Angiosarcoma de cuero cabelludo. revisión de la literatura actual a propósito de un caso / Angiosarcoma of the scalp. a case report and review of the literature

RESUMEN El angiosarcoma es un tumor de células neoplásicas de origen vascular, cuya presentación clínica es variada y su diagnóstico es tardío. Se presenta el caso de una paciente de 83 años, con múltiples úlceras dolorosas en cuero cabelludo, con diagnóstico incierto, por lo que se realiza biopsiaincisional de la lesión, detectándose un angiosarcoma. La inmunohistoquímica de la lesión fue positiva para CD34 y vimentina, negativo para S-100 y Melan-A. Este tumor se presenta en adultos mayores, siendo altamente invasivo y de mal pronóstico. Su diagnóstico requiere un alto índice de sospecha y a la fecha, no existe un tratamiento definido para esta patología.

SUMMARY Angiosarcoma is an aggressive malignant tumor of the vascular endothelial cells, and its clinical presentation is varied and of late diagnosis. The present case has a female patient, aged 83 who has multiple painful ulcers in scalp, whose lack of treatment response required a biopsy, where it was found an angiosarcoma. The immunohistochemistry of the lesion was positive for CD34 and vimentin, and negative for S-100 and Melan-A. This tumor develops in older people and is highly invasive withpoor prognosis. Its diagnosis requires high rates of suspicion and todate there is not a defined treatment for this pathology.

Alergia a la proteína de lentejas en el sur de Chile: Reporte de un caso y revisión de la literatura / Allergenicity of lentils in the south of Chile: Reporting a case and Review

El término alergia alimentaria, involucra entidades tan diversas como la proteína de leche de vaca hasta alergias al maní y a las legumbres. La prevalencia mundial de esta entidad ha ido en aumento y en Chile, no existen casos reportados en la literatura que orienten el diagnóstico. Por lo general el médico general es el primero en enfrentarse a estos casos, por lo tanto, deberá conocer muy bien su red de derivación, para dar una solución expedita a cada paciente que lo visita, por una alergia alimentaria. Se presenta el caso de un infante de 3 años, que presentó una reacción urticarial posterior a la ingesta de lentejas cocidas, por tercera vez. Requirió manejo con corticoides y anti-histamínicos para disminuir las molestias. Se concluye que el tratamiento indicado para la alergia alimentaria a lentejas, es la exclusión de la dieta, sin conocer la temporalidad de ésta ni su reinicio, aunque varias guías sugieren intentar realimentación a la edad de 4 a 5 años del infante.

The food allergy, involves entities as diverse as cow's milk protein to peanut allergies as to legumes. The global prevalence of this entity has been increasing. In general, the medical doctor is the first to face these cases, therefore, should know very well their referral network to give an expeditious approach to each patient who visits him for a food allergy. We present the case of a 3-year-old infant who presented an urticarial reaction after the third ingestion of cooked lentils. He required corticosteroids and antihistamine management to reduce discomfort. The treatment indicated for food allergy to lentils is the exclusion of the diet, without knowing the temporality of this or its re-initiation, although several guides suggest attempting feedback at the age of 4 to 5 years.

Asociación del déficit de vitamina D con patologías de la piel humana / Association of vitamin D deficiency with human skin pathologies

La vitamina D es una de las vitaminas fundamentales en el día a día del ser humano. No solo juega un rol importante en la homeostasis del calcio y salud ósea, sino también en distintos sistemas del organismo. El déficit de esta vitamina se ha asociado a enfermedades como: cánceres, hipertensión y síndrome metabólico. La epidermis es la principal fuente de vitamina D del organismo, seguida de una dieta rica en vegetales, pescados y leche fortificada. Esta capa de la piel no sólo es productora, sino además presenta diversas patologías producto del déficit de este nutriente. La vitamina D regula la función de la barrera cutánea, a través de la modulación de la expresión de filagrina e involucrina. La filagrina es una proteína estructural de la piel, que produce agregación y compactación de los filamentos intermedios de queratina. Esta proteína estaría implicada en el desarrollo de la dermatitis atópica. La vitamina D promueve la diferenciación celular e inhibe la proliferación y reduce el crecimiento de tumores, tal como ocurre en el melanoma maligno, a través de la expresión de su receptor (VDR). Dado los actuales descubrimientos respecto del déficit de este nutriente, la recomendación actual es consumir productos lácteos de forma habitual, asociado a la exposición de 5 minutos diarios idealmente en horarios de menor irradiación UV, manteniendo el uso de bloqueador solar y ropa adecuada durante el día. En conclusión, la vitamina D no sólo presenta utilidad en la mantención del equilibrio óseo, sino que interactúa a través de su receptor en diversos tejidos del organismo, permitiendo la homeostasis de la piel.

