Non-functioning pituitary adenomas infrequently harbor G-protein gene mutations.

BACKGROUND: Mutations of the genes encoding the alpha subunit of the stimulatory G protein (Gs) and of the inhibiting Gi2 protein (GNAS1 and GNAI2 genes, respectively) have been described in various endocrine neoplasias, including pituitary tumors. AIM: To search for mutations of GNAS1 and GNAI2 in a continuous series of non-functioning pituitary adenoma (NFPA) patients neurosurgically treated. SUBJECTS AND METHODS: The surgical samples of 22 patients who have been defined and characterized on a clinical, biochemical, histological, and immunohistochemical point of view have been processed for investigating the presence of the above mutations by PCR amplification of the hot spots exons 8 and 9 of GNAS1, and exons 5 and 6 of GNAI2, followed by direct sequencing. Moreover, the promoter region of GNAI2, in order to assess the prevalence of single nucleotide polymorphisms (SNP), was investigated in the same series. RESULTS: A CGT>TGT mutation at codon 201 of GNAS1 gene in a single case of NFPA was found, but no mutation of GNAI2A was demonstrated. CONCLUSIONS: This finding suggests and confirms that G-protein mutations are rare and not crucial in NFPA development. Additionally, we found a silent SNP at codon 318 in the promoter of the Gi2alpha gene in one out of the 22 NFPA.

Survival of a neglected case of brain abscess caused by Cladophialophora bantiana.

Cladophialophora bantiana is an uncommon fungus related to the black yeasts which causes, if untreated, mostly fatal cerebral infections in immunosuppressed and competent patients. We report a case of a patient who survived a recurrent cerebral abscess caused by C. bantiana despite delayed and apparently inappropriate therapy.

An immunohistochemical study of extracellular matrix proteins laminin, fibronectin and type IV collagen in paediatric glioblastoma multiforme.

AIMS: In the recent decades many studies have been addressed in the literature to assess specific factors related to glioblastoma multiforme (GBM) invasion. However, few studies have evaluated tumour cell's interaction with specific extracellular matrix (ECM) components, and, moreover, there is a lack of information regarding the occurrence of these phenomena in paediatric GBM. METHODS AND RESULTS: ECM proteins were evaluated in six cases of paediatric GBM assessing the immunohistochemical expression of laminin, fibronectin, and type IV collagen. We used a semiquantitative scale, ranging from not detected (zero) to marked (3). Laminin expression was minimal in three cases, moderate in one case, marked and generalised in one patient and marked and focal in the last case. Fibronectin expression was minimal in three patients; moderate immunoreactivity was documented in one case. Conversely, one case was classified as marked with generalised distribution and the remaining case as marked with focal immunostaining. Type IV collagen expression was minimal in three cases, moderate in one, marked with focal reaction in one and marked with generalised reaction in the remaining case. CONCLUSIONS: This study provides additional insights into tumour invasion features of paediatric GBM, as ECM plays a pivotal role in numerous cellular functions during normal and pathological processes. Although based on a limited number of patients, this investigation may serve as a challenge for the management of paediatric GBM, stimulating trials with larger patient numbers aimed at documenting specific factors influencing GBM prognosis.

A preliminary study of angiogenesis in paediatric glioblastoma multiforme and its correlation with survival.

OBJECTS: There is a distinct challenge in bringing modern insights into glial tumour genesis to bear on improved outcomes for patients. Insights provided by neuroncological, neuroradiological, neuropathological, and neurosurgical investigations may offer significant advantages in the management of paediatric GBM. The goal of this study was to evaluate angiogenesis as a potential indicator of survival in paediatric glioblastoma multiforme (GBM). METHODS: Angiogenesis was evaluated in six cases of paediatric GBM with multiple criteria, including contrast enhancement on preoperative CT scan, histological vascular hyperplasia (VH) and endothelial proliferation (EP) and immunohistochemical tenascin-C (TN-C) expression. We employed a semiquantitative scale, ranging from not detected (zero) to marked (+3), for each investigational parameter. We evaluated the influence of angiogenesis on survival in each case. CONCLUSIONS: In this preliminary study, angiogenesis provided information that correlated with survival, albeit in a limited number of patients. As we gain better understanding of the molecular biology of brain tumours, with the multitude of genetic alterations and growth factors new therapeutic approaches may emerge, which may hold the promise for cure.

Immunohistochemical tenascin-C expression in paediatric supratentorial glioblastoma multiforme.

