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B W Scheithauer

Publications and source records attributed to B W Scheithauer.

At least 109 records · Page 6Linked to original sources
PubMed1999

Tumor suppressor gene alterations in malignant gliomas: histopathological associations and prognostic evaluation.

We have examined a series of 135 gliomas for alterations of the p53, CDKN2A (p16) and PTEN tumor suppressor genes (TSGs) in order to evaluate the incidence of their inactivation as a function of tumor malignancy and cellular differentiation, and to examine potential associations with patient outcome. The composition of this series, classified using WHO criteria, is as follows: 27 grade 2 tumors (11 astrocytomas, 12 oligoastrocytomas, 4 oligodendrogliomas), 42 grade 3 tumors (22 astrocytomas, 16 oligoastrocytomas, 4 oligodendrogliomas), and 66 grade 4 tumors (63 astrocytomas and 3 oligoastrocytomas). Similar frequencies of p53 mutation were observed among grade 2 (37.0%), and grade 3 tumors (38.1%), as well as between astrocytomas and mixed tumors. CDKN2A and PTEN mutations were clearly associated with increasing tumor malignancy (occurring in 0% of grade 2 tumors, 14.3% and 4.8% respectively of grade 3 tumors, and 27.3% and 30.3% respectively of grade 4 tumors) and were observed at substantially higher rates among astrocytomas. For the tumor suppressor genes examined, there was no relationship between the occurrence of any two TSG inactivation events. With regard to outcome, the p53 genetic status showed no significant relationship with patient survival. The CDKN2 and PTEN alterations were negative prognostic indicators of survival when evaluated in all 135 gliomas, but failed to predict outcome when evaluated in either of the high grade (3 or 4) tumor groups.

Adolescent↗
PubMed1999

Meningioma metastatic to the lung.

Meningiomas constitute 15% to 18% of all primary intracranial and intraspinal tumors. Distant extracranial metastases are reported to occur in fewer than 1 in 1000 cases. Of 1992 primary intracranial meningiomas seen at Mayo Clinic Rochester from 1972 through 1994, we identified 3 (0.15%) with documented extracranial metastasis. A review of the literature suggests that previous craniotomy, venous sinus invasion, local recurrences, histological malignancy, and papillary morphology may be risk factors for systemic spread, as demonstrated in our cases. Although rare, metastatic meningioma should be considered in the differential diagnosis of abnormal findings on chest radiography in patients with known or suspected intracranial meningioma.

Adolescent↗
PubMed1998

The results of radiotherapy for ependymomas: the Mayo Clinic experience.

PURPOSE: This analysis was performed to examine the outcome of patients with histologically confirmed ependymomas of the brain or spinal cord who received postoperative radiotherapy. METHODS AND MATERIALS: Eighty patients with histologically confirmed ependymomas were evaluated retrospectively. All were treated with various combinations of surgery, radiotherapy (RT), and chemotherapy. Follow-up ranged from 5 to 30 years (median 10.4 years). RESULTS: The 5- and 10-year survival rates for the entire study group were 79% and 73%, respectively. Patients with low-grade (1 and 2 of 4) tumors had a 5-year survival rate of 87% as compared to 27% for those with high-grade (3 and 4 of 4) tumors (p < 0.0001). Patients with tumors of the spine had a 5-year survival rate of 97% as compared to 68% for those with infratentorial tumors, and 62% for those with supratentorial tumors (p = 0.03). Patients with myxopapillary ependymomas of the spine had a 5-year survival rate of 100% as compared with 76% for patients with other histological subtypes of ependymoma (p = 0.02). Multivariate analysis revealed that the survival rate was independently associated with tumor grade (p = 0.0007) and histological subtype (p = 0.02). Twenty-eight patients (35%) experienced local failure and 10 patients (13%) developed leptomeningeal seeding. The 5-year leptomeningeal failure rate was 10% in patients with low-grade tumors as compared to 41% for patients with high grade tumors (p = 0.01). CONCLUSION: Patients with low-grade tumors, especially those with myxopapillary subtypes, have high 5-year survival rates when treated with post-operative radiotherapy. High grade ependymomas are associated with a much poorer outcome. New forms of therapy are required to improve the outcome of patients with high-grade ependymomas.

