Review: Challenges in the histopathological classification of ganglioglioma and DNT: microscopic agreement studies and a preliminary genotype-phenotype analysis.

Low-grade epilepsy-associated brain tumours (LEAT) are the second most common cause for drug-resistant, focal epilepsy, that is ganglioglioma (GG) and dysembryoplastic neuroepithelial tumours (DNT). However, molecular pathogenesis, risk factors for malignant progression and their frequent association with drug-resistant focal seizures remain poorly understood. This contrasts recent progress in understanding the molecular-genetic basis and targeted treatment options in diffuse gliomas. The Neuropathology Task Force of the International League Against Epilepsy examined available literature to identify common obstacles in diagnosis and research of LEAT. Analysis of 10 published tumour series from epilepsy surgery pointed to poor inter-rater agreement for the histopathology diagnosis. The Task Force tested this hypothesis using a web-based microscopy agreement study. In a series of 30 LEAT, 25 raters from 18 countries agreed in only 40% of cases. Highest discordance in microscopic diagnosis occurred between GG and DNT variants, when oligodendroglial-like cell patterns prevail, or ganglion cells were difficult to discriminate from pre-existing neurons. Suggesting new terminology or major histopathological criteria did not satisfactorily increase the yield of histopathology agreement in four consecutive trials. To this end, the Task Force applied the WHO 2016 strategy of integrating phenotype analysis with molecular-genetic data obtained from panel sequencing and 450k methylation arrays. This strategy was helpful to distinguish DNT from GG variants in all cases. The Task Force recommends, therefore, to further develop diagnostic panels for the integration of phenotype-genotype analysis in order to reliably classify the spectrum of LEAT, carefully characterize clinically meaningful entities and make better use of published literature.

Thyroid metastasis from renal cell carcinoma-A case report after 9 years.

INTRODUCTION: The thyroid gland is a rare site of clinically detectable tumor metastasis. As thyroid tumors are usually assumed to be primary in origin, its recognition as a secondary is difficult. PRESENTATION OF CASE: We report a case of an 80-year old female who was referred to the Department of Surgery for a symptomatic thyroid nodule. Her medical history included a radical nephrectomy for renal cell carcinoma (RCC) nine years ago. During follow-up a pancreatic nodule was noted suggestive of a neuroendocrine tumor and the von Hippel-Lindau syndrome had to be ruled out. The fine-needle aspiration biopsy (FNAB) guided by ultrasound (US) of the thyroid nodule was inconclusive and a hemithyroidectomy and isthmectomy were performed. Histological examination revealed metastasis of a clear cell carcinoma. DISCUSSION: RCC disseminates in an unpredictable manner and can show late recurrences. Although secondary involvement of the thyroid gland by RCC is rare, it is still one of the more common neoplasms to metastasize to this site. There are no specific clinical features and few characteristic findings of metastatic thyroid carcinoma on imaging studies. FNAB is a useful procedure to diagnose metastatic thyroid cancer, but one should remain suspicious when the result for malignant cells is negative or indeterminate. After thyroidectomy the diagnosis of RCC is confirmed immunohistochemically. There is a clear survival benefit if a surgical approach to the thyroid metastasis is chosen. CONCLUSION: Thyroid metastasis should be considered in patients with a thyroid nodule and positive history for RCC.

Dermatosis de presentación neonatal en madre e hija: «incontinentia pigmenti» / Neonatal presentation dermatosis in mother and daughter: incontinentia pigmenti

Introducción: La presentación neonatal de las dermatosis vesiculosas supone numerosos diagnósticos diferenciales. Caso clínico: Recién nacido de sexo femenino que en el primer día de vida presentó lesiones vesiculosas de distribución lineal, más marcadas en las extremidades inferiores. En el día 4 se inició tratamiento con flucloxacilina intravenosa debido a una infección secundaria de las lesiones (10 días de tratamiento). Los marcadores de infección sistémica fueron negativos, y sólo destacaba una eosinofilia. La biopsia de piel mostró el estadio vesiculoso de incontinentia pigmenti. La evolución se caracterizó por una recurrencia de las lesiones en las primeras semanas de vida y el desarrollo posterior de una lesión verrugosa. La paciente tenía antecedentes maternos de lesiones similares al nacer; actualmente la madre tiene alopecia cicatricial e hipopigmentación de las extremidades inferiores. Conclusión: La incontinentia pigmenti es una genodermatosis sistémica rara que afecta al sexo femenino. La distribución típica de las lesiones cutáneas junto con una historia similar en las mujeres de la familia son factores que sugieren la presencia de esta entidad clínica (AU)

