Malignant peripheral nerve sheath tumors. A clinicopathologic study of 28 cases

BACKGROUND: In order to improve management, the files and tissue sections of 28 cases of malignant peripheral nerve sheath tumors (MPNST) diagnosed at the University of Virginia Health Sciences Center between 1960 and 1990 were reviewed. METHODS: Clinical data tabulated included age, sex, race, the presence or absence of von Recklinghausen neurofibromatosis type 1 (NF-1), tumor size, tumor location, type of treatment, and status of surgical margins. Pathologic study included assessment of mitotic rate, divergent differentiation, cellular atypia, necrosis, and vascular reaction. RESULTS: The median disease-free survival time was 11 months, and the median overall survival time was 44 months. Overall survival and disease-free survival were significantly influenced by patient age, tumor location, tumor size, extent of surgery, and quality of margins. Patients with a family history of neurofibromatosis also had better disease-free survival. None of the other clinical variables correlated with survival. CONCLUSIONS: The authors recommended that patients with NF-1 be followed closely for MPNST development. For most cases, treatment should include aggressive surgery with wide surgical margins combined with adjuvant radiation therapy. Chemotherapy may have a role for treatment failures.     

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.     

Hepatocyte growth factor and c-MET in benign and malignant peripheral nerve sheath tumors

Hepatocyte growth factor (HGF), secreted by mesenchymal cells, has pleiotropic biological activities on several cell types. HGF and its receptor, the c-met proto-oncogene product (c-MET) have been implicated in the genesis and progression of several carcinomas and sarcomas. It has been suggested that MET/HGF autocrine signaling may contribute to tumorigenesis in sarcomas. HGF has been recently found to be a mitogen for rat Schwann cells and to be present in neurofibromas in NF1 patients. In this investigation, we assessed the immunoreactive patterns of HGF and MET in benign and malignant peripheral nerve sheath tumors (PNST) using archival formalin-fixed tissue. The standard avidin-biotin-peroxidase method was used. All benign tumors were negative with HGF. Eight cases of MPNST were positive with both HGF and MET. In some malignant PNST, positivity with both ligand and the receptor may be indicative of an autocrine mediated signal transduction and may implicate HGF/MET in tumor progression. Immunoreactivity with MET was strikingly greater in MPNST in contrast to benign PNST; this finding may prove to be helpful in distinguishing some histologically low-grade MPNST from cellular and atypical benign PNST.     

Poorly differentiated synovial sarcoma: immunohistochemical distinction from primitive neuroectodermal tumors and high-grade malignant peripheral nerve sheath tumors

Synovial sarcoma is a relatively common sarcoma in adults, which in its classic bimorphic form infrequently poses a diagnostic problem. Monomorphic spindled variants, as well as the less common poorly differentiated variants, may be confused with other soft-tissue sarcomas; the poorly differentiated variant (PDSS), in particular, may be histologically indistinguishable from other small, blue, round cell tumors, including primitive neuroectodermal tumors (PNETs). Detection of the synovial sarcoma-associated t(X;18) by either cytogenetic or molecular genetic approaches may be necessary to confirm the diagnosis of synovial sarcoma in difficult cases. We evaluated 10 cases of PDSS from eight patients using a panel of antibodies (including those to intermediate filament proteins, nerve-sheath associated markers, and neuronal and neuroectodermal associated markers) in order to better establish the immunophenotype of this tumor and to help distinguish it from the tumors with which it may be confused, particularly PNETs and high-grade malignant peripheral nerve sheath tumors (MPNSTs). Our results showed PDSS to have significant immunophenotypic overlap with both PNETs and MPNSTs. In most instances these three entities may be differentiated by a panel of antibodies that should include those to both low and high molecular weight cytokeratins, epithelial membrane antigen, type IV collagen, CD99, CD56, and S-100 protein. Our results also suggest that synovial sarcoma may be a tumor showing combined neuroectodermal and nerve sheath differentiation--perhaps because of translocation-associated expression of specific proteins--rather than a carcinosarcoma of soft tissues or a tumor of specialized arthrogenous mesenchyme.     

