Schwannoma: un caso atípico de dolor pleurítico / Schwannoma: a rare cause of pleuritic pain

Spinal schwannomas account for 30% of primitive spinal tumors. Symptoms are related to tumor location and its proximity to spinal cord and nerve roots. Radiographic and histopathologic examinations are vital diagnostic tools. Complete surgical resection is the mainstay of treatment and offers an excellent prognosis. (AU)

Are preoperative complete blood count parameters in peripheral nerve sheath tumors useful diagnostic tools?

OBJECTIVES: This study aims to evaluate the diagnostic value of complete blood count (CBC) parameters in patients with peripheral nerve sheath tumors (PNSTs). PATIENTS AND METHODS: A total of 181 patients (83 males, 98 females; median age: 44 years; range, 15 to 83 years) who underwent surgical treatment for PNSTs in our tertiary oncology center between January 2010 and December 2019 were retrospectively analyzed. Eighty-two patients were diagnosed with a neurofibroma, 79 with a schwannoma, and 20 with a malignant PNST (MPNST). The patient group was evaluated as malignant (n=20) and benign (n=161). Age- and sex-matched patients admitted to our outpatient clinic of orthopedic and traumatology with non-specific symptoms other than tumor, infection, fracture, and rheumatological or hematological diseases were included as the control group (n=165). Data including age, sex, definitive histopathological diagnosis, and pre-treatment CBC values were obtained from the hospital records. Pre-treatment CBC values such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated for both malignant and benign groups and control groups. Diagnostic values of NLR, PLR, and LMR between PNST groups were assessed using the receiver operating characteristic (ROC) curve analysis. RESULTS: Neurofibroma, schwannoma, and MNPST groups had significantly higher median NLR, compared to the control group (p<0.001), while the median LMR was significantly lower in these groups (p<0.05). However, the median PLR was higher only in the MPNST group, compared to the control group (p<0.001). Post-hoc analyses revealed that median NLR, PLR, and LMR ratios were similar in PNST groups, compared to the control group. In addition, the median NLR, PLR, and LMR ratios were similar between malignant and benign patient groups. The highest area under the curve (AUC) was found for NLR (AUC=0.756) and LMR (AUC=0.716) in the MPNST group. CONCLUSION: Our study results suggest that NLR, PLR, and LMR may have an added value in the early diagnosis of PNSTs and are valuable for differentiating patients from healthy individuals, although their value in differential diagnosis is still unclear.

Serum Levels of APRIL Increase in Patients with Glioma, Meningioma and Schwannoma

Objective: Brain tumors are of high mortality and morbidity for which there is still no cure. The TNF family cytokine, A Proliferation Inducing Ligand (APRIL), is shown to help proliferation and development of tumor cells. We assessed serum levels of APRIL in patients with glioma, meningioma and schwannoma in comparison to healthy individuals. Methods: Peripheral blood samples of 68 patients with brain tumors, divided into three groups of gliomas (n=25), meningiomas (n=30) and schwannomas (n=13), as well as 45 healthy individuals were obtained. Serum samples were prepared and stored in -40°C until usage. Using a commercial ELISA method, APRIL concentration was measured in each serum sample. The obtained data were then analyzed using SPSS software. Results: APRIL serum levels were higher in all patients compared to the controls (P<0.001). Moreover, APRIL serum levels were higher in each of the tumor bearing groups (gliomas, meningiomas and schwannomas) in comparison to the controls (P<0.001, <0.001 and =0.001, respectively). Comparing APRIL between the patients groups showed no significant difference. Age and gender showed no significant correlation with serum APRIL levels, although the age of patients in glioma group was significantly lower than controls (P=0.017). The serum APRIL levels in gliomas with histological grade showed no difference, but in meningiomas, it was lower in tumors with higher grades (P= 0.011). Conclusion: Increased serum levels of APRIL in patients with meningioma and schwannoma as well as glioma may indicate a common role of this cytokine in brain tumors.

Elevated serum IL-17A but not IL-6 in glioma versus meningioma and schwannoma.

BACKGROUND: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. MATERIALS AND METHODS: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. RESULTS: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera (0.29 ± 0.54, 0.03 ± 0.15 and 0.16 ± 0.68 vs. 0.00 ± 0.00 pg/ml; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls (2.34 ± 4.35 vs. 4.67 ± 4.32 pg/ml; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. CONCLUSIONS: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

Schwannoma of the stomach with elevated preoperative serum carbohydrate antigen 19-9: report of a case.

