Primary well differentiated neuroendocrine tumor of the filum terminale. Case report and literature review. / Tumor neuroendocrino bien diferenciado intradural-extramedular primario del filum terminale. Presentación de un caso y revisión de la literatura.

OBJECTIVE: To present a case of a well-differentiated primary intradural-extramedullary neuroendocrine tumor of the filum terminale and to conduct a literature review. CASE: A 68-years old patient was assessed after presenting lower back pain and sciatica with ineffective pain relief. The patient presented an intradural-extramedullary lumbar lesion arising from the filum terminale, which was partially resected. The pathology diagnosis was a well-differentiated primary neuroendocrine tumor (carcinoid tumor). After a multidisciplinary evaluation, fractionated stereotactic radiotherapy was administered. No progression or metastatic spread was observed in successive assessments. DISCUSSION: Neuroendocrine tumors are heterogeneous neoplasms derived predominantly from enterochromaffin cells, in which chemotherapy plays a very limited role. In contrast, radiotherapy has been described in partially resected lesions. CONCLUSION: Well-differentiated primary neuroendocrine tumors with intradural-extramedullary lumbosacral location are an exceptional rarity. Isolated surgical resection, or associated with an adjuvant radiotherapy treatment in subtotal resections, could be considered an effective therapeutic strategy.

[Radiotherapy for Alleviation of Paraparesis due to Leptomeningeal and Cauda Equina Metastasis of HER2-Positive Breast Cancer: A Case Report].

Leptomeningeal metastasis is a rare entity and its diagnosis is often difficult. Moreover, evidence-based therapeutic strategies have not yet been established. A 52-year-old woman presented with high fever and was diagnosed with bacterial meningitis at first examination;although her fever was alleviated, she experienced motor weakness in both of her lower extremities. Ga scintigraphy highlighted the hot-spot areas of the disease in the cranial bone. She was then transferred to our department. Open biopsy of the skull showed metastasis of the cancer. Chest CT results indicated right breast cancer and Gd-DTPA imaging showed obvious enhancement of the pia mater around the conus medullaris and cauda equina. However, cerebrospinal fluid(CSF)cytological examination did not show the presence of any positive cells;consequently, mastectomy was performed in the thoracic surgical department. The severity of paraparesis and pain in her legs increased;however, repeat MRI 1 month later showed no evidence of any change. Therefore, we performed biopsy of the cauda equina and arachnoid lesions. The pathological diagnosis was metastasis of breast cancer with positive human epidermal growth factor receptor 2(HER2)immunological staining. The results of a repeat cytological examination of the CSF during the surgery were negative. Local radiotherapy(25 Gy/5 Fr)as a monotherapy was selected for the patient, because her family did not approve of the combination of radiotherapy and chemotherapy. The severity of both paraparesis and limb pain decreased immediately after the radiotherapy.

Ganglioneuroblastoma of filum terminale: case report.

OBJECT: Neuroblastic tumors can be classified as neuroblastoma, ganglioneuroblastoma (GNB), or ganglioneuroma. Ganglioneuroblastomas consist of small, round, immature neuroblast cells and matured ganglion cells. They are most commonly found in the mediastinum and retroperitoneum; intraspinal GNBs are extremely rare. There are only 5 cases of intraspinal GNB reported in the English literature. The authors report a case of GNB of the filum terminale. The duration of follow-up after the initial treatment is longer than in any other published reports. METHODS: A 36-year-old woman underwent resection of an intradural extramedullary tumor at L1-2 in 1993. Pathological diagnosis was GNB. After surgery, her symptoms resolved and she recovered to a normal condition. In 2009, when she was 53 years old, she presented to the hospital with paralysis of both legs. Magnetic resonance imaging suggested recurrence of spinal tumor. She underwent subtotal resection of the tumors, followed by 4 weeks of radiation therapy. RESULTS: Neurological symptoms improved, and, after radiation therapy, the patient was able to walk with a crutch. Histological investigation of the excised tumor indicated that it was a nodular type GNB, which was consistent with the diagnosis from the time of the initial surgery in 1993. Follow-up MRI studies showed no growth of residual tumors in the 3 years following the surgery. CONCLUSIONS: The authors present a rare case of spinal GNB. The duration of follow-up after the initial surgery in 1993 represents the longest description of clinical course after treatment for spinal GNB.

Preclinical evaluation of the combination of mTOR and proteasome inhibitors with radiotherapy in malignant peripheral nerve sheath tumors.