Adolescent↗
PubMed1998

Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex.

BACKGROUND: The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the brain, heart, skin, and kidney. Malignant tumors also can occur in patients with tuberous sclerosis, particularly in the kidney, although they occur less frequently than benign tumors. The types of malignancy that occur in TSC have not been characterized fully. METHODS: Clinical and pathologic features of 8 malignant tumors from 6 TSC patients ranging in age from 22 months to 21 years are reviewed. Six tumors were renal, one was from the inguinal region, and one was from the brain. The tumors were analyzed for loss of heterozygosity (LOH) in the chromosomal regions of the TSC1, TSC2, and VHL genes. RESULTS: Three patients (ages 7, 8, and 20 years) had renal cell carcinomas (RCCs). Two of these patients had multifocal RCCs. All three patients with RCC also had prominent multifocal dysplasia of renal cyst epithelium. Two patients (ages 20 and 21 years) had malignant angiomyolipomas (1 renal and 1 inguinal). One patient (age 22 months) had a Grade 4 giant cell astrocytoma (glioblastoma multiforme). LOH in the region of the TSC2 gene was found, either in the malignant tumor or in benign tumors, in all five patients whose DNA could be analyzed. CONCLUSIONS: Children with TSC, as well as adults with the disease, are at risk for developing malignant tumors. Two types of renal malignancy occur in TSC: RCC, which appears to arise from dysplastic renal cyst epithelial cells, and malignant angiomyolipoma. Tumors cytologically similar to malignant angiomyolipomas also may occur at extrarenal sites. LOH analyses suggest that the majority of patients with TSC who develop malignant tumors have germline TSC2, rather than TSC1, gene mutations.

Adult↗
PubMed1998

Malignant peripheral nerve sheath tumor: analysis of treatment outcome.

PURPOSE: To analyze the results of therapy for malignant peripheral nerve sheath tumor (MPNST) and to identify prognostic factors of survival, and of local and distant control of disease. METHODS AND MATERIALS: From 1975 through 1993, 134 MPNSTs were diagnosed and treated at our institution. Tumor sites included extremities in 36 (27%) cases and non-extremities in 98 (73%). Median follow-up for survivors was 53 months (range: 7-280). There were 14 tumors of histologic grade I disease (10%), 43 of grade II disease (32%), 43 of grade III disease (32%), and 32 of grade IV (24%). Seventy-three patients (54%) underwent radiation therapy (RT) as part of their initial treatment of the primary tumor, including 14 (10%) who had brachytherapy and 16 (12%) who had intraoperative electron irradiation (IOERT) as part of their radiation course. RESULTS: The 5- and 10-year survival rates were 52% and 34%, respectively. Local and distant failure rates at 5 years were both 49%. On univariate analysis, prognostic factors significantly related to survival (log-rank: p < 0.05) included tumor size, location of disease, history of neurofibromatosis type 1 (NF-1), history of prior irradiation, surgical margin status, use of IOERT or brachytherapy, disease stage, histologic grade and tumor subtype, as well as mitotic rate and the presence or absence of necrosis. On multivariate analysis, only history of prior irradiation (p = 0.023), and surgical margin status (p = 0.0044) remained significant. For local control of disease, univariate analysis showed location of disease, surgical margin status, history of NF-1, history of prior irradiation, mitotic rate, radiation dose > or = 60 Gy, and use of IOERT or brachytherapy to be significant prognostic factors. On multivariate analysis, only surgical margin status (p = 0.0024), RT dose (p = 0.021), and use of IOERT or brachytherapy (p = 0.016) remained significant. For distant control of disease, significant prognostic factors on univariate analysis included tumor size, stage, tumor grade, mitotic rate, presence or absence of necrosis, and histologic subtype. On multivariate analysis, tumor size (p = 0.0065), grade (p = 0.036), and histologic subtype (p = 0.001) remained significant. Patients with perineurial MPNSTs had a much lower rate of distant metastasis and a better overall survival as compared with other histologic subtypes. CONCLUSION: Management of patients with MPNST involves a multi-modality approach. The goal of surgery is complete resection with negative margins. Adjuvant irradiation to doses > or = 60 Gy and the inclusion of IOERT or brachytherapy are associated with improved local control of disease.