Tenascin-C (TN-C) plays an important part in the growth of neoplastic tissue, leading to new vessel development. TN-C has been assessed in adult glioblastoma multiforme (GBM) and has been evaluated as anti-neoplastic therapy. No studies have focused on this tissue in paediatric GBM. Tissues were obtained from six paediatric supratentorial GBMs. Immunohistochemistry was performed using a mouse antibody directed against human TN-C, and expression in tumour vasculature was described on the basis of TN-C immunoreactivity. The expression was minimal in three, moderate in two, and intense in one specimen. TN-C was not correlated with clinical history, neurological findings, or with tumour site. Although based on a limited number of patients, this study provides additional insights into tumour growth modulation and cytogenetic profile of paediatric GBM. The detailed understanding of events responsible for GBM growth is a prerequisite for the development of therapeutic modalities leading to improved prognosis and cure.

Shrinkage of a PRL-secreting pituitary macroadenoma resistant to cabergoline.

Cabergoline decreases both serum PRL levels and size of prolactinomas, including some tumors resistant to other dopamine-agonists. It is common observation that the shrinkage of the adenoma is preceded by suppression of PRL levels. A minority of patients, who do not show a significant decrease of PRL after a short trial with dopamine-agonists, undergoes neurosurgery or radiotherapy. We report on the case of a 14-year-old girl with a huge prolactinoma who showed, during cabergoline treatment (0.5 mg twice a week), a significant shrinkage of the pituitary mass but no decrease of the very high PRL values. She was referred to us after partial removal of the suprasellar extension of the pituitary tumor. The post-surgical evaluation showed very high PRL levels (9352 microg/l; 20941 microg/l before surgery), which did not decrease during the 2-year treatment with cabergoline (nadir value: 8735 microg/l). However, one month after the beginning of therapy, MRI showed a significant shrinkage of the tumor (tumor volume 5.7 ml, compared with 45.1 ml prior to surgery and 24.4 ml after surgery). Subsequently MRIs demonstrated a progressive reduction of the size with a complete disappearance of the suprasellar and parasellar tissue (tumor volume 1.8, 0.9 and 0.2 ml, at 3, 6 and 12 months, respectively). The MRI performed at the 24th month showed a secondary empty sella, with residual tumor tissue in the right sphenoidal sinus. Increasing cabergoline, up to 3 mg a week, failed to induce any decrease of PRL levels. In conclusion, in such macroprolactinomas the shrinkage of tumor is not strictly correlated with (or it is partially dissociated from) the inhibition of PRL hypersecretion. The choice of other therapeutic options in cabergoline-resistant macroprolactinomas needs careful neuroradiological evaluation after a short trial of pharmacological treatment.

Morphological and immunohistochemical considerations on the basal ganglia in pigeon (Columba livia).

Morphological and immunohistochemical studies carried out particularly around the level of the basal ganglia (BG) in birds, are reported and commented on. Our results showed, on paraffin embedded avian BG, both the histological features and the immunohistochemical findings on immunofluorescence distribution of some neuropeptides (especially Metenkephalin) in the striatal complex. By comparing our results of Metenkephalin immunoreactivity (Menkir) with the referred analogous ones of Substance P (SP) quoted in literature, we confirmed the strikingly similar labelling at the levels of the Lobus paraolfactorius (LPO) and Paleostriatum augmentatum (PA), in contrast with the very low immunoreactivity at the Paleostriatum primitivum (PP) levels. We were able also to demonstrate the strong MEnk-ir of the neurons of the Nucleus accumbens, Nucleus septalis and paraventricularis. All these findings are also in accord to the interpretation by many AA (Wynne and Gunturkun, 1995; Reinez et al., 1983), about the anatomical correspondence between the LPO-PA complex of birds and the caudate-putamen in mammals. Some MEnk + 'wooly like fibres' described in our specimens in the PA (on the contrary reported in the Gpe segment of mammals) apparently escape these correspondence.

Temporal osteoclastoma: an exceptional lesion in infancy.

Osteoclastoma is a rare skeletal lesion, characterized by large multinucleated giant osteoclastic cells; this lesion usually affects young adults with a prevalence of 1 case/1 million population. We report the case of a 9-year-old girl with a right temporal tumescence: X-ray, CT and MRI revealed the presence of a right temporal hyperostotic ring-like area over the lambdoid suture, with irregular margins and calcareous deposits. The tumour was expanding mainly toward the endocranium involving both cranial tables and diploë, without infiltrating the brain parenchyma. The child underwent complete microsurgical removal of the lesion. Histopathological findings revealed the giant cell tumour osteoclastoma. Correct modern preoperative neuroimaging workup, coupled with microneurosurgical technique, allowed successful lesion removal with good outcome. A review of the more recent literature and of mechanisms of pathology together with neuroradiological protocol and results of treatment are discussed.

Xanthomatous posterior pyramid meningioma in a 2-year-old girl.

