Pituitary metastasis arising from hepatocellular carcinoma: a case report and update of the literature.

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the third leading cause of cancer-associated deaths worldwide. Most cases arise in patients with cirrhosis, and early detection through periodic screening can make it potentially curable. The presence of extrahepatic metastases (EHM) affects treatment decisions and curability. The lungs are the most common site for EHM, followed by lymph nodes, bones, and the adrenal glands. Interestingly, approximately only 15 cases of HCC metastasizing to the pituitary gland have been reported so far.The most common symptoms of pituitary metastasis (PM) arising from HCC are nerve palsies affecting the third, fourth, and sixth cranial nerves. Other symptoms, such as diabetes insipidus or pituitary insufficiencies, are present in a minority of cases. Detecting PM is difficult given its rarity. Gold-standard treatments for these patients have not yet been established, but the prognosis is dismal, with a median overall survival of only 4.5 months. In this paper, we present an interesting case of PM as the first symptom of an HCC in a 75-year-old female. We also present an overview of all cases reported to date with emphasis on symptom presentation and survival after diagnosis.Given the improvement of systemic therapy, more cases are diagnosed in both oligometastatic and palliative conditions. Therefore, better approaches and treatment modalities for extrahepatic metastases due to HCC should be defined.

In-depth mutational analyses of colorectal neuroendocrine carcinomas with adenoma or adenocarcinoma components.

Neuroendocrine carcinomas (NECs) of the colorectum are rare but highly aggressive neoplasms. These tumors show some shared genetic alterations with colorectal adenocarcinomas, and most of them have adjacent glandular adenoma or adenocarcinoma components. However, genetic data on colorectal NECs still are sparse and insufficient for definite conclusions regarding their molecular origin. Based on morphological characterization, panel and whole-exome sequencing, we here present results from an in-depth analysis of a collection of 15 colorectal NECs with glandular components, 10 of which by definition were mixed adenoneuroendocrine carcinomas (MANECs). Among shared genetic alterations of both tumor components, we most frequently found TP53, KRAS and APC mutations that also had highest allele frequencies. Mutations exclusive to glandular or neuroendocrine components outnumbered shared mutations but occurred at lower allele frequencies. Our findings not only provide additional evidence for a common clonal origin of colorectal NECs and adjacent glandular tumor components, but strongly suggest their development through the classical adenoma-carcinoma sequence. Moreover, our data imply early separation of glandular and neuroendocrine components during malignant transformation with subsequent independent mutational evolution.

Neovascularization, vascular mimicry