Synchronous skull base and spinal metastases in a patient with treatment-resistant, high-grade serous adenocarcinoma of tubo-ovarian origin.

Brain metastases (BMs) arising from ovarian cancer remain rare. Spinal cord metastases are even rarer, accounting for just 0.4% of total metastatic spinal cord compressions. In this report, we describe a case of a woman in her 70s who developed sequential brain and spinal cord metastases during her treatment for high-grade serous ovarian cancer, without a germline or somatic BRCA mutation. Following completion of neoadjuvant chemotherapy, interval debulking surgery and adjuvant chemotherapy, relapsed disease was ultimately identified as a single BM, curiously mimicking an acoustic neuroma. Subsequently, spinal cord metastases rapidly developed. Throughout, multidisciplinary team meetings guided decisions on patient management. In this report, we highlight the rarity of such a presentation and discuss the possible role of disease pathophysiology, associated systemic anticancer therapy resistance, and treatment possibilities for both cerebral and spinal metastases.

Spinal intramedullary uterine carcinosarcoma metastasis.

Intramedullary spinal cord metastases (ISCM) are a rare and challenging manifestation of metastatic cancer that have devastating impacts on the individual's neurological function, survival expectancy and overall quality of life. Given the rarity and poor prognosis, there is a lack of consensus in management. Uterine carcinosarcoma itself is a rare cancer, accounting for less than 3% of all uterine cancers. It carries a poor prognosis, with only one-third of patients surviving beyond 5 years. There are no previous reports of uterine carcinosarcoma metastases to the spinal cord. Here, we present the case of a woman in her late 70s with a uterine carcinosarcoma intramedullary metastasis that was refractory to radiotherapy treatment and responded favourably to surgical debulking.

Schwannomas Mimicking Leptomeningeal Spread in the Setting of Breast Cancer: A Case Report.

BACKGROUND: Breast cancer is currently the most diagnosed cancer globally. For patients who complete breast cancer treatment, developing a survivorship plan is important, including serial history, physical examinations, and annual mammograms to look for recurrence and metastasis. CASE REPORT: This is a case report of a 76-year-old female with a history of recurrent breast cancer who presented with lower-back pain and found to have MRI findings initially concerning for intradural extramedullary metastatic disease. Biopsy was later found to be consistent with benign spinal schwannomas. CONCLUSION: We present a unique case of spinal masses in the setting of breast cancer initially concerning for leptomeningeal spread, later found to have benign schwannomas that mimicked leptomeningeal spread on imaging. To our knowledge, this is the first reported case of schwannomas mimicking leptomeningeal spread in a patient with a history of recurrent breast cancer. After metastasis is excluded, schwannomas should be considered in the differential of benign spinal lesions.

CNS Tumors - clinical and radiological aspects.