We herein report a case of a gastric schwannoma with elevated preoperative serum carbohydrate antigen 19-9 (CA19-9) (155.2 U/ml, normal range 0-36.9 U/ml). A 59-year-old Japanese man was admitted to our hospital for treatment of a submucosal tumor of the stomach detected by barium meal, upper gastrointestinal endoscopy, and computed tomography. Endoscopic examination revealed a 3-cm diameter submucosal tumor in the antrum of the stomach, but biopsy of the lesion was unable to confirm the diagnosis. Positron emission tomography to evaluate the malignant potential showed a high uptake of (18)F-fluorodeoxyglucose in the tumor. Laparoscopy-assisted distal gastrectomy was therefore performed. The histopathological findings of the surgical specimen revealed a benign gastric schwannoma, positive for S-100 protein. The postoperative serum CA19-9 levels gradually decreased and normalized. To the best of our knowledge, this is the first report of a gastric schwannoma with elevated serum CA19-9.

Noradrenalin-secreting retroperitoneal schwannoma resected by hand-assisted laparoscopic surgery: report of a case.

A 66-year-old woman was admitted to our hospital for investigation of a retroperitoneal mass. She was asymptomatic but her serum noradrenalin and vanillylmandellic acid levels were increased remarkably. Computed tomographic angiography showed a mass in the left side of the superior mesenteric artery (SMA) divergence, 6 x 4 cm in size, supplied mainly by the left adrenal artery. We performed hand-assisted laparoscopic surgery (HALS) using a Cavitron ultrasonic surgical aspirator. Abdominal exploration revealed that the tumor was located in the left side of the SMA root, but was not adhered to the adjacent organs. Her vital signs remained stable during the operation. Microscopic examination revealed a palisade formation, confirming a histopathological diagnosis of degenerated schwannoma (Antoni type B). Immunohistologically, the tumor cells were stained with S-100 protein and neuron-specific enolase. Her noradrenalin level normalized immediately after the operation and she remains in good health 3 years 2 months later.

Increased levels of plasma tissue factor pathway inhibitor in patients with glioblastoma and intracerebral metastases.

Tissue Factor Pathway Inhibitor (TFPI) prevents further participation of Tissue Factor (TF) in the coagulation process by forming a stable quaternary complex of TF-FVIIa-FXa-TFPI. Recently, plasma TFPI level were found to be elevated in patients with malignant disease outside the brain. Therefore the aim of this study was to investigate the TFPI plasma level in patients with primary brain tumors and intracerebral metastases. From May 2000 to December 2001 the total tissue factor pathway inhibitor antigen (TFPI) was preoperatively determined in blood samples of 225 patients with primary or metastatic brain tumors. Tumor histology classified as benign (WHO grade I and II) and malignant (WHO grade III and IV, intracerebral metastases) was correlated to plasma TFPI-levels. Plasma TFPI was significantly higher in patients with malignant tumors including intracerebral metastasis compared to benign tumors (80.1 +/- 34.31 versus 64.3 +/- 25.8 ng ml-1 [p < 0.01; t-test]). To exclude the influence of primary systemic neoplasms with secondary brain metastasis on plasma TFPI-level a subgroup of patients with primary brain tumors (meningioma, astrocytoma, oligodendroglioma and glioblastoma) was separated. In this group TFPI-level was also significantly elevated in patients with malignant (n = 66) (78.6 +/- 29.9) compared to benign brain tumors (n = 127) (64.3 +/- 25.8 ng ml-1 [p < 0.01; t-test]). To the authors' knowledge this is the first study describing the correlation of increased plasma TFPI and malignancy in patient with brain tumors. Further studies are needed to clarify the pathogenic mechanism and the clinical relevance of this phenomenon.

Role of autologous blood transfusion in sacral tumor resection: patient selection and recovery after surgery and blood donation.

We carried out sacral en-bloc resection in six patients (three with chordoma; one with pheochromocytoma; one with malignant schwannoma; and one with giant cell tumor) using preoperatively collected autologous blood, to avoid homologous blood transfusion. An average of 3200 ml was collected preoperatively, with patients receiving recombinant human erythropoietin (r-HuEPO), at a total dose of 130 000 units on average. In four patients, we were able to accomplish the surgery without homologous blood transfusion. Postoperatively, the hemoglobin level in these four patients recovered to the pre-collective level in 4.5 weeks, on average. These clinical results indicate that en-bloc sacrectomy, which requires a large volume of blood transfusion, can be accomplished with preoperatively collected autologous blood alone.

