ABSTRACT
Non-small cell lung cancer (NSCLC) is frequently associated with central nervous system metastases resulting in poor outcomes. As newer targeted therapies become available determining which patients can benefit from these therapies has remained challenging, and current molecular testing options rely on a panel of only a handful of known oncogenic drivers. Here, we demonstrate a targeted approach at uncovering clinically relevant variants in cancer-associated genes using genomic sequencing. Our patient underwent targeted sequencing of 212 cancer-associated genes, revealing mutations in six; two of which were in EGFR, an important target for therapy in NSCLC. A multidisciplinary approach involving surgical resection, radiation, and targeted therapy based on the genomic profile and tumor pathology ultimately lead to positive therapeutic response and stable disease. Our report provides a proof of principle for incorporating higher throughput genomic sequencing techniques directly into patient care. We also report an atypical response of an EGFR mutation positive metastatic tumor to immune checkpoint therapy, despite recent reports suggesting that these patients do not benefit from immune checkpoint inhibitors. A brief review of current literature is discussed here to explore links between EGFR mutations and PD-L1 expression, as well as response to targeted therapies.
Subject(s)
Brain Neoplasms/genetics , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/secondary , High-Throughput Nucleotide Sequencing/methods , Lung Neoplasms/genetics , Lung Neoplasms/pathology , B7-H1 Antigen/genetics , Brain Neoplasms/surgery , Carcinoma, Non-Small-Cell Lung/surgery , Combined Modality Therapy , ErbB Receptors/genetics , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy , Male , Middle Aged , Mutation/genetics , Neurosurgical Procedures/methods , SmokingABSTRACT
INTRODUCTION: While there are numerous published cases of arteriovenous malformations (AVMs) developing in the setting of malignancy, it is extremely rare to find them concurrently associated in the brain. CLINICAL CASE: This is the case of a 55-year-old male who presented to the emergency department complaining of headaches, memory and visual changes. Neuro-imaging revealed a right temporal parietal AVM and an adjoining hyperenhancing occipitotemporal lobe lesion with concern for a possible evolving stroke. The patient was treated with radiosurgery for the AVM. His symptoms progressed one month later, and repeat imaging suggested interval enlargement of the previously presumed stroke that was intricately associated with the AVM, in addition to two new small enhancing lesions of the left temporal lobe. Microsurgical resection of the temporal lobe mass revealed adenocarcinoma of the lung. CONCLUSION: This case represents a previously undocumented confluence of cranial AVM that initially masked a non-small cell lung cancer brain metastasis.
Subject(s)
Adenocarcinoma of Lung/therapy , Brain Neoplasms/surgery , Carcinoma, Non-Small-Cell Lung/surgery , Intracranial Arteriovenous Malformations/surgery , Neoplasm Metastasis/therapy , Adenocarcinoma of Lung/complications , Adenocarcinoma of Lung/diagnosis , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/diagnosis , Humans , Intracranial Arteriovenous Malformations/diagnosis , Male , Middle Aged , Neoplasm Metastasis/diagnosis , Temporal Lobe/surgeryABSTRACT
INTRODUCTION: Aneurysmal bone cysts (ABCs) are rare, rapidly expansile, benign, vascular lesions capable of causing local bone destruction. The majority of cases present as multi-cystic lytic lesions (with solid-variant ABCs representing<10% of all presentations) of the long bones or vertebrae, rarely occurring in the head/neck region. CLINICAL CASE: A 44-year-old female presented with nine days of worsening pain, ptosis and proptosis in the right eye. CT and MR imaging revealed a 3.2cm extra-axial multiloculated right frontal lobe mass in the orbit with fluid-fluid levels secondary to layering of solid blood components. A right craniotomy was performed and the lesion was resected piecemeal with subsequent high speed burring to remove residual tissue. Histological evaluation revealed spindle and giant cell infiltration of the bone without vascular channels. Based on these findings, the lesion was diagnosed as a solid-variant orbital ABC without paranasal sinus involvement. The patient recovered fully with no residual symptoms. CONCLUSION: This case report details a rare presentation of ABC (solid-variant presenting outside of the vertebrae/long bones) with discussion concerning possible treatment modalities and guidance for follow-up.