Adolescent↗
PubMed1998

The prognostic significance of MIB-1, p53, and DNA flow cytometry in completely resected primary meningiomas.

BACKGROUND: Despite the availability of clinical and pathologic parameters of prognosis, the behavior of an individual meningioma may be difficult to predict. In a recent review of gross totally resected (GTR) meningiomas, the authors found strong associations between microscopic brain invasion, increased mitotic rate (> or = 4/10 high-power fields), the presence of at least 3 of 4 morphologic variables (sheeting, hypercellularity, macronucleoli, and small cells), and decreased recurrence free survival (RFS). In this study, they assessed the prognostic value of three ancillary techniques: DNA flow cytometry, MIB-1 labeling, and p53 protein expression. METHODS: The authors evaluated primary GTR meningiomas from 425 patients with DNA flow cytometry, immunostaining for MIB-1, and determination of p53 protein expression. The patients were followed until death or for a median of 8.9 years. RESULTS: An MIB-1 labeling index (LI) of > or = 4.2%, identified in 8% of cases, was strongly associated with decreased RFS in univariate analysis (P=0.0001). Fourteen percent contained aneuploid cell populations, and 48% exhibited a p53 LI of >10%. Neither variable was associated with decreased RFS. Further analysis revealed a close association between MIB-1 LI and mitotic index, the latter being the parameter of greatest significance in multivariate analysis. CONCLUSIONS: MIB-1 LI is a useful adjunct to routine histologic evaluation of meningiomas and appears to be of greatest value in the evaluation of tumors exhibiting borderline atypia. In contrast, our data suggest that, regarding patients with primary GTR meningiomas, neither flow cytometry nor p53 immunohistochemistry provides useful prognostic information.

Adolescent↗
PubMed1998

Management of recurrent meningeal hemangiopericytoma.

BACKGROUND: Meningeal hemangiopericytoma is an uncommon neoplasm with a high propensity for recurrence. The purpose of this study was to analyze the efficacy of different treatment options in patients with recurrent disease. METHODS: The records of all patients with recurrent meningeal hemangiopericytoma treated at the study institution between 1976 and 1996 were reviewed. RESULTS: Thirty-four consecutive patients were studied. The mainstay of treatment was brain surgery in 21 patients (62%); the median time to recurrence from surgery was 12 months. Ten patients (29%) had 20 recurrent central nervous system (CNS) lesions treated by stereotactic radiosurgery. Of these, 3 previously nonirradiated patients (all with lesion size < 25 mm) achieved a complete response, which persisted at a median of 3 years. In 14 lesions (70%) a partial response (PR) occurred with a median duration of 12 months, whereas 3 lesions (15%) remained stable. Two patients with inoperable CNS lesions received external beam radiation therapy and both had PRs lasting 14 and 24 months, respectively. Nine patients (26%) received radiation therapy for metastatic disease. Of these, seven patients remained stable with good symptomatic relief, and two patients experienced tumor progression. Chemotherapy with doxorubicin-containing regimens was administered in 7 patients (21%); there was only 1 PR that lasted 8 months. The median survival from first recurrence was 4.6 years. CONCLUSIONS: Surgical management is important for the successful treatment of patients with recurrent meningeal hemangiopericytoma. Radiosurgery plays a definite role in the treatment of smaller recurrent CNS lesions. Radiation therapy is helpful in the management of inoperable tumors. More effective chemotherapeutic agents are needed.

Adult↗
PubMed1998

Amyloidomas of the nervous system: a monoclonal B-cell disorder with monotypic amyloid light chain lambda amyloid production.

