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.

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.

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.

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.

[Inverted papillomas--cases at our service and review of the literature]. / Papilomas invertidos--casuística del servicio y revisión de la literatura.

Inverted papillomas are rare tumours representing about 2.2% of all urothelial tumours (benign or malignant). Inverted papillomas are predominantly seen in the bladder but these tumours have also been described in other locations, all over the urinary tract. The authors report six additional cases of such tumours describing the individual characteristics of each case, presenting symptoms, treatment employed and follow up available. A review of the literature relative to aetiology, clinical signs and symptoms, diagnostic criteria, treatment options and outcome has also been carried out.

[Solitary fibrous tumor. Two additional cases with urologic implications]. / Tumor fibroso solitario. Dos casos adicionales con implicaciones urológicas.

Solitary fibrous tumour is a well defined pathological entity originally described as a tumour of the pleura, but the occurrence of this neoplasm has increasingly been described at other sites. At present the development of these tumours is recognized as possible in virtually all anatomical sites. The rarity of this type of pathology has not allowed up to the present time clarification of the histogenesis, clinical behaviour, treatment and prognosis of these tumours. Differential diagnosis becomes important, especially in extra-thoracic sites so as not to mistake them for much more aggressive mesenquimal tumours. Two additional cases of this neoplasm are presented, one of them responsible for obstructive uropathy, accidentally found in a patient suffering renal trauma. The second tumour was located in the spermatic cord. A review of the theme is presented based on the available literature.

[Atypical meningioma]. / Meningeomas invulgares.

One case of intradiploic meningioma, causing partial occlusion of the superior longitudinal sinus, with subsequent visual trouble and another of lipomatous meningioma with great fat content and very calcified, that was found in a LCR fistula study of the cranial anterior stage, are described by the authors as atypical meningiomas.

Predictors of outcome and pathological considerations in the surgical treatment of intractable epilepsy associated with temporal lobe lesions.

OBJECTIVES: To evaluate the influence of clinical, investigative, and pathological factors on seizure remission after temporal lobectomy for medically intractable epilepsy associated with focal lesions other than hippocampal sclerosis. METHODS: From a series of 234 consecutive "en bloc" temporal resections for medically intractable epilepsy performed between 1976 and 1995, neuropathological examination disclosed a focal lesion in 80. The preoperative clinical, neuropsychological, interictal EEG, and neuroimaging characteristics of these patients were assembled in a computerised database. The original neuropathological material was re-examined for lesion classification and completeness of removal. The presence of additional cortical dysplasia and mesial temporal sclerosis was also noted. Survival analysis was performed using Kaplan-Meier curves and actuarial statistics. Logistic regression analysis was used to establish the independent significance of the clinical variables. RESULTS: The probability of achieving a 1 year seizure remission was 71% by 5 years of follow up. Factors predicting a poor outcome on multivariate analysis included the need for special schooling and a long duration of epilepsy. Generalised tonic-clonic seizures, interictal EEG discharges confined to the resected lobe, demonstration of the lesion preoperatively on CT, and complete histological resection of the lesion were not predictive of outcome. Neuropsychological tests correctly predicted outcome in left sided cases but apparently congruent findings in right sided resections were associated with a poor outcome. Pathological reclassification established the dysembryoplastic neuroepithelial tumour as the commonest neoplasm (87%) in this series, with a significantly better seizure outcome than for developmental lesions, such as focal cortical dysplasia. CONCLUSIONS: The findings highlight the importance of dysembryoplastic neuroepithelial tumour in the pathogenesis of medically refractory lesional temporal lobe epilepsy and the prognostic significance of preoperative duration of epilepsy emphasises the need for early recognition and surgical treatment. Cognitive and behavioural dysfunction, however, is associated with a lower seizure remission rate, independent of duration of epilepsy.