About one half of malignant peripheral nerve sheath tumors (MPNST) have Neurofibromin 1 (NF1) mutations. NF1 is a tumor suppressor gene essential for negative regulation of RAS signaling. Survival for MPNST patients is poor and we sought to identify an effective combination therapy. Starting with the mTOR inhibitors rapamycin and everolimus, we screened for synergy in 542 FDA approved compounds using MPNST cells with a native NF1 loss in both alleles. We further analyzed the cell cycle and signal transduction. In vivo growth effects of the drug combination with local radiation therapy (RT) were assessed in MPNST xenografts. The synergistic combination of mTOR inhibitors with bortezomib yielded a reduction in MPNST cell proliferation. The combination of mTOR inhibitors and bortezomib also enhanced the anti-proliferative effect of radiation in vitro. In vivo, the combination of mTOR inhibitor (everolimus) and bortezomib with RT decreased tumor growth and proliferation, and augmented apoptosis. The combination of approved mTOR and proteasome inhibitors with radiation showed a significant reduction of tumor growth in an animal model and should be investigated and optimized further for MPNST therapy.

Poor treatment outcome of neuroblastoma and other peripheral nerve cell tumors may be related to under usage of radiotherapy and socio-economic disparity: a US SEER data analysis.

PURPOSE: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) neuroblastoma (NB) and other peripheral nerve cell tumors (PNCT) outcome data. This study found under usage of radiotherapy in these patients. MATERIALS AND METHODS: This study analyzed socio-economic, staging and treatment factors available in the SEER database for NB and other PNCT. For the risk modeling, each factor was fitted by a generalized jinear model to predict the outcome (soft tissue specific death, yes/no). The area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. A random sampling algorithm was used to estimate the modeling errors. Risk of neuroendocrine (other endocrine including thymus as coded in SEER) death was computed for the predictors. RESULTS: There were 5261 patients diagnosed from 1973 to 2009 were included in this study. The mean follow up time (S.D.) was 83.8 (97.6) months. The mean (SD) age was 18 (25) years. About 30.45% of patients were un-staged. The SEER staging has high ROC (SD) area of 0.58 (0.01) among the factors tested. We simplified the 4-layered risk levels (local, regional, distant, un-staged/others) to a simpler 3-tiered model with comparable ROC area of 0.59 (0.01). Less than 50% of PNCT patients received radiotherapy (RT) including the ones with localized disease. This avoidance of RT use occurred in adults and children. CONCLUSION: The high under-staging rate may have prevented patients from selecting definitive radiotherapy (RT) after surgery. Using RT for, especially, adult PNCT patients is a potential way to improve outcome.

Primary cauda equina lymphoma treated with high-dose methotrexate.

A 69-year-old man presented with a very rare case of primary central nervous system lymphoma originating in the cauda equina manifesting as progressive paraparesis. The patient underwent a biopsy, and was treated with intravenous high-dose (3.5 g/m(2)) methotrexate chemotherapy and local irradiation. Histological study revealed large B cell type lymphoma. Follow-up magnetic resonance imaging showed complete remission of the lesion, but the patient died of pneumonia at 18 months after the initial onset without tumor recurrence, so the efficacy of this strategy remains unknown.

Adjunctive radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion.

Perineural invasion is a feature associated with significantly poorer outcomes when present in cutaneous squamous cell carcinoma (CSCC). The incidence of this subset of CSCC continues to rise in the US, as does the confusion surrounding exactly how it should be managed. While management typically involves excision, considerable debate exists as to the appropriate use of adjuvant radiotherapy (ART) in addition to excision. This article reviews the current relevant evidence for the use of ART.

Large cell neuroendocrine carcinoma of the lung metastatic to the cauda equina.

BACKGROUND CONTEXT: Large cell neuroendocrine carcinoma of the lung is an aggressive tumor with unique histopathological features. It is not known to metastasize to the spine. PURPOSE: To report a metastatic case of this rare tumor to the cauda equina. STUDY DESIGN: Case report. METHODS: Retrospective case review and review of the literature. RESULTS: The authors report a rare case of a large cell neuroendocrine lung metastasis to the lumbar spine, causing right foot drop. Magnetic resonance imaging revealed a heterogeneously enhancing intradural extramedullary mass at L2/L3 level compressing the surrounding nerve roots. During surgery, the identified nerve roots were encased by the tumor, and the dissection was tedious. Postoperatively, the patient reported significantly improved back pain and he had severe foot weakness. The functional outcome was poor because the patient lost entirely his foot function; however, his back pain improved significantly after surgery. CONCLUSIONS: This is the first published study in which the authors described a metastasis of a rather uncommon lung cancer to the cauda equina. When a lesion of the cauda equina presents with a rapid progressive neurological deficit, leptomeningeal metastasis should be in the differential diagnosis.

Vagal paraganglioma of the neck: a case report.

Vagal paragangliomas are rare in the head and neck. Complementary use of computed tomography and magnetic resonance imaging can facilitate the diagnosis and help determine the best management approach. Most paragangliomas should be treated with surgery. We report a case of vagal paraganglioma of the neck in a 50-year-old man. The patient was treated with superficial parotidectomy via a transcervical approach. No postoperative morbidity was noted, and at 3 years of follow-up, he was free of disease.