Tumors of the central nervous system (CNS) include primary tumors - itraaxial, growing from brain and spinal cord cells (neuroepithelial tumors) or extraaxial, growing from surrounding structures (brain and spinal cord, nerve sheaths, vascular structures, lymphatic tissue, germ cells, malformations, pituitary glands). Much more often they are located in the intracranial space a solitary or multiple metastatic spread of malignancy originating from another organ (eg lung, breast, malignant melanoma, Grawitzs tumor). The occurrence of metastases of solid tumors is then in the intraaxial or extraaxial region, leptomeningeal or dural. Even morphologically benign tumors with their occurrence in a closed CNS compartment can have malignant behaviour and cause severe slowly developing to acute neurological symptoms, including intracranial hypertension. Primary tumors of the central nervous system present 1-2% of all cancers, with a higher incidence in adults after the age of 60, with a slight predominance in men, with higher mortality in men than in women. About 5% of CNS tumors are hereditary (e.g., Li-Fraumeni syndrome, neurofibromatosis type I, II). The causes of most brain and spinal cord tumors are unclear, the effect of radiation has been definitely demonstrated, there is an increased risk in transplant patients and AIDS (Acquired Immune Deficiency Syndrome) patients, and the potentiating effects of some chemicals and viruses on the development of CNS neoplasms are uncertain. The effectiveness of treatment of brain and spinal cord tumors is influenced by the existence of the so-called hematoencephalic barrier, which protects the brain from the penetration of toxic substances, but at the same time prevents the penetration of most cytostatics to the tumor target. Another obstacle may be the localization of the tumor in areas difficult to access for histological verification (brain stem, optical chiasma) due to the high risk of complications even after stereotactic biopsy. In some cases, in an effort not to cause an irreversible neurological deficit by inconsiderate tissue collection, the sample of histological material can then become inconclusive to tumor cells, i.e., tumor cells are not captured. Last but not least, the radiosensitivity of some brain structures is also limiting, which makes it impossible to apply a higher dose of ionizing radiation to a tumor affecting sensitive tissues or located near of these sensitive tissues. The rapid development of immunohistochemical (IHC) and molecular genetic analysis methods has significantly refined diagnostics and thus theoretically facilitates the choice of the optimal treatment procedure for the individual patient. While advances in modern conformal photon and particle (currently the most frequently proton) radiotherapy, stereotactic radiosurgery has enabled accurately targeted irradiation of the CNS tumor site and at the same time spare the high-risk brain structures, thereby significantly reduce the risk of acute and late neurotoxicity, pharmacotherapy options are still limited. Just molecular-genetic knowledge already provides us with predictive and prognostic information. They should increasingly stratify patients for targeted therapy.

A Solitary Spinal Cord Metastasis From Lung Cancer Displayed on 18 F-FDG PET/CT.

ABSTRACT: Chest CT images were acquired in a 79-year-old man to evaluate a right lung mass revealed by chest radiography. The image findings suggested possible pulmonary malignancy. FDG PET/CT was performed for staging, which displayed not only a hypermetabolic mass in the upper lobe of right lung but also increased FDG uptake of the spinal cord at T11 to T12 level. A lesion corresponding to the hypermetabolic region of the spinal cord was revealed by MRI. The intramedullary spinal cord metastasis from lung squamous cell carcinoma was confirmed through the pathological examination after the spinal cord lesion was resected.

Leptomeningeal Metastases of the Spine: A Systematic Review.

BACKGROUND/AIM: Leptomeningeal metastases (LMs) of the spine have complex management. We reviewed the literature on spine LMs. MATERIALS AND METHODS: PubMed, EMBASE, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA guidelines to include studies of spine LMs. RESULTS: We included 46 studies comprising 72 patients. The most frequent primary tumors were lung (19.4%) and breast cancers (19.4%). Median time from primary tumors was 12 months (range=0-252 months). Cauda equina syndrome occurred in 34 patients (48.6%). Nodular spine LMs (63.6%) were more frequent. Concurrent intracranial LMs were present in 27 cases (50.9%). Cerebrospinal fluid cytology was positive in 31 cases (63.6%). Cases were managed using palliative steroids (73.6%) with locoregional radiotherapy (55.6%) chemotherapy (47.2%), or decompressive laminectomy (8.3%). Post-treatment symptom improvement (32%) and favorable radiological response (28.3%) were not different based on treatment (p=0.966; p=0.727). Median overall-survival was 3 months (range=0.3-60 months), not significantly different between radiotherapy and chemotherapy (p=0.217). CONCLUSION: Spine LMs have poor prognoses. Radiotherapy, chemotherapy, and surgery are only palliative, as described for intracranial LMs.

Evolution of a refractory prolactin-secreting pituitary adenoma into a pituitary carcinoma: report of a challenging case and literature review.