Vitamin D is one of the essential vitamins in the evolutionary development on earth. The best known of this function is the regulation of calcium homeostasis. Deficiency of this vitamin has been associated with some cancers, hypertension and metabolic syndrome. The epidermis is the main source of vitamin D in the body, followed by a diet increased vegetables, fish and fortified milk. The epidermis is not productive but also presents several pathologies resulting from the deficiency of this nutrient. The VD regulates the function of the cutaneous barrier through the modulation of filagrine and involucrin expression. Filagrine is a structural protein in the skin that produces aggregation and compaction of intermediate keratin filaments. This protein would be involved in the development of atopic dermatitis. Vitamin D promotes cell differentiation and inhibits proliferation and reduces the growth of tumors, as in malignant melanoma, through receptor expression (VDR). Given the current findings regarding the deficiency of this nutrient, the current recommendation is to consume dairy products in a habitual way, associated to the exposure of only 5 minutes daily ideally at times of lower UV irradiation, maintaining the use of sunscreen and proper clothing during the day. In conclusion, vitamin D, not only has utility in maintaining the bone balance, but interacts through its receptor in various tissues of the body, allowing the homeostasis of the skin, vascular tissue among others.

Percutaneous biopsy through the foramen ovale for parasellar lesions: surgical anatomy, method, and indications.

Knowledge of the pathological diagnosis before deciding the best strategy for treating parasellar lesions is of prime importance, due to the relative high morbidity and side-effects of open direct approaches to this region, known to be rich in important vasculo-nervous structures. When imaging is not evocative enough to ascertain an accurate pathological diagnosis, a percutaneous biopsy through the transjugal-transoval route (of Hartel) may be performed to guide the therapeutic decision.The chapter is based on the authors' experience in 50 patients who underwent the procedure over the ten past years. There was no mortality and only little (mostly transient) morbidity. Pathological diagnosis accuracy of the method revealed good, with a sensitivity of 0.83 and a specificity of 1.In the chapter the authors first recall the surgical anatomy background from personal laboratory dissections. They then describe the technical procedure, as well as the tissue harvesting method. Finally they define indications together with the decision-making process.Due to the constraint trajectory of the biopsy needle inserted through the Foramen Ovale, accessible lesions are only those located in the Meckel trigeminal Cave, the posterior sector of the cavernous sinus compartment, and the upper part of the petroclival region.The authors advise to perform this percutaneous biopsy method when imaging does not provide sufficient evidence of the pathological nature of the lesion, for therapeutic decision. Goal is to avoid unnecessary open surgery or radiosurgery, also inappropriate chemo-/radio-therapy.

[Criteria of diagnosis and grading of oligodendrogliomas or oligo-astrocytomas according to the WHO and Sainte-Anne classifications]. / Oligodendrogliomes et oligo-astrocytomes critères diagnostiques et grading de malignité selon l'OMS et l'hôpital Sainte-Anne.

Two main classification systems are used in France for the histological typing and grading of oligodendrogliomas: the WHO and Sainte-Anne Hospital (SA) classifications. According to the WHO, the typing of diffuse gliomas is based on the predominant cell type, oligodendroglial versus astrocytic. In contrast, the SA classification is based on the distinction of two patterns of tumor growth, solid tumor tissue versus isolated tumor cells and also relies on imaging and clinical features. According to this approach, the SA classification includes in the category of oligodendrogliomas, the fibrillary or gemistocytic diffuse astrocytomas (WHO grade II) as well as a substantial proportion of astrocytomas WHO grade III, 2) the WHO uses multiple histological criteria for the grading of oligodendrogliomas (grade II versus grade III), including the degree of differentiation, cellular atypia, mitotic activity and necrosis. In contrast, the SA grading of these tumors (grade A versus B) only uses two criteria: the presence or absence of endothelial hyperplasia, and the presence or absence of contrast enhancement. This last criterion allows overcoming the problems related to the representativeness of surgical samples. Difficulties and discrepancies regarding the diagnosis of oligodendrogliomas are in part due to the lack of immunomarker for the identification of tumoral oligodendrocytes. The potential interest of new markers of oligodendroglial precursors for the diagnosis of these tumors will further be discussed.