Radiotherapy for perineural invasion in cutaneous head and neck carcinomas: toward a risk-adapted treatment approach.

BACKGROUND: We retrospectively reviewed outcomes in patients treated with radiotherapy (RT) for cutaneous head and neck carcinoma with perineural invasion (PNI), with the aim of developing risk-adapted treatment guidelines. METHODS: A total of 118 patients were treated with RT between April 1992 and July 2000. Ninety-seven patients had PNI discovered through histology (pPNI) and 21 patients had symptoms/signs of PNI (cPNI). All received RT (median dose, 55 Gy; range, 17-74): 114 postoperatively and 4 definitively. Median follow-up was 84 months (range, 4-201). RESULTS: The 5-year local control (LC) rates were 90% with pPNI and 57% with cPNI (p < .0001). The pPNI and cPNI groups also differed in relapse-free survival (76% vs 46%, p = .003), disease-specific survival (90% vs 76%, p = .002), and overall survival (69% vs 57%, p = .03). pPNI patients with BCC histology (n = 42) had better LC (97% vs 84%, p = .02) than pPNI SCC (n = 55). CONCLUSION: Surgery plus RT provides a high rate of LC in patients with pPNI, particularly those with BCC. Therapeutic improvements are needed for patients with cPNI.

Malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumors (MPNSTs) are a rare variety of soft tissue sarcoma of ectomesenchymal origin. MPNSTs arise from major or minor peripheral nerve branches or sheaths of peripheral nerve fibers and are derived from Schwann cells or pluripotent cells of neural crest origin. Arthur Purdy Stout played a pivotal role in the development of our current understanding of the pathogenesis of peripheral nerve sheath tumors by identifying the Schwann cell as the major contributor to the formation of benign and malignant neoplasms of the nerve sheath. Although this fact remains essentially true, the cell of origin of the MPNST remains elusive and has not yet conclusively been identified. Some have suggested these tumors may have multiple cell line origins. In the present review, MPNSTs and their epidemiology, diagnosis, management, and treatment are discussed.

Malignant peripheral nerve sheath tumor with Horner's syndrome: a case report.

We report on a 42-year-old woman with malignant peripheral nerve sheath tumor (MPNST) arising from the cervical sympathetic nerve. A collar incision and partial sternotomy were performed at the second intercostal space. The mass was spindle shaped and connected to the sympathetic trunk on the cranial and caudal sides, and it compressed the left carotid sheath on the median side. After the patient's uneventful recovery from surgery, adjuvant radiotherapy was administered to the area of resection. The patient remains well 5 years after surgery with no evidence of recurrence.

Intraneural synovial sarcoma originating from the median nerve.

A 33-year-old female presented with a rare synovial sarcoma manifesting as a painful 12 x 15 mm tumor in the median palmar carpus. Preoperative neurological examination detected only radiating spontaneous pain in her right radial palm and decreased right grasping power. Magnetic resonance (MR) imaging confirmed the presence of the tumor. The preoperative diagnosis was schwannoma originating from the right median nerve. Subcapsular removal of the tumor was performed for preservation of the nerve function. However, postoperative histological and immunohistochemical studies suggested synovial sarcoma originating from the median nerve. No systemic metastasis was detected and the residual tumor capsule was totally removed. Local radiation therapy of 40 Gy, 2 Gy per day, was administered. Fourteen months later, local recurrence was detected on MR imaging. Total removal of the recurrent tumor was performed. Synovial sarcoma was finally diagnosed by the identification of SYT-SSX1 fusion gene transcripts using reverse transcriptase-polymerase chain reaction with a frozen tumor tissue sample.

Multifocal peripheral nerve involvement associated with multiple myeloma.

Infiltration of myeloma cells along the peripheral nerve is extremely rare, while multiple myeloma occasionally infiltrates the central nervous system. We present details of a patient in whom multiple myeloma had infiltrated a branch of the femoral nerve of the right inguinal region as well as the left ulnar nerve. The infiltration formed soft tissue masses, with the thickened nerves shown to be penetrating the center of the masses on ultrasonography and magnetic resonance imaging.

Metastatic hemangiopericytoma to the cauda equina: a case report.