BACKGROUND: Pituitary carcinomas (PCs), defined as distant metastases of pituitary neoplasms, are very rare malignancies. Because the clinical presentation of PCs is variable, early diagnosis and management remain challenging. PCs are always refractory to comprehensive treatments, and patients with PCs have extremely poor prognoses. CASE PRESENTATION: We describe one case of a prolactin-secreting pituitary adenoma (PA) refractory to conventional therapy that evolved into a PC with intraspinal metastasis. A 34-year-old female was diagnosed with an invasive prolactin-secreting PA in 2009 and was unresponsive to medical treatment with bromocriptine. The tumor was gross totally removed via transsphenoidal surgery (TSS). However, the patient experienced multiple tumor recurrences or regrowth despite comprehensive treatments, including medical therapy, two gamma knife radiosurgeries (GKSs), and four frontal craniotomies. In 2016, she was found to have an intradural extramedullary mass at the level of the fourth lumbar vertebra. The intraspinal lesion was completely resected and was confirmed as a metastatic PC based on histomorphology and immunohistochemical staining. The literature on the diagnosis, molecular pathogenesis, treatment, and prognosis of patients with prolactin-secreting PCs was reviewed. CONCLUSION: PCs are very rare neoplasms with variable clinical features and poor prognosis. Most PCs usually arise from aggressive PAs refractory to conventional therapy. There is no reliable marker to identify aggressive PAs with a risk for progression to PCs; thus, it is difficult to diagnose these PCs early until the presence of metastatic lesions. It is still very challenging to manage patients with PCs due to a lack of standardized protocols for diagnosis and treatment. Establishing molecular biomarkers and the pathobiology of PCs could help in the early identification of aggressive PAs most likely to evolve into PCs.

Stereotactic body radiotherapy for intramedullary metastases: a retrospective series at the Oscar Lambret center and a systematic review.

BACKGROUND: Intramedullary metastasis (IMM) is a rare disease with poor prognosis. The incidence of IMMs has increased, which has been linked to improved systemic treatment in many cancers. Surgery and/or radiotherapy are the most commonly used treatments; only small-sample retrospective studies and case reports on stereotactic body radiotherapy (SBRT) have reported acceptable results in terms of local control and clinical improvement, with no reported toxicity. Thus, we performed this monocentric retrospective study on five cases treated with SBRT for IMMs, which we supplemented with a systematic review of the literature. METHODS: We included all patients treated for IMM with SBRT. The target tumor volume, progression-free survival, prescription patterns in SBRT, survival without neurological deficit, neurological functional improvement after treatment, and overall survival were determined. RESULTS: Five patients treated with a median dose of 30 Gy in a median number of fractions of 5 (prescribed at a median isodose of 86%) included. The median follow-up duration was 23 months. Two patients showed clinical improvement. Three patients remained stable. Radiologically, 25% of patients had complete response and 50% had stable disease. No significant treatment-related toxicity was observed. CONCLUSION: SBRT appears to be a safe, effective, and rapid treatment option for palliative patients.

Resection of Cervical Intradural Extramedullary Melanoma Metastasis with Pial Invasion: 2-Dimensional Operative Video.

Intradural extramedullary metastatic melanoma is a rare entity with only 13 other cases reported in the literature.1 Of these, only 3 have been described in the cervical spine.2-4 Metastatic melanoma to the brain has historically portended a grim prognosis; however, due to the paucity of reported intradural lesions, the clinical course, including surgical findings, is less well known. This video illustrates a case of a 59-year-old man with new left arm pain and numbness found to have cervical intradural extramedullary metastatic melanoma (Video 1). This video also demonstrates surgical principles and techniques for removal of a rare cervical intradural extramedullary melanoma metastasis using standard cervical laminectomy with intraoperative ultrasound for tumor localization. Considering its rarity, visualizing the intraoperative resection is important for surgeons who may potentially treat such pathology. Patient consented for the procedures and for publication of the video.

Rare case of intramedullary spinal cord metastasis from nasopharyngeal carcinoma.