Subject(s)
Bone Cysts, Aneurysmal/pathology , Bone Cysts, Aneurysmal/surgery , Craniotomy , Orbit/surgery , Spine/surgery , Adult , Bone Cysts, Aneurysmal/diagnosis , Craniotomy/methods , Female , Giant Cells/microbiology , Humans , Magnetic Resonance Imaging/methods , Neck/pathology , Neck/surgery , Pain/physiopathology , Pain/surgeryABSTRACT
BACKGROUND: Melanoma lesions in the brainstem can be difficult to distinguish radiographically and clinically from cavernous malformations. However, the treatment modalities and clinical course of these two diseases differ considerably. We report two cases of melanoma presenting as brainstem hemorrhages. CASE DESCRIPTION: A 69-year-old male was found to have a hemorrhagic lesion of the right dorsal midbrain. After a repeat hemorrhage, the lesion was resected and found to be hyperchromatic. Nonetheless, the patient suffered rebleeding and died 3 months later. A 62-year-old female was similarly found to have an acute pontine hemorrhage. After resection of the lesion, she underwent whole-brain radiation therapy but ultimately died 5.5 months later. The histopathology of both lesions was consistent with melanoma. CONCLUSIONS: Melanoma in the brainstem can mimic cavernous malformations. While management of these lesions includes stereotactic radiosurgery, whole-brain radiation, and surgical resection, metastatic brainstem melanoma follows an aggressive clinical course with a poor prognosis.
Subject(s)
Brain Stem Neoplasms/diagnosis , Hemangioma, Cavernous, Central Nervous System/diagnosis , Melanoma/diagnosis , Aged , Brain Stem Neoplasms/pathology , Brain Stem Neoplasms/surgery , Diagnosis, Differential , Fatal Outcome , Female , Hemangioma, Cavernous, Central Nervous System/pathology , Hemangioma, Cavernous, Central Nervous System/surgery , Humans , Intracranial Hemorrhages/etiology , Male , Melanoma/pathology , Melanoma/surgery , Middle Aged , Neoplasm Metastasis/pathology , Prognosis , Radiosurgery , Treatment OutcomeABSTRACT
OBJECTIVE: Type I spinal arteriovenous lesions represent dorsal dural arteriovenous fistulae with no spinal artery involvement. We report an exception to this and propose dividing Type I lesions into dorsal and ventral categories. METHODS: A 51-year-old patient presented with a partial Brown-Sequard syndrome. An angiogram revealed a spinal arteriovenous fistula, most prominently being fed a radicular artery arising from the right vertebral artery with only ventral venous drainage. RESULTS: This feeder was selected and embolized with onyx, however residual fistula persisted and the patient subsequently underwent microsurgical disconnection. At six-month follow-up, patient motor deficits have resolved and difficulty with proprioception is improving. CONCLUSION: Type I dural arteriovenous fistulae are associated with dorsal venous drainage. Our case demonstrates an exception to this. Recognizing this exception was crucial, because it allowed for simple microsurgical disconnection. We propose that type I dural arteriovenous fistulae be subdivided into ventral and dorsal based on their drainage pattern. This differentiation is critical because lesions with ventral drainage have traditionally been classified as type IV. These lesions have a different treatment method given involvement of spinal arteries.