Lipoblastoma/lipoblastomatosis: a clinicopathologic study of 25 tumors

Lipoblastoma/lipoblastomatosis is an uncommon benign adipose tissue tumor of children. Since 1958, 25 of these tumors from 24 patients have been reviewed in the Department of Pathology at The Children's Hospital of Philadelphia. Tumors were resected from 19 boys (79%) and five girls, and 20 patients (84%) were < or =5 years of age at diagnosis. Twenty-three tumors presented as painless superficial soft-tissue masses; one tumor was retroperitoneal and was discovered because of vomiting; one hand tumor was present at birth. Tumors occurred in an extremity (n = 11 patients), the head and neck (n = 5), groin (n = 2), axilla (n = 2), back (n = 1), chest (n = 1), flank (n = 1), labia (n = 1), and retroperitoneum (n = 1). Thirteen tumors occurred on the left side, and five occurred on the right. Lesions measured 1.0-21.0 cm in greatest dimension; 15 of 25 (60%) measured < or =5.0 cm. The largest (retroperitoneal) tumor weighed 450 g. Eleven tumors were discrete lipoblastoma, and 14 had irregular margins (lipoblastomatosis). Microscopically, the tumors displayed adipocytes in different stages of maturation; lobules bordered by septae that were cellular in 11 cases; prominent blood vessels in 19 cases; and myxoid foci in 13 cases. Chart review of 22 patients showed that one tumor recurred 4 years after resection; one tumor recurred after 7 years as fibrolipoma; and one incompletely resected tumor enlarged and at second resection was lipoma. There were no metastases. Three patients also had hemangioma. Juvenile aponeurotic fibroma occurred in one patient near the site of resection of a lipoblastoma 4 years earlier. We conclude that lipoblastoma/lipoblastomatosis behaves benignly, occurs in both superficial and deep sites, occasionally attains large size, may mature, can recur, and may be associated with other benign soft-tissue lesions. Complete surgical excision is the treatment of choice.     

Intraosseous malignant peripheral nerve sheath tumor in a patient with neurofibromatosis

Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas that almost always arise in soft tissue. They can develop in pre-existing neurofibromas or schwannomas, de novo from peripheral nerves, or following radiation therapy. Primary intraosseous MPNST is rare and has been reported most frequently in the mandible. Of the reported cases involving the long bones, none has been associated with neurofibromatosis type 1 (NF-1). We report a case of MPNST arising in the femur in a patient with NF-1.     

p53 expression in neurofibroma and malignant peripheral nerve sheath tumor. An immunohistochemical study of sporadic and NF1-associated tumors

OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.     

Adenocarcinoma combined with malignant peripheral nerve sheath tumor of the gallbladder

Adenocarcinoma of the gallbladder combined with a malignant peripheral nerve sheath tumor (MPNST) in the gallbladder in an 81-year-old woman is reported. The resected gallbladder showed two distinct tumor components, the epithelioid type of MPNST and adenocarcinoma with areas of mucin production. Although the immediate postoperative course was uneventful, a pathologic fracture of her right upper femur developed 4 months after the cholecystectomy. The pathology was determined to be a feature of metastatic MPNST rather than of adenocarcinoma. A whole body bone scan revealed multiple metastases, including the left parietal skull, left ninth rib, seventh thoracic vertebra, and right upper third of the femur. Despite cholecystectomy and postoperative irradiation therapy, she died 6 months after diagnosis of the tumor. Without an autopsy the primary site of the MPNST was unknown. We found that the prognosis was very poor in patients with distal metastatic MPNST, especially in older patients.     

Malignant peripheral nerve sheath tumors: the St. Jude Children's Research Hospital experience

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon in young patients. To contribute to the understanding of these tumors, we reviewed the records of all patients treated for PNSTs at one institution over a 30-year period. METHODS: We reviewed the records of eight patients treated for benign PNSTs and 28 patients treated for 29 MPNSTs. We focused on the latter group, statistically testing several clinical factors for their significance in affecting survival. RESULTS: Five-year survival in patients with MPNSTs was 39%. The most significant prognostic factor was gross tumor resectability (p = 0.0004). Five-year survival for patients with resectable tumors was 65%, whereas no patient with unresectable disease survived > 25 months. Tumor grade, site, and patient race were also significant factors by univariate analysis but were not significant when adjusted for resectability. CONCLUSION: Gross tumor resection is crucial in treating malignant PNSTs. Supplemental radiation therapy is recommended for positive microscopic margins. More effective treatment is still being sought for unresectable disease.     