INTRODUCTION: Central nervous system (CNS) metastasis from nasopharyngeal carcinoma (NPC) is rare and presents with high morbidity and mortality. As a rare entity, a few patients with CNS metastasis from NPC have been reported, and no studies were available on treatment and prognosis. Based on our clinical experience, early diagnosis with incorporation of a clear palliative plan is imperative in providing holistic care for patients with locally-invasive and metastatic nasopharyngeal carcinoma. CASE REPORT: Our study reports a case of a 48-year-old Filipino male with known NPC Stage IVB who developed acute symptoms of constipation, urinary retention, and bilateral lower limb weakness and numbness. Magnetic resonance imaging showed intramedullary lesions in multiple segments of the spinal cord. Steroid and radiotherapy of the spine were initiated with noted transient improvement of the motor strength. Subsequently, he developed cancer-related stroke. The patient progressively deteriorated despite best medical care.

Response to BRAF and MEK1/2 inhibition in a young adult with BRAF V600E mutant epithelioid glioblastoma multiforme: A Case Report and Literature Review.

Epithelioid glioblastoma multiforme (eGBM) is a rare and aggressive variant of glioblastoma multiforme (GBM) that predominantly affects younger patients and can be difficult to distinguish from other gliomas. Data on how patients with eGBM might be best treated are limited, although genomic analyses have shown that almost half of tumours harbour activating BRAF gene mutations. Here we present the case of a young female with BRAF V600E-mutant eGBM who had a prolonged response to targeted therapy with the BRAF and MEK1/2 inhibitors dabrafenib and trametinib. We review current knowledge about eGBM, including the emerging role for BRAF- ± MEK1/2- targeted therapy.

Intramedullary spinal cord metastases: Report of three cases and review of the literature.

Intramedullary spinal cord metastases (ISCM) is a rare, but devastating complication of malignant disease. Prognosis is poor, with an overall median survival (OS) of 4 months from the time of diagnosis. Yet, ISCMs are being increasingly diagnosed, related to advances and increased use of imaging and therapies that prolong survival in patients with cancer. Prompt and accurate diagnosis of ISCM is necessary for effective treatment, and magnetic resonance imaging (MRI) is the preferred imaging technique. The optimal management of these patients is controversial because of the multitude of clinical circumstances and the lack of controlled studies on the efficacy of the different therapeutic approaches. Increased awareness of this rare entity may lead to an earlier diagnosis at a stage when neurological deficits are reversible, and therefore, more effective palliation may be achieved. Therefore, we carried out this retrospective research of 3 observations of ISCM, associated with a detailed review of the literature describing the diagnostic, therapeutic and evolutionary characteristics of this special rare entity.

FDG PET/CT Findings of Extrarenal Wilms Tumor Originating From the Spinal Cord.

Extrarenal Wilms tumor (ERWT) is an extremely rare neoplasm of childhood. It occurs predominantly in retroperitoneum and pelvic or inguinal region without involvement of the kidneys. Although the importance of FDG PET/CT in Wilms tumor is well known, its use in ERWT is limited. Herein, we present FDG PET/CT findings of a 3-year-old girl with a lumbar mass, which was later diagnosed with ERWT.

Extensive craniospinal disseminated metastasis after the resection of intradural extramedullary ependymoma in the craniocervical junction: a case report and literature review.

PURPOSE/AIM: Intradural extramedullary (IDEM) ependymomas are very rare, and IDEM ependymomas with craniospinal disseminated metastasis are exceptionally rare; only 2 preoperative cases have been confirmed, and postoperative cases have not been reported. CASE REPORT: We present a case of a 21-year-old female with an IDEM ependymoma of the craniocervical junction who experienced head and neck pain for more than 1 month. Magnetic resonance imaging (MRI) of the cervical spine revealed a large IDEM cystic lesion located in the medulla oblongata and the upper cervical spinal cord. The patient underwent surgery without complications, and the tumor was completely removed. Histopathological examination revealed a diagnosis of aplastic ependymoma, World Health Organization (WHO) grade III. The patient failed to follow-up with radiotherapy for one month after discharge. Nearly three months after surgery, craniospinal disseminated metastasis was found in the patient; subsequently, chemoradiotherapy was administered to prolong the survival time of the patient. Unfortunately, the patient underwent radiotherapy and chemotherapy for only 7 days; then, the patient gave up treatment and died 5 months later. CONCLUSIONS: To the best of our knowledge, no other cases of craniocervical junction anaplastic ependymomas with craniospinal disseminated metastasis have been reported in the literature. Total resection does not completely prevent recurrence and metastasis, and MRI of the entire neuraxis and timely postoperative craniospinal radiotherapy are necessary for the treatment of this disease.