A group of schwannomas with interstitial deletions on 22q located outside the NF2 locus shows no detectable mutations in the NF2 gene.

Schwannomas are tumors arising mainly at cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type2 (NF2). The NF2 gene has been cloned and comprehensive analysis of its mutations in schwannomas shows that up to 60% of tumors carry inactivating mutations. Thus, the genetic mechanism behind the development of more than 40% of schwannomas without NF2 mutations is unknown. We have therefore studied tumor tissue from 50 human schwannomas by allelotyping and have found chromosome 22 deletions in over 80% of the cases. We detected 14 cases (27%) that revealed partial deletions of one copy of chromosome 22, i.e., terminal and/or interstitial deletions. We sequenced the NF2 gene in seven of these tumors and detected only one case with mutations. The deletion mapping of chromosome 22 in tumors with partial deletions indicates that several regions, in addition to the NF2 locus, harbor genes involved in schwannoma tumorigenesis. Our findings suggest that heterogeneity in the mechanisms leading to the development of schwannomas probably exists. These findings are in agreement with the recent analysis of schwannomas from familial and sporadic cases of schwannomatosis and point to a possible role of an additional gene, which, in cooperation with the NF2 tumor suppressor, causes schwannomas.

Increased serum levels of type IV collagen and laminin in a patient with a giant retroperitoneal schwannoma.

A 63 year old woman presented with a giant abdominal tumor. Ultrasonography, computerized tomography and drop-infused pyelography revealed a suspected retroperitoneal tumor. The tumor was removed surgically and weighted 2800 g. The pathological diagnosis of the tumor was schwannoma. Strong immunohistochemical staining specific for type IV collagen and laminin was observed in the tumor, and these components were localized in the pericellular region of Schwann cells. The serum levels of these antigens, as determined by radio-immunoassay, were very high before the operation but decreased rapidly thereafter.

The neurofibromatosis type 2 gene is inactivated in schwannomas.

Schwannomas are tumors arising from schwann cells surrounding peripheral nerves. Although most schwannomas are sporadic, they are seen in approximately 90% of individuals with neurofibromatosis type 2 (NF2), an autosomal dominantly inherited disease with an incidence of 1:40000 live births. The NF2 gene has recently been isolated on chromosome 22 and encodes a putative membrane organizing protein named schwannomin. It is believed to act as a tumor suppressor gene based on the high frequency of loss of heterozygosity (LOH) on this autosome in both sporadic and NF2 associated schwannomas and meningiomas and the identification of inactivating mutation in NF2 patients. In this study we examined 61 schwannomas including 48 sporadic schwannomas (46 of which are vestibular schwannomas) and 12 schwannomas obtained from NF2 patients, for mutations in 10 of the 16 coding exons of the NF2 gene. Twelve inactivating mutations were identified, 8 in sporadic tumours and 4 in tumors from people with NF2. These results support the hypothesis that loss of function of schwannomin is a frequent and fundamental event in the genesis of schwannomas.

Retroperitoneal neurilemoma presenting with humoral hypercalcemia associated with markedly elevated plasma prostaglandin levels.

A 72-year-old woman complaining of somnolence and thirst was diagnosed to have a hypercalcemic crisis (corrected serum calcium level, 17.4 mg/dl) associated with encephalopathy and nephropathy. Imaging diagnostic techniques demonstrated a retroperitoneal tumor at the median site of right renal pelvis. Hormonal studies revealed that plasma levels of thromboxane B2, prostaglandin (PG) E2, 6-keto prostaglandin F1 alpha (PGF1 alpha) and prostaglandin F2 alpha (PGF2 alpha) were markedly elevated. The tumor was successfully removed by operation; her serum calcium level and PG levels normalized without any treatment indicating that this case belongs to the category of humoral hypercalcemia of malignancy (HHM). Pathologically, this tumor was diagnosed to be a benign neurilemoma. Parathyroid hormone-related protein (PTHrP) radioimmunoassay and Northern blot hybridization for PTHrP mRNA were negative. The current case demonstrates that hypercalcemic crisis could be induced by a curable benign neurilemoma, and suggests that this HHM-like morbidity was associated with markedly elevated plasma PG levels.

Clonal analysis of human meningiomas and schwannomas.

