features, and even metastases, the vast majority of all benign and malignant glomus tumors are indolent and cured surgically, with adjuvant therapy needed only for occasional patients with more advanced disease. The four patients with glomus tumors reported are currently alive and free of disease as of last follow up. The patient with the glomangiosarcoma developed widespread metastases and died of disease 68 weeks after initial therapy.     

Irinotecan: a potential new chemotherapeutic agent for atypical or malignant meningiomas

OBJECT: There is currently no effective chemotherapy for meningiomas. Although most meningiomas are treated surgically, atypical or malignant meningiomas and surgically inaccessible meningiomas may not be removed completely. The authors have investigated the effects of the topoisomerase I inhibitor irinotecan (CPT-11) on primary meningioma cultures and a malignant meningioma cell line in vitro and in vivo. METHODS: The effects of irinotecan on cellular proliferation in primary meningioma cultures and the IOMM-Lee malignant meningioma cell line were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. Apoptosis following drug treatment was evaluated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and the DNA laddering assays. The effects of irinotecan in vivo on a meningioma model were determined with a subcutaneous murine tumor model using the IOMM-Lee cell line. Irinotecan induced a dose-dependent antiproliferative effect with subsequent apoptosis in the primary meningioma cultures (at doses up to 100 microM) as well as in the IOMM-Lee human malignant meningioma cell line (at doses up to 20 microM) irinotecan. In the animal model, irinotecan treatment led to a statistically significant decrease in tumor growth that was accompanied by a decrease in Bcl-2 and survivin levels and an increase in apoptotic cell death. CONCLUSIONS: Irinotecan demonstrated growth-inhibitory effects in meningiomas both in vitro and in vivo. Irinotecan was much more effective against the malignant meningioma cell line than against primary meningioma cultures. Therefore, this drug may have an important therapeutic role in the treatment of atypical or malignant meningiomas and should be evaluated further for this purpose.     

Intracranial injection of human meningioma cells in athymic mice: an orthotopic model for meningioma growth

OBJECT: Although human meningioma cells have been heterotopically implanted in nude mice, introducing these cells into intracranial locations seems more likely to reproduce normal patterns of tumor growth. To provide an orthotopic xenograft model of meningioma, the authors implanted a controlled quantity of meningioma cells at subdural and intracerebral sites in athymic mice. METHODS: Malignant (one tumor), atypical (two tumors), or benign (three tumors) meningiomas were placed into primary cell cultures. Cells (10(6)/10 microl) from these cultures and from an immortalized malignant meningioma cell line, IOMM-Lee, were injected with stereotactic guidance into the frontal white matter or subdural space of athymic mice. Survival curves were plotted for mice receiving tumor cells of each histological type and according to injection site. Other mice were killed at intervals and their heads were sectioned whole. Hematoxylin and eosin staining of these sections revealed the extent of tumor growth. CONCLUSIONS: The median length of survival for mice with malignant, atypical, or benign tumors was 19, 42, or longer than 84 days, respectively. Atypical and malignant tumors were invasive, but did not metastasize extracranially. Malignant tumors uniformly showed leptomeningeal dissemination and those implanted intracerebrally grew locally and spread noncontiguously to the ventricles, choroid plexus, convexities, and skull base. Tumors formed in only 50% of mice injected with benign meningioma cells, whereas injection of more aggressive cells was uniformly successful at tumor production. The three types of human meningiomas grown intracranially in athymic mice maintained their relative positions in the spectrum of malignancy. However, atypical meningiomas became more aggressive after xenografting and acquired malignant features, implying that there had been immune constraint in the original host. Tumor cells injected into brain parenchyma migrated to more optimal environments and grew best there. This model provides insights into the biology of meningiomas and may be useful for testing new therapies.     

Pulmonary meningioma. Immunohistochemical and ultrastructural features

Two cases of solitary primary pulmonary tumors showing the immunohistochemical and ultrastructural features of meningothelial meningiomas are presented. The benign clinical and radiologic course, the negative computed tomography scan of the brain (case 1), and negative neuropathologic investigation (case 2) support the diagnosis of a primary pulmonary meningioma rather than a metastazing malignant intracranial meningioma. Negative neuroendocrine markers (neuron-specific enolase, chromogranin, bombesin) and the lack of neurosecretory granules by electron microscopy confirm the diagnosis of this rare pulmonary tumor.     