Subject(s)
Arteriovenous Fistula/surgery , Brown-Sequard Syndrome/surgery , Central Nervous System Vascular Malformations/surgery , Arteriovenous Fistula/diagnosis , Brown-Sequard Syndrome/pathology , Cerebral Angiography/methods , Dura Mater/pathology , Dura Mater/surgery , Embolization, Therapeutic/methods , Humans , Middle Aged , Spinal Cord/blood supply , Treatment OutcomeABSTRACT
Rapidly expanding infectious pseudoaneurysms of the internal carotid artery can have deleterious consequences. A patient is reported who presented with such an aneurysm. The morphology of the aneurysm was not amenable to microsurgical treatment. The aneurysm was successfully treated with covered stents. This is only the third report of a patient with an infectious pseudoaneurysm in the internal carotid artery treated with a covered stent. At the 1 year follow-up visit, the patient continues to do well.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Anticoagulants/therapeutic use , Carotid Artery Injuries/microbiology , Carotid Artery Injuries/therapy , Staphylococcal Infections/drug therapy , Stents , Carotid Artery Injuries/diagnostic imaging , Coated Materials, Biocompatible , Combined Modality Therapy , Humans , Male , RadiographyABSTRACT
Primary intraosseous lytic meningiomas are rare tumors, with only 16 cases described in the literature. We present a case in which CT and MR imaging with contrast agent helped diagnose preoperatively an enlarging skull mass as a primary intraosseous lytic meningioma in a 70-year-old woman. Radiographic findings revealed a lytic mass centered on the coronal suture line that separated and thinned both the outer and inner tables of the frontal bone.
Subject(s)
Meningioma/diagnostic imaging , Meningioma/pathology , Skull Neoplasms/diagnostic imaging , Skull Neoplasms/pathology , Aged , Female , Humans , Meningioma/surgery , Skull Neoplasms/surgery , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: The bony and vascular anatomic features in the region of the petrous apex can vary significantly. These variations affect the operative view obtained via extended subtemporal or anterior transpetrosal approaches to cranial base lesions for individual patients. The goal of this study was to evaluate three-dimensional computed tomography as a means of obtaining detailed preoperative anatomic information regarding bony and vascular landmarks and spatial relationships in the region of the petrous carotid artery and petrous apex. METHODS: We radiographically studied 15 patients (30 sides), using 0.8- to 1-mm-thick, reconstructed, computed tomographic images. Special attention was given to the course of the petrous carotid artery. RESULTS: The petrous carotid artery was located lateral to the trigeminal impression. The size of the petrous apex medial to the horizontal petrous carotid artery was observed to be variable. The width of bone from the trigeminal impression to the wall of the internal auditory canal averaged 9.6 mm (range, 5.2-16.1 mm). A variable amount of bone overlying the internal auditory canal (4.5 mm) was also present. Multiple other relationships among key landmarks were quantified. CONCLUSION: There is significant variability in the anatomic features of the petrous apex among patients. For each patient, detailed preoperative information regarding the amount of bone to be removed during a cranial base procedure can be obtained using three-dimensional computed tomography. This information may be critical for determination of the amount of extra exposure that can be achieved via an anterior petrosectomy for each patient.
Subject(s)
Carotid Arteries/surgery , Imaging, Three-Dimensional , Skull Base/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Female , Humans , Imaging, Three-Dimensional/standards , Male , Middle Aged , Petrous Bone , Tomography, X-Ray Computed/standardsABSTRACT
BACKGROUND: Guillain-Barre Syndrome (GBS) is believed to be caused by autoimmune mechanisms that are predominantly T-cell mediated. We report GBS in organ transplant patients and bone marrow transplant patients, both of whom have iatrogenically suppressed T-cell function. METHODS: We reviewed the Duke University Medical Center database from 1989-1999 for all patients who met the criteria for GBS. There were a total of 212 patients. Of these patients, two had undergone organ transplantation and two had undergone autologous bone marrow transplantation. RESULTS: Our report supports the notion that the humoral immune system is involved in the pathogenesis of GBS. Contrary to previous reports, however, functional recovery can occur without return of T-cell function. CONCLUSIONS: This suggests that in organ transplant patients, GBS may be humorally mediated and, even more importantly, responds well to treatment.
