Giant Intrathoracic Schwannoma of the Left Vagus Nerve Manifesting as Atrial Fibrillation.

Posterior mediastinal tumors are not infrequent, and among them neurogenic masses and schwannomas are the most common histologic varieties. These benign, initially asymptomatic tumors later become symptomatic as a result of mass effect. Surgical excision is the preferred therapy, and the approach can be determined according to the dimensions of the lesion. This report describes the case of a giant schwannoma originating from the left vagus nerve in a middle-aged woman whose symptoms were exertion-induced dyspnea and atrial fibrillation.

Available Therapies for Patients with Neurofibromatosis-Related Nervous System Tumors.

OPINION STATEMENT: Though the majority of nervous system tumors are sporadic, several clinically relevant genetic syndromes are associated with a predisposition to tumors of the central and peripheral nervous system including neurofibromatosis type 1 (NF1), type 2 (NF2), and schwannomatosis (SWN). These represent prototypical tumor suppressor syndromes where loss of a tumor suppressor gene-protein impairs the cell's ability to regulate cell proliferation. While clinical manifestations vary widely for each of these syndromes, tumors arising in the peripheral nerve sheath are a unifying feature. Clinical clues should prompt the clinician to recognize the underlying genetic syndrome and screen for associated tumors including, among others, plexiform neurofibromas and gliomas in NF1 and vestibular schwannomas, meningiomas, and spinal ependymomas in NF2. Improvements in mechanistic understanding of how the genetic mutations that underlie these syndromes contribute to tumor formation have led to new advances in targeted therapies. MEK inhibitors have shown promise for treating progressive plexiform neurofibromas in NF1. Bevacizumab has been shown to improve hearing and treat vestibular schwannomas in NF2. This article reviews the currently available data on management of tumors associated with these three syndromes.

Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study.

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943-2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9-2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2-5.3) and leukemia (2.8; 95% CI 2.4-3.2). The AER decreased from 331 (278-383) excess neurologic disorders per 100,000 person-years 5-9 years after diagnosis to 82 (46-118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.

Facial Paralysis Secondary to Extensive Perineural Spread of Adenocarcinoma of the Parotid Gland Identified by PET/CT.

Brain MRI in an 82-year-old man with presumed Bell's palsy revealed a clinically unsuspected right parotid gland mass but no other acute findings. Biopsy revealed poorly differentiated adenocarcinoma. Staging F-FDG PET/CT revealed an FDG-avid parotid mass, abnormal FDG uptake along the course of the facial nerve from mass to skull base, and multiple FDG-avid right level II neck lymph nodes and hepatic metastases. The PET/CT findings and prolonged clinical course suggest that diffuse perineural spread of tumor from a smoldering parotid neoplasm, and not idiopathic Bell's palsy, was responsible for the patient's facial paralysis.

Evaluation of tumor-induced osteomalacia with 111In-pentetreotide scintigraphy.

In cases of nonhereditary osteomalacia associated with hypophosphatemia and inadequate response to vitamin D supplementation, one should consider the possibility of tumor-induced osteomalacia, a paraneoplastic syndrome caused by small mesenchymal tumors often found in obscure locations. We present a case of tumor-induced osteomalacia in which (111)In-pentetreotide scintigraphy aided in accurate localization of the culprit brachial plexus tumor and cure after resection.

Implementing routine screening for distress, the sixth vital sign, for patients with head and neck and neurologic cancers.