[Results of the Sainte-Anne - Lyons series of 318 oligodendroglioma in adults]. / Résultats de la série Sainte-Anne - Lyon de 318 oligodendrogliomes intracrâniens de l'adulte.

INTRODUCTION: Incidence of cerebral oligodendrogliomas is increasing because of better recognition made possible by improved classifications. We studied a homogeneous series using the Sainte-Anne grading scale in order to better understanding the history of these tumors with or without treatment and to assess prognosis and associated factors. PATIENTS AND METHODS: A retrospective series of 318 adult patients with oligodendroglioma (OLG) treated at Hôpital Sainte-Anne, Paris (SA) and Hôpital Neurologique, Lyons (L) between 1984 and 2003 was analyzed: 182 grade A OLG (SA + L), 136 grade B among which a homogenous series of 98 (SA) were included. For grade A: age at diagnosis ranged from 21 to 70 (mean: 41), sex ratio was 1.28. For grade B: age at diagnosis ranged from 12 to 75 (mean: 45.5), sex-ratio was 1.58. The main first symptoms were: epilepsy (A: 91.5%; B: 76%), intracranial hypertension (A: 7.9%; B: 14.6%), neurological deficit (A: 5.1%; B: 17.7%). The most frequent locations were: frontal, insular and central for both A and B. Mean size was 55 mm for grade A, 62 mm for B. Calcifications were found in 20% of A, 48.5% of B. No tumor was enhanced on imaging (CT/MRI) in grade A, all but 7 in grade B. All patients underwent surgery either for biopsy (A: 47.2%; B: 53%), or removal which was partial (A: 26.4% vs B: 19.4%) or extended (A: 36.3% vs B: 37.8%). Fifty-six patients underwent 2 procedures and 12 three procedures. Radiotherapy was performed in 76.9% of grade A, and 91% of B patients, in the immediate postoperative period for 71% A and 82.7% B. Chemotherapy was delivered for 36% of grade A (in the event of transformation to grade B or failure of radiotherapy) and 67.5% of B patients. Among grade A tumors, 38% transformed into grade B within a mean delay of 51 months with a mean follow-up of 78 months. RESULTS: Median survival was 136 months for grade A and 52 for grade B. Survival at 5, 10 and 15 was 75.5%, 51% and 22.4% for grade A vs 45.2%, 31.3% and 0% for grade B respectively. In univariate and multivariate analysis, grade A survival was associated with age at diagnosis, tumor size, large removal and response to radiotherapy. Grade B survival was associated with age at diagnosis, wide removal and sharply defined limits of the tumor on imaging. CONCLUSIONS: Analysis of both published data and this series underlines many prognostic parameters. It shows that OLG are heterogeneous tumors even in each grade (A and B). Treatment should consequently progress towards more targeted procedures for patients mainly with postoperative radiotherapy and chemotherapy.

High and low grade oligodendrogliomas (ODG): correlation of amino-acid and glucose uptakes using PET and histological classifications.

Classification and treatment strategy of oligodendrogliomas (ODG) remain controversial. Imaging relies essentially on contrast enhancement using CT or MRI. The aim of our study was to use positron emission tomography (PET) using [18F]-flurodeoxyglucose (FDG) and [11C]-L-methyl-methionine (MET) to evaluate metabolic characteristics of ODG. We studied 19 patients with proven ODG, comparing standardized uptake values (SUV) and maximal tumor/contralateral normal tissues ratios (T/N). Imaging findings were compared with WHO, Smith and Daumas-Duport classifications. Uptake of FDG was decreased only in 8 patients, independently of grading, while MET uptake was always increased. MET uptake was significantly higher for high grade tumors grouped according to Smith or Daumas-Duport classifications, while no significant difference in MET uptake was found when using WHO classification. A different correlation was found between FDG and MET uptakes in normal tissues and high grade tumors. A trend for improved progression free survival was found for tumors that lacked contrast enhancement on MRI or those showing low FDG or MET uptake. In conclusion, MET appeared more sensitive than FDG to detect proliferation in ODG. The preferential protein metabolism, already noticeable for low-grade tumor, correlated with glucose metabolism and helped to separate, in vivo, high and low grade tumors.

[Calcified brain metastases of a pulmonary neuroendocine carcinoma]. / Métastases cérébrales calcifiées d'un carcinome bronchique neuro-endocrine.