Extraskeletal osteosarcomas: a clinicopathologic study of 25 cases

OBJECTIVE: To describe a clock drawing task (CLOX) designed to elicit executive impairment and discriminate it from non-executive constructional failure. SUBJECTS: 90 elderly subjects were studied (45 elderly and well persons from the independent living apartments of a continuing care retirement community and 45 patients with probable Alzheimer's disease). The clock drawing performance of elderly patients was compared with that of 62 young adult controls. METHODS: Subjects received the CLOX, an executive test (EXIT25), and the mini mental state examination (MMSE). The CLOX is divided into an unprompted task that is sensitive to executive control (CLOX1) and a copied version that is not (CLOX2). Between rater reliability (27 subjects) was high for both subtests. RESULTS: In elderly subjects, CLOX subscores correlated strongly with cognitive severity (CLOX1: r=-0.83 v the EXIT25; CLOX2: r=0.85 v the MMSE). EXIT25 and MMSE scores predicted CLOX1 scores independently of age or education (F(4,82)=50.7, p<0.001; R2=0.71). The EXIT25 accounted for 68% of CLOX1 variance. Only the MMSE significantly contributed to CLOX2 scores (F(4,72)= 57.2, p<0.001; R2=0.74). CLOX subscales discriminated between patients with Alzheimer's disease and elderly controls (83.1% of cases correctly classified; Wilkes' lambda=0.48, p<0.001), and between Alzheimer's disease subgroups with and without constructional impairment (91.9% of cases correctly classified; Wilkes' lambda=0.31, p<0.001). CONCLUSIONS: The CLOX is an internally consistent measure that is easy to administer and displays good inter-rater reliability. It is strongly associated with cognitive test scores. The pattern of CLOX failures may discriminate clinical dementia subgroups.     

Epithelioid smooth-muscle tumors of the uterus: a clinicopathologic study of 18 patients

Epithelioid smooth-muscle tumors of the uterus are uncommon neoplasms for which prognostic factors have not been well established. A retrospective follow-up study of 18 uterine epithelioid smooth-muscle tumors was performed. Patients ranged in age from 27 to 83 years (mean, 45 years) and were separated into three groups based on the nuclear grade of the epithelioid tumor cells. Two tumors had grade 1 nuclei; both were examples of intravenous leiomyomatosis. They had highest mitosis counts of 1 and 3 mitotic figures (MF)/10 high-power fields (HPF), no tumor cell necrosis was found, and both patients were alive with no evidence of disease at 64 and 5 months' follow-up. Ten tumors had grade 2 nuclei. All had highest mitosis counts of 0 to 3 MF/10 HPF, except one (5 MF/10 HPF). Tumor cell necrosis was absent in nine and only one had an infiltrative border. Tumor size ranged from 1.5 to 14 cm. Two tumors contained pleomorphic ("symplastic") multinucleated giant cells similar to those seen in bizarre leiomyomas. All nine patients with follow-up were alive with no evidence of disease 5 to 203 months postoperatively (median, 74 months). One patient had also received adjuvant radiation therapy. Six tumors had grade 3 nuclei. Highest mitosis counts of 4 to 9 MF/10 HPF were found in five; one had 1 MF/10 HPF. Maximum tumor size ranged from 4.5 to 13 cm. Two had tumor cell necrosis, and two had an infiltrative border. Two of these patients died of tumor 11 and 132 months postoperatively. The former had widespread metastases at initial surgery (stage IVb); the latter patient (stage I) developed the first of seven tumor recurrences 3 years postoperatively. Both patients had also received adjuvant chemotherapy. Of the remaining four patients, two were alive with no evidence of disease at 48 and 83 months, one was alive (tumor status unknown) at 28 months, and one was lost to follow-up. Based on our findings and those in the literature, we conclude that uterine smooth-muscle tumors with a predominance of epithelioid cells are extremely uncommon and metastasize infrequently. No single histologic feature is predictive of metastatic potential. Clinically malignant tumors (i.e., epithelioid leiomyosarcomas) typically have the combination of significant nuclear atypia (either grade 2 or grade 3 nuclei) and some mitotic activity (usually at least 3 to 4 MF/10 HPF); most also have tumor cell necrosis.     

Partial moles: a clinicopathologic study of 25 cases

This study is based on a review of all moles diagnosed at the Kaplan Hospital in Israel from 1968 to 1977. Histologic reevaluation revealed that of a total of 72 moles, 47 (65%) were complete and 25 (35%) partial. In contrast to complete moles, about one third of the partial moles showed fetal parts. An analysis of the patient records showed smaller uteri, less vaginal bleeding, absence of severe vomiting, lower gonadotropin levels, and normal follow-up in patients with partial moles as compared with those who had complete moles. These results indicate that the partial mole is a distinct clinicopathologic entity that can be suspected by the clinician and confirmed by the pathologist on morphologic grounds, even in the absence of cytogenetic analysis.     

