Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system

Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon neoplasms derived from melanocytes that normally can be found in the leptomeninges. They cover a spectrum of malignancy grades ranging from low-grade melanocytomas to lesions of intermediate malignancy and overtly malignant melanomas. Characteristic genetic alterations in this group of neoplasms have not yet been identified. Using direct sequencing, we investigated 19 primary melanocytic lesions of the CNS (12 melanocytomas, 3 intermediate-grade melanocytomas, and 4 melanomas) for hotspot oncogenic mutations commonly found in melanocytic tumors of the skin (BRAF, NRAS, and HRAS genes) and uvea (GNAQ gene). Somatic mutations in the GNAQ gene at codon 209, resulting in constitutive activation of GNAQ, were detected in 7/19 (37%) tumors, including 6/12 melanocytomas, 0/3 intermediate-grade melanocytomas, and 1/4 melanomas. These GNAQ-mutated tumors were predominantly located around the spinal cord (6/7). One melanoma carried a BRAF point mutation that is frequently found in cutaneous melanomas (c.1799 T>A, p.V600E), raising the question whether this is a metastatic rather than a primary tumor. No HRAS or NRAS mutations were detected. We conclude that somatic mutations in the GNAQ gene at codon 209 are a frequent event in primary melanocytic neoplasms of the CNS. This finding provides new insight in the pathogenesis of these lesions and suggests that GNAQ-dependent mitogen-activated kinase signaling is a promising therapeutic target in these tumors. The prognostic and predictive value of GNAQ mutations in primary melanocytic lesions of the CNS needs to be determined in future studies.     

Primary atypical melanocytoma arising from the cavernous sinus in a child

Introduction

Primary melanocytic lesions of the central nervous system originate from leptomeningeal melanocytes, with a spectrum ranging from well-differentiated benign meningeal melanocytomas to malignant melanomas. Atypical melanocytomas are borderline tumors, which have clinical and pathological characteristics between benign melanocytomas and malignant melanomas. Melanocytomas are rare in children and infrequently arise from the cavernous sinus. Approximately five patients with such an origin site have been reported.

Materials and methods

We report a 15-year-old girl with an atypical melanocytoma arising from the cavernous sinus. She underwent partial resection of the tumor and postoperative gamma knife surgery (GKS). She is stable 39 months after surgery.

Conclusion

We discuss the first pediatric case with an intracranial atypical melanocytoma arising from the cavernous sinus.

     

中枢神经系统原发性黑色素肿瘤的临床特征及病理特征分析

目的探讨中枢神经系统原发性黑色素肿瘤的临床表现、病理特征及手术效果。方法回顾性分析2003年3月至2017年2月手术治疗的3例中枢神经系统原发性黑色素性肿瘤的临床资料,1例位于颞叶,1例位于小脑,1例位于右侧桥小脑角区。结果 2例全切,1例次全切。术后随访1~3个月,3例一般情况良好。结论中枢神经系统原发性黑色素肿瘤确诊依赖病理检查,临床分型对判断预后有重要意义。     

Multiple calcifying pseudoneoplasms of the neuraxis

Calcified pseudoneoplasms of the neuraxis (CAPNON) are a rare diagnostic entity. They have been reported intra‐cranially as well as in the spine, and are most commonly found at the skull base. This is a case report of a 38‐year‐old woman who presented with bilateral CAPNON, diagnosed 8 years apart. While there are approximately 46 reported in the current literature of cerebral and spinal fibro‐osseous lesions, this is the first report of separate lesions.     

Primary spinal melanoma: A case report

Primary spinal cord melanoma is a rare disease that accounts for only 1% of all melanocytomas. Here we report a case of primary melanoma of the cervical spinal cord. In our case, 26-year-old female who were admitted to the hospital for left arm pain. Spinal magnetic resonance image (MRI) revealed a spinal cord tumor at the level of C2-3. The MRI images showed that the tumor compressed the spinal cord. At surgery, the spinal cord was under pressure and covered with shaped blackish brown neoplastic tissue. There were not any metastatic lesions. The patient is still alive six months after surgery.     