We describe an unusual case of pulmonary neuroendocrine carcinoma of intermediate cell type, revealed by calcified metastatic nodules of the brain in a 49-year-old man. Histological examination of the brain lesions disclosed necrosis and calcification in the center with small and medium-sized carcinoma cells. Pathophysiological mechanisms of such calcifications in metastasis lesions are reviewed.

Establishment of human tumoral ependymal cell lines and coculture with tubular-like human endothelial cells.

Ependymomas, rare neoplasms of the central nervous system, occur predominantly in children. They are highly vascularized, and histological findings show many perivascular rosettes of tumoral cells radially organized around capillaries. Treatment of ependymomas relies on surgery combined with radio- or chemotherapy, but the efficiency of chemotherapy is limited, probably because of their multidrug resistance (MDR) phenotype. Progress in the therapy of these neoplasms is dramatically limited by the absence of cell line models. We established conditions for the long-term culture of human tumoral ependymocytes and their 3D coculture in Matrigel with endothelial cells. Histological, immunological, and ultrastructural studies showed that the morphological features (microvilli, cilia, and caveolae) of these cultured cells were similar to those of the tumor in vivo. The cells expressed potential oncological markers related to the immature state of tumoral cells (nestin and Notch-1), their tumorigenicity [caveolae and epidermal growth factor-receptor (EGF-R)], or the MDR phenotype [P-glycoprotein (P-gp)]. The expression of P-gp, EGF-R, and caveolin-1 by these tumoral ependymocytes could be useful in studies on new drugs. This coculture model might represent a new powerful tool to study new therapeutic delivery strategies in tumoral cells.

Myelopathy and sciatica induced by an extradural S1 root haemangioblastoma.

Haemangioblastomas are vascular tumours which mainly involve the central nervous system and retina, often in the setting of von Hippel-Lindau disease. Haemangioblastomas occurring outside the central nervous system are uncommon. Wherever it is, recognising this tumour prior to surgery is desirable, as preoperative embolisation may be considered. We report the clinical, imaging and pathological features of a sporadic sacral root haemangioblastoma in a 58-year-old man with chronic sciatica and myelopathy. The diagnosis was questioned preoperatively because an enlarged sacral foramen, seen to be filled by a highly vascular, enhancing mass and dilated vessels. Myelopathy was attributed to the presumed high venous pressure resulting from increased flow in veins draining the vascular tumour. Microneurosurgical excision was performed after endovascular embolisation and led to persistent clinical improvement.

Central nervous system cavernomas in the pediatric age group.

Pediatric CNS cavernomas still are diagnostically and therapeutically challenging lesions. With the help of magnetic resonance imaging, the natural history of cavernomas now guiding therapeutic strategies is well documented in adults but remains poorly known in the pediatric age group, since most previous studies dealt with adult and pediatric patients together. This paper focuses on clinical, imaging, and therapeutic features and differential diagnosis of CNS cavernomas with an emphasis on their specificities in the pediatric age group. It is based upon a critical review of the literature and our single-center experience with 36 children (35 with cerebral cavernomas and one with spinal cord cavernoma) operated on during the period of 1985-1999 as well as with seven additional unoperated pediatric cases. Our experience resembles that of other authors regarding the high hemorrhagic risk in children compared to adults. These angiographically occult vascular malformations are often revealed by the sudden onset of intracerebral hematoma with acute focal neurologic deficits, concomitant manifestations, and/or signs of raised intracranial pressure. True epilepsy is less common and may be related to chronic or recurrent microbleeding. Evocative imaging findings are also somewhat different in the two age groups, and we propose here an imaging classification of cerebral cavernomas based on both morphological and signal characteristics that is applicable to the pediatric age group. A sharply demarcated spherical intracerebral hematoma or heterogeneous lesion should always make one consider the hypothesis of a cavernoma. For symptomatic lesions and most rapidly growing asymptomatic lesions, the treatment of choice is complete microsurgical excision preceded by careful anatomical and functional evaluation. Improvements in surgical techniques and anesthesiology over recent years have brought good results in most operated children. The limited role of radiosurgery in the management of pediatric cerebral cavernomas is discussed. There is still a need for well-conducted specific evaluation of the natural history of these lesions in the pediatric age group to aid in systematic research, follow-up, and therapeutic strategies for asymptomatic cavernomas.

Differential expression of somatostatin receptors in ependymoma: implications for diagnosis.