Malignant peripheral nerve sheath tumor: analysis of treatment outcome

Although previous studies have examined the functional role of the neurons in the area ventrolateral to the hypoglossal nucleus (perihypoglossal neurons) in the trigemino-hypoglossal reflex, no convincing evidence for the direct connection from the perihypoglossal neurons to the hypoglossal motoneurons has yet been provided. In addition, the role of the perihypoglossal neurons in swallowing has not been studied. The purpose of this study was to investigate (1) the input-output relationship of the perihypoglossal neurons and (2) whether the afferent feedback was essential for their swallowing-related activity in chloralose-anesthetized cats. Before and after the cats were paralyzed, single-unit activities were recorded extracellularly from 30 perihypoglossal neurons during swallowing elicited by electrical stimulation of the superior laryngeal nerve. These perihypoglossal neurons responded with spike potentials after short latencies to stimulation of the inferior alveolar and hypoglossal nerves. The neurons also responded with spike potentials to single shocks applied to the superior laryngeal nerve, but were activated transiently at the initial phase of repetitive stimulation of the nerve and kept silent until the occurrence of swallowing before and after the animal was paralyzed. They showed burst activities in coincidence with swallowing. Averaging of intracellular potentials of a hypoglossal motoneuron by simultaneously recorded extracellular spikes of a perihypoglossal neuron revealed monosynaptic inhibitory post-synaptic potentials. We conclude that, in the region ventrolateral to the hypoglossal nucleus, there are neurons which relay trigeminal, hypoglossal, and vagal afferents. Furthermore, some of these perihypoglossal neurons are inhibitory hypoglossal premotor neurons that are involved in the central programming of swallowing.     

K-ras mutations in nonmucinous ovarian epithelial tumors: a molecular analysis and clinicopathologic study of 144 patients

BACKGROUND: Coronary stent deployment failure may be more common in clinical practice than generally appreciated. The incidence of failed deployment in routine clinical practice and the clinical sequelae have not been described. This study sought to determine the incidence and consequences of failed coronary stent deployment and to identify clinical and angiographic characteristics associated with deployment failure. METHODS AND RESULTS: A series of 1303 consecutive procedures involving attempted coronary stenting were reviewed retrospectively. Failed stent deployment was defined as failure of the stent to be either delivered to or adequately deployed at the target lesion site. Clinical records and angiograms were reviewed and qualitative coronary angiography was performed for all cases of failed deployment. Deployment was unsuccessful in 108 (8.3%) cases involving 134 stents. Stenting was attempted as a primary procedure in 40%, as bailout in 18%, and for suboptimal angioplasty in 43% of cases. In 87% of cases, attempts were made to withdraw the stent from the coronary artery. Stent retrieval was successful in 45%, peripheral embolization occurred in 38% of patients, and in 4% the stent dislodged in the left main artery. In 35% of cases, additional stent(s) were successfully deployed. Deployment failure was associated with an overall in-hospital adverse outcome in 19% of patients, including 16% urgent coronary artery bypass grafting, 5% nonfatal myocardial infarction, and 3 in-hospital deaths. At 6-month follow-up, 39% of patients had had at least 1 adverse clinical outcome of death, myocardial infarction, or repeat target lesion revascularization. CONCLUSIONS: Failure to deploy stents is a serious and relatively common problem that is associated with significant morbidity and mortality rates. Improved deployment strategies, including new stent designs, are required to improve procedural outcomes.     

Morphologic prognostic factors of malignant mixed müllerian tumors of the ovary: a clinicopathologic study of 15 cases

Interleukin-2 (IL-2)-based therapy induces a vascular leak syndrome (VLS), manifested by hypotension, tachycardia, and oliguria, as is also seen with septic shock. The optimal method for treating such VLS is not known. A prospective randomized trial was undertaken to compare crystalloid and colloid fluid resuscitation for patients receiving bolus IL-2-based therapy for metastatic cancer. All patients received maintenance crystalloid fluid administration and were randomized to receive crystalloid (0.9% normal saline) or colloid (5% human serum albumin) fluid boluses to maintain acceptable vital signs and urine output. Patients refractory to fluid boluses were given dopamine for oliguria and/or phenylephrine for hypotension. Of 107 patients who completed one cycle of therapy on study, 76 completed a full treatment course (two cycles) on study. The total number of saline and albumin fluid boluses given were 9.5 +/- 0.9 versus 7.7 +/- 0.7 (p = 0.36, n = 107) for the first cycle and 19.2 +/- 1.8 versus 16.1 +/- 1.6 (p = 0.33, n = 76) for a complete course, respectively. Although patients receiving saline boluses had significantly more oliguria during a course of therapy, weight gain, number of IL-2 doses, tachycardia, hypotension, vasopressor use, hospital stay, and clinical response rates did not significantly differ between arms. Changes in hematocrit, hemoglobin, protein, albumin, blood urea nitrogen (BUN), and creatinine were analyzed, and patients receiving crystalloid showed greater decreases in albumin (p < 0.0001) and total protein (p < 0.05) as expected. A 40-fold greater cost associated with albumin suggested that crystalloid resuscitation be used to treat the VLS associated with IL-2 therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Salivary gland malignant myoepithelioma: a clinicopathologic and immunohistochemical study of ten cases

