Primary papillary epithelial tumour of the sella: expanding the spectrum of TTF-1-positive sellar lesions.

AIM: To describe four novel primary epithelial tumours of the sella with papillary architecture and Thyroid Transcription Factor 1 (TTF-1) expression. METHODS: Paraffin-embedded tissue from the four cases and recurrence of patient 1 was investigated with haematoxylin-eosin, special histochemical stains, immunohistochemistry with a broad panel of antibodies and next-generation sequencing. The ultrastructure of one tumour was studied in tissue retrieved from paraffin. RESULTS: The lesions occurred in three females aged 20, 26 and 42 years and a male aged 49 years. They presented with signs and symptoms secondary to pituitary stalk compression. Preoperative neuroimaging documented mixed solid and cystic, enhancing sellar masses with suprasellar extension. Histologically, the tumours showed thin papillae lined by a single layer of cytokeratin and TTF-1-positive cuboidal and cylindrical cells with mildly atypical nucleus. Next-generation sequencing performed in three cases did not identify any mutations. The main differential diagnosis included metastasis from lung or thyroid carcinoma, extraventricular choroid plexus papilloma and sellar ependymoma. CONCLUSION: We suggest the descriptive term of primary papillary epithelial tumour of the sella (PPETS) for this entity and propose that it could represent the intracranial equivalent of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma. The cell of origin of PPETS remains undetermined although the intense and ubiquitous expression of TTF-1 may suggest a derivation from the infundibulum or ventricular recess. Our study expands the spectrum of sellar TTF-1-positive tumour and challenges the view that they all derive from pituicytes.

Papillary craniopharyngioma in a 4-year-old girl with BRAF V600E mutation: a case report and review of the literature.

INTRODUCTION: Craniopharyngiomas are one of the most frequently diagnosed hypothalamo-pituitary tumors in childhood. The adamantinomatous histological subtype accounts for most pediatric cases, while the papillary variant is almost exclusively diagnosed in adults. Here, we report a case of papillary craniopharyngioma in a very young child, confirmed by molecular tissue analysis. CASE REPORT: A 4-year-old girl was being investigated for symptomatic central hypothyroidism. Brain MR imaging revealed a large solid/cystic suprasellar mass, splaying the optic chiasm and measuring 3 × 1.9 × 2.3 cm. The patient underwent a transsphenoidal near total resection of the lesion, which was encased within a tumor capsule. Post-operatively, the patient developed transient diabetes insipidus but otherwise recovered well. The pathology of the lesion was consistent with a papillary craniopharyngioma with regions of stratified squamous epithelium accompanied by superficial goblet cells and ciliated cells. Subsequent next-generation sequencing analysis of the lesion confirmed the presence of a BRAF V600E mutation (BRAFc.1799T>A p. (Val600Glu). To date, she remains free from progression 1 year following surgery. CONCLUSION: This is the youngest case published to date of papillary craniopharyngioma with a confirmed BRAF V600E mutation. The case encourages discussion about the most appropriate adjuvant therapy for tumor progression in such cases, given the risks of radiotherapy to the developing brain and the increasing availability of oral BRAF inhibitor therapy.

Qualitative grading of disc degeneration by magnetic resonance in the lumbar and cervical spine: lack of correlation with histology in surgical cases.

