Composite phaeochromocytoma with malignant peripheral nerve sheath tumour: A case report with summary of prior published cases.

Composite phaeochromocytomas (CP) are extremely uncommon adrenal medullary tumours where phaeochromocytoma coexists with another adrenal medullary tumour also of neural crest origin. CP includes combination of phaeochromocytoma along with a component of neuroblastoma, ganglioneuroblastoma, ganglioneuroma, benign nerve sheath tumour or a malignant peripheral nerve sheath tumour (MPNST). Here we describe the morphological and immunohistochemical details of a case of CP with MPNST in a 30 years old lady, without history of neurofibromatosis. Only 6 cases of CP with MPNST have been reported so far. We have tabulated a summary of these prior published cases of phaeochromocytoma with MPNST. To our knowledge, this is the first literature review describing the clinico-pathological characteristics of these rare tumours.

A Rare WHO Grade I Lesion of the Posterior Fossa with Recurrence Biological Behavior ­ Dysplastic Gangliocytoma of the Cerebellum: Case Report

Dysplastic gangliocytoma of the cerebellum (DGC) or Lhermitte-Duclos Disease is a rare lesion (World Health Organization [WHO] grade I) characterized by thickened folia and replacement of the internal granular layer by abnormal ganglion cells. More commonly, the compromised patients are young adults presenting ataxia, seizures, obstructive hydrocephalus, and increased intracranial pressure. Dysplastic gangliocytoma of the cerebellum is intimately associated with Cowden syndrome, a hereditary disorder caused by a germline mutation in the PTEN tumor suppressor gene on chromosome 10q23. Large neurons of DCG show vesicular nuclei with prominent nucleoli. Expansion of the internal granular layer determines vacuolization of the molecular layer and white matter, which can be related to the bright stripes identified on T2-weighted magnetic resonance imaging. Herein, the authors report a female patient who developed long- time recurrence of DGC and discuss pathological findings and differential diagnosis of this rare cerebellar lesion.

Lhermitte-Duclos Disease and Cowden Syndrome: A Case Report and Literature Review

Lhermitte-Duclos disease (LDD), also known as dysplastic gangliocytoma of the cerebellum, is a rare, usually benign, slow-growing tumor, that commonly affects patients aged 30 to 50 years-old. The manifestations of dysplastic cerebellar gangliocytoma are nonspecific and are related both to the mass effect produced by its growth and to the location of the lesion. Cerebellar symptoms such as ataxia are often present. In 40% of cases, the tumor is associated with Cowden syndrome, which is part of a group ofgenetic disorders called polypoid hamartoma complex. In this case report, the patient presented expansive lesion in the posterior fossa, compatible with LDD, associated with macrocephaly. These findings are consideredmajor criteria for Cowden syndrome. When together, they confirm the diagnoses. To our knowledge, this is the first report of the association of LDD and Cowden syndrome in Brazil.

Long-term follow-up results of the observation program for neuroblastoma detected at 6-month mass screening.

We conducted an observation program of neuroblastoma in infants, detected by mass screening at 6 months of age; we followed up with them for 15 years. No recurrence was observed after disappearance of tumors, and persistent tumors showed no malignant transformation or metastasis. Histology of the resected tumors showed age-related differentiation.

A practical guide for the diagnosis of primary enteric nervous system disorders.

OBJECTIVE: Primary gastrointestinal neuropathies are a heterogeneous group of enteric nervous system (ENS) disorders that continue to cause difficulties in diagnosis and histological interpretation. Recently, an international working group published guidelines for histological techniques and reporting, along with a classification of gastrointestinal neuromuscular pathology. The aim of this article was to review and summarize the key issues for pediatric gastroenterologists on the diagnostic workup of congenital ENS disorders. In addition, we provide further commentary on the continuing controversies in the field. RESULTS: Although the diagnostic criteria for Hirschsprung disease are well established, those for other forms of dysganglionosis remain ill-defined. Appropriate tissue sampling, handling, and expert interpretation are crucial to maximize diagnostic accuracy and reduce interobserver variability. The absence of validated age-related normal values for neuronal density, along with the lack of correlation between clinical and histological findings, result in significant diagnostic uncertainties while diagnosing quantitative aberrations such as hypoganglionosis or ultrashort Hirschsprung disease. Intestinal neuronal dysplasia remains a histological description of unclear significance. CONCLUSIONS: The evaluation of cellular quantitative or qualitative abnormalities of the ENS for clinical diagnosis remains complex. Such analysis should be carried out in laboratories that have the necessary expertise and access to their own validated reference values.