Meningiomas are common lesions in adults but unusual in infancy and meningiomas located in the posterior cranial fossa are even more rare. Metaplastic changes of meningothelial meningiomas can lead to the rarely observed xanthomatous form. We describe the case of a posterior pyramid xanthomatous meningioma in a 2-year-old girl. After detailed neuroradiological evaluation, the histological diagnosis was confirmed with the aid of immunohistochemical evaluation. A critical case evaluation in the light of the more recent literature, the surgical strategy and technique, and an immunohistological hypothesis are reported.

[Immunohistochemical findings in Huntington's Chorea: report of 9 cases]. / Osservazioni immunoistochimiche sulla Corea di Huntington: studio di 9 casi.

The results of an immunohistochemical investigation on neostriatum of 9 cases of Huntington's disease are reported. In all cases the typical neuropathological findings were present (striatum atrophy, neuronal degeneration, gliosis). We did investigate on paraffin slides Synaptophysin (SYN), Neurofilament-protein (NF68), GFAP as well as the neuropeptides Met-Enkephalin (MEnk), Substance P (SP), Somatostatin (SS) and Neuropeptide Y (NPY). These neuropeptides, in particular MEnk and SP, are reported to coexist with the inhibitory neurotransmitter GABA in the neurons of basal ganglia. In all cases, GFAP activity was increased. In 7 cases activity of SYN and NF68 was decreased. In 2 cases, however, SYN-immunoreactivity was increased; these findings might represent an expression of "regenerative" changes in surviving neurons. The reactions for neuropeptides did disclose, in accordance with the results of former investigators, a decreased activity of MEnk- and SP-neurons, whereas SS- and/or NPY-neurons appeared almost unchanged.

Desmoplastic non-infantile ganglioglioma.

A case of temporal desmoplatic ganglioglioma surgically removed in a 17-year-old patient is reported. Immunohistochemistry showed glial and neuronal differentiation of tumour cells. The frequent occurrence of a desmoplastic component in gangliogliomas is stressed. The present case and other reports from the literature confirm that such desmoplastic neoplasms can not be regarded as exclusively infantile tumours, as recently proposed by the WHO-classification of Brain Tumours.

[Gerstmann-Sträussler-Scheinker syndrome in a Sicilian patient. Neuropathological aspects]. / Sindrome di Gerstmann-Sträussler-Scheinker in un soggetto siciliano. Aspetti neuropatologici.

A case of Gerstmann-Sträussler-Scheinker syndrome observed in a 54 year-old woman is reported. The disease lasted over 4 years and was mainly characterized by ataxia and progressive dementia. The patient belongs to a Sicilian family and some of her relatives have been (or still are) affected by similar clinical syndromes. The neuropathological investigation disclosed an impressive number of PAS-positive amyloid deposits (plaques) in the cortex of the cerebrum and in particular of the cerebellum, in the basal ganglia and thalami as well. These plaques were of different size and morphology: multicentric and Kuru-like, cotton-wool and Alzheimer-like, compact and punctate. In some of them, remnants of dystrophic neurites were detected with ubiquitin-reaction and with the metallic method of Gallyas. No reactions were observed with tau-protein, GFAP and Campbell's method. The immunohistochemical investigations for prion-protein, kindly performed by Prof. Kretzschmar (Goettingen) confirmed that the plaques did not contain beta-protein A4, but reacted positively with anti-prion-protein. These results confirmed the diagnosis of GSS syndrome. The importance on an exact neuropathological investigation employing immunohistochemical reactions and metallic methods in every case of progressive degenerative encephalopathy with PAS-positive (amyloid) deposits (dementia of Alzheimer type, suspected Prion-encephalopathies, etc.) is emphasized. Potential infectivity of the tissue in prion-encephalopathies is deactivated soaking the blocks for histology in formic acid (95-100%) for one hour, followed by formalin for at least three days. Moreover the pretreatment with formic acid does enhance the positivity of PAS-reaction.

[Neuromalaria: neuropathological study of 3 cases and review of the literature]. / Neuromalaria: studio neuropatologico di 3 casi e revisione della letteratura.

Human Cerebral Malaria (HCM) is an encephalopathy which occurs in some patients infected with P. falciparum (PF). Besides people in the endemic tropical-subtropical zones there is a numerically smaller group of non immune visitors or returning from which are at risk for disease. The histological classical hallmarks of HCM are sequestration of PF-infected erythrocytes in vessels, cerebral oedema, petechial hemorrhages "ring hemorrhages" and so-called Dürk's granulomas. Even though the histological and clinical picture are described for more than a century, some aspects of the pathogenesis of this disease remain obscure. We report the neuropathological findings of three European cases of HCM consisting of a slight diffuse oedema both of cortex and white matter and numerous capillaries filled with parasitized erythrocytes (PRBC). The pathogenetic aspects especially as to concern the sequestration of cerebral vessels are reviewed particularly in regard to the recent immunohistochemical evidence of "intercellular adhesion molecules" (ICAM-1, E-selectin etc.) as ligands to endothelial cells for PRBC.

