Salivary gland tissues and derived primary and metastatic neoplasms: unusual pitfalls in the work-up of sellar lesions. A systematic review.

PURPOSE: Salivary gland (SG) tissue and derived neoplasms may occur in the sellar region. As the current literature is mostly limited to case reports, the puzzling case of an inflammatory SG removed by transsphenoidal surgery (TS) and mimicking a prolactinoma prompted us to perform the first systematic review of these unusual conditions. METHODS: A systematic literature search was conducted according to the PRISMA guidelines. Forty-four individual cases-non-neoplastic enlarged salivary glands (NNESG, n = 15), primary benign (n = 7) and malignant (n = 8) ectopic salivary tumours (ST) and sellar metastasis from eutopic primary ST (n = 14)-were suitable for the analysis of clinical, radiological and pathological characteristics. Therapeutic outcome was reviewed as a secondary endpoint. RESULTS: All cases were diagnosed after surgery. NNESG commonly affected young and/or female patients, typically leading to headaches and hyperprolactinemia and originating close to the neurohypophysis. Submucosal SG should be excluded before concluding to an intrasellar NNESG after TS. No gender or age predominance was found for primary ectopic ST, which present as large tumors, with histological phenotypes similar to common ST. Hypopituitarism and diabetes insipidus were more frequent in ST than in NNESG. NNESG and benign ectopic ST rarely recur. Malignant ectopic ST should be distinguished from secondary localizations of eutopic ST reaching the sella by contiguity or metastatic spread; both share a frequent unfavorable outcome. CONCLUSION: Sellar neoplasms derived from SG are rare but misleading conditions and pituitary dysfunction is likely to be more common than currently reported. Appropriate pathological evaluation and multidisciplinary approach are required.

Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) - a molecularly defined glioneuronal CNS tumour class displaying recurrent monosomy 14.

AIMS: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. PATIENTS AND METHODS: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. RESULTS: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. CONCLUSIONS: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters.

Brain gliomas and growth factors: immunohistochemical, immunofluorescence, flow cytometry and RT-PCR profile in pediatric age.

Gliomas represent over 50% of tumors occurring in children. Evidence suggests that glioma stem cells (GSCs), maintained by the transforming growth factor-beta (TGF-ß1) pathway, and vascularization substantially contribute to tumor aggressiveness. The identification of important angiogenic factors such as vascular endothelial growth factor (VEGF) may represent a crucial step in the therapeutic approach against tumor growth and metastatic diffusion. The aim of this study was to identify the expression of TGF-ß1, VEGF and VEGF-receptors in brain gliomas. Specimens of 16 gliomas and 4 controls from children aged 0.2-14 years were used in the study. Immunohistochemical analysis and gene expression study from specimens was performed. Flow cytometry analysis on GSCs was performed to ascertain the expression of VEGF and VEGF-R2 in the tumor stem cell compartment. Newly diagnosed gliomas mainly showed moderate to strong VEGF immunostaining and increased expression of pro-inflammatory molecules in glioma cells. The proportion of TGF-ß1 positive endothelial cells was markedly lower in normal brain vessels compared to tumor vessels. These findings demonstrate that the glioma mass is constituted by a phenotypically immature anoxic central area with a proliferating hypoxic layer; the peripheral area is characterized by cell types with a higher degree of differentiation expressing pro-angiogenic factors. Our data have proven that GSCs play a central role in promoting glioma neovascularization. These findings are useful to understand glioma vascularization, have relevant implications in the therapeutic options and may favor new insights into stem cells biology and suggest therapeutic opportunities for the anti-vascular treatment strategy.

The miR-139-5p regulates proliferation of supratentorial paediatric low-grade gliomas by targeting the PI3K/AKT/mTORC1 signalling.