BACKGROUND: Clinically, magnetic resonance (MR) imaging is the most effective non-invasive tool for assessing IVD degeneration. Histological examination of the IVD provides a more detailed assessment of the pathological changes at a tissue level. However, very few reports have studied the relationship between these techniques. Identifying a relationship may allow more detailed staging of IVD degeneration, of importance in targeting future regenerative therapies. OBJECTIVES: To investigate the relationship between MR and histological grading of IVD degeneration in the cervical and lumbar spine in patients undergoing discectomy. METHODS: Lumbar (N = 99) and cervical (N = 106) IVD samples were obtained from adult patients undergoing discectomy surgery for symptomatic IVD herniation and graded to ascertain a histological grade of degeneration. The pre-operative MR images from these patients were graded for the degree of IVD (MR grade) and vertebral end-plate degeneration (Modic Changes, MC). The relationship between histological and MR grades of degeneration were studied. RESULTS: In lumbar and cervical IVD the majority of samples (93%) exhibited moderate levels of degeneration (ie MR grades 3-4) on pre-operative MR scans. Histologically, most specimens displayed moderate to severe grades of degeneration in lumbar (99%) and cervical spine (93%). MR grade was weakly correlated with patient age in lumbar and cervical study groups. MR and histological grades of IVD degeneration did not correlate in lumbar or cervical study groups. MC were more common in the lumbar than cervical spine (e.g. 39 versus 20% grade 2 changes; p < 0.05), but failed to correlate with MR or histological grades for degeneration. CONCLUSIONS: In this surgical series, the resected IVD tissue displayed moderate to severe degeneration, but there is no correlation between MR and histological grades using a qualitative classification system. There remains a need for a quantitative, non-invasive, pre-clinical measure of IVD degeneration that correlates with histological changes seen in the IVD.

Melanoma of the sellar region.

Metastatic melanoma has a propensity for multiple intra cranial deposits. Rarely, metastatic melanoma to the pituitary gland has been reported, usually in conjunction with widespread systemic metastases. We describe a patient with metastatic melanoma to the pituitary gland as the first clinical presentation of widespread metastatic disease and review the relevant literature.

Minimally invasive decompression and stabilisation for extensive haemangiomas of lumbar spine.

INTRODUCTION: Vertebral haemangiomas are a common incidental finding and are largely asymptomatic. Extensive haemangiomas of the spine causing neurological deficits are exceedingly rare. Traditional open surgical approaches in these cases can be complicated by life-threatening blood loss. PATIENT CASE HISTORY: We describe 2 patients (ages 27 and 53 years) who presented with severe back pain and lower limb weakness. Radiological investigations revealed very extensive lesions of the L1 and L4 vertebral bodies, respectively, with severe narrowing of the lumbar canal. After selective embolisation of the spinal arterial feeders, both patients underwent a posterior decompression, vertebroplasty, and bilateral pedicle screw fixation in a minimally invasive fashion. Blood loss was minimal and a rapid clinical recovery was seen. CONCLUSIONS: Combinations of embolisation, vertebroplasty and minimally invasive posterolateral instrumentation are treatment strategies that can be used to treat extensive vertebral haemangiomas presenting with neurological deficits.

Endoscopic transsphenoidal surgery for isolated fibrous dysplasia of the clivus.

INTRODUCTION: Fibrous dysplasia is a non-neoplastic disorder of bone, related to abnormal proliferation of fibro-blasts. CASE REPORT: We report a 41-year-old female who presented with hyperprolactinaemia and an incidental clival lesion on MR scan. This was sub-totally resected via an endoscopic transsphenoidal approach and fibrous dysplasia was confirmed histologically. Her postoperative re-covery was un-eventful and at 8 months follow-up, she remains well, other than for the intermittent headaches and with no pituitary hormone deficiencies. CONCLUSION: The present case highlights the need to consider fibrous dysplasia in the differential diagnosis of isolated clival lesions.

Blindness from multiple cerebral gliomas mimicking metastatic brain disease.

Multiple brain lesions are usually due to metastatic spread. The authors describe an unusual case of a 56-year-old male presenting with visual loss secondary to multiple intracranial lesions, with infiltration of the optic chiasm and an incidental renal lesion. Open biopsy of the brain lesion confirmed glioblastoma multiforme.

Dumbbell-shaped intrathoracic-extradural haemangioma of the thoracic spine.

Spinal haemangiomas are benign vasoproliferative lesions that are typically intra-osseous and generally asymptomatic, although localized pain can be a symptom. Capillary and cavernous variants have been described. We describe a rare case of a dumbbell-shaped haemangioma of the thoracic spine with both an intraspinal-extradural and intrathoracic component.