This study examined the benefits of incorporating screening for distress as a routine part of care for patients with head and neck and neurologic cancers in a tertiary cancer center. Using a comparative 2-cohort pre-post implementation sequential design, consecutive outpatients with head and neck and neurologic cancers were recruited into 2 separate cohorts. Cohort 1 included patients attending clinics during April 2010, before the implementation of the screening program. The program was then implemented and patients completed the Screening for Distress Minimum Dataset (the Edmonton Symptom Assessment System [ESAS] and the Canadian Problem Checklist [CPC]) at each clinic visit. Cohort 2 included patients attending clinics during March 2011. Consenting patients completed screening and outcome measures (ESAS, CPC, and either the Functional Assessment of Cancer Therapy-Brain or the Functional Assessment of Cancer Therapy-Head and Neck). A total of 146 patients (78 head and neck and 68 neurologic) provided data for Cohort 1, and 143 (81 head and neck and 62 neurologic) provided data for Cohort 2. Compared with Cohort 1, patients with neurologic cancers in Cohort 2 reported significantly higher scores on the Functional Assessment of Cancer Therapy: General total and emotional quality of life subscale; fewer high scores (≥ 4) on the ESAS breathlessness item; and fewer problems with fears/worries, frustration/anger, finding meaning in life, and worry about friends/family. Head and neck patients in Cohort 2 reported significantly higher emotional quality of life and fewer problems with eating and weight than those in Cohort 1. Although no definitive causal attributions can be made, patients exposed to routine screening for distress reported better well-being and fewer emotional, physical, and practical problems than historical controls.

Patterns of mediastinal tumors operated at the Tikur Anbessa Hospital, Addis Ababa, Ethiopia over a six years period.

BACKGROUND: The mediastinum is the space that lies between the two pleural cavities containing many vital structures in it. When tumors or cysts arise in the mediastinum they can be either asymptomatic or present as space occupying lesions causing symptoms and signs by their effect on the neighboring organs. Though mediastinal tumors are routinely treated at the study center, there are no studies in Ethiopia concerning the patterns, and modes of treatments of Mediastinal space occupying lesions. OBJECTIVE: To review all the primary mediastinal tumors and cysts operated upon at the Tikur Anbessa Teaching Hospital, Addis Ababa University over a six year period, from August 2005-2011. METHODOLOGY: Clinical retrospective review. RESULTS: In the six years, 73 patients were operated, 49 (67.1%) were males, the and male to female ratio being 2.04:1. The mean age of patients was 35.9 +/- 10.5 years (range 14 to 74). Forty-five (61.6%) had lesions of the anterior mediastinum, 23 (31.5%) in the posterior mediastinum and 5 (6.8%) in the middle. The commonest anterior mediastinal tumors were thymic origin (24/45), and thymic lesions were found more common in females (17:7 ratio). From the 23 patients with posterior mediastinal tumors, 18 had benign neurogenic tumors (4 of which were dumbbell tumors). Chest pain and shortness of breath (dyspnea) were the two most common symptoms in 31 (42.4%) of the patients. Twenty three patients (31.5%) were asymptomatic, and all had benign lesions. None of the malignant lesions were asymptomatic. Eleven (15%) patients; eight with anterior and three with posterior mediastinal masses, had undergone pre-operative tissue diagnosis procedure by image guided FNAC. Fifty-nine (80.8%) patients were operated with intent of therapeutic surgical procedures. There were 28 (38.5%) midline sternotomies, 40 (54.7%) thoracotomies, four underwent a left sided mediastinotomies and one mediastinoscopy performed. The rate of malignancy in this study was 24 (32.8%), of which 19 (79.1%) were in the anterior compartment. A total of 13 (17.8%) patients had complications in the hospital and four (5.4%) of the patients died CONCLUSION: Primary mediastinal tumors are not so rare in the setting. We would also like to recommend further large scale prospective studies which also included long-term outcome so that we can further understand the situation in the country.

Mononeuritis multiplex in a patient with B-cell prolymphocytic leukaemia: a diagnostic challenge.

B-cell prolymphocytic leukaemia (BPLL) is a haematological malignancy defined as lymphocytosis and splenomegaly with >55% circulating cells being clonal prolymphocytes of B-cell origin. The evolution of this disease is more aggressive than chronic lymphocytic leukaemia. We reported a case of a 62-year-old man with BPLL who, on treatment, attained cytological, immunophenotypic and complete cytogenetic remission. He subsequently developed an asymmetric sensorimotor neurological disorder, suggestive of lymphomatous infiltration (neurolymphocytosis). Repetition of the MRI and the electromyography was essential for diagnosis. Progressive mononeuritis multiplex in B-cell leukaemias/lymphomas is rare and may be the only presenting symptom of relapsed or progressive disease. Repeat imaging studies based on judicious evaluation of the clinical scenario for exclusion of other causes of neurological symptoms is necessary. This can be challenging in patients with long-standing malignancies who have received multiple courses of chemotherapy and/or radiotherapy.