AIMS: Paediatric low-grade gliomas (pLGGs) are a heterogeneous group of brain tumours associated with a high overall survival: however, they are prone to recur and supratentorial lesions are difficult to resect, being associated with high percentage of disease recurrence. Our aim was to shed light on the biology of pLGGs. METHODS: We performed microRNA profiling on 45 fresh-frozen grade I tumour samples of various histological classes, resected from patients aged ≤16 years. We identified 93 microRNAs specifically dysregulated in tumours as compared to non-neoplastic brain tissue. Pathway analysis of the microRNAs signature revealed PI3K/AKT signalling as one of the centrally enriched oncogenic signalling. To date, activation of the PI3K/AKT pathway in pLGGs has been reported, although activation mechanisms have not been fully investigated yet. RESULTS: One of the most markedly down-regulated microRNAs in our supratentorial pLGGs cohort was miR-139-5p, whose targets include the gene encoding the PI3K's (phosphatidylinositol 3-kinase) catalytic unit, PIK3CA. We investigated the role of miR-139-5p in regulating PI3K/AKT signalling by the use of human cell cultures derived from supratentorial pLGGs. MiR-139-5p overexpression inhibited pLGG cell proliferation and decreased the phosphorylation of PI3K target AKT and phosphorylated-p70 S6 kinase (p-p70 S6K), a hallmark of PI3K/AKT/mTORC1 signalling activation. The effect of miR-139-5p was mediated by PI3K inhibition, as suggested by the decrease in proliferation and phosphorylation of AKT and p70 S6K after treatment with the direct PI3K inhibitor LY294002. CONCLUSIONS: These findings provide the first evidence that down-regulation of miR-139-5p in supratentorial pLGG drives cell proliferation by derepressing PI3K/AKT signalling.

BRAF V600E expression and distribution in desmoplastic infantile astrocytoma/ganglioglioma.

AIMS: Desmoplastic infantile astrocytoma/ganglioglioma (DIA/DIG) is a rare primary neuroepithelial brain tumour typically affecting paediatric patients younger than 24 months. Knowledge about genetic alterations in DIA/DIG is limited. However, a previous study on BRAF V600E mutation in paediatric glioma revealed a BRAF mutation in one of two tested DIAs/DIGs. The limited number of cases in that study did not allow any conclusion about mutation frequency of BRAF in this tumour entity. METHODS: We collected a series of 18 DIAs/DIGs for testing BRAF V600E mutational status by BRAF V600E immunohistochemistry (clone VE1). Cases with sufficient DNA were tested for BRAF V600E mutation by pyrosequencing. RESULTS: Three out of 18 DIAs/DIGs presented with VE1 binding. A considerable proportion of BRAF V600E mutated tumour cells was detected in the cortical tumour component, whereas the pronounced leptomeningeal tumoural stroma was predominantly negative for VE1 binding. Pyrosequencing confirmed BRAF V600E mutation in two of three VE1-positive cases. CONCLUSION: BRAF V600E mutation affects a subset of DIAs/DIGs and offers new therapeutic opportunities.

Neurotrophins, their receptors and KI-67 in human GH-secreting pituitary adenomas: an immunohistochemical analysis.

Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM.

Single brain metastases from cervical carcinoma: report of two cases and critical review of the literature.

Single brain metastases from cervical carcinomas are rare. We report two cases of solitary brain metastases, showing different histological types, which have been excised with microsurgical technique. Neuroendocrine differentiation does not seem to be connected to clinical behavior, indeed a poor prognosis depends on poorly differentiated histological types. In our cases, brain metastases were a late event and they have been successfully excised in microsurgery, thanks to their solitary and resectable nature, and a well-controlled primary disease.

Four-year clinical and neuroradiological follow-up of a papillary tumor of the pineal region.