Meningiomas and schwannomas are two of the most common tumors of the human nervous system. To determine whether these tumors arise from a single cell or from multiple cells, we used molecular genetic techniques to study X chromosome inactivation in meningiomas and schwannomas isolated from females including one who had neurofibromatosis type 2. The tumors were also screened for loss of heterozygosity at several loci on chromosome 22 using polymorphic DNA markers. Among nine meningiomas, at least three of which showed loss of alleles on chromosome 22 and five of which retained heterozygosity for the chromosome 22 alleles examined, all nine tumors were monoclonal. Among eight schwannomas, at least seven of which retained heterozygosity for chromosome 22 loci, seven were monoclonal. We conclude that human meningiomas and schwannomas arise from a single cell.

Heparin-associated thrombocytopenia in the neurosurgical patient.

Although thrombocytopenia occurs in approximately 10% of medical patients who receive heparin, this complication has not been described in neurosurgical patients. We report the clinical course of two patients who in the immediate postoperative period developed heparin-associated thrombocytopenia that resulted in significant morbidity. In these two cases, the origin of the heparin was in "flush" solutions used to maintain the patency of indwelling vascular catheters and was infused at a dose of 250 to 500 units/day. The minimal daily dose previously reported to result in thrombocytopenia is 9000 units/day administered in divided doses subcutaneously. The case reports indicate that heparin in "flush" solutions should be considered as a cause for unexpected thrombocytopenia and that platelet counts should be monitored in patients receiving heparin in any amount.

Serum cholesterol and primary brain tumours: a case-control study.

The objective of this study was to test the hypothesis that a positive relationship exists between high levels of serum cholesterol and primary brain tumours. A record-based case-control study was performed on male Jewish residents of Israel who were hospitalized at the Hadassah Ein Karem hospital in the years 1978-1982. A record check identified 37 cases of brain tumour who fulfilled the criteria for inclusion in the study and whose hospital files included the necessary data. For each case two controls were chosen randomly from all patients with inguinal hernia who met the respective matching criteria of age and year of hospitalization. The mean cholesterol value of the cases with brain tumours was 22 mg dl-1 higher than that of the controls. This difference was statistically significant (P = 0.007). Controlling for weight, region of birth, season of year, social class, medications and length of hospitalization before the measurement of cholesterol did not reduce the cholesterol difference, and in some instances increased it.

Serum sialic acid is a biologic marker for malignant disease.

Serial serum sialic acid (N-acetylneuraminic acid) was measured in 16 patients with advanced cancer of various histologic types. In the 15 evaluable patients serial changes in sialic acid correlated with the clinical course. Isolated sialic acid values were not predictive of clinical response. Serial determination of serum sialic acid appears to be a useful monitor of tumor burden.

Estrogen- and progesterone-receptor proteins in intracranial tumors.

Estrogen and progesterone receptors have been measured in 13 intracranial tumors (eight meningiomas, two acoustic neurinomas, one primary tumor of neuroectodermal origin, one giant-celled glioblastoma, and one metastasis of carcinoma). Evidence is provided of the presence of progesterone receptors in meningiomas (87.5%). We could not find clear evidence of estrogen receptors in any tumor of this series. Presence of progesterone receptors in meningiomas suggests an explanation for the greater incidence of these tumors in women and their rapid growth during pregnancy.

[Hypophosphoremic osteomalacia of connective tissue tumors]. / L'ostéomalacie hypophosphorémique des tumeurs du tissu conjonctif.

The authors undertake a general review of the association between hypophosphoraemia and connective tissue tumour, based upon three personal cases and 27 cases of benign connective tissue tumours, as well as cases of hypophosphoraemia related to malignant tumours or to diffuse dysplasia of connective tissue origin, collected from the literature. This syndrome is distinguished from hypophosphoraemia induced by other tumours (myeloma, carcinoma of the prostate) which are based upon different mechanisms. Hypophosphoraemia, associated with a fall in plasma levels of 1-25 (OH)2 D3 by inhibition of renal 1 alpha hydroxylase, suggests the existence of a complex tubular deficit. Removal of the tumour, most often vascular and intra- or para-osseous, results in rapid normalisation of laboratory then radiological and clinical abnormalities. The physiopathology of the syndrome remains very mysterious. It may be likened to certain tubulotoxic syndromes due to cadmium and in particular to maleic acid. However no precise data yet exists regarding any possible abnormal tumour secretion. In practice, any case of hypophosphoraemic osteomalacia requires investigation to locate a possible tumour of connective tissue, and this all the more so when it is accompanied by very low plasma levels of 1-25(OH)2 D2.