The Central Dot Sign : A Specific Post-gadolinium Enhancement Feature of Intramedullary Spinal Cord Metastases.

PURPOSE: Peripheral enhancement characteristics on magnetic resonance imaging (MRI), namely the rim and flame signs, are specific for intramedullary spinal cord metastases (ISCM) compared to primary cord masses. The study compared the frequency of a novel finding-the central dot sign-in ISCMs versus primary intramedullary masses. METHODS: In this study 45 patients with 64 ISCMs and 64 control patients with 64 primary intramedullary cord masses were investigated and 2 radiologists blinded to lesion type independently evaluated MR images for the presence of a central dot sign: a punctate focus of enhancement in/near the center of an enhancing intramedullary mass. The frequency of this sign in the two patient groups was compared. RESULTS: A total of 63 enhancing ISCMs in 44 patients and 54 enhancing primary cord masses in 54 patients were included. The central dot sign was identified in 6% (4/63) of enhancing ISCMs in 9% (4/44) of patients and in none (0/54) of the enhancing primary cord masses (p = 0.038, per patient). The specificity for diagnosing ISCMs among spinal cord masses was 100%. The central dot sign was present in the axial plane only in two ISCMs and in the axial and sagittal planes in two ISCMs. The two ISCMs harboring the central dot sign also demonstrated both the previously described rim and flame signs, and two also demonstrated the rim sign alone. CONCLUSION: The central dot sign is not sensitive but highly specific for ISCMs compared to primary spinal cord masses. The rim and/or flame signs may or may not be concurrently present in ISCMs.

Intramedullary Spinal Cord Metastasis from Primary Lung Neuroendocrine Carcinoma: A Case Report and Operative Video.

BACKGROUND: Intramedullary spinal cord metastasis (ISCM) account for a minority of all spinal cord tumors. Rarely, symptoms from ISCM may be the initial presentation of an unknown primary carcinoma. Intramedullary metastasis from a second malignancy or from an unknown neuroendocrine malignancy is extremely rare and has never been reported in the literature. Because of the rarity of these tumors and the low volume of cases, well-defined treatment guidelines do not exist for the management of ISCM. Here we present a rare and one of the first reports of an intramedullary metastatic neuroendocrine tumor. CASE DESCRIPTION: A 66-year-old woman with a history of breast cancer presented with worsening bilateral lower extremity numbness for 2 months. Imaging revealed an intramedullary spinal cord tumor at the T4 level. The patient underwent microsurgical resection of the intramedullary spinal cord tumor. At operation, the tumor had an exophytic component. Subtotal resection was achieved. Pathology revealed a neuroendocrine metastasis, likely pulmonary in origin. She achieved partial resolution of neurologic symptoms at follow-up. CONCLUSIONS: Neuroendocrine ISCM are rare and lack well-defined treatment guidelines. Care should be individualized in these cases. Whenever feasible, surgical resection should be considered. Despite multidisciplinary care, the prognosis is dismal with limited life expectancy. Larger, multiinstitutional, or national database studies are needed that compare treatment modalities in the management of ISCM to identify the therapy with the best outcomes.

FDG PET/CT in Recurrent Glioblastoma Multiforme With Leptomeningeal and Diffuse Spinal Cord Metastasis.

ABSTRACT: Glioblastoma multiforme is one of the most common malignant types of tumor arising from the central nervous system known for its devastating intracranial progress and dismal prognosis. Macroscopically evident and symptomatic spinal cord metastasis detected with FDG PET/CT imaging is a rare event. We present a rare case of symptomatic diffuse spinal metastases of glioblastoma multiforme in a 25-year-old woman, who has been previously treated surgically with gross tumor resection followed by adjuvant radiotherapy and chemotherapy with temozolomide.