BACKGROUND: Amyloidomas or localized tumor-like amyloid deposits rarely affect the nervous system. To the authors' knowledge, no comprehensive studies on central and peripheral nervous system amyloidomas have been published. The amyloid subtype of amyloidomas of the nervous system only recently was characterized and almost invariably was found to be of amyloid light chain (AL) lambda type. The nature of the plasma cell population responsible for AL amyloid production has not been investigated further. METHODS: The current analysis included the clinical findings, neuroimaging characteristics, and pathology of seven amyloidomas (four cerebral and three involving peripheral nerves). All were subjected to histochemical staining (Congo red, thioflavine S) and to immunohistochemical study using primary antibodies detecting serum amyloid component P, serum amyloid protein A (SAA), transthyretin, beta2 microglobulin (beta2m), and free immunoglobulin (Ig) light chain. For the detection of mRNA of light chain Ig, fluorescein-conjugated kappa and lambda mRNA oligonucleotide probes were used. For the assessment of B-cell clonality, polymerase chain reaction (PCR) was applied on extracted DNA from two cases using VH FRIII and JH primers. Two cases were assessed ultrastructurally. RESULTS: All amyloidomas were organ restricted and unrelated to systemic amyloidosis. The clinical symptoms of the cerebral lesions were nonspecific, whereas neurologic deficits were noted in the distribution of the involved peripheral nerves. Cerebral deposits, either solitary or multiple, were associated spatially with the choroid plexus and secondarily extended into white matter. All peripheral nerve amyloidomas involved the gasserian ganglion of the trigeminal nerve. Imaging by computed tomography and magnetic resonance imaging scans revealed hyperdense and contrast-enhancing mass lesions unassociated with significant edema. Immunohistochemically, the amyloid was present in the interstitium and within the walls of the intralesional vessels, was invariably of AL lambda subtype, and was negative for free Ig kappa light chains, SAA, transthyretin, and beta2m. Plasma cells along the perivascular sheaths and occasionally squeezed between amyloid masses showed no cytologic atypia. In situ hybridization for Ig light chain mRNA reflected a massive preponderance of lambda-producing cells. PCR revealed monoclonal rearrangement of the heavy chain Ig gene. CONCLUSIONS: The results of the current study provide strong support for the concept that amyloidomas of the nervous system are neoplasms of an AL lambda-producing B-cell clone capable of terminal differentiation. Nevertheless, all seven patients lacked clinical evidence of an aggressive or systemic lymphoplasmacytic neoplasm. Unlike plasmacytomas, the relatively indolent course of most nervous system amyloidomas is reminiscent of the similarly indolent biologic behavior of extranodal, low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.

Adult↗
PubMed1998

Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma.

We report a case of a 15-year-old girl with new onset seizures, who had a mixed dysembryoplastic neuroepithelial tumor (DNT) and ganglioglioma of the right parieto-occipital lobe. The tumor appeared well demarcated and exhibited a low T1 and a high T2 signal on magnetic resonance imaging. Architecturally it was in large part intracortical and multinodular, but also featured a leptomeningeal component. The former corresponded to DNT, a proliferation of oligodendroglia-like cells (OLCs) arranged in nodules, as well as comprising a diffuse internodular element featuring "floating neurons" in a mucoid matrix. The leptomeningeal portion of the lesion was a ganglioglioma consisting of large neurons and astrocytes in association with marked desmoplasia. Spatially, the two components abutted one another but appeared distinct. Immunohistochemistry showed the neurons of the ganglioglioma to be positive for class III beta-tubulin, synaptophysin, and chromogranin A, whereas the astrocytic cells stained only for glial fibrillary acidic protein. Most OLCs in the DNT were positive for S-100 protein. This apparently mixed lesion suggests that a close histogenetic relationship exists between DNT and ganglioglioma. We postulate that the pluripotential progenitor cells residing in the subpial granular layer may have given rise to the cortical DNT and to the leptomeningeal ganglioglioma. To our knowledge, this is the first detailed histological, immunochemical and ultrastructural report of a mixed DNT and ganglioglioma.

Adolescent↗
PubMed1998

Anti-neuronal nuclear autoantibodies, types 1 and 2: their utility in the study of tumors of the nervous system.