Spinal-cord MRI in multiple sclerosis

The potential of MRI of the spinal cord as a diagnostic tool in MS has recently gained much interest. Dual echo spin echo MRI is most sensitive for the detection of spinal-cord abnormalities, which range from multiple focal lesions to confluent areas of high signal intensity. In some patients, commonly those with primary progressive disease, diffuse areas of slightly increased signal intensity are found. Disappointingly, the relation between MRI findings and clinical disability is weak. Studies relating MRI findings with histopathology have revealed substantial axonal loss in the spinal cords of patients with MS, whether focal lesions are present of not. Further, diffuse cord atrophy is found in advanced MS, which may reflect axonal loss. In the diagnostic setting, spinal-cord imaging is valuable. First, asymptomatic spinal-cord lesions are very rare in disorders other than MS. For example, in a patient with equivocal brain findings such as an elderly patient with vascular-ischaemic lesions, a normal spinal-cord examination can help rule out MS. Second, presence of asymptomatic spinal lesions may help confirm a diagnosis of MS when few or no brain lesions are present.     

Expanded endonasal endoscopic approach for resection of a large skull base aneurysmal bone cyst in a pediatric patient with extensive cranial fibrous dysplasia

Aneurysmal bone cysts (ABCs) are uncommon non-neoplastic, hemorrhagic, and expansile osseous lesions. These lesions most commonly occur in the first two decades of life and affect the long bones and spinal column. Skull base involvement is rare. The authors report the case of a 16-year-old boy who presented with acute visual decline and was found to have a large skull base ABC centered in the sphenoid sinus. In addition, the patient had extensive cranial fibrous dysplasia. The patient underwent a staged expanded endonasal endoscopic approach for complete resection of this lesion with excellent return of his vision. This case adds to the growing body of evidence supporting a role for expanded endonasal endoscopic procedures in pediatric patients with skull base pathologies.     

Acute, monocular vision loss from Rathke's cleft cyst

Rathke's cleft cysts are benign, non-neoplastic sellar lesions that are often asymptomatic. The rare patient with symptoms may present with pituitary dysfunction, headache, or visual problems. Visual deficits are generally consistent with a chiasmal syndrome as associated with other sellar lesions. Therefore, the most commonly described deficit is bitemporal hemianopsia. We describe a 16-year-old female patient who presented with rare, rapidly progressing monocular blindness without signs of apoplexy or hemorrhage. She had complete return of vision after surgical decompression. The rapid loss and recovery of vision suggest that ischemic factors, rather than deformation of the optic apparatus, contributed to her symptoms. The relevant literature is reviewed.     

Spinal arachnoid cyst without neural tube defect

Symptomatic arachnoid cysts of the spine are rare lesions in the pediatric age group. Although most commonly occurring in association with neural tube defects, such as myelomeningocele and diastematomyelia, in some cases the cysts appear in children without spinal anomalies. We describe a 12-month-old girl with lumbar intradural arachnoid cyst with progressive weakness of the lower limbs. There was full recovery after fenestration of the cyst. Received: 27 March 2000 Accepted: 24 May 2000     

Primary cerebellopontine angle melanoma: a case report and review

Primary melanomas at the cerebellopontine (CP) angle are extremely rare and considered a diagnostic dilemma. With only 16 prior cases reported so far, there is not enough material in world literature. We report a 29-year-old male who presented with vertigo, headache and features of lower cranial nerve involvement with MRI revealing a melanotic lesion at CP angle. The patient underwent right suboccipital craniectomy and only subtotal excision of the tumor was possible. Histopathologically it turned out to be malignant melanoma. Since a thorough search for any possible primary was futile, it was considered a primary melanoma. Patient was given adjuvant radiotherapy. Ten months later, he presented with weakness and multiple spinal metastases and two months later he succumbed to his disease. We did a comprehensive review of literature about various melanocytic tumors at the CP angle. Pathologically, melanocytic tumors range from benign melanocytomas to malignant melanoma with variable prognosis. The clinical presentation depends upon whether the lesions are diffuse or discrete. Surgery is the primary modality of treatment and the amount of tumor excised is related to the prognosis. We conclude the discussion with a novel classification for melanotic tumors of CNS and the current diagnostic pathway for a melanotic lesion at the CP angle.     

Hamartomas and epilepsy: clinical and imaging characteristics.