BACKGROUND: Malignant myoepithelioma (MME) of the salivary gland, also known as myoepithelial carcinoma, is rare and its biologic behavior has not been clarified fully. METHODS: Ten cases of MME were analyzed for their clinicopathologic features and immunohistochemical characteristics, focusing on prognostic factors and tumor differentiation. In addition, six cases of benign myoepithelioma (BME) also were examined for comparison. RESULTS: The ten patients with MME (3 men and 7 women) ranged in age from 48-81 years (mean, 61.9 years). Seven cases of MME arose in the parotid salivary gland, two in the submandibular salivary gland, and one in minor salivary glands of the soft palate. In the current series, the incidence of MME was 0.45% among 1945 cases of major salivary gland tumors. Seven cases of MME developed from a benign preexisting tumor (six in pleomorphic adenoma and one in BME). Four of nine patients with MME died of the disease and two patients developed a recurrence. It was shown that MMEs were comprised of one cell type or a combination of two cell populations; these included, in order of incidence, epithelioid, spindle, and plasmacytoid cells. Patients with MME with marked cellular pleomorphism and perineural invasion had a poor prognosis. Immunohistochemically, putative myoepithelial markers such as muscle actins, cytokeratin 14, vimentin, and calponin, and S-100 protein were expressed highly in MME. High and low molecular weight cytokeratins and epithelial membrane antigen also frequently were positive in MME. p53 expression was observed in five MME cases, four of which either recurred or were fatal. Cellular proliferative activity assessed by mitotic count and the Ki-67 labeling index was significantly higher in MME cases than in BME cases. In limited cases, such cellular proliferative activity was shown to have prognostic value. Ultrastructurally, the tumor cells displayed certain myoepithelial characteristics. CONCLUSIONS: MME is a rare salivary gland tumor showing clinicopathologic diversity and presenting with various stages of myoepithelial differentiation. Histologic aggressiveness, marked cellular pleomorphism, p53 expression, and high cell proliferative activity were found to be correlated with a poor clinical outcome.     

Liposarcomas of the oral tissues: a clinicopathologic study of four tumors

Liposarcomas of the oral tissues are rare. There have been 28 previously reported in the literature. A clinicopathologic study of 4 patients with liposarcoma involving the oral tissues is presented--one in the tongue, one in the palate, and two in the submandibular space. Two of the tumors were myxoid, one was of well-differentiated type and one was of pleomorphic type. Three of the lesions were diagnosed clinically as benign. The most important lesson to be learned from the histopathology is the positive identification of atypical lipoblasts. Follow-up data indicate that prognosis generally corresponds to the tumor type. The patients with myxoid and well-differentiated liposarcoma remain alive and with no evidence of disease. The patient who died of tumor had a pleomorphic liposarcoma. Treatment of these lesions should consist of wide surgical excision and consideration of adjunctive or palliative radiotherapy.     

A resected case of malignant peripheral nerve sheath tumor (MPNST) necessary to distinguish from Askin tumor

The aim of this study was to compare the morpho-functional modifications of the right cardiac sections of the athlete's heart, with those of sedentary healthy control subjects. We studied 24 endurance athletes (mean age 28.17 +/- 7.28 years), 21 power athletes (mean age 25.86 +/- 4.96 years), and 20 sedentary healthy control subjects (mean age 33.22 +/- 6.67 years). We examined the right cavities by standard echocardiographic projections and the following parameters were evaluated: right ventricular longitudinal diameter; under tricuspid valve and medium ventricular transversal diameter immediately under the tricuspid plane and at medium ventricular level; right atrial transversal and longitudinal diameters. All parameters were corrected for body surface area. Our data showed that the right ventricle presents morphological adaptations to endurance exercise; modification is represented mainly by an increase in the mean transversal ventricular diameter with a consequent reduction in the transversal/longitudinal diameter ratio accompanied by modification of the ventricular geometry. In addition the data showed an increase in longitudinal and transversal diameters of the right atrium. On the contrary, the power athletes did not show statistical modification of the right ventricle and atrium. The different modifications of the right heart side diameter are probably due to the different hemodynamic loading, which is involved in the endurance and power training respectively.     