This is a comprehensive immunohistochemical study of selected archival tumors of the nervous system applying human anti-neuronal nuclear autoantibodies of types 1 and 2 (ANNA-1 and -2), serum markers of paraneoplastic syndromes associated primarily with small cell lung cancer (SCLC). Neither ANNA-1 nor ANNA-2 bound to glial tumors regardless of histological grade and subtype; instead they labeled neurons in overrun normal parenchyma. Central neurocytomas and the neuronal components of mixed glioneuronal tumors were also immunoreactive for both. In addition, varying proportions of tumor cells were stained in dysembryoplastic neuroepithelial tumor, subependymal giant cell astrocytoma (SEGA), tuber and neuroblastoma. All other tumors were nonreactive, namely choroid plexus papilloma, pituitary adenoma, pineocytoma, pheochromocytoma, thymic and pulmonary carcinoid, chordoma, meningioma, schwannoma and metastatic melanoma. SCLC was immunonegative for ANNA-1 and ANNA-2 in paraffin preparations, but displayed strong immunoreactivity for both in frozen sections: this discrepancy was not observed in other tumors studied. In conclusion, the human IgG autoantibodies ANNA-1 and ANNA-2 provide novel tools for studying the cytogenesis of tumors of the nervous system in that they permit the identification of both normal and neoplastic, poorly differentiated and small neuronal cells that may escape detection using commercially available anti-neuronal antibodies.

Antibodies, Antinuclear↗
PubMed1998

Pituitary adenylate-cyclase-activating polypeptide (PACAP) binding sites and PACAP/vasoactive intestinal polypeptide receptor expression in human pituitary adenomas.

Pituitary adenylate-cyclase-activating polypeptide (PACAP) stimulates release of several anterior pituitary hormones by interacting with PACAP receptors on pituitary cells. To learn more about the distribution and possible regulatory roles of PACAP and its receptors in human pituitary adenomas, we investigated the expression of vasoactive intestinal polypeptide (VIP) and PACAP binding sites using receptor autoradiography, PACAP and PACAP/VIP receptor (PVR) mRNAs by reverse transcription polymerase chain reaction (RT-PCR), conventional in situ hybridization, and catalyzed reporter deposition in situ hybridization (CARD-ISH) analyses. PACAP mRNA was expressed in normal human hypothalamus, which was used as a positive control, but not in pituitary adenomas. Receptor autoradiography showed PACAP types I and II binding sites in all groups of pituitary adenomas, except prolactinomas. The highest levels were present in gonadotroph and null cell adenomas. PVR-2 mRNA was expressed in normal pituitaries and in all groups of pituitary adenomas by RT-PCR, whereas PVR-1 and -3 mRNAs were expressed in all groups of pituitary adenomas, except for most prolactinomas. Conventional in situ hybridization studies with digoxigenin-labeled probes demonstrated weak staining for PVR-1, -2, and -3 mRNAs in most tissues. The CARD-ISH technique, which increased the sensitivity of the in situ hybridization method, also revealed PVR-2 mRNA expression in all adenomas, whereas PVR-1 and -3 mRNAs were detected in nearly all adenomas except for prolactinomas. The presence of PACAP mRNA in the hypothalamus, but not in normal anterior pituitary or in pituitary adenomas, and the differential expression of PVRs in adenomas indicate a selective regulatory endocrine and paracrine role of PACAP in normal and neoplastic anterior pituitary cells.

Adenoma↗
PubMed1998

Phase II trial of recombinant interferon-alpha-2a and eflornithine in patients with recurrent glioma.

Interferons alpha and beta have been reported to cause tumor regression in a small proportion of patients with recurrent glioma. Eflornithine, an irreversible inhibitor of ornithine decarboxylase, reduces cellular polyamine levels and has also been reported to cause tumor regression in patients with recurrent anaplastic astrocytoma and glioblastoma multiforme. In vitro evidence suggests that interferon and eflornithine are synergistic. In this phase II trial, we investigated the combination of recombinant alpha interferon (36 x 10(6) units/m2 subcutaneously days 3 to 7) and eflornithine (2.25 g/m2 QID PO days 1 to 7) repeated every 28 days. All 29 patients entered in the study were evaluable for toxicity and efficacy. Toxicity consisted primarily of fever, chills, myalgia, weakness and fatigue as well as cortical dysfunction including somnolence, confusion, and exacerbation of underlying neurologic deficits. One patient died from cerebral herniation attributable to interferon. None of the patients experienced objective tumor regression. Seven patients (24%) were stable for more than six months, but the disease stability could also be explained by indolent underlying disease or inability to distinguish recurrent tumor from delayed radiation effects. Intermittent high-dose recombinant interferon alpha plus eflornithine demonstrated no definite antitumor effects in this trial.