Bilateral secondary neurolymphomatosis of the internal auditory canal nerves: a case report.

BACKGROUND: Neurolymphomatosis describes the malignant lymphomatous infiltration of nerves. METHODS: We encountered a unique case of a 47-year-old patient with non-Hodgkin's lymphoma presenting with bilateral sensorineural hearing loss, vestibular dysfunction and bilateral facial nerve palsy. RESULTS: Magnetic resonance imaging demonstrated enhancement and thickening of internal auditory canal nerves bilaterally consistent with neurolymphomatosis. Patient was treated with combined intrathecal chemotherapy and total brain irradiation. CONCLUSIONS: One must always remain vigilant for metastatic disease in patients with sensorineural hearing loss and/or vestibular dysfunction and facial nerve palsy in the context of known malignancy.

Laparoscopic management of sacral nerve root schwannoma with intractable vulvococcygodynia: report of three cases and review of literature.

Herein we report the feasibility of laparoscopic resection of schwannomas of the sacral nerves roots in 3 women with intractable vulvodynia and coccygodynia. Laparoscopic en bloc resection of the sacral schwannomas was performed, with primary control of the tumor blood supply and with exposure and sparing of the sacral nerve roots. In all 3 patients, laparoscopy was successful, with minimal blood loss and without complications. Histologic examination confirmed the diagnosis of schwannoma without malignant transformation in all 3 women. At mean follow-up of 27.66 months, no patient reported recurrence or worsening of symptoms. All patients are able to walk normally without gait aids. Primary control of the tumor blood supply during laparoscopic surgery to resect deep sacral masses reduces considerably the risk of operative hemorrhage. Compared with classic neurosurgical approaches, laparoscopic exposure of the rectum, ureters, and sacral nerve roots renders the procedure safer and easier, with less risk of postoperative functional morbidity.

Bone metastases and skeletal-related events in patients with malignant pheochromocytoma and sympathetic paraganglioma.

CONTEXT: Bone metastases (BM) can cause severe pain, spinal cord compression, pathological fractures, and/or hypercalcemia. These skeletal-related events (SREs) may cause immobilization, loss of independence, poor quality of life, and reduced survival. There is limited information on the clinical effects of BM and SREs in patients with malignant pheochromocytoma or sympathetic paraganglioma (PHEO/sPGL). OBJECTIVES: We studied the prevalence and clinical characteristics of BM and SREs in patients with PHEO/sPGL and investigated the risk factors for SRE development. DESIGN: Using a large institutional database, we conducted a retrospective study of 128 patients with malignant PHEO/sPGL at The University of Texas MD Anderson Cancer Center from 1967 through 2011. RESULTS: Of the patients, 91 (71%) had BM, and 57 of these (63%) developed metachronous BM at a median time of 3.4 years (range, 5 months to 23 years) after the primary tumor diagnosis. Metastatic disease was confined exclusively to the skeleton in 26 of 128 (20%) patients. Sufficient information to assess SRE occurrence was available for 67 patients, and 48 of 67 (72%) patients had at least 1 SRE. The median overall survival for the 128 patients was 12 years for patients with only BM, 7.5 years for patients with nonosseous metastases, and 5 years for patients with both BM and nonosseous metastases (log rank test P value = .005). We were unable to identify factors predictive of SRE development, but the occurrence of a first SRE was associated with the development of subsequent SREs in 48% of subjects. In responsive patients, the use of systemic therapy was associated with fewer SREs (P < .0001). CONCLUSIONS: BM and SREs are frequent in patients with malignant PHEO/sPGL. SREs often develop shortly after the diagnosis of BM; severe pain is the most frequent SRE. These patients should be followed long-term by a multidisciplinary team to promptly identify the need for medical or surgical intervention.