Resection for pulmonary metastasis of gastrointestinal stromal tumor of the stomach at 10 years after gastrectomy; report of a case

A 70-years-old male, who had received gastrectomy for leiomyosarcoma of the stomach 10 years ago, was found to have a left lung tumor on chest X-ray and computed tomography (CT). The tumor was diagnosed to be a pulmonary metastasis of gastric leiomyosarcoma. On admission, another tumor was detected at left occipital region by brain CT and was thought to be meningioma. Left lower lobectomy and brain tumor resection were performed serially. The histologic and immunohistochemical findings showed that both tumors were metastases of gastrointestinal stromal tumor (GIST) of the stomach after long disease-free interval. Compared with the primary tumor, cellular density, mitotic figures, bizarre nuclei, and necrotic foci were prominent in the metastatic tumors. This case suggest that GIST may recurrent as pulmonary metastasis after long disease-free interval and should be follow up longer after resection. Patient prognosis with pulmonary metastases is considered to be reflected more exactly in biological malignant potential of metastatic tumor rather than that of primary tumor.     

Primary pulmonary malignant meningioma

Primary pulmonary meningiomas are relatively rare and mostly benign. To exclude pulmonary metastasis of an intracranial meningioma, imaging studies of the brain should be performed. We believe that only one primary pulmonary malignant meningioma in which a metastasis from the brain was excluded has been reported. In this report we describe a second case with malignant features.     

Seeding of malignant meningioma along a surgical trajectory on the scalp. Case report and review of the literature

The authors report the case of an 11-year-old boy with a malignant meningioma of the right frontal meninges. The tumor was asymptomatic, despite visible exophytic extracranial growth. Neuroimaging demonstrated an en plaque meningioma bulging into the brain. Six months after the tumor had been totally removed by surgery, an isolated subcutaneous metastasis developed at the right preauricular area of the scalp, originating at the scar left by the first surgery. After removal of this metastasis, radiotherapy was conducted. To date the follow-up examinations have not revealed any additional metastases. To the best of the authors' knowledge, this is the first report of a seeding of a subcutaneous metastasis in a child with a malignant meningioma. The authors review the literature with reference to malignant meningiomas and their formation of metastasis. In cases of malignant meningiomas, piecemeal tumor removal carries the risk of iatrogenic cell dissemination even when precautions are taken.     

Metastatic solitary fibrous tumor of the meninges. Case report

Solitary fibrous tumor (SFT) is a unique tumor composed of interstitial dendritic cells that was first described in the thorax and subsequently reported in diverse organs. Extrathoracic SFTs are predominantly benign but rare malignant cases have been documented. In the nervous system, SFT has been described as a meningeal lesion although all 14 previously reported cases were benign. The authors report the first case of a meningeal SFT occurring in a 55-year-old woman. The tumor first presented as a meningeal lesion that after three recurrences over a 10-year period metastasized to the soft tissues and lungs. The potentially malignant nature of cranial SFTs, especially those with atypical histological features and high mitotic counts, should be recognized.     

Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients

Adrenal cortical neoplasms in pediatric patients (<20 years) are rare. The clinical manifestations and biologic behavior of these lesions can be quite distinct from their histologically similar counterparts in the adult population, making pathologic criteria for distinguishing benign from malignant tumors equivocal. We undertook a study of 83 adrenal cortical neoplasms to determine if adult clinical and histologic features can be applied to pediatric patients in an outcome-based analysis. Most of the patients (50 girls and 33 boys) presented with hormone-related symptoms present for a mean of 6.8 months. The tumors ranged in size from 2 to 20 cm (mean 8.8 cm). Histologic parameters examined included capsular and/or vascular invasion, extraadrenal soft tissue extension, growth pattern, cellularity, necrosis, cytoplasmic eosinophilia, nuclear pleomorphism, nuclear-to-cytoplasmic ratio, prominent nucleoli, mitotic figures, atypical mitotic figures, bands of fibrosis, and calcifications. Immunophenotypically, there was reactivity with inhibin, vimentin, CK5, and focally with p53 and Ki-67. All patients underwent adrenalectomy, and 20 patients received adjuvant therapy. All patients with tumors classified as adenomas (n = 9) were alive, without evidence of disease (mean 14.7 years), whereas 21 patients with carcinomas had died with disease (mean 2.4 years). Only 31% of histologically malignant tumors behaved in a clinically malignant fashion. Features associated with an increased probability of a malignant clinical behavior included tumor weight (>400 g), tumor size (>10.5 cm), vena cava invasion, capsular and/or vascular invasion, extension into periadrenal soft tissue, confluent necrosis, severe nuclear atypia, >15 mitotic figures/20 high power fields, and the presence of atypical mitotic figures. Vena cava invasion, necrosis, and increased mitotic activity (>15 mitotic figures/20 high power fields) independently suggest malignant clinical behavior in multivariate analysis.     