A 30 year perspective of the quality of evidence published in 25 clinical journals: signs of change?

METHODS: The quality of clinical studies published in five different specialties, over three decades was evaluated. Computerised search of the Medline database was undertaken to evaluate the articles published in 25 clinical journals in 1983, 1993, and 2003 from five different specialties (medicine, surgery, paediatrics, anaesthesia, and psychiatry). The number of randomised controlled trials (RCTs), meta-analyses, and other clinical trials (non-RCT) were noted. RESULTS: From the 27,030 articles evaluated, there were 2283 (8.4%) RCTs, 166 (0.6%) meta-analyses, and 4153 (15.4%) other clinical trials. For the proportion of RCTs, the rank order of the specialties was; anaesthesia (503; 18%), psychiatry (294; 9.6%), medicine (899; 8.1%), paediatrics (326; 6.4%), and surgery (261; 5.3%) (p<0.001). For the proportion of meta-analysis, the rank order of the specialties was; psychiatry (36; 1.2%), medicine (105; 0.9%), paediatrics (15; 0.3%), anaesthesia (6; 0.2%), and surgery (4; 0.1%) (p<0.001). Overall, from 1983 to 2003, there were increases in the proportion of RCTs (449, 5.9% to 1027, 9.6%), meta-analysis (0, 0% to 127, 1.2%), and other clinical trials (897, 12% to 1983, 19%) (p<0.001). This trend was apparent in each clinical specialty (p<0.001). CONCLUSIONS: Over the three decades evaluated, clinical trials, notably RCTs and meta-analysis form only a small proportion of articles published in prominent journals from five clinical specialties. This is notwithstanding the modest increases in the proportions of RCTs and meta-analysis over the same period.

A case of familial third ventricular colloid cyst.

Colloid cyst of the third ventricle is a rare benign intracranial lesion, and familial cases are rarer still. They may be asymptomatic or present with symptoms of raised intracranial pressure, including sudden death. Surgical excision is curative. We report a 24 year old pregnant woman with familial colloid cyst, who presented with headaches and suffered a cardiorespiratory arrest. Early computed tomography scan of the brain is advised in patients with a family history of third ventricular colloid cyst presenting to the accident and emergency department with headache.

Use of quantitative assessment scales in cervical spondylotic myelopathy--survey of clinician's attitudes.

BACKGROUND: There is considerable uncertainty regarding the selection criteria of patients and timing of surgery for cervical spondylotic myelopathy (CSM). Attempts have been made to quantify CSM severity using various assessment scales to provide an adjunct to clinical decision-making. The aim of the present study was to determine, by means of a 7-item questionnaire the attitudes of clinicians regarding the importance of quantitative assessment scales in the management of CSM, their actual use in clinical practice and how current scales fall short of the ideal. FINDINGS: Clinical history, examination, radiological imaging and quantitative functional assessment were regarded by 117 clinicians as being almost equally important in the management of CSM. However, only 22 (19%) of clinicians admitted to using an assessment scale in clinical practice and 4 (3%) believed there was a 'gold-standard' assessment scale. These clinicians also considered 'ease of use' to be the most important attribute of an ideal assessment scale, followed by 'reproducibility', 'sensitivity to change' and 'validity'. CONCLUSIONS: The discrepancy between the importance attached to quantitative measurement and its actual use suggests that current scales are under-utilised or unsuitable for clinical practice. A new easy-to use scale may be required that better reflects clinical requirements.

The time course of visual field recovery following transphenoidal surgery for pituitary adenomas: predictive factors for a good outcome.