Introduction: Neonatal presentation of a vesicular dermatosis puts many differential diagnoses. Case report: Newborn female who presented, in the first day of life, vesicular lesions of linear distribution, more pronounced in lower extremities. In day 4 started intravenous flucloxacillin because of secondary infection of the lesions (10 days of treatment). Markers of systemic infection were negative, emphasizing only eosinophilia. Skin biopsy showed the vesicular stage of incontinentia pigmenti. The evolution was characterized by recurrence of lesions in the first weeks of life and subsequent development of warty lesions. Her mother had similar lesions in the first days of life and now she has scarring alopecia and hypopigmentation of the lower extremities. Conclusion: Incontinentia pigmenti is a rare systemic genodermatosis affecting women. The typical skin lesions associated with similar story in the women of the family suggests this clinical entity (AU)

Diffuse form of dysembryoplastic neuroepithelial tumour: the histological and immunohistochemical features of a distinct entity showing transition to dysembryoplastic neuroepithelial tumour and ganglioglioma.

AIMS: A diffuse variant of dysembryoplastic neuroepithelial tumour (dDNT) has previously been described, which although composed of oligodendroglia-like cells (OLC), astrocytes and mature neurones, lacks the multinodularity and 'specific component' of typical DNT. The dDNT poses a significant challenge to the neuropathologist. This study was undertaken to further characterize the histological and immunohistochemical features of dDNT. MATERIALS AND METHODS: Review of our archived material from epilepsy surgery identified 16 cases, in which features of dDNT predominated. Their histological and immunohistochemical features, including CD34 and nestin immunohistochemistry, were analysed. RESULTS: Seven cases had the characteristics of pure dDNT. A further two cases of dDNT showed extension into the white matter with occasional dysplastic neurones. Two additional cases had similar features but with the presence of either single, or multiple small nodular clusters of OLC, in keeping with transition to classical DNT. Five cases showed ganglioglioma-like areas, of which three cases had micronodule formation but with predominant dDNT pattern. In all the cases the dDNT areas showed strong CD34 and less intense nestin immunoreactivity and microglial activation highlighting the full extent of the lesions. There was variable overlap between CD34 and nestin positivity within the micronodular and/or ganglioglioma-like areas. CONCLUSIONS: Immunoreactivity for CD34 and nestin characterizes the dDNT and helps to distinguish it from other lesions associated with epilepsy. Histological evidence indicative of transition of dDNT to other forms of DNT and ganglioglioma suggests that dDNT might be an early histogenetic form of these glioneuronal tumours.

Primary pleomorphic sarcoma of lung--11 year survival.

Primary sarcomas of the lung are uncommon, potentially aggressive neoplasms that need to be distinguished from other malignant pulmonary tumors and whose biological behavior is as yet not fully understood. Primary undifferentiated pleomorphic sarcoma was diagnosed in the right lung of a 66 year-old man, who has survived over 11 years after treatment with endobronchial tumor debulking by laser therapy and radiotherapy.

Comprehensive review of extraventricular neurocytoma with report of two cases, and comparison with central neurocytoma.

Two new cases of extraventricular neurocytoma are reported. The first concerns an 18-year-old female with a left frontal lobe lesion and the second occurred in a 54-year-old female in the thoracic spinal cord. The first patient is free of disease after 18 months of follow up. The second patient is stable after 16 months of follow up. Both were operated - total excision in Case 1 and partial resection in Case 2. The latter underwent adjuvant radiotherapy due to atypical histological features. Cases of extraventricular neurocytoma are reviewed. Differences and similarities between extraventricular and central neurocytoma are outlined.

Solitary fibrous tumor of the thoracic spine.

Intraspinal solitary fibrous tumors are rare: to our knowledge, the literature reports only 27 cases. We present a histologically and immunohistochemically confirmed solitary fibrous tumor involving the intradural extramedullary compartment of the thoracic spine. Microsurgical gross-total resection was achieved. A definitive role for adjuvant treatments in this type of tumor has not been established and therefore, they were not used. The patient was well, without clinical or radiological recurrence, 18 months after surgery.