Histopathologic features predicting recurrence of meningiomas following subtotal resection

Histopathologic features that predict recurrence of meningiomas following subtotal resection were identified by reviewing the initial surgical specimens from 82 patients (38 with tumor recurrence and 44 without) treated at the Massachusetts General Hospital between 1962 and 1984. There was no correlation between histologic subtype and tendency toward tumor recurrence; however, the few examples of hemangiopericytoma, angioblastic meningioma, or sarcomatous meningioma were observed almost exclusively in patients with recurrent tumors. Seven histopathologic features were positively correlated with recurrence of meningiomas, including the following: hypervascularity of tumors, hemosiderin deposition, growth of tumor cells in sheets rather than the usual growth patterns of meningiomas, prominent nucleoli, mitotic figures, single-cell and small-group necrosis, nuclear pleomorphism, and overall atypical or malignant tumor grade (all p less than 0.005). In addition, sheeting of tumor cells, prominent nucleoli, and the presence of less than 10% meningothelial pattern were correlated with significantly abbreviated progression-free survival, i.e., more rapid progression of tumor with shorter intervals between treatment and tumor recurrence. These findings suggest that the presence of features such as large prominent nucleoli, tumor growth in sheets, individual-cell necrosis, and nuclear pleomorphism may be used to predict recurrence of subtotally resected meningiomas that would not be classified as malignant by traditional criteria.     

Atypical and malignant glomus tumors: analysis of 52 cases, with a proposal for the reclassification of glomus tumors

Occasional glomus tumors display unusual features, such as large size, deep location, infiltrative growth, mitotic activity, nuclear pleomorphism, and necrosis. Although a small number of purportedly malignant glomus tumors have been described, histologic criteria for malignancy in glomus tumors have never been elaborated. The authors studied 52 unusual glomus tumors (retrieved from their consultation files) previously diagnosed as "atypical" or "malignant" by virtue of nuclear atypia, infiltrative growth, or mitotic activity. They evaluated size, depth, growth pattern, cellularity, nuclear grade, number of mitotic figures per 50 high-power fields (HPF), atypical mitotic figures, vascular space involvement, and necrosis to define criteria for malignancy in glomus tumors. Estimated relative risk was calculated and the Fisher exact test was used for statistical analysis. The 27 female patients and the 25 male patients ranged in age from 8 to 83 years (median age, 43 years). The tumors measured from 0.2 to 12 cm (median size, 2 cm) and occurred predominantly in the extremities, in both the superficial (n = 35) and deep (n = 17) soft tissues. Atypical features were usually observed centrally with a rim of benign-appearing glomus tumor. Follow-up information (n = 35; range, 5 months-23 years; mean 5.5 years) showed seven recurrences, eight metastases, and seven deaths from disease. Five-year cumulative metastatic risk increased significantly for tumors with a deep location (p = 0.005), with a size of more than 2 cm (p = 0.004), and with atypical mitotic figures (p = 0.004). Mitotic activity of more than 5 mitoses/50 HPF, high cellularity, the presence of necrosis, and moderate to high nuclear grade approached but did not reach significance. High nuclear grade alone, infiltrative growth, and vascular space involvement were not associated with metastasis. The authors propose the following classification scheme and criteria. Malignant glomus tumor: Tumors with a deep location and a size of more than 2 cm, or atypical mitotic figures, or moderate to high nuclear grade and > or =5 mitotic figures/50 HPF. Symplastic glomus tumor: Tumors with high nuclear grade in the absence of any other malignant feature. Glomus tumor of uncertain malignant potential: Tumors that lack criteria for malignant glomus tumor or symplastic glomus tumor but have high mitotic activity and superficial location only, or large size only, or deep location only. Glomangiomatosis: Tumors with histologic features of diffuse angiomatosis and excess glomus cells. Using this classification scheme, metastasis was observed in 38% of tumors fulfilling the criteria for malignancy. In contrast, metastatic disease was not seen in any specimen classified as symplastic glomus tumor, glomus tumor of uncertain malignant potential, or glomangiomatosis.     

A case of recurrent convexity meningioma with malignant transformation 26 years after total tumor removal

Meningiomas are common intracranial tumors, the majority of which are considered benign. However, they sometimes show altered biologic behavior, associated with local aggressiveness and late distant metastasis. We report a patient with a convexity meningioma, which recurred as a malignant transformation 26 years after a total tumor removal. A 75-year-old man was transferred to a local hospital because of general convulsions and left hemiparesis. The patient had had an operation for the total removal of a right frontal convexity meningioma at the age of 46 and had been free of its effects until the age of 72. Brain magnetic resonance imaging (MRI) showed a recurrent tumor located in the anterior area of the previous craniotomy. Over the following two and a half years, MRI revealed rapid enlargement and infiltration of the tumor into the brain parenchyma. The primary tumor was nodular, macroscopically well demarcated from the surrounding brain tissue and, histologically, was a transitional type of meningioma without any atypical features. In contrast, the recurrent tumor, whose border was ill-defined, had invaded the neighboring brain. A histological specimen of the recurrent tumor showed highly malignant features such as necrosis, intracerebral infiltration, dense cellularity, and high proliferating activity as demonstrated by a cell kinetic study using the MIB 1 staining index. We should be mindful that recurrence from common benign type meningiomas may occur as malignant transformations after more than two decades.     