Subject(s)
Bone Marrow Transplantation/statistics & numerical data , Guillain-Barre Syndrome/epidemiology , Organ Transplantation/statistics & numerical data , Postoperative Complications , T-Lymphocytes/immunology , Adult , Aged , Bone Marrow Transplantation/immunology , Child , Databases as Topic , Female , Guillain-Barre Syndrome/immunology , Humans , Immunosuppression Therapy , Male , Middle Aged , Retrospective Studies , Transplantation ImmunologyABSTRACT
A 25-yr-old male presented with a cerebellar mass, underwent a suboccipital craniotomy, and was diagnosed with medulloblastoma. Six months later he developed a large mass in the right iliac crest. Fine-needle aspiration biopsy (FNAB) confirmed the diagnosis of metastatic medulloblastoma. The diagnosis of metastatic medulloblastoma is usually suspected clinically or radiographically, and is uncommonly confirmed by cytologic evaluation. Here we report on a rare case of FNAB used to diagnose metastatic medulloblastoma.
Subject(s)
Bone Neoplasms/pathology , Bone Neoplasms/secondary , Cerebellar Neoplasms/pathology , Medulloblastoma/pathology , Medulloblastoma/secondary , Pelvic Neoplasms/pathology , Pelvic Neoplasms/secondary , Adult , Biopsy, Needle , Humans , MaleABSTRACT
In contrast to peripheral nerves, damaged axons in the mammalian brain and spinal cord rarely regenerate. Peripheral nerve injury stimulates neuronal expression of many genes that are not generally induced by CNS lesions, but it is not known which of these genes are required for regeneration. Here we show that co-expressing two major growth cone proteins, GAP-43 and CAP-23, can elicit long axon extension by adult dorsal root ganglion (DRG) neurons in vitro. Moreover, this expression triggers a 60-fold increase in regeneration of DRG axons in adult mice after spinal cord injury in vivo. Replacing key growth cone components, therefore, could be an effective way to stimulate regeneration of CNS axons.
Subject(s)
Axons/metabolism , Calmodulin-Binding Proteins , Growth Cones/metabolism , Nerve Regeneration/physiology , Nerve Tissue Proteins , Neurons/metabolism , Spinal Cord/metabolism , Animals , Axons/drug effects , Axotomy , Cell Separation , Cytoskeletal Proteins/genetics , Cytoskeletal Proteins/metabolism , Cytoskeletal Proteins/pharmacology , GAP-43 Protein/genetics , GAP-43 Protein/metabolism , GAP-43 Protein/pharmacology , Ganglia, Spinal/cytology , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , Gene Expression , Growth Cones/drug effects , In Vitro Techniques , Mice , Mice, Transgenic , Nerve Growth Factors/biosynthesis , Nerve Growth Factors/genetics , Nerve Growth Factors/pharmacology , Nerve Regeneration/drug effects , Neurons/drug effects , Spinal Cord/cytology , Spinal Cord/drug effectsABSTRACT
Failure to differentiate between the different types of lumbosacral lipomas may lead to inaccurate assumptions and inappropriate management of patients. The goal of this study was to determine whether there is a difference in clinical outcome between patients with lipomyelomeningocles, intraspinal lipomas, and lipomas of the filum terminale. One hundred and fourteen patients with spinal dysraphism were seen at Duke University Medical Center between 1995-1999. All patients who had undergone previous operative intervention for these lesions were excluded. Twenty-two patients with intradural lipomas were identified. Of these, 14 (64%) had lipomyelomeningoceles and 8 (36%) had intraspinal lipomas. Twenty-five patients had filum terminale lipomas. Operative management consisted of lumbosacral laminectomies with microsurgical resection of the lipoma and division of the fatty filum. Average age at presentation in symptomatic patients with lipomas of the filum terminale was 17.7 years, and 23 years in the symptomatic intraspinal lipoma group. Patients with lipomyelomeningoceles ranged in age from 1 day to 18 years, with the majority being younger than 2 years. After an average follow-up of 8 months all patients showed improvement in motor strength following operative intervention. Greater improvements in sensory, bladder, and pain scores were associated with filum terminale lipomas. The least improvements in these categories were seen in the lipomyelomeningocele group. Motor strength is the most likely deficit to improve following operative intervention. Lipomyelomeningoceles, intraspinal lipomas, and filum termniale lipomas have different clinical outcomes following operative intervention.