OBJECTIVE: To report the quantitative assessment of visual fields (VF) in patients with pituitary macroadenomas, and the time course and predictive factors for recovery of vision. METHODS: Retrospective study of 41 patients with pituitary adenomas and visual disturbance. Patients underwent pre- and postoperative VF assessment at one week, three to six months, one year, two years, and five years using the Humphrey field analyser, which gives a quantitative measure of VF in each quadrant. RESULTS: 36/41 patients (88%) presented with a visual disturbance. Mean (SEM) duration of symptoms was 94 (50) weeks (range 0.5 to 1500); 12 (29%) had optic atrophy at presentation. Impairment of VF was greatest in the upper temporal quadrant, followed by the lower temporal. VF recovery was progressive and apparent even at the five year follow up (p<0.001). Overall, VF returned to normal in 35% of eyes, improved in 60%, and remained unchanged in 5%. Patients whose VF returned to normal had a shorter duration of symptoms (16 (5) v 137 (56) weeks; p<0.05), better preoperative visual acuity (p<0.05), and a smaller degree of impairment in preoperative lateral quadrant VF (p<0.01) than those whose VF only improved. On multivariate analysis, the only predictive factor for VF recovery was the degree of impairment in VF preoperatively. CONCLUSIONS: Transphenoidal surgery for pituitary macroadenoma results in a progressive recovery of VF in 95% of patients. The extent of the VF recovery is mainly dependent on the preoperative VF deficit, which emphasises the need for early intervention in these patients.

Intradural metastatic spinal cord compression from ACTH-secreting pituitary carcinoma.

Pituitary carcinomas are uncommon and intradural metastatic spread to the spine is rarer still. We describe a 27-year old man with metastatic spinal cord compression from an adrenocorticotrophic hormone (ACTH) cell pituitary carcinoma, 16 years following the initial presentation. He had three previous resections of the pituitary tumour and post-operative radiotherapy. The intradural, extramedullary spinal metastases causing thoracic and lumbar cord compression were excised, with neurological improvement. Spinal metastases in pituitary carcinoma are uncommon, but aggressive surgical resection of the spinal metastases produces good symptomatic relief.

Non-traumatic compression fractures of the thoracic spine following a seizure -- treatment by percutaneous kyphoplasty.

A 26-year-old male presented with acute mid-thoracic back pain following a witnessed grand mal seizure. There was no trauma and the patient was on steroids for systemic lupus erythematosus. X-rays and CT scans of the thoracic spine revealed compression fractures at T5 and T6, with 50 % loss of vertebral height and kyphosis. He underwent percutaneous kyphoplasty of both vertebrae, with symptomatic improvement. Non-traumatic compression fractures of the thoracic spine following seizures are a rare injury. This may be related to the compressive forces exerted on the vertebral column by the contractions of the truncal muscles, during a seizure. These compression fractures are suitable for treatment by minimally invasive techniques, such as kyphoplasty.

A knot in the catheter--an unusual cause of ventriculo-peritoneal shunt blockage.

A 25-year-old woman, who was 25 weeks pregnant, underwent insertion of a VP shunt for hydrocephalus, secondary to a bithalamic glioma. Two months later, she represented with symptoms of raised intracranial pressure and MR scan revealed increased ventricular size. On exploration of the shunt, manometry with saline confirmed blockage of the catheter distal to the valve. On re-opening the abdominal wound, the peritoneal catheter was found to be knotted, 2 cm from the end. This segment of the catheter was replaced, with resolution of symptoms, post-operatively. The present case illustrates that a knot in the peritoneal catheter is an extremely rare cause of shunt malfunction. Possible mechanisms underlying it are discussed.

14 mmHg: a case of raised intracranial pressure?

A 40-year-old woman presented with chronic headaches. She had undergone ventriculo-peritoneal (VP) shunt 7 years previously for treatment of hydrocephalus secondary to aqueduct stenosis. Intracranial pressure (ICP) monitoring revealed a resting ICP of less than 5 mmHg. Headaches were thought to be due to low ICP and the shunt tubing was ligated. Over the next 4 h there was an increase in ICP to 14 mmHg, decrease in GCS to 13 and ventriculomegaly on CT. These changes were reversed by the removal of the ligature. This unusual case highlights the fact that, in some shunted patients with over drainage of ventricles and a low resting ICP, small increases in ICP are poorly tolerated. This may be due to altered visco-elastic properties of the ventricles and the brain parenchyma.