Peculiar meningeal tumour in a 4-months old baby: malignant fibrous histiocytoma?

The histological examination of a meningioma-like tumour operatively removed from the left frontoparetial region of a 4-months-old baby, disclosed a high-cellular malignant neoplasia built up by streams of elongated spindle-shaped cells, and with a predominant storiform-pattern as usually seen in malignant fibrous histiocytoma (MFH). Immunohistochemical reactions for alfa-I-ACT and Lys were negative; tumor cells expressed vimentin. Electronmicroscopy disclosed fibroblast-like cells. This tumour was compared with a recurring malignant fibroblastic meningioma characterised, in the recurrence, by storiform areas. In this second tumour, alfa-I-ACT was highly positive. Questions concerning the occurrence of primary cerebral MFHs are discussed. The immunohistochemical findings in-the tumours of the present investigation underline the not-specificity of so-called histiocytic markers.

Gliomatosis cerebri. Clinical, neuropathological, immunohistochemical and morphometric Studies.

Clinico-neuropathological findings recorded from one case of cerebral gliomatosis are reported in this paper. Immunocytochemical methods (GFAP, protein S-100) were used together with morphometric computer-assisted analysis for more effective investigation of certain cytopathological features such as the relationship between cerebral gliomatosis and low-graded astrocytoma. Immunohistochemically, most of the proliferating cells were positive to GFAP and/or to protein S-100, which was in fair agreement with publications elsewhere in the literature. However, varying amounts of spindle-shaped cells remained unstained. The nature of such cells is unclear. The morphometric study showed the majority of cellular parameters of cerebral gliomatosis to be comparable to cellular parameters recordable from "peripheral" regions of a series of low-grade astrocytomas.

Amyotrophic choreo-acanthocytosis: a neuropathological and immunocytochemical study.

A 47 year old man, one of a sibship affected by amyotrophic choreo-acanthocytosis was studied neuropathologically after some years of clinical observation. Besides the classic optical findings (neuronal loss, astrocytic gliosis and "status spongiosus" in the basal ganglia, namely in the caudate nucleus) a few MEnk+ and NPY+ neurons were observed immunocytochemically in the striatum. In the spinal cord also, while no neuronal loss was perceivable, both mild demyelination and interfibrillary astrocytic hyperplasia of the long tracts were present. On the other hand, microscopic findings of muscle and peripheral nerve showed no differences from what was previously intra-vitam appreciated in the same patient. The neuropathological and immunocytochemical findings of this case are discussed in relation to the differential diagnosis between amyotrophic choreo-acanthocytosis and Huntington's disease.

Complex partial status epilepticus simulating an ischemic insult: case report.

A patient presenting complex partial status epilepticus (CPSE) had a clinical history and neurological picture on admission that mimicked a cerebrovascular insult. On admission she was confused and totally unresponsive to verbal stimuli. EEG showed high voltage paroxysmal activity on the left hemisphere, prominent on the temporoccipital leads and tending to spread to the opposite regions. Intravenous diazepam led to resolution of the clinical and EEG picture within 24 hours, only a medium voltage slow wave focus being present on the left temporal regions. CPSE should be considered whenever a prolonged impairment of consciousness is present. Only accurate EEG recordings permit correct diagnosis in doubtful cases.

Spontaneous bilateral anterior cerebral artery occlusion resulting in akinetic mutism. A case report.

An unusual case concerning a patient with akinetic mutism (AM) due to spontaneous bilateral anterior cerebral artery occlusion is reported. Brain CT scan revealed the presence of mild low density foci presenting an irregular enhancement, which followed the distribution of mesial frontal gyri and paracentral lobulus, bilaterally. Right and left carotid angiographies showed bilateral occlusion of the anterior cerebral artery. Our case is characterized by an exclusive localization of the infarction in the frontal cortex. This finding suggests that a limited damage involving the anterior cerebral arteries territory could be, on its own, responsible for the AM syndrome.

[Juvenile spongiform encephalopathy with unusual pathomorphologic findings]. / Encefalopatia spongiforme giovanile con insoliti reperti patomorfologici.

A 27-year-old man presented disturbances of gait and language, quickly followed by intellectual deterioration, tetraplegia, anarthria and myoclonus. Histological examination of a cerebral biopsy showed not only cortical changes consistent with the diagnosis of Creutzfeldt-Jakob disease, but also many amyloid-plaques with variable morphology. The diagnostic interpretation of the case particularly as to concern his relationship to s.c. Gerstmann-Strüssler syndrome is discussed.