Somatostatin receptors (SSts) have been found in a variety of brain tumors, e.g., meningiomas, medulloblastomas and astrocytomas. Our aim was to investigate their expression in ependymomas. Using RT-PCR, expression of mRNA for the different SSt subtypes was analyzed and quantified in 28 ependymomas and correlated with different variables (age, tumor location, histological grade, recurrence and survival). In addition, in 8 cases, protein expression was studied in vitro, using immunohistochemistry, and in vivo, by somatostatin scintigraphy. mRNAs for all 5 subtypes were variably expressed in each ependymoma. The Southern blotting signal obtained after SSt(1) and SSt(2) amplification was higher than that for the other receptor subtypes. No significant correlation was seen between the level of SSt(1) and SSt(2) mRNA expression and age, location, histological grading, recurrence or survival. In the 8 cases, SSt(1) staining was negative in 3 and low in 5. Staining for SSt(2A) was positive but low in every specimen analyzed. SSt(1) and SSt(2) immunoreactivity was seen only in the cytoplasm of tumoral cells. Somatostatin scintigraphy showed clear uptake, which agreed with MRI data in the majority of cases. However, no correlation was seen between tracer uptake intensity and histological grade, SSt(1) and SSt(2) mRNA expression or immunostaining intensity. This evidence for the expression of SSt(2) receptors in ependymomas opens interesting prospects for their follow-up.

Cardiac contusion in blunt chest trauma: a combined study of transesophageal echocardiography and cardiac troponin I determination.

BACKGROUND: The role of cardiac troponin I (cTnI) is well established in acute myocardial ischemia. However, its role in myocardial contusion remains to be clarified. Since transesophageal echocardiography (TEE) appears, at present, to be the best method for the diagnosis of myocardial contusion, the aim of this study was to measure the concentration of cTnI in patients with blunt chest trauma studied using TEE. METHODS: Thirty-two patients (27 males, 5 females, mean age 44+/-20 years), admitted to the Trauma Center of our Institution with clinical and/or radiological signs of acute blunt chest trauma, underwent biplane TEE within 24 hours of injury; serial blood samples were taken to measure cTnI levels (normal values < 0.4 ng/ml), using fluorimetric enzyme immunoassay. RESULTS: Abnormal levels of cTnI were found in 17 patients (53%): 7 patients had levels of cTnI between 0.4 and 1 ng/ml, whereas 10 patients had levels > 1 ng/ml. Segmental wall motion abnormalities consistent with myocardial contusion could be identified by echocardiography in 6/10 patients with cTnI levels > 1 ng/ml (60%) but in no patients with normal cTnI levels or with titers between 0.4 and 1 ng/ml; mean cTnI levels showed a significant difference between the two groups of patients with and without echocardiographic signs of myocardial contusion (2.6+/-1.6 vs 0.6+/-1.4 ng/ml, p < 0.001). CONCLUSIONS: Abnormal titers of cTnI suggesting myocardial contusion may be found in more than half of patients with blunt chest trauma; however, myocardial injury can be detected by TEE only for cTnI levels > 1 ng/ml; cTnI concentrations ranging between 0.4 and 1 ng/ml might be indicative of myocardial microlesions, not detectable by echocardiography, even if TEE is used; cTnI assay could therefore be suggested as a screening test before performing TEE after blunt chest trauma.

[Transformation of mycosis fungoides to pleomorphic T-cell lymphoma and central nervous system involvement]. / Mycosis fongoïde avec transformation en un lymphome cutané pléiomorphe et localisation secondaire cérébrale.

INTRODUCTION: Although mycosis fungoides is a malignant T-cell lymphoma involving mainly the skin, neurological complications are possible, with a poor prognosis. EXEGESIS: A 59-year-old man, treated for mycosis fungoides with transformation to a pleomorphic T-cell lymphoma for 1 year, was seen for mental status changes with confusion. A brain parenchyma localisation was found. CONCLUSION: This observation emphasizes the exceptional neurological tropism in the patients with mycosis fungoides. A transformation to a more aggressive cutaneous T-cell lymphoma seems necessary to induce a central nervous system involvement.

[Multiple intracranial and intraspinal meningiomas successively discovered in the absence of neurofibromatosis: 2 cases]. / Méningiomes multiples intracrânien et intrarachidien de découverte successive en l'absence de neurofibromatose: deux observations.