Bilateral spinal neurofibromas in patients with neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a neurocutaneous syndrome that can be inherited as autosomal dominant or may appear due to a de novo mutation. We present 8 patients (5 M and 3 F) with sporadic or non-familial spinal neurofibromatosis 1 (non-FSNF1) associated with bilateral spinal neurofibromas involving all of the paraspinal nerves. To our knowledge, this is the first series of such association described in the literature. Their ages ranged from 6 months to 20 years (average 9.8 years) at the time of radiological diagnosis. This presentation appears to be earlier than in familial spinal neurofibromas in NF1 (FSNF1). Predisposition to malignancy probably is greater in the non-FSNF1 type. MRI studies were performed routinely in all patients with NF1 and these were complemented with MRI enhanced with gadolinium and repeated at different ages in cases with paraspinal tumors. Coronal views provided the best evidence for the presence of neurofibromas in every spinal nerve. The size of the tumors and the clinical complications increased with advancing age in most patients. Giant plexiform tumors were often seen in the cervico-thoracic region. Malignant peripheral nerve sheath tumors (MPNST) were found in one patient with a sciatic tumor and another patient died suddenly at home without necropsy or pathological study. Voluminous paraspinal neurofibromas can be at risk for malignancy. More frequent neuroimaging studies may be necessary for an earlier detection. Early surgical treatment to anticipate the occurrence of MPNST during surveillance could be an option. Bilateral spinal neurofibromas are found in both patients who inherited the NF1 and in those due to de novo mutations.

Congenital agenesis of right parotid gland confounds MIBG scan interpretation in craniocervical neuroblastoma.

A 10-month-old boy with left infraorbital temporal neuroblastoma presented for I-123 metaiodobenzylguanidine scan with SPECT/CT for staging. Symmetrical metaiodobenzylguanidine uptake in salivary glands is usually considered normal. In this case of right parotid agenesis, symmetrical uptake was misleading. Tumor in the right mandibular ramus masqueraded as normal parotid gland. Repeat imaging 3 months after chemotherapy revealed absence of physiologic right parotid gland activity. Correlation with CT from SPECT/CT demonstrated right parotid agenesis, confirmed on MRI. Few cases of unilateral parotid agenesis are reported in published literature. We also discuss the potential added value of higher-quality CT images in SPECT/CT tumor imaging.

Preventive or late administration of anti-NGF therapy attenuates tumor-induced nerve sprouting, neuroma formation, and cancer pain.

Early, preemptive blockade of nerve growth factor (NGF)/tropomyosin receptor kinase A (TrkA) attenuates tumor-induced nerve sprouting and bone cancer pain. A critical unanswered question is whether late blockade of NGF/TrkA can attenuate cancer pain once NGF-induced nerve sprouting and neuroma formation has occurred. By means of a mouse model of prostate cancer-induced bone pain, anti-NGF was either administered preemptively at day 14 after tumor injection when nerve sprouting had yet to occur, or late at day 35, when extensive nerve sprouting had occurred. Animals were humanely killed at day 70 when, in vehicle-treated animals, significant nerve sprouting and neuroma formation was present in the tumor-bearing bone. Although preemptive and sustained administration (days 14-70) of anti-NGF more rapidly attenuated bone cancer nociceptive behaviors than late and sustained administration (days 35-70), by day 70 after tumor injection, both preemptive and late administration of anti-NGF significantly reduced nociceptive behaviors, sensory and sympathetic nerve sprouting, and neuroma formation. In this model, as in most cancers, the individual cancer cell colonies have a limited half-life because they are constantly proliferating, metastasizing, and undergoing necrosis as the parent cancer cell colony outgrows its blood supply. Similarly, the sensory and sympathetic nerve fibers that innervate the tumor undergo sprouting at the viable/leading edge of the parent tumor, degenerate as the parent cancer cell colony becomes necrotic, and resprout in the viable, newly formed daughter cell colonies. These results suggest that preemptive or late-stage blockade of NGF/TrkA can attenuate nerve sprouting and cancer pain.

Tandem intercostal thoracic schwannomas resected using a thoracoscopic nerve-sparing technique: case report.