Papillary tumor of the pineal region (PTPR) is a rare variety of CNS neoplasms and, since its first definition in 2003, only 64 cases have been described. PTPR is a primary neoplasm morphologically characterized by papillary structure staining for cytokeratin, transthyretin, neurone-specific enolase and S-100 protein. We report on a case of about 4 years' clinical history and neuroradiological follow-up of PTPR, in a 47-year-old Indian patient, with the aim of increasing the knowledge of its natural history. We describe through CT and MRI scans the natural evolution of this neoplasm, enhancing changes and morphologic structures involved, together with the final surgical treatment and pathological details. A mean growth rate average was calculated for this kind of lesion. In conclusion, the inexorable progressive growing nature of this tumor leads us to advocate an aggressive attitude among neurosurgeons and radiotherapists, with a precocious surgical approach when the suspicion rises.

TP53, ß-Catenin and c-myc/N-myc status in embryonal tumours with ependymoblastic rosettes.

BACKGROUND: The primitive neuroectodermal tumours of central nervous system (CNS-PNET) are a heterogeneous group of neoplasms, occurring in the CNS and composed of undifferentiated or poorly differentiated neuroepithelial cells which may display divergent differentiation along neuronal, astrocytic and ependymal lines. The WHO classification includes in this group of tumours also ependymoblastomas and medulloepitheliomas. Several groups have reported examples of CNS-PNET with combined histological features of ependymoblastoma and neuroblastoma, defined as 'embryonal tumour with abundant neuropil and true rosettes'. The presence of the amplification of chromosome region 19q13.42, common in both ependymoblastoma and embryonal tumour with abundant neuropil and true rosettes, suggests that they represent a histological spectrum of a single biological entity. METHODS: We examined 24 cases of ependymoblastoma/embryonal tumour with abundant neuropil and true rosettes (EPBL/ETANTR) for the presence of mutations of TP53 and ß-Catenin and for amplification of c-myc/N-myc. RESULTS: The single strand conformation polymorphism-mutational screening did not identify any mutation in exons 5 to 8 of the TP53 gene. However, we found a point mutation affecting codon 34 (GGA → GTA) of ß-Catenin gene resulting in a Glycine → Valine substitution. No cases presented c-myc/N-myc amplification. CONCLUSIONS: EPBL/ETANTRs show molecular features different from other CNS-PNET and medulloblastomas. The presence of alterations in the ß-Catenin/WNT pathway seems to be noteworthy due to the close relationship between this pathway and miR-520g encoded in chromosome 19q13.42 region amplified in these tumours.

Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide.

Epigenetic silencing of the O(6)-methylguanine-DNA-methyltransferase (MGMT) gene by promoter methylation is correlated with improved progression-free survival (PFS) and overall survival (OS) in adult patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. The aim of this study is to determine the correlation between MGMT and survival in elderly patients with GBM treated with radiotherapy (RT) and temozolomide (TMZ). Eighty-three patients aged 70 years or older with histologically confirmed GBM treated with RT plus TMZ between February 2005 and September 2009 were investigated in this study. The methylation status of the MGMT promoter was determined by polymerase chain reaction analysis. Median PFS and OS were 7.5 and 12.8 months, respectively. The MGMT promoter was methylated in 42 patients (50.6%) and unmethylated in 41 patients (49.4%). Median OS was 15.3 months in methylated patients and 10.2 months in unmethylated patients (P = 0.0001). Median PFS was 10.5 months in methylated tumors and 5.5 months in unmethylated tumors (P = 0.0001). On multivariate analysis MGMT methylation status emerged as the strongest independent prognostic factor for OS and PFS (P = 0.004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ.

Type-3 metabotropic glutamate receptors negatively modulate bone morphogenetic protein receptor signaling and support the tumourigenic potential of glioma-initiating cells.

