Genome-wide methylation profiling and copy number analysis in atypical fibroxanthomas and pleomorphic dermal sarcomas indicate a similar molecular phenotype.

BACKGROUND: Atypical fibroxanthomas (AFX) and pleomorphic dermal sarcomas (PDS) are lesions of the skin with overlapping histologic features and unspecific molecular traits. PDS behaves aggressive compared to AFX. Thus, a precise delineation, although challenging in some instances, is relevant. METHODS: We examined the value of DNA-methylation profiling and copy number analysis for separating these tumors. DNA-methylation data were generated from 17 AFX and 15 PDS using the Illumina EPIC array. These were compared with DNA-methylation data generated from 196 tumors encompassing potential histologic mimics like cutaneous squamous carcinomas (cSCC; n = 19), basal cell carcinomas (n = 10), melanoma metastases originating from the skin (n = 11), leiomyosarcomas (n = 11), angiosarcomas of the skin and soft tissue (n = 11), malignant peripheral nerve sheath tumors (n = 19), dermatofibrosarcomas protuberans (n = 13), extraskeletal myxoid chondrosarcomas (n = 9), myxoid liposarcomas (n = 14), schwannomas (n = 10), neurofibromas (n = 21), alveolar (n = 19) and embryonal (n = 17) rhabdomyosarcomas as well as undifferentiated pleomorphic sarcomas (n = 12). RESULTS: DNA-methylation profiling did not separate AFX from PDS. The DNA-methylation profiles of the other cases, however, were distinct from AFX/PDS. They reliably assigned to subtype-specific DNA-methylation clusters, although overlap occurred between some AFX/PDS and cSCC. Copy number profiling revealed alterations in a similar frequency and distribution between AFX and PDS. They involved losses of 9p (22/32) and 13q (25/32). Gains frequently involved 8q (8/32). Notably, a homozygous deletion of CDKN2A was more frequent in PDS (6/15) than in AFX (2/17), whereas amplifications were non-recurrent and overall rare (5/32). CONCLUSIONS: Our findings support the concept that AFX and PDS belong to a common tumor spectrum. We could demonstrate the diagnostic value of DNA-methylation profiling to delineating AFX/PDS from potential mimics. However, the assessment of certain histologic features remains crucial for separating PDS from AFX.

Antiglioma effects of a new, low molecular mass, inhibitor of fibroblast growth factor.

Despite the deployment of multimodal therapies involving neurosurgical resection, radio- and polychemotherapy, the prognosis for glioblastoma patients remains poor. These tumors are pathologically characterized by their associated angiogenesis and diffuse brain invasion, processes that are probably closely linked to the unfavorable prognosis of this disease. Accordingly, pharmacological inhibition of glioblastoma invasion and approaches that impede angiogenesis are considered to be promising therapeutic strategies to combat these tumors. Nevertheless, the anti-angiogenic therapies for glioblastoma currently available are transient and palliative at best. Blocking the effects of fibroblast growth factor (FGF) may represent a novel mean of inhibiting the angiogenesis associated with glioblastoma, as it mediates the angiogenesis induced by other factors and it is an angiogenic factor by itself. In addition, the survival of glioma cells and their resistance to chemotherapeutic agents are highly FGF-dependent. We show here that a recently described inhibitor of FGF, 2,5-dihydroxyphenyl-sulfonate (2,5DHPS, dobesilate), stimulates the apoptosis of tumor cells, inhibits glioblastoma invasion and suppresses its associated angiogenesis. Moreover, this agent augments the efficiency of chemotherapeutic agents in a rat model of orthotopic brain tumor. These results suggest that 2,5DHPS treatment may represent a promising therapy for malignant glioma.

Neoplasias mucinosas papilares intraductales de páncreas: presentación de dos casos / Intraductal papillary mucinous neoplasm of the pancreas: a report of two cases

Las neoplasias mucinosas papilares intraductales de páncreas (NMPI) constituyen una entidad bien reconocida, relativamente rara, entre las neoplasias pancreáticas. La OMS las define como neoplasias papilares productoras de mucina que se desarrollan en el conducto de Wirsung o en sus ramas principales. Presentamos 2 casos de NMPI. El primero corresponde a un varón de 69 años que presenta una tumoración única de 7,5cm en cabeza de páncreas con dilatación del conducto de Wirsung que se diagnosticó como NMPI de tipo intestinal. El segundo se trataba de una mujer de 60 años con una tumoración quística multifocal en cabeza de páncreas de 2cm y afectación del borde de resección del cuerpo y la cola del páncreas que se diagnosticó como NMPI de tipo foveolar. En el estudio inmunohistoquímico, las tumoraciones presentaron una expresión diferente para citoqueratinas, siendo la NMPI de tipo intestinal positivo para CK-7 y CK-20 y negativo para CK34βE12; y el foveolar, positivo para CK-7 y CK34βE12 y negativo para CK-20. Estas neoplasias tienen un pronóstico excelente tras la cirugía en ausencia de componente invasor. La diferente expresión de citoqueratinas encontradas en nuestro estudio puede ser útil para determinar el tipo de neoplasia en biopsias de pequeño tamaño(AU)

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a well known but relatively infrequent entity. The World Heath Organization defines it as a papillary mucin producing neoplasm developing in the duct of Wirsung or in its principal branches. We present two cases of IPMN of the pancreas. The first was diagnosed as an intestinal type IPMN occurring in a 69 year old male who presented with a single, 7.5cm tumour in the head of the pancreas with a dilated duct of Wirsung. The second case was a foveolar type IPMN found in a 60 year old woman with a 2cm, multifocal, cystic tumour in the head of the pancreas involving the resection margins in the body and tail of the pancreas. The immunohistochemistry revealed a different expression of cytokeratins in each case; the intestinal type IPMN was positive for CK7 and CK20 and negative for CK34βE12, whilst the foveolar type tumour was positive for CK7 and CK34βE12 but negative for CK20. The post operative prognosis is excellent when no invasion has occurred. The difference in cytokeratin expression found in the reported cases could prove useful in the diagnosis of small biopsy samples(AU)