Dumbbell ganglioneuroma mimicking lumbar neurofibroma: a case report and review of the literature.

Spinal ganglioneuromas may grow in a dumbbell fashion. We report the first case of an intradural, extramedullary ganglioneuroma in the lumbar spine and review the pertinent literature. Although rare, we propose that ganglioneuroma be considered a differential diagnosis in patients presenting with a large mass occupying both intraspinal and extraspinal compartments.

Ganglioneuroma de glándula suprarrenal / Adrenal ganglioneuroma

OBJETIVO: Presentar el caso clínico de un ganglioneuroma de suprarrenal diagnosticado, en un adulto, de manera incidental. MÉTODOS/RESULTADOS: Mujer de 44 años diagnosticada de incidentaloma de 2,3 cm en la glándula suprarrenal izquierda en un TAC realizado por estudio de hemoptisis. Con estudio analítico completo de masa suprarrenal no funcionante, se realizó a los 6 meses una RMN en la que se objetiva un nódulo suprarrenal izquierdo de 3,7 cm. Ante el crecimiento progresivo de la masa se decide tratamiento quirúrgico mediante suprarrenalectomía laparoscópica izquierda, estableciendo el diagnóstico anatomopatológico definitivo de ganglioneuroma de glándula suprarrenal. CONCLUSIÓN: El Ganglioneuroma es un tumor caracterizado por una mezcla de células de Schwann y células ganglionares maduras. Su localización en la glándula suprarrenal es inusual, presentando predisposición por otras regiones. Al tratarse de lesiones asintomáticas suelen ser detectadas de manera incidental al realizar una prueba de imagen. Presenta unas características radiológicas que lo diferencian del resto de masas suprarrenales. El tratamiento es quirúrgico, mediante suprarrenalectomía (AU)

OBJECTIVE: To present one case of adrenal ganglioneuroma incidentally diagnosed in an adult. METHODS/RESULTS: 44-year-old woman with a 2.3 cm incidentaloma in the left adrenal gland diagnosed by CT scan. At 6 months, MRI was performed and a left adrenal nodule 3.7 cm was shown. Due to the progressive growth of the mass, surgery was indicated and left laparoscopic adrenalectomy was carried out. The final pathologic diagnosis was adrenal ganglioneuroma. CONCLUSIONS: The ganglioneuroma is a tumor composed of Schwann cells and ganglion cells. Its location in the adrenal gland is unusual, most frequently affecting other regions. Being asymptomatic lesions, they are often detected incidentally when performing imaging tests. There are radiological features that differentiate them from other adrenal masses. The treatment of choice is surgery, with adrenalectomy (AU)

Manifestaciones radiológicas del ganglioneuroma mandibular en edad pediátrica / Imaging signs of ganglioneuroma of the mandible in a seven-year-old girl

El ganglioneuroma es una neoplasia benigna, rara en la edad pediátrica. Está formado por células ganglionares maduras, células de Schwann y tejido conectivo. Las localizaciones más frecuentes son el mediastino posterior, el retroperitoneo, la glándula suprarrenal y el cuello, siendo excepcional su desarrollo en el hueso. Presentamos el caso de una niña de 7 años diagnosticada de un ganglioneuroma intraóseo mandibular, tratada hace 5 años de neuroblastoma suprarrenal (estadio M). A la paciente se le realizó una gammagrafía ósea y una tomografía computarizada (TC) mandibular, donde se observó una lesión en la rama mandibular derecha. En este artículo desarrollaremos el diagnóstico diferencial de las mismas y las principales manifestaciones radiológicas. El número de lesiones óseas mandibulares en la edad pediátrica es muy amplio y la apariencia radiológica de la mayoría de estas es inespecífica (AU)