Targeted-therapies enhancing differentiation of glioma-initiating cells (GICs) are potential innovative approaches to the treatment of malignant gliomas. These cells support tumour growth and recurrence and are resistant to radiotherapy and chemotherapy. We have found that GICs express mGlu3 metabotropic glutamate receptors. Activation of these receptors sustained the undifferentiated state of GICs in culture by negatively modulating the action of bone morphogenetic proteins, which physiologically signal through the phosphorylation of the transcription factors, Smads. The cross-talk between mGlu3 receptors and BMP receptors was mediated by the activation of the mitogen-activated protein kinase pathway. Remarkably, pharmacological blockade of mGlu3 receptors stimulated the differentiation of cultured GICs into astrocytes, an effect that appeared to be long lasting, independent of the growth conditions, and irreversible. In in vivo experiments, a 3-month treatment with the brain-permeant mGlu receptor antagonist, LY341495 limited the growth of infiltrating brain tumours originating from GICs implanted into the brain parenchyma of nude mice. While clusters of tumour cells were consistently found in the brain of control mice, they were virtually absent in a large proportion of mice treated with LY341495. These findings pave the way to a new non-cytotoxic treatment of malignant gliomas based on the use of mGlu3 receptor antagonists.

Two-hit model for progression of medulloblastoma preneoplasia in Patched heterozygous mice.

Inactivation of one Ptc1 allele predisposes humans and mice to spontaneous medulloblastoma development, and irradiation of newborn Ptc1 heterozygous mice results in dramatic increase of medulloblastoma incidence. While a role for loss of wild-type (wt) Ptc1 (LOH) in radiation-induced medulloblastomas from Ptc1(neo67/+) mice is well established, the importance of this event in spontaneous medulloblastomas is still unclear. Here, we demonstrate that biallelic Ptc1 loss plays a crucial role in spontaneous medulloblastomas, as shown by high rate of wt Ptc1 loss in spontaneous tumors. In addition, remarkable differences in chromosomal events involving the Ptc1 locus in spontaneous and radiation-induced medulloblastomas suggest distinct mechanisms for Ptc1 loss. To assess when, during tumorigenesis, Ptc1 loss occurs, we characterized cerebellar abnormalities that precede tumor appearance in Ptc1(neo67/+) mice. We show that inactivation of only one copy of Ptc1 is sufficient to give rise to abnormal cerebellar proliferations with different degree of altered cell morphology, but lacking potential to progress to neoplasia. Furthermore, we identify biallelic Ptc1 loss as the event causally related to the transition from the preneoplastic stage to full blown medulloblastoma. These results underscore the utility of the Ptc1(neo67/+) mouse model for studies on the mechanisms of medulloblastoma and for development of new therapeutic strategies.

Alternative splicing of the ErbB-4 cytoplasmic domain and its regulation by hedgehog signaling identify distinct medulloblastoma subsets.

Medulloblastoma (MB) results from aberrant development of cerebellar neurons in which altered hedgehog (Hh) signalling plays a major role. We investigated the possible influence of Hh signalling on ErbB-receptor expression in MB, in particular that of the ErbB-4 CYT-1 and CYT-2 isoforms generated by alternative splicing of the cytoplasmic domain. ErbB-4 expression was downregulated in Hh-induced MBs from Patched-1(+/-) mice. Hh signalling (reflected by enhanced expression of the Gli1 transcription factor) inhibited ErbB-4 expression in mouse cerebellar granule progenitors and human MB cells. Analysis of 26 human primary MBs revealed a subset of 11 tumors characterized by low Gli1 levels, upregulated ErbB-4 expression and increased CYT-1:CYT-2 ratios. Interestingly, CYT-1 and Gli1 levels were inversely correlated. ErbB-4 CYT-1 and CYT-2 had different phenotypic effects in cultured MB cells: in response to neuregulin treatment, CYT-2 overexpression inhibited proliferation whereas CYT-1, which includes a phosphatidylinositol 3-kinase (PI3K)-binding site that is missing in CYT-2, enhanced resistance to starvation- and etoposide-induced apoptosis by activating PI3K/Akt signalling. CYT-1:CYT-2 ratios displayed correlation with tumor histotype and ErbB-2 levels, which are established prognostic indices for MB. These findings demonstrate that low-level Hh signalling in human MB is associated with the selective maintenance of high ErbB-4 CYT-1 expression, an alteration that exerts tumor-promoting effects.