Histologically malignant solitary fibrous tumor of the orbit.

An intra-conical histologically malignant solitary fibrous tumor of the orbit presented in a 28 year-old female with intact vision and exophthalmos. Total resection was achieved by means of a frontal craniotomy and orbital roof osteotomy. Evidence of a beneficial role for adjuvant treatments in this particular tumor is controversial and vision impairment is a possible side effect. Therefore they were not employed. The patient is well after two years of follow-up.

Cavernous malformation of the trigeminal nerve.

A cavernous malformation involving the Gasserian ganglion, 2nd and 3rd divisions of the trigeminal nerve on the left side was resected via an extradural route in a 54 year old male. Cavernous malformations of the cranial nerves are rare. Specific origin from the trigeminal nerve has not been previously reported.

Is it worth pursuing surgery for epilepsy in patients with normal neuroimaging?

OBJECTIVE: To determine whether it is worth pursuing surgery for the treatment of epilepsy in patients with normal neuroimaging. METHODS: Two patient populations were studied: (1) 136 consecutive patients who were surgically treated; (2) 105 consecutive patients assessed with chronically implanted intracranial electrodes within the same period. Sixty patients belonged to both groups, and included all 21 patients who had normal neuroimaging. RESULTS: There were no differences in the proportion of patients with favourable outcome between those with normal and those with abnormal neuroimaging, irrespective of whether intracranial recordings were required. Among the 19 operated patients with normal neuroimaging, 74% had a favourable outcome (Engel's seizure outcome grades I and II), and among the 93 patients with abnormal neuroimaging, 73% had favourable outcome (p = 0.96). In patients with temporal resections, 92% of the 13 patients with normal neuroimaging had a favourable outcome, whereas among the 70 patients with abnormal neuroimaging, 80% had a favourable outcome (p = 0.44). In patients with extratemporal resections, two of the six patients with normal neuroimaging had a favourable outcome, while 12 of the 23 patients with abnormal neuroimaging had a favourable outcome (p = 0.65). Among the 105 patients studied with intracranial electrodes, five suffered transitory deficits as a result of implantation, and two suffered permanent deficits (one hemiplegia caused by haematoma and one mild dysphasia resulting from haemorrhage). CONCLUSIONS: It is worth pursuing surgery in patients with normal neuroimaging because it results in good seizure control and the incidence of permanent deficits associated with intracranial studies is low.

Cavernous malformation of the trigeminal nerve

Una malformación cavernosa afectando el ganglio de Gasser, la segunda y tercera divisiones del nervio trigémino fue resecada por vía extradural en un varón de 54 años. Las malformaciones de los nervios craneales son raras. Su origen específico en el nervio trigémino no ha sido descrito previamente

A cavernous malformation involving the Gasserian ganglion, 2nd and 3rd divisions of the trigeminal nerve on the left side was resected via an extradural route in a54 year old male. Cavernous malformations of the cranial nerves are rare. Specific origin from the trigeminal nerve has not been previously reported

Analysis of the influence of the variable size on the characteristics and behavior of meningiomas.

Seventy-two patients submitted to meningioma surgery at Pedro Hispano Hospital from 1997 to 2001 were reviewed to analyze the association between size (largest diameter of the lesion obtained from imaging examinations) and other variables regarding the biological behavior and clinical outcome of these patients. Statistically significant associations were found between tumor size and location, type of first symptom, type of physical examination, histological grade, surgical complications, postoperative CSF bursae and the need for blood transfusion. Patient's age, gender, duration of first symptom, clinical status at discharge and persistent complaints were not associated to tumor size. There was a trend towards a statistically significant association between tumor size and both grade of resection and persistent deficits. The causes and implications of the findings are discussed. Tumor size is a parameter that may interfere with the neurosurgeon's capacity to treat these patients as well as with their recovery.