Ganglioneuromas are benign tumors that are rare in children. They are made up of mature ganglion cells, Schwann cells, and connective tissue. The most common sites involved are the posterior mediastinum, retroperitoneum, suprarenal gland, and neck. They rarely involve bone. We present the case of a seven-year-old girl diagnosed with an intraosseous ganglioneuroma in the mandible. She had been treated for a suprarenal neuroblastoma (stage M) five years earlier. Bone scintigraphy and computed tomography of the mandible showed a lesion in the right mandibular ramus. Many osseous lesions can affect the mandible in children and the radiological appearance of most of them is unspecific. We discuss the differential diagnosis and main imaging findings of osseous lesions involving the mandible in children (AU)

Loss of mitochondria in ganglioneuromas.

A shift in cellular energy production from oxidative phosphorylation (OXPHOS) to glycolysis, even under aerobic conditions, is called the Warburg effect. To elucidate changes of the mitochondrial energy metabolism in ganglioneuroma (GN) individual OXPHOS enzymes were analyzed by activity assays and by immunohistochemical staining methods. GN (n=7) showed a significant reduction in the activity and content of OXPHOS enzymes. Citrate synthase activity was also severely diminished in GN compared to normal cortical kidney (p=0.0002) and adrenal (p=0.0024) tissues. Furthermore, the mitochondrial membrane protein porin was undetectable or significantly reduced. Accordingly, a reduction of the copy number of mitochondrial DNA was observed in GN compared to cortical kidney tissue. The striking decline of mitochondrial mass is specific for GN but not for neuroblastoma, in which a reduction of the OXPHOS complexes without reduction of mitochondrial mass was reported. Knowledge of the mechanism by which tumor cells achieve the Warburg effect will provide a starting point for functional studies aimed at restoring aerobic energy metabolism as a potential new therapeutic strategy to treat malignancies.

Intraoperative neurophysiological monitoring during complex spinal deformity cases in pediatric patients: methodology, utility, prognostication, and outcome.

INTRODUCTION: Complex spinal deformity (CSD) problems in pediatric patients result from a wide variety of congenital, acquired, neoplastic, or traumatic abnormalities that result in a combination of spinal deformity and spinal cord impingement. While these problems are rare, decompression, correction, instrumentation, and fusion are quite hazardous. Intraoperative neurophysiological monitoring (IONM) seems particularly beneficial in these patients. METHODOLOGY: Somatosensory evoked potentials, transcranial electrical motor evoked potentials (MEPs), direct waves, and electromyography were used in a variety of CSD cases over a period when IONM was routine for most spinal cases. Examples of cases in which IONM provided important intraoperative information and significantly affected the course of the operation are illustrated. RESULTS: IONM is a useful tool particularly in CSD cases in pediatric patients but requires special expertise and anesthetic considerations. Loss of MEP appears to have particularly important adverse prognostic information. Conversely, maintenance of IONM provides significant reassurance that the spinal cord function is being maintained. Preserved but persistently diminished MEPs usually predict a neurological injury that will significantly improve and possibly completely recover. Issues concerning training, certification, oversight, standardization of equipment, and technique are partially but incompletely resolved. DISCUSSION: IONM is an extremely valuable tool for management of CSD pediatric patients. The utility of IONM is such and the detection of unexpected or unanticipated neurological injury frequent enough that a strong argument that it be used in every spinal surgery case can be made.

Advanced MR imaging in Lhermitte-Duclos disease: moving closer to pathology and pathophysiology.