Differential expression of neurogenins and NeuroD1 in human pituitary tumours.

Basic helix-loop-helix (bHLH) transcription factors are involved in neuroendocrine cell growth and differentiation. Though NeuroD1 is viewed as corticotroph specific, its overexpression in non-corticotroph pituitary adenomas (PAs) may reflect the activation of molecular pathways involving other bHLH factors, like neurogenins. To search for neurogenin-NeuroD1 molecular pathways in the human normal and tumoural pituitary. Fifty-one PAs--22 clinically non-secreting (CNS) and 29 secreting respectively--and normal human pituitaries (NP) were studied for NeuroD1 and neurogenins (Ngn1, Ngn2 and Ngn3) gene expression by RT-PCR and quantitative real-time RT-PCR (qRT-PCR). Immunohistochemistry for Ngn2/3 was performed in some cases. NeuroD1, Ngn2, Ngn3 and Ngn1 were observed in up to 84.3, 76.5, 30.4 and 9.1% of PA respectively, only NeuroD1 and Ngn2 being frequently overexpressed when compared with NP. Whereas NeuroD1 expression was higher in corticotroph and CNS adenomas (P=0.0001 versus Pit-1-dependent PA), Ngn2 expression was higher in secreting PA, especially in Pit-1-dependent PA (P=0.007 and P=0.0006 versus CNS respectively). Pit-1-dependent PA which received pre-operative pharmacological treatment expressed higher Ngn2 levels than untreated cases (P=0.025). Nuclear Ngn2 was observed in NP and in most PA, especially ACTH- and GH-secreting adenomas. Nuclear Ngn3 was observed in a minority of secreting PA. Ngn2 is normally expressed in the anterior pituitary and frequently expressed in PA, but does not account for NeuroD1 overexpression where present. Owing to their low and inconstant expression, the biological significance of Ngn1/3 in the adult pituitary is uncertain.

PHCCC, a specific enhancer of type 4 metabotropic glutamate receptors, reduces proliferation and promotes differentiation of cerebellar granule cell neuroprecursors.

Exposure of immature rat cerebellar granule cell cultures to the type 4 metabotropic glutamate (mGlu4) receptor enhancer N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC) reduced [3H]thymidine incorporation. Its action was sensitive to the growth conditions and was attenuated by two mGlu4 receptor antagonists. An antiproliferative action of PHCCC was also seen in cultures from wild-type, but not mGlu4, knock-out mice. At least in rat cultures, PHCCC was not neurotoxic and enhanced neuritogenesis. Although PHCCC reduced the increase in cAMP formation and phospho-AKT levels induced by forskolin, none of these transduction pathways significantly contributed to the reduction of [3H]thymidine incorporation. Interestingly, PHCCC reduced the expression of Gli-1, a transcription factor that mediates the mitogenic action of Sonic hedgehog. Finally, we treated newborn rats with PHCCC either intracerebrally (infusion of 5 nmol/2 microl in the cerebellar region once every other day) or systemically (5 mg/kg, i.p., once daily) from postnatal days 3-9. Local infusion of PHCCC induced substantial changes in the morphology of the developing cerebellum. In contrast, systemic injection of PHCCC induced only morphological abnormalities of the cerebellar lobule V, which became visible 11 d after the end of the treatment. These data suggest that mGlu4 receptors are involved in the regulation of cerebellar development.

Central nervous system mesenchymal chondrosarcoma.

