[The role of angiogenesis in renal carcinoma]. / Ruolo dell'angiogenesi nel carcinoma renale.

Renal cell carcinoma is characterized by intense angiogenesis associated with the inactivation of the von Hippel-Lindau oncosuppressor gene with consequent hyperexpression of proangiogenic factors. Functional and molecular characterization of renal tumor endothelial cells has demonstrated an increase in angiogenesis and cell survival. The proangiogenic phenotype was due to hyperactivation of the PI3K/Akt/mTor pathway, which downregulates the synthesis of the antiangiogenic factor thrombospondin-1. Moreover, renal tumor endothelial cells presented an immature and embryonic phenotype with expression of the embryonic kidney-specific gene PAX-2. It is conceivable that the endothelium present in renal carcinoma is heterogeneous, with a possible origin from adjacent vessels, resident or circulating stem cells, or from the tumor cells themselves. The relevance of the angiogenic process in renal carcinoma is underlined by the therapeutic effect of antiangiogenic drugs. Different drugs against VEGF, such as the anti-VEGF monoclonal antibody bevacizumab, and small molecule tyrosine-kinase inhibitors, such as sunitinib and sorafenib, showed a clinical effect in patients with metastatic carcinoma. However, antiangiogenic therapy, although beneficial, is not sufficient per se. These studies suggest a role for the angiogenic program in the growth and dissemination of renal carcinoma and indicate the need for new therapeutic strategies.

[New therapeutic options in the treatment of hepatocellular carcinoma]. / Attuali possibilità terapeutiche nel trattamento del carcinoma epatocellulare.

Hepatocellular carcinoma (HCC) is the fourth cause of death for cancer, the first in northern Africa and is the eighth tumor for incidence in the world. Risk factors are: liver cirrhosis, HBV, HCV and natural toxins (i.e. aflatoxin). A screening program is feasible and based on serum alpha-fetoprotein dosage and periodic liver ultrasonography. Instrumental diagnosis is based on ultrasonography associated with angiography or spiral TC associated with systemic portography. The best therapy of HCC is based on a multimodal approach: surgery when feasible, associated with or in alternative to intratumoral ethanol injection (PEI), transcatheter arterial chemoembolization (TACE), chemotherapy and radiotherapy. These different therapeutical approaches are related to the liver extent of the disease and liver functioning. Poor results obtained with chemotherapy led to research different therapeutical approaches as hormonal substances, immune modulators or genetic modulators. Most patients present with advanced disease, and their survival rate decreases with the increase of liver cirrhosis concomitant with HCC. Better results should be obtained with the use of different therapeutical approaches as angiogenetic inhibitors, today only for experimental use at present.

[Two cases of melanoma metastasis. Description and review of the literature]. / Due casi di metastatizzazione di melanoma. Descrizione e revisione della letteratura.

The metastases of malignant melanoma can appear after many years to primitive diagnosis and can involve many organs. There are reported two cases of metastatic melanoma presenting in a parotid gland and in the small bowel. The rarity of the metastatic melanoma to parotid gland and the difficulty of diagnosing intestinal involvement are discussed together with a review of the literature. The surgical treatment was justified by therapeutic and diagnostic aim, without positive influence on survival.

[Solitary fibrous tumor of the pleura. Clinical case]. / Tumore fibroso solitario della pleura. Caso clinico.

Solitary fibrous tumors of the pleura represent a rare clinicopathological entity: 456 cases only have been reported since 1991. A interesting case of solitary fibrous tumor of the pleura is described here, because it turned up in a female patient followed up for a bilateral breast cancer and so with the exact determination of the period of beginning. The complex morphological picture is illustrated in relation to other cases reported in the literature. Immunohistochemical results are stressed, particularly as regards the coexpression of vimentin and desmin without necrosis and the low number of mitosis. As there are no criteria to determine the possible aggressive or malignant behaviour of the tumor, surgical resection of the lesion is indispensable both to resolve the diagnosis and to carry out the only proposable therapy.

Intranodular reactive endothelial hyperplasia in adenomatous goitre.

Endothelial hyperplasia has rarely been recognized in the thyroid. Ischaemic events or hemorrhage, sometimes as a result of fine needle aspiration procedures, have been regarded as possible causes. To clarify the morphological pattern and the clinical significance of this lesion, we studied a series of adenomatous goitres and selected 11 cases showing prominent endothelial hyperplasia in an individual nodule. Grossly, the parenchyma of the affected nodule was substituted by greyish, friable tissue surrounded by a fibrous capsule and by a thin rim of residual thyroid parenchyma. Microscopically, fibrinous and haemorrhagic material was crossed by intercommunicating vascular channels or papillary structures. These were lined by plump endothelial cells. In only one case had pre-operative fine needle aspiration biopsy been performed: smears yielded a haemorrhagic background, fibrin and numerous elongated cells; colloid and follicular cells were virtually absent. In both surgical and cytological specimens a differential diagnosis with a vascular neoplasm, a rare occurrence in the thyroid, was taken into consideration. We conclude that intranodular reactive endothelial hyperplasia is a relatively common occurrence (1.6%) in adenomatous goitre and is of diagnostic interest in both surgical and cytological specimens, since it can mimic vascular tumours and may lead to unnecessary treatment if misdiagnosed.