BACKGROUND CONTEXT: Hemangiopericytoma is an aggressive tumor associated with high recurrence and metastasis. Metastases are usually delayed, long after diagnosis of the primary lesion. Metastatic hemangiopericytoma to the spinal cord is especially rare. PURPOSE: To report a rare clinical presentation of a metastatic intradural, intramedullary hemangiopericytoma to the cauda equina from a cerebellar hemangiopericytoma. STUDY DESIGN: Case report with a review of the literature. METHODS: Clinical history, physical findings, and magnetic resonance imaging studies of a patient with a metastatic intradural, intramedullary hemangiopericytoma to the cauda equina are reported. RESULTS: A case report is presented of a female with an intradural, intramedullary lesion at the L4-S1 level, presenting initially with progressive pain and motor weakness affecting the left lower extremity. She had a history of a cerebellar hemangiopericytoma, which had been treated with total resection and radiotherapy 4 years earlier. This patient developed urinary urgency and frequency. Pathological analysis revealed a hemangiopericytoma, which had a similar character to a cerebellar lesion. After radiotherapy, the tumor was mostly diminished and her symptoms totally resolved. CONCLUSIONS: Hemangiopericytomas have a strong tendency to both local recurrence and metastasis. Common metastatic sites are the skeletal system, lung, liver, and abdominal cavity. To the authors' knowledge, there have been no reports of spinal intradural, intramedullary metastasis of hemangiopericytoma.

[Olfactory neuroblastoma with spinal metastasis: case report].

Olfactory neuroblastoma is a rare tumor of the nasal cavity. It is a locally aggressive tumor with local recurrence, and distant metastasis occurs in 22-40% of patients. We report a case of olfactory neuroblastoma with cauda equina metastases. A 49-year old male had undergone surgery twice previously; the first for olfactory neuroblastoma in October, 1990, and the second for its intracranial and orbital metastasis in September, 1999. He complained of lumbago in autumn, 2005 and MRI showed two enhanced lesions in the cauda equina. The mass was partially removed and histologically diagnosed as olfactory neuroblastoma metastasis. Whole-spine irradiation of 32 Gy and lumber-spine irradiation of 10 Gy were performed. The mass at L2/3 was disappeared after the irradiation although the mass at L4/5 was not changed in size. The patient was discharged without neurological deficit and is now kept under observation as an outpatient. Olfactory neuroblastoma with spinal metastasis is rare and only 11 cases have been reported in the literature. A very poor prognosis was observed in the patients of olfactory neuroblastoma with spinal metastasis. Olfactory neuroblastoma is a radiosensitive tumor, and radiotherapy for spinal metastasis was reported to be effective. However, effectiveness of chemotherapy was still uncertain. The patient with olfactory neuroblastoma should be observed carefully even though no local recurrence had been detected over 10 years. Radiotherapy and further treatment including chemotherapy should be considered in case of spinal metastasis.

What is the role of adjuvant radiotherapy in the treatment of cutaneous squamous cell carcinoma with perineural invasion?

BACKGROUND: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) is infrequent, occurring in 2.5% to 14% of patients, but it is important prognostically, because it carries an increased risk of recurrence and metastasis. Although both excision and Mohs micrographic surgery (MMS) are used to treat SCC with PNI, postoperative radiation therapy (XRT) often is recommended to minimize the risk of recurrence. To date, the effectiveness of adjuvant XRT in this setting has not been determined definitively. METHODS: The authors evaluated the effectiveness of adjuvant XRT in treating SCC with PNI by performing a thorough literature review. RESULTS: For SCC with PNI, the local control rate after MMS with or without XRT was from 92% to 100% compared with a control rate from 38% to 100% after standard excision with or without XRT. A better prognosis was associated with negative pretreatment magnetic resonance imaging or computed tomography findings than with positive radiographic evidence of PNI. Primary SCC with PNI was associated with better local control than recurrent SCC with PNI. When treatment outcomes were stratified by PNI type, SCC with microscopic PNI and SCC with extensive PNI had local control rates from 78% to 87% and from 50% to 55%, respectively. Adjuvant XRT was associated in selected patients with 100% local control. CONCLUSIONS: Few studies addressed the effectiveness of adjuvant XRT in patients who have SCC with PNI. Although XRT has been established as an adjuvant treatment for selected patients, the extent of nerve involvement by tumor, particularly in the setting of other high-risk features, may be helpful in defining its role. In the future, a multicentered, prospective, randomized clinical trial will be needed to assess the true efficacy of adjuvant XRT in the treatment of patients with SCC and PNI.

CyberKnife radiosurgery for extremity schwannomas: technical note and case report.

Peripheral nerve sheath tumors are uncommon. Although surgical resection remains the treatment of choice for most symptomatic lesions, the potential for intraoperative injury to the nerve is not insignificant. This concern is of particular relevance in those patients with a genetic proclivity to develop multiple peripheral nerve sheath tumors. Here we report four symptomatic peripheral extremity schwannomas all in 1 patient who was treated with CyberKnife radiosurgery. The radiosurgical Dmax in each case was between 24.4 and 25.32 Gy. At 1-year follow-up, patient symptoms had been ameliorated, no tumor had increased in size and there was no compromise in neurological function. Although this experience is still very preliminary, it represents the first published description of a peripheral nerve sheath tumor being treated with stereotactic radiosurgery.