PURPOSE: Cerebral hamartomas are lesions marked by a disorganized arrangement of mature neural elements and represent a rare cause of medically intractable focal epilepsy. We present the clinical presentation and imaging findings of this rare entity. METHODS: History and neurophysiological studies of 14 patients with pathologically confirmed hamartomas who had surgery for intractable focal epilepsy were reviewed. MRIs were available for review in 10 patients. RESULTS: The lesions were most commonly located in the temporal and frontal lobes. Seizure semiology was concordant with the anatomic location of the hamartoma in all patients. Nine of the thirteen patients (69%) with the hamartoma confined to one lobe had interictal spikes and sharp waves at the corresponding electrodes. The ictal pattern was confined to the same lobe of the hamartoma in five of nine patients with ictal recordings. Although imaging characteristics were variable, all patients had signal increase on T2-weighted images and 50% of them had mild mass effect. Neocortical involvement was present in the majority of patients (7/10), blurring of the gray/white matter interface was seen in seven patients. Five of those seven patients were found to have associated cortical dysplasia by pathology. CONCLUSION: Hamartomas represent a rare entity and may cause devastating epilepsy. Imaging characteristics are difficult to distinguish from those of some other developmental tumors. Hamartomas are frequently associated with microscopic cortical dysplasia (CD), thus underlining their malformative etiology.     

Giant,calcified colloid cyst of the lateral ventricle

We report a patient with a giant, calcified colloid cyst in the left lateral ventricle. Colloid cysts are slow growing, benign lesions, commonly originating in the roof of the anterior third ventricle near the foramen of Monro. Many colloid cysts are small lesions which are either discovered incidentally or cause headache, visual changes, memory deficits, and/or syncope. Giant colloid cysts are rare. A 40-year-old man presented with a month long history of worsening headaches and was found to have a multiloculated 5 cm intraventricular mass with an anterior hyperdensity, suggestive of calcification, arising within the lateral ventricles. He underwent an interhemispheric transcallosal approach for resection of the mass. The pathology was consistent with a giant colloid cyst with calcification in the anterior cyst wall. Giant, calcified mass is a rare presentation of colloid cyst. Although rare, this diagnosis remains an important consideration in the differential diagnosis of any calcified, cystic intraventricular mass.     

Cerebellopontine angle lesions in children

Background Cerebellopontine angle (CPA) lesions are more commonly found in adults in which they account for 5–10% of all intracranial tumors. However, they are uncommon in children, with an incidence of only 1%. Materials and methods This is a review of the management of CPA lesions in children admitted to the Hospital Nacional de Pediatría “Profesor Doctor Juan P. Garrahan” (Argentine National Pediatrics Hospital “Professor Juan P. Garrahan”) between January 1988 and December 2003. Results The series included 30 children with 33 CPA lesions, 20 arising from the subarachnoid space of the CPA and 13 from the vicinity and growing mainly into the CPA. Twenty-seven tumors were located in the left CPA (82%) and six (12%), on the right. Ten of the 30 patients developed hydrocephalus, but only three of these required treatment. All patients underwent retrosigmoid suboccipital craniotomy and microsurgical resection. Gross total removal was achieved in 12 cases, subtotal in 18, and fenestration of the cyst wall in the three arachnoid cysts. Ten patients have no sequelae, ten have mild deficit, three have severe deficits, and seven have died. Conclusion The CPA is a rare location for lesions in children, with clear predominance on the left side. Benign lesions are more frequent. Even though schwannoma is the most frequently found lesion, the histology varies widely.     

Intracranial lipomas--a clinical study

OBJECTIVE: This study aimed to investigate the localization of the lipoma, as well as associated intracranial and extracranial lesions in 14 patients immediately following hospital admission. The pathological findings from the neurological examinations of these patients are also investigated. METHODS: Fourteen patients who were admitted to our clinic with a variety of symptoms and diagnosed with intracranial lipoma were included in the study. Problems presented upon admission, neurological findings, and other existing system abnormalities were evaluated. Localization of the lipomas and accompanying pathologies were determined by using computerised tomography and magnetic resonance imaging. RESULTS: The most frequent reasons for admission of patients with intracranial lipomas were: headache 7 (50%), trauma 3 (21.5%), epilepsy 3 (21.5%) and one with symptoms due to the local mass effect of tumor (7%). Although the pericallosal region is accepted as the region where lipomas commonly occur, this study found the most frequent occurrence in the quadrigeminal cistern. Intracranial lipoma calcification was only evident in 1 of the 14 patients. In addition, contrary to the expectations, intracranial and extracranial lesions accompanying lipomas were rare. All patients received systematic treatment. CONCLUSION: This study showed that intracranial lipomas are more frequent in the quadrigeminal region of the brain; most are asymptomatic, generally caught incidentally; and accompanying intracranial and extracranial pathologies are less common than expected.     