Adult↗
PubMed1998

Central nervous system atypical teratoid tumor/rhabdoid tumor: response to intensive therapy and review of the literature.

Central nervous system atypical teratoid/rhabdoid tumor (ATT/RT) of infancy and childhood is a unique histologic entity with an extremely aggressive natural history. Standard therapy for infant and childhood medulloblastoma, for which this entity is often mistaken, has been ineffective; most children survive less than 12 months after diagnosis. Intensified therapy has been recently used for children with this disease, with promising results [1,2]. We report four cases of ATT/RT in young children; all had subtotal resections and localized disease at diagnosis. One child treated prior to bone marrow transplant availability died of progressive disease 9 months after diagnosis. Another child, treated with high-dose chemotherapy and radiotherapy in preparation for bone marrow transplant, had a recurrence and died 20 months after diagnosis, without undergoing the transplant. Two children received high-dose chemotherapy and autologous bone-marrow transplant and had a good response to treatment; one survived 19 months, the other child is free of disease 46 months from diagnosis. Intensified therapy has altered the natural history of central nervous system ATT/RT.

Brain Neoplasms↗
PubMed1998

The results of radiotherapy for brainstem tumors.

OBJECTIVE: This analysis was performed to examine the outcome of adult and pediatric patients with brainstem tumors. METHODS AND MATERIALS: Forty patients with brainstem glioma were evaluated retrospectively. Included were 24 females and 16 males ranging in age from 3 to 81 years (median, 29.5 years). These patients were treated with various combinations of surgery, chemotherapy, and radiotherapy (RT). The length of follow-up in survivors ranged from 0.6 to 20 years (median: 3.2 years, mean: 6 years). Survival rates were calculated with the Kaplan Meier method and differences between survival curves were calculated using the log-rank test. RESULTS: The overall 2 and 5-year survival rates were 44% and 34%, respectively. The median survival time was 19 months. The 5-year survival rate was 54% for patients with tumors outside the pons compared to 21% for those with tumors involving the pons (p = 0.04). The 5-year survival rate was 59% for patients with exophytic tumors as compared to 23% for those with intrinsic tumors (p = 0.05). Patients undergoing subtotal resection had a 5-year survival rate of 53% compared to 28% for those having only a biopsy or no surgical intervention (p = 0.04). None of the other potential prognostic or treatment related factors evaluated [patient age, tumor grade, tumor histology, radiotherapy parameters (including BID fractionation, 3-D treatment planning, or the use of doses > 55 Gy), or the administration of adjuvant chemotherapy] evaluated were associated with patient survival. CONCLUSIONS: Brainstem gliomas generally occur in younger individuals. The survival rates were better for patients with exophytic tumors, those involving sites other than the pons, and tumors amenable to subtotal resection. Improvements in the outcome of patients with brainstem gliomas will require new therapeutic approaches.

Adolescent↗
PubMed1998

Papillary glioneuronal tumor: a new variant of mixed neuronal-glial neoplasm.

We describe the clinicopathologic features of nine cases of a unique papillary glioneuronal tumor (PGNT) exhibiting astrocytic as well as extensive and varied neuronal differentiation. The four male and five female patients studied ranged in age from 11 to 52 years (mean 27.7 years). They either presented with mild neurologic symptoms or were asymptomatic. Magnetic resonance imaging showed demarcated cystic, 1.5-cm to 7-cm contrast-enhancing masses; five involved the temporal lobe, two the parietal, and two the frontal. All but one were totally resected. No recurrence was noted despite a follow-up period of 3 years. Two microscopic components were evident: 1) compact pseudopapillae composed of hyalinized vessels covered by a single layer of glial fibrillary acid protein (GFAP)-positive astrocytes and 2) synaptophysin-positive neuronal cells of varying size, including neurocytes, ganglioid cells, and ganglion cells within neuropil. Immunostains for chromogranin-A were negative, as was in situ hybridization for chromogranin-A mRNA. Ultrastructurally, neuronal cells featured microtubule-containing processes and aberrant synaptic terminals, but dense core granules were rare. Overall, cellularity was moderate and atypia was minimal. No mitotic activity or necrosis was noted. The proportions of the two components varied, but essential morphologic findings were identical in all cases. In that the clinical, radiographic, and morphologic characteristics of PGNT are distinctive, it appears to represent a previously undescribed form of mixed neuronal-glial tumor of the central nervous system.