Cell kinetics in two cases of meningioma with ultra-late pulmonary metastases]

In order to elucidate the influence of surgical intervention on cell kinetics, we investigated the DNA ploidy pattern and mitotic index in two patients with metastatic pulmonary meningioma more than 10 years after the first operation for primary brain lesions. The first patient, with hemangiopericytomatous meningioma, showed a diploid pattern in all resected specimens and intrathoracic metastases obtained at autopsy, and also showed a constant mitotic indices throughout the clinical course. The second patient, with meningothelial meningioma, also showed a diploid pattern and constant mitotic indices throughout the clinical course. There was no difference in the two parameters between this second patient and 5 non-metastatic control cases. In conclusion, there was no positive correlation between these two parameters and the acceleration of tumor growth detected at every surgical intervention.     

Gliosarcoma--a case report

A 60-year-old woman was admitted to our clinic on September 29, 1983 because of a five months history of personality change and progressive left sided motor weakness. Neurological examination on admission revealed left hemiparesis and papilledema. She was severely demented. Skull X-rays were normal. CT scan showed a large right parietoccipital mass which was markedly enhanced by contrast medium. Right internal carotid angiogram showed abnormal vascular shadow, early draining veins and tumor stain in parietoccipital region. Right external carotid angiogram showed that the tumor was partly fed by the middle meningeal artery in "sunburst" pattern. The tumor was resected subtotally through right parietoccipital craniotomy on October 4, 1983. At operation, well demarcated, reddish-grey tumor attached to the dura was found. Several branches of the middle meningeal artery were penetrated into the tumor through the attachment. The tumor grossly appeared to be a meningioma in its superficial part, but demarcation was found being obscured in removing the deeper part of the tumor. Pathological findings: The specimens obtained from the superficial part of the tumor showed admixture of two distinctive neoplastic tissues. One was malignant mesenchymal features. Fibrosarcomatous nature was obvious, characterized by cells with moderately chromatic, fusiform nuclei arranged in parallel rows and eosinophilic fibers deeply stained in silver preparation for reticulin. The other was gliomatous tissue forming islands surrounded by the sarcomatous tissues. Both tissues were histologically malignant, as evidenced by mitotic figure, high cellularity, atypical features and variability. In deeper part, sarcomatous findings was less noticed and features of glioblastoma multiforme more prominent, characterized by marked astrocytic anaplasia, endothelial proliferation and extensive perinecrotic pseudopalisading.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coexistence of intracranial meningioma and primary malignant lymphoma--case report.

The authors present a case of multiple primary intracranial tumors of different cell types. A 62-year-old female presented with symptoms suggestive of an intracranial mass lesion. Computer tomographic scans revealed two lesions, one in the right temporal lobe and one in the posterior fossa. Both tumors were approached in one operation. The right temporal tumor was diagnosed as primary malignant lymphoma, and the right posterior fossa tumor as meningioma. Phacomatosis was ruled out as a possible etiology. Multiple primary intracranial tumors of different cell types are rare, and this is the first report of coexistent intracranial meningioma and malignant lymphoma.     

Malignant calcifying epithelial odontogenic tumor of the mandible: report of a case with pulmonary metastasis showing remarkable response to platinum derivatives.

We describe a case of CEOT of the mandible, which underwent malignant transformation and developed metastatic tumors of the lung after repeated local recurrence. The primary tumor revealed typical histological features of benign CEOT showing sheets of polyhedral epithelial cells associated with abundant eosinophilic amyloid-like materials. On the other hand, the locally recurrent tumors had malignant features, such as increased nuclear pleomorphism with frequent mitotic figures and vascular invasion of tumor cells, as well as increased proliferative activity assessed by immunostaining for Ki-67. Chemotherapy was carried out against the pulmonary metastatic lesions, which showed a drastic response after 3 courses of intravenous administration of cisplatin (CDDP). To date, a total of 6 courses of CDDP and 6 courses of nedaplatin (CDGP) have been done, and the remaining pulmonary tumors have been dormant. This suggests that platinum derivatives could be a chemotherapeutic agent of choice against this rare tumor.