Central nervous system mesenchymal chondrosarcomas are rare malignant tumors that constitute a separate entity from the classical chondrosarcoma and myxoid variant. Clinical behaviour of central nervous system chondrosarcomas is still unknown. We describe two rare examples of intracranial mesenchymal chondrosarcoma with a review of the literature, in an attempt to clarify the clinical characteristics, prognosis and treatment of choice of these unusual tumors. Among the 55 reported cases, 23 had postoperative radiotherapy. Although there is no statistical significance according to the Log-Rank test (p=0.7), the patients treated with radiation therapy seem to have a better chance of survival. Patients who had adjuvant chemotherapy (only 5) showed survival times similar to those patients who had none. Although clinical behaviour of central nervous system chondrosarcomas remains to be defined, data from our series as well as literature show that radical removal is the best therapeutic choice. In addition, patients treated with postoperative radiotherapy seem to show a trend toward increased survival.

The spatio-temporal pattern of the axonopathy associated with the neurotoxicity of 3,4-dimethyl-2,5-hexanedione in the rat.

The neurotoxicity of the gamma-diketone 3,4-dimethyl-2,5-hexanedione(DMHD) was studied to determine the distribution of the neuropathologic changes and the temporal sequence during the intoxication period and following five and 15 weeks of recovery. Intoxication with 3,4-dimethyl-2,5-hexanedione at a daily dose of 0.25 mmoles/kg led to a profound clinical neuropathy, resulting in paralysis of all four limbs after 12-15 days. The cumulative toxic dose for this gamma-diketone was 3-4 mmoles/kg, indicating that dimethyl substitution increased the neurotoxicity of gamma-diketones by a factor of 20-30. The neuropathy was characterized histologically by giant axonal swellings in the proximal axon of the lower motor neuron in a distribution similar to IDPN (beta,beta'-iminodipropionitrile)-neuropathy, with swellings in the anterior horn, intraspinal anterior root, and the proximal anterior root. These swellings developed from six to 12 days of intoxication and were still evident after 15 weeks of recovery. The fact that dimethyl substitution of 2,5-hexanedione accelerated the neuropathy and was characterized by proximal axonal swellings has two important implications: 1) that formation of pyrrole derivatives may be an important step in the pathogenesis of gamma-diketone neuropathies, and 2) that the neurofilament neuropathies may represent a continuum of toxic neuropathies in which the rate of action of the neurotoxin ultimately determines the proximo-distal location of the axonal swellings.

The guanine triphosphatase (GTPase) activating protein (GAP)-related domain of the neurofibromatosis type 1 gene is not mutated in neural crest-derived sporadic tumours.

We conducted a mutation analysis of the most conserved region of the neurofibromatosis type 1 (NF1) gene, the guanine triphosphatase (GTPase) activating protein (GAP)-related domain (NF1 GRD), to which the function of tumour suppressor is attributed. Sixty primary neuroectodermal tumours were analysed. The rationale for the study was based on the likelihood of finding structural alterations resulting in loss of function of this region in tumours of neuroepithelial tissues, where the activity of neurofibromin seems to be crucial in regulating the mechanisms of signal transduction and cell transformation mediated by p21 ras. Following analysis of the whole NF1 GRD sequence, no mutations were identified in the tumours analysed. We conclude that the loss of NF1 gene tumour suppressor function, that might lead or contribute to the development of malignancies in neuroectodermal tissues, is not due to structural abnormalities of the region of the gene which interacts with p21 ras.

Suprasellar papillary squamous epithelioma ("papillary craniopharyngioma").

Six cases of a distinctive suprasellar papillary neoplasm are presented and the features of this lesion are contrasted with those of the classical adamantinomatous craniopharyngioma. Characteristics distinguishing the former from the latter include a predominate, and perhaps exclusive, occurrence in adulthood; frequent radiologic solidity and absence of calcification; macroscopic papillary nature; and, microscopically, a well-differentiated papillary squamous epithelium without calcification, palisaded cells, or keratoid nodules. We suggest that this papillary lesion is a clinicopathologic entity distinct from the classical adamantinomatous craniopharyngioma.