Adolescent↗
PubMed1998

Perineurial malignant peripheral nerve sheath tumor (MPNST): a clinicopathologic, immunohistochemical, and ultrastructural study of seven cases.

Most malignant peripheral nerve sheath tumors (MPNST) are schwannian in nature. The pathologic features of MPNST with perineurial cell differentiation remain to be characterized. To determine the clinicopathologic, immunohistochemical, and ultrastructural characteristics of perineurial MPNST, 121 MPNST from the Mayo Clinic Tissue Registry were examined. Of these 23 spindle cell tumors with long processes disposed in whorls or storiform patterns, features typical of perineurioma, were studied. On the basis of immunohistochemistry (epithelial membrane antigen+/S-100-), 5 perineurial MPNST were identified among 23 tumors selected. These and two previously characterized perineurial MPNST are the subject of this study. None of seven tumors was associated with NF-1. Patients included five males and two females ranging in age from 11 to 83 years (mean, 45.7 years). The tumors measured 1.5 to 30 cm (mean, 9.1 cm) and arose in the extremities (two), trunk (two), face (one), mediastinum (one), and retroperitoneum (one). Only one tumor was nerve associated (phrenic nerve). All tumors were surgically removed. No encapsulation or neurofibroma components were noted. Necrosis was seen in three lesions. Four tumors were classified as high-grade malignant and three as low grade. Mitotic indices varied from 1 to 85/10 high-power fields (median, 16). Immunoreactivities included epithelial membrane antigen (100%), vimentin (100%), Leu-7 (57%), and CD34 (14%). Stains for S-100 protein, muscle markers, and cytokeratin were nonreactive. Ultrastructurally, perineurial-like cells were noted in three tumors and cells intermediate between perineurial and Schwann cells in one. Four tumors recurred and two metastasized; no deaths of disease were noted at follow-ups of 28 to 98 months (mean, 66.9). In conclusion, 4% of MPNST show perineurial cell differentiation. An NF-1 association has yet to be described. Nerve involvement is infrequent. Their immunophenotype (epithelial membrane antigen+/S-100-) frequently indicates ultrastructural perineurial differentiation. The prognosis of perineural MPNST appears to be more favorable than that of conventional MPNST.

Adult↗
PubMed1998

"Rhabdoid" meningioma: an aggressive variant.

It is has been suggested that rhabdoid morphology is associated with a poor prognosis, regardless of tumor histogenesis. We report a series of 15 meningiomas with rhabdoid features. Nine patients had undergone multiple resections. In six, the rhabdoid component was histologically apparent only in recurrences. Rhabdoid morphology was defined as sheets of loosely cohesive cells with eccentric nuclei and hyaline, paranuclear inclusions. Ultrastructurally, the latter consisted of whorls of intermediate filaments often entrapping lysosomes or other organelles. Meningothelial features included whorl formation and nuclear pseudoinclusions, immunohistochemical coexpression of vimentin and epithelial membrane antigen, and the ultrastructural finding of interdigitating cell membranes and intercellular junctions. At the histologic level, a conventional meningioma component was noted in most tumors; only four lesions were entirely rhabdoid. Histologic malignancy (brain invasion or anaplasia) was observed in nine cases, another two tumors being considered malignant on the basis of extracranial metastasis. In the majority, increased cell proliferation was evidenced by a high mitotic rate or MIB-1 LI. At last follow-up, 13 patients (87%) had experienced at least one recurrence and 8 (53%) were dead of disease. Median time to death was 5.8 years after initial surgery and 3.1 years after the first appearance of rhabdoid morphology. Our findings corroborate those from a smaller series recently reported by Kepes et al. on the same entity (Kepes JJ, Moral LA, Wilkinson SB, Abdullah A, Llena JF. Rhabdoid transformation of tumor cells in meningiomas: A histologic indication of increased proliferative activity. Report of four cases. Am J Surg Pathol 1998;22:231-8). They further suggest that rhabdoid meningiomas are highly aggressive tumors and that the rhabdoid phenotype represents a marker of malignant transformation in meningiomas.

Adolescent↗