INTRODUCTION: Lhermitte-Duclos disease (LDD, dysplastic gangliocytoma) is an extremely rare cerebellar lesion of uncertain etiology. The debate as to whether it constitutes a neoplastic, malformative, or hamartomatous lesion is still continuing. In this report we explore the usefulness of susceptibility-weighted imaging (SWI), diffusion weighted imaging (DWI), perfusion imaging, and chemical shift imaging (CSI) in demonstrating the pathology and pathophysiology in two patients with LDD. METHODS: MR imaging of the brain and the cervicodorsal spine was performed on a 1.5-T scanner in a 47-year-old woman presenting with numbness and paresthesia of both upper and lower limbs, and in a 17-year-old male with right frontal headache associated with neck pain. RESULTS: Routine imaging in the first patient showed a left-side cerebellar mass with characteristic 'tiger-striped' thick folia associated with Chiari I malformation, tonsillar herniation and cervicodorsal syringomyelia and in the second patient a right cerebellar mass with similar findings. The SWI demonstrated the characteristic deep running veins between the folia, which is thought to be the cause for vascular contrast enhancement. Diffusion showed a T2 shine-through effect with mild increased diffusivity, and perfusion showed increase in relative cerebral blood volume, relative cerebral blood flow, and mean transit time in the lesion. MR spectroscopy demonstrated reduction in metabolites and a prominent lactate peak in both the patients. The pathological and pathophysiological significance of these findings is discussed. CONCLUSION: MRI with the newer imaging capabilities can demonstrate the pathology and pathophysiology in Lhermitte-Duclos disease better. SWI helps in detecting the veins around the thickened folia.

Retroperitoneal ganglioneuroma with lymphnode metastasis: a case report.

Ganglioneuroma is a benign, most differentiated tumor of neural crest origin. These tumors though benign, can very rarely metastasize to regional lymphnodes or to distant sites. We report a case of a 52 year old lady who presented to the surgical OPD with dyspeptic symptoms of 2 months duration. Ultrasonography and CT scan of the abdomen showed a homogenous mass in the region of the right adrenal gland, extending between the inferior vena cava and the aorta. A clinical and radiological diagnosis of an adrenal tumor was made. Microscopically, the tumor histology was that of a ganglioneuroma (schwannian stroma-dominant) mature type. The lymph node attached to the tumor showed metastasis, the metastatic foci having the same morphology as the primary tumor. The right adrenal gland was free of tumor. The case is illustrative due to its clinical presentation mimicking an adrenal incidentaloma, and a rare phenomenon of a benign tumor exhibiting completely differentiated lymph node metastasis.

Microsurgical excision of ganglioneuroma arising from the C8 nerve root within the neuroforamen.

Ganglioneuromas are benign, slow-growing tumors originating from sympathetic nerves or peripheral nerves, often associated with multiple tumor syndromes. They occasionally occur as spinal lesions and grow within the spinal canal or as paraspinal lesions. In this report, we describe a rare solitary ganglioneuroma arising from the cervical nerve root (C8) within the intervertebral foramen in adults. The tumor could be detected as a mass limited to the neuroforamen at an early stage by MR images. Unilateral microsurgical foraminotomy and EN BLOC resection of the tumor resulted in disappearance of the symptoms. Microsurgical resection of the relevant nerve root through limited medial foraminotomy at an intricate anatomical region of the cervico-thoracic junction was appropriate in the current case for complete resection of the tumor as well as to prevent postoperative structural weakness that could result in late segmental instability.

Ampullary ganglioneuroma: an unusual feature of neurofibromatosis type 1--a case report.

The case of a 65 year old man is presented. He had a history of dyspepsia and was diagnosed as neurofibromatosis clinically. Upper G.I. endoscopy showed thickened folds in duodenum. A polyp was seen at the junction of D1 and D2 adjacent to the ampulla. Duodenal biopsy results were suggestive of ganglioneuroma.

Lhermitte-Duclos disease: a report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathway.