Long-term outcomes in the treatment of pediatric skull base chordomas in the endoscopic endonasal era.

OBJECTIVE: Pediatric skull base chordoma is a rare entity that is traditionally considered to display aggressive behavior with an increased risk of recurrence. There is an absence of literature examining outcomes in the pediatric population in general and using the endoscopic endonasal approach (EEA). METHODS: The authors retrospectively reviewed all patients with skull base chordomas presenting by the age of 18 years to the Children's Hospital of Pittsburgh or the University of Pittsburgh Medical Center from 2004 to 2019. Clinical outcomes, the number and location of recurrences, and progression-free survival time were determined. RESULTS: Twenty patients met the study criteria. The most common presenting complaints were diplopia (n = 7), headache (n = 6), and swallowing difficulty (n = 4). Three cases were incidentally discovered. Twelve patients underwent single-stage EEA alone, 2 patients had two-stage EEA, and 6 patients had combined EEA with open far-lateral or extreme-lateral approaches. Fourteen patients underwent gross-total resection (GTR), and 6 patients had near-total resection. Larger tumors were more likely to require staging or a combined approach (86% vs 7%) and were less likely to receive GTR (33% vs 86%) but had comparable recurrence and mortality rates. Five patients developed CSF leaks requiring reoperation, 2 patients developed a permanent abducens nerve palsy, 1 patient suffered an internal carotid artery injury, 1 patient developed an epidural hematoma, and 1 patient developed a subdural empyema. Four (20%) patients had recurrence during follow-up (mean radiographic follow-up 59 months and mean time to local recurrence 19 months). Two patients with recurrence underwent further resection, and 1 patient elected to stop treatment. Both patients who underwent repeat resection experienced a second recurrence, one of whom elected to stop treatment. Both patients who died had an elevated Ki-67 (p = 0.039), one of whom developed de-differentiated histology. A third patient died of progressive spinal metastases without local recurrence and is one of 2 patients who developed postoperative spinal metastases. Both patients whose tumors became de-differentiated progressed from tumors with an initial Ki-67 of 15 or greater (p = 0.035) and received prior radiotherapy to the bulk tumor (p = 0.03). CONCLUSIONS: The majority of pediatric skull base chordomas, when managed at a specialized center with a goal of GTR, may have a better outcome than traditionally believed. Elevated Ki-67 rates may predict poor outcome and progression to de-differentiation.

Clinical outcome of surgical management for symptomatic metastatic spinal cord compression from prostate cancer.

BACKGROUND: Metastatic spinal cord compression (MSCC) from prostate cancer (PC) influences not only patients' prognosis but also their quality of life. However, little is known about the clinical outcome of surgery for MSCC from PC. We evaluated both the oncological and functional outcomes of decompression and reconstruction surgery for patients with symptomatic MSCC from PC. METHODS: We assessed 19 patients who underwent decompression and reconstruction surgery for symptomatic MSCC from PC. Of these 19 patients, 8 had metastatic hormone-naïve PC (mHNPC) and 11 had metastatic castration-resistant PC (mCRPC). RESULTS: The median age of the patients with mHNPC and mCRPC was 72 and 65 years, respectively. The median prostate-specific antigen level at the time of diagnosis of MSCC in patients with mHNPC and mCRPC was 910 and 67 ng/mL, respectively. Although two of eight patients (25.0%) with mHNPC were ambulatory preoperatively, six patients (75.0%) were ambulatory postoperatively. Among 11 patients with mCRPC, only 3 (27.3%) were ambulatory preoperatively, while 6 (54.5%) were ambulatory postoperatively. The median postoperative overall survival among patients with mHNPC and mCRPC were not reached and 8 months, respectively. CONCLUSIONS: Decompression and reconstruction surgery for symptomatic MSCC from PC might contribute to a favorable functional outcome among men with mHNPC and mCRPC. However, its role in improving the oncological outcome remains unclear. The treatment strategy should be chosen by shared decision-making among patients, urologists, radiation oncologists, and orthopedic surgeons.