Convexity dural chondroma: a case report and review of the literature.

The majority of intracranial chondromas arise from cartilage rests in the synchondrosis at the base of the skull. Chondromas are most commonly found in the sellar and parasellar regions, usually located extradurally. In rare instances, these tumours originate from the dura mater of the convexity. We report a rare case of a chondroma arising from the convexity dura mater. The origin of this tumour is analysed and the literature reviewed.     

Medullary neurosarcoidosis presenting with intractable hiccoughs

Hiccoughs (singultus) are a complex physiological process characterized by sudden brief involuntary contractions of the diaphragm. They most commonly occur from peripheral mechanisms that result in diaphragmatic irritation, but also occur from brain stem lesions such as that seen in Wallenberg's syndrome. They are uncommon in sarcoidosis and it is remarkably rare when hiccoughs are the presenting symptom of neurosarcoidosis. We report a patient with sarcoidosis who presented with intractable hiccoughs due to an inflammatory medullary lesion. Evaluation revealed an enhancing lesion in the dorsomedial medulla that resolved after aggressive immune-modulating therapy. In the absence of a clear peripheral lesion that would potentially affect the diaphragm, the diagnosis of neurosarcoidosis involving the brainstem should be considered in patients with sarcoidosis.     

Lemierre’s Syndrome presenting with neurological and pulmonary symptoms: Case report and review of the literature

Lemierre’s Syndrome (LS) is a potentially life-threatening condition, characterized by clinical or radiologic evidence of internal jugular vein thrombosis following an oropharyngeal infection, most commonly by Fusobacterium necrophorum. A high index of suspicion and early recognition is important for successful management and to prevent systemic complications like multiorgan failure with extremely high morbidity, prolonged hospitalization and, not uncommonly, death. We are reporting a rare case of LS that was complicated with internal jugular vein and cavernous sinus thrombosis along with lung metastatic lesions, which was diagnosed and treated at our institute.     

Clinical and imaging features of the room tilt illusion

Room tilt illusion (RTI) is a transient disorder of the environmental visuo-spatial perception consisting of paroxysmal tilts of the visual scene. It is attributed to an erroneous cortical mismatch of the visual and vestibular three-dimensional coordinate maps. Thirteen subjects were included in this retrospective case series. Clinical presentation was 180o rotation of the visual scene following the coronal plane in seven patients. The most common cause for RTI in our series was posterior circulation ischaemia (five cases). Cases of endolymphatic sac tumour, critical illness neuropathy, acute traumatic myelopathy and multiple system atrophy causing RTI are reported for the first time. No case of supratentorial focal lesion was found. In order to describe the clinical and imaging features of RTI, 135 cases previously reported in the literature were reviewed along with our series. There was a male predominance (60.2?%). Mean age was 51.2?±?20.3?years. The most common location of the injury was the central nervous system (CNS) (61.4?%). Supratentorial and infratentorial structures accounted for the same frequency of lesions. The most common aetiology was cerebral ischaemia (infarction or transient ischaemic episode; 27.7?%). These patients were significantly older and their lesions commonly involved posterior fossa structures when compared to patients with non-vascular disorders. In summary, RTI is a manifestation of several CNS and vestibular disorders, and rarely of peripheral nervous system disorders, triggered by disruption of vestibular and sensory perception or integration. Cerebral ischaemic disorders are the most common aetiology for this rare syndrome.     

Primary solitary hydatid cyst in paraspinal cervical muscles: a case report and review of the literature

Hydatid disease caused by Echinococcus granulosus and Echinococcus multilocularis commonly presents with pulmonary and hepatic cysts. Primary paraspinal muscle cysts are a rare presentation. We report a case of hydatid cyst within paraspinal muscles presenting with cervical mass and associated pain. The hydatid disease serological test was negative. Neither hepatic nor pulmonary cystic lesions were found. Radiographic findings were unspecific for hydatid cysts. Surgical resection was planned due to the provisional diagnosis of muscular cystic neoplasm. During surgery, a cyst containing a clear liquid was found. The cyst wall was excised and the surgical field was irrigated with hypertonic saline. The patient's symptoms resolved by discharge day. Postoperative pathological examinations revealed a muscular hydatid cyst.