Multiple meningiomas in different neuroaxial compartments are quite rare. We describe the case of a 44-year-old woman who developed three intracranial meningiomas and 8 years later a T3 dorsal meningioma. Histologically, the frontal and dorsal tumors appeared as benign psammomatouss meningiomas. Both tumors were removed successfully. The second patient was a 31-year-old woman who developed right benign fronto-parietal transitional meningioma. She presented local and spheno-orbital recurrences, then a lombo-sacral lesion. The histological picture worsened from benign to malignant with multiple recurrences. Several mechanisms could account for multiple meningiomas. Such meningiomas could arise from a single primary tumor via subarachnoidal spread of a benign or malignant nature. Alternatively, they could be atypical forms of neurofibromatosis type 2 or tumors with a multifocal origin.

[Central nervous system neurocytomas: clinicopathological analysis of tree cases]. / Neurocitomas do sistema nervoso central: análise clínico-patológica de três casos.

Central nervous system neurocytoma is a rare benign tumor of neuronal origin. Because of some clinical and radiological findings CNS neurocytomas were confused with other intraventricular lesions (ependymomas, choroid plexus papilloma, oligodendrogliomas, subependymal astrocytomas). Pathological diagnosis improved with immunohistochemical and electron microscopic studies. We present three cases of intraventricular neurocytomas confirmed by immunohistochemical studies. According to the literature clinical signs, radiological features, surgical and pathological findings are discussed.

[Practical recommendations for management of the biopsy in an expansive intra-cerebral process]. / Recommandations pratiques pour la prise en charge de la biopsie d'un processus expansif intra-cérébral.

Diagnosis of an intracerebral mass requires a good collaboration between clinicians and pathologists. Different techniques may be necessary. The interest of cytological preparations and immunohistochemistry is reported. The main characteristic features of cerebral tumors are described and the differential diagnosis with reactive and inflammatory masses simulating neoplasia is discussed.

Parenchymal pineal tumors: a clinicopathological study of 76 cases.

PURPOSE: The aim of this study was to identify factors that could lead to optimization of the management of pineal parenchymal tumors (PPT) which remains equivocal and controversial. METHODS AND MATERIALS: In order to determine factors that influence PPT prognosis, a series of 76 consecutive patients from 12 European centers with histologically proven tumors was retrospectively reviewed. The clinical records and material for histologic review were available in all cases. Follow-up was achieved in 90% of cases. RESULTS: According to WHO classification, there were 19 pineocytomas, 28 intermediate and mixed PPT, and 29 pineoblastomas. According to a four-grade institutional classification, there were 11 Grade 1, 27 Grade 2, 20 Grade 3, and 18 Grade 4. Surgical resection was attempted in 44 patients, whereas 30 had biopsy only. In one case, diagnosis was made at autopsy and in another on spinal deposits. Forty-four patients were irradiated following surgery, 15 patients received chemotherapy. Forty-one patients were alive (median follow-up: 85 months); 9 patients died perioperatively; 26 patients relapsed. Univariate analysis showed a good outcome correlated with age above 20 years, tumor diameter less than 25 mm, and low-grade histology. Multivariate analysis confirmed histology and tumor volume to be significant independent prognostic factors. The extent of surgery and radiotherapy had no clear influence on survival. CONCLUSIONS: This review highlights the prognostic features of PPT and may help to determine treatment strategies based on radiologic and pathologic characteristics.

Pineal parenchymal tumors: a correlation of histological features with prognosis in 66 cases.

The WHO classification of CNS tumors divides pineal parenchymal tumors (PPT) into pineocytoma (PC), pineoblastoma (PB) and mixed pineocytoma-pineoblastoma or PPT with intermediate differentiation. The reported incidence of mixed/intermediate PPT varies and this may reflect the difficulty in classifying tumors of this type. In an attempt to overcome the problem of the classification of PPT with intermediate differentiation, we describe the relationship between histological features and patient survival in a large cooperative series of 66 PPT from 12 neurosurgical centres. All tumors were studied with both light microscopy and immunohistochemically using antibodies against glial markers or neural/neuroendocrine markers. Our series included 11 PC, 39 mixed/intermediate PPT and 16 PB. A number of mitoses greater than 6 and the presence of necrosis were associated with a poorer outcome, while positive immunostaining for neurofilaments was associated with a better survival. We propose a new prognostic grading of 4 grades, grade I for PC, grade II for PPT with fewer than 6 mitoses and positive immunolabelling for neurofilaments, grade III for PPT with either 6 or more than 6 mitoses or fewer than 6 mitoses but without immunostaining for neurofilaments and grade IV for PB.