Malignant peripheral nerve sheath tumor of bone in children and adolescents

In situ vascular endothelium is characterized by many cytoplasmic vesicles (caveolae) and vacuoles. In venules these are organized into prominent clusters called vesiculo-vacuolar organelles or VVOs. VVOs provide an important pathway for plasma protein extravasation in response to vasoactive mediators. In contrast, cultured endothelial cells isolated from many sources lack VVOs and generally have few caveolae. Our goal was to preserve VVOs in cultured endothelium. Bovine adrenal microvascular endothelial cells (BCEs) cultured on floating Matrigel-collagen Type I gels with vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) exhibited typical VVOs by electron microscopy. Both in vivo and in culture VVOs were caveolin-positive by immunoelectron microscopy. On the basis of caveolin immunostaining, VVOs could also be detected by light (confocal) microscopy. When BCEs were cultured without VPF/VEGF, caveolin staining was finely punctate and electron microscopy confirmed the near absence of VVOs. BCE VVOs were sensitive to N-ethylmaleimide. Other types of endothelium cultured on Matrigel-collagen gels with or without VPF/VEGF exhibited few caveolae and no VVOs. Therefore, preservation of VVOs in cultured endothelium required a specific combination of endothelial cells (BCEs), surface matrix (Matrigel-collagen), and growth factor (VPF/VEGF). These endothelial cells should be useful for in vitro studies of trans-endothelial transport.     

Stromal tumors of the jejunum and ileum: a clinicopathologic study of 39 cases

Recently, cell size, cell density, and growth pattern were found to be reliable histologic parameters in separating benign from malignant duodenal stromal tumors. However, there are few data on the histologic features and important prognostic parameters of stromal tumors from other parts of the small bowel. Thus, we studied the clinical and pathologic features of 39 stromal tumors of the jejunum and ileum to determine which parameters would be most useful in distinguishing a benign from a malignant tumor. In all cases, the following histologic parameters were recorded: (a) predominant growth pattern (organoid, fascicular, solid, or mixed), (b) cellularity (low or high), (c) predominant cell type (spindled, epithelioid, or mixed), (d) nuclear pleomorphism (minimal, moderate, or severe), (e) the presence or absence of tumor cell necrosis, (f) the presence or absence of mucosal infiltration, (g) the presence or absence of skeinoid fibers, and (h) the number of mitotic figures per 50 high-power microscopic fields (HPF). Clinical follow-up was obtained in all cases, and the patients were considered to have suffered an adverse outcome if they developed metastatic disease or died as a complication of their tumor. In the absence of these features, patients were not considered to have suffered an adverse outcome. Twenty-five patients suffered an adverse outcome. Twenty-one patients died of disease from 1 month to 9 years (median: 2 years). One patient died at 4 days because of postoperative complications. Three patients were alive with metastatic disease at 6 months, 6 years, and 7 years. Twenty-four of these 25 patients developed metastatic disease, most commonly to the liver. Fourteen patients did not suffer an adverse outcome. Eleven patients were alive without disease from 2 to 11 years (median: 3 years), and three patients died of unrelated causes at 1, 1, and 3 years. Although there was some overlap in features between clinically benign and malignant tumors, features that were significantly associated with an adverse outcome included tumor size > 5 cm, mitotic counts > 5 mitotic figures per 50 HPF, high cellularity, the absence of a predominant organoid growth pattern, the absence of skeinoid fibers, the presence of severe nuclear pleomorphism, and the presence of mucosal infiltration and tumor cell necrosis (p < 0.05 using the chi-square and Fisher's exact tests). Features that were significantly associated with decreased survival included tumor size > 5 cm, mitotic counts > 5 mitotic figures per 50 HPF, high cellularity, the absence of skeinoid fibers, and the presence of tumor cell necrosis (p < 0.05 using the Mantel-Haenszel log-rank test). Given the fact that there is some overlap in these features between clinically benign and malignant tumors, a multiparametric analysis using the above features is the most effective way of predicting clinical behavior.