BACKGROUND AND IMPORTANCE: To describe a novel nerve-sparing technique for the resection of intercostal nerve schwannomas. This case demonstrates that intercostal neuralgia can be caused by intercostal schwannomas and that it can be relieved by their removal. CLINICAL PRESENTATION: A young woman with schwannomatosis had progressively worsening intercostal neuralgia caused by compression of the intercostal nerve against the rib by tandem intercostal schwannomas. After the tumors were removed, her symptoms were completely relieved. A thoracoscopic technique was used to define the involved fascicles and to facilitate removal of the tumors while sparing the uninvolved nerve. CONCLUSION: The patient's radicular pain was relieved completely by the tumor resection. Thoracoscopic surgery offers a safe and minimally invasive technique for removal of intercostal schwannomas and is a valid alternative to open thoracotomy. Removal of thoracic schwannomas can relieve intercostal neuralgia.

Bone mineral density in newly diagnosed children with neuroblastoma.

BACKGROUND: Neuroblastoma is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy which is characterized by bone metastasis. Previous reports on bone mineral density (BMD) in patients with leukemia and solid malignancies concentrate on long-term survivors and on the effect of chemotherapeutic agents and irradiation. Also, evaluation of BMD in neuroblastoma was reported in few studies which were conducted upon adult survivors of childhood cancer. Previous studies on both acute leukemia and lymphoma patients suggested that the disease process itself played a role in decrease BMD. METHODS: We evaluated 27 patients with newly diagnosed neuroblastoma for both lumbar (L2-L4) BMD and total BMD using dual energy X-ray absorptiometery (DXA) scan to highlight the effect of neuroblastoma as a disease process on BMD as this disease characterized by bone metastasis. RESULTS: Three out of the 27 patients showed low bone mass in both lumbar and total BMD studies. CONCLUSION: Low bone mass may occur in early disease process of neuroblastoma and it is important to consider BMD assessment during the early course of the disease as well as the long-term survivors as a part of the patient screening in suspected cases.

Aortic body tumor in full-sibling English bulldogs.

A 10-year-old, neutered male English bulldog died acutely from respiratory distress after a short history of progressive dyspnea. Less than 2 months later, a spayed female full sibling of that dog died suddenly during a nail trim. An aortic body tumor was the cause of death in both dogs based on postmortem and histological examinations. A pheochromocytoma was also diagnosed in the neutered male. Neither dog had a history of brachycephalic airway syndrome, and the implication for a genetic predisposition toward the development of paraganglioma is discussed. This is the first case report of aortic body tumors in sibling dogs, although the condition may not be an uncommon phenomenon.

Frequent abnormalities of the immune system in gliomas and correlation with the WHO grading system of malignancy.

AIM: To investigate the cellular and humoral immunity status of gliomas, and their association with the WHO grading system. MATERIAL AND METHODS: We have conducted a case-control study of 49 patients with gliomas and 30 healthy controls. We used ELISA assays, radial immunodiffusion, indirect immunofluorescence, latex test and flow cytometry assays to estimate preoperative in serum the immunological profile. RESULTS: Patients with glioma had significantly reduced amounts of IL2 (p=0.000), TNF-a (p=0.033), IgG (p=0.011), IgA (p=0.027),C4 (p=0.026) ,CD3+ (p=0.001), CD4+ (p=0.000), CD8+ (p=0.002), ratio CD4/CD8 (p=0.000), CD19+ (p=0.04) and elevated IL10 (p=0.05) compared with healthy controls. No statistically significant differences were observed concerning viral agents, total NK cells, IgM, IgE, IL16, granzyme-b, RF, ANA, ENA, anti-dsDNA and anti-cardiolipin antibodies. A higher WHO grade, after controlling for age and gender, was associated with decreased number of CD3+ (p=0.011), CD4+ (p=0.015), CD8+ (p=0.048) and ratio CD4/CD8 (p=0.027), as well as with decreased IL2 (p=0.018), C4 (p=0.02), and IgG (p=0.05). IL2 and CD4+ counts were significant predictors of grade. CONCLUSIONS: A shift from Th1 to Th2, a CD3+ and CD19+ lymphocytopenia, a diminished fraction CD4/CD8 and a reduced amount of immunoglobulins and complement were observed in the patients with gliomas. A higher WHO grade of the tumor was associated with greater impairments of immunity. Since defects of both humoral and cellular immunity were equally observed and significant predictors of grade were assessed, a preoperative evaluation of the immune system of patients with gliomas is being proposed.