Analysis of the influence of the variable size on the characteristics and behavior of meningiomas

Se han revisado setenta y dos enfermos sometidos a cirugía de meningioma en el Hospital Pedro Hispano entre 1997 y 2001, para evaluar la asociación entre el tamaño (mayor diámetro de la lesión obtenido a partir de los exámenes de imagen) y otras variables concernientes a la caracterización y comportamiento de la lesión. Se han encontrado asociaciones, con significación estadística, con la localización, tipo de primer síntoma, tipo de examen físico, grado histológico, aparición de complicaciones, bolsas de LCR y transfusiones de sangre. La edad, el sexo, la duración de primer síntoma, el estado al alta hospitalaria y los síntomas persistentes no se relacionan con el tamaño. Se encontró alguna relación con el tipo de exéresis y señales persistentes. Se discuten las causas e implicaciones de los hallazgos. El tamaño es un parámetro que puede interferir en la capacidad del neurocirujano para tratar estos pacientes y en la capacidad de recuperación de los mismos

Seventy-two patients submitted to meningioma surgery at Pedro Hispano Hospital from 1997 to 2001 were reviewed to analyze the association between size (largest diameter of the lesion obtained from imaging examinations) and other variables regarding the biological behavior and clinical outcome of these patients. Statistically significant associations were found between tumor size and location, type of first symptom, type of physical examination, histological grade, surgical complications, postoperative CSF bursae and the need for blood transfusion. Patient’s age, gender, duration of first symptom, clinical status at discharge and persistent complaints were not associated to tumor size. There was a trend towards a statistically significant association between tumor size and both grade of resection and persistent deficits. The causes and implications of the findings are discussed. Tumor size is a parameter that may interfere with the neurosurgeon’s capacity to treat these patients as well as with their recovery

Single-pulse electrical stimulation identifies epileptogenic frontal cortex in the human brain.

OBJECTIVE: To assess the value of single-pulse electrical stimulation (SPES) to identify frontal epileptogenic cortex during presurgical assessment. METHODS: SPES (1-millisecond pulses, 4 to 8 mA, 0.1 Hz) has been used during chronic recordings in 30 patients with intracranial electrodes in the frontal lobes. As a result of presurgical assessment, 17 patients were considered to have frontal epilepsy and 13 extrafrontal epilepsy. RESULTS: Two types of responses to SPES were seen: 1) early responses: starting immediately after the stimulus and considered as normal responses; 2) late responses: two types of responses seen in some areas after the initial early response: a) delayed responses: spikes or sharp waves occurring between 100 milliseconds and 1 second after stimulation. Frontal delayed responses were seen in 11 frontal patients and 1 extrafrontal patient, whereas extrafrontal delayed responses were seen in 1 frontal and 10 extrafrontal patients. b) Repetitive responses: two or more consecutive sharp-and-slow-wave complexes, each resembling the initial early response. Repetitive responses were seen only when stimulating the frontal lobes of 10 frontal patients. Among the 17 frontal patients, 13 had late responses exclusively in the epileptogenic frontal lobe, whereas only 3 showed them in both frontal lobes. Frontal late responses were associated with neuropathologic abnormalities, and complete resection of abnormal SPES areas was associated with good postsurgical seizure outcome. CONCLUSIONS: Single-pulse electrical stimulation (SPES) could be an important additional investigation during presurgical assessment to identify frontal epileptogenicity. SPES can be useful in patients who have widespread or multiple epileptogenic areas, normal neuroimaging, or few seizures during telemetry.

Skull osteosarcoma: illustrated review.

A case of conventional intramedullary osteosarcoma (epithelioid subtype) with 10 years of evolution and another of high grade surface osteosarcoma of the chondroblastic type, both in the skull, gave rise to several diagnostic and therapeutic difficulties. Key points concerning the definition, classification, imaging, clinical series data and treatment options available for skull osteosarcoma are highlighted.

Schwannoma of the abducens nerve in the cavernous sinus.

Six cases of cavernous abducens nerve schwannoma have been reported. A new case of a 39 year old female with abducens nerve paresis, exophtalmos, chemosis and headache due to a 1,36 x 2,58 cm cystic right cavernous abducens nerve schwannoma is presented and discussed. The cavernous sinus was opened between the trochlear and ophthalmic nerves. A portion of the tumor capsule adherent to the internal carotid artery was not resected. No deficits were added by surgery. After 30 months of follow up there is no evidence of relapse and only abducens nerve paresis persists.