Lhermitte-Duclos disease (LDD) is a rare cerebellar tumor associated with Cowden disease (CD) and germline mutations in the PTEN gene. To further define these relationships, we reviewed clinical and pathologic findings in 31 LDD cases and analyzed the status of the PTEN pathway in 11 of them. We hypothesized that the granule cell hypertrophy in LDD is secondary to activation of mammalian target of rapamycin (mTOR), a downstream effector in the PTEN/AKT pathway and a major regulator of cell growth. Histopathologically, in addition to the classical findings of LDD, we observed prominent vascular proliferation and vacuolization of the white matter in many of the lesions. Four patients met diagnostic criteria for CD, and many of the remaining patients had some clinical features of CD. Immunohistochemical analysis showed high levels of phospho-AKT and phospho-S6 in the large ganglionic cells forming the lesions, indicating activation of the PTEN/AKT/mTOR pathway and suggesting a central role for mTOR in the pathogenesis of LDD. These data support recommendations for genetic testing and screening for CD in patients with LDD and suggest a novel therapy for LDD through pharmacologic inhibition of mTOR.

Atypical ganglion cell tumor of the sciatic nerve.

CONTEXT: Although herniation of a lumbosacral intervertebral disk is a major cause of sciatic distribution pain, relentlessly progressive symptoms or signs should alert one to the possibility of a tumor involving the nerve. OBJECTIVE: To describe the clinical, neurophysiological, and histological features of a pathologically unique tumor involving the sciatic nerve. SETTING: Tertiary referral university hospital. PATIENT: A 36-year-old woman was seen with a 6-year history of increasingly severe symptoms in the distribution of the left sciatic nerve. RESULTS: Electromyography indicated a sciatic nerve lesion in the region of the greater sciatic notch. Magnetic resonance imaging demonstrated a tumor involving the left sciatic nerve in this area. Light microscopy, electron microscopy, and immunohistochemistry results confirmed the presence of an atypical ganglion cell tumor of the sciatic nerve that exhibited prognostically conflicting clinical and histological features. CONCLUSIONS: To our knowledge, this is the first report of an atypical ganglion cell tumor affecting the sciatic nerve, and illustrates the value of detailed neurophysiological examination in localizing the site of peripheral nerve injury to facilitate focused neuroimaging when standard investigations are uninformative. Longer follow-up is required to determine the true biologic potential of this lesion.

Ganglion cells in the posterior pituitary: result of ectopia or transdifferentiation?

Histologic examination revealed large ganglion cells within the posterior pituitary of an 80-year-old woman who died of myocardial infarction. Apparently fully mature, the cells were an incidental finding scattered within hyperplastic foci of pars intermedia (PI)-derived cells (basophil invasion) on histologic examination of the pituitary obtained at autopsy. Immunocytochemistry showed staining reactivity for neuron-specific enolase, synaptophysin, alpha subunit of the glycoprotein hormones and beta-endorphin. The presence of these ganglion cells with features similar to those of magnocellular hypothalamic neurons could be considered the result of abnormal migration during the early phase of embryonic life, or differentiation/maturation of neuroblasts, presumed to occur in the embryonic neurohypophysis. Alternatively, transdifferentiation from proliferating PI cells may explain the emergence of neurons; a hypothesis supported by the proximity and shared alpha subunit, and beta-endorphin immunoreactivities of the two cell types.

The human cerebellum and associative learning: dissociation between the acquisition, retention and extinction of conditioned eyeblinks.

The present paper is part of a systematic exploration of the neural substrates of conditioned eyeblink responses in humans. Normal subjects and patients with lesions restricted to the cerebellum were examined for their ability to acquire new classically conditioned eyeblinks to an auditory conditioned stimulus and whether they were able to perform and extinguish a previously learned natural anticipatory eyeblink response - the kinesthetic threat eyeblink response (KTER). In classical conditioning to an auditory conditioned stimulus, cerebellar patients failed to acquire new conditioned responses. In contrast to this impairment, in the KTER task both cerebellar patients and control subjects exhibited a high incidence of anticipatory eyeblinks which were initiated before the forehead tap. These results indicate that the cerebellar circuits, which are critical for the acquisition of new conditioned responses, are not essential for the storage and expression of naturally acquired conditioned responses. In the extinction experiment, cerebellar patients failed to extinguish their KTERs. This finding suggests that in humans, the acquisition of new and the extinction of previously learned conditioned responses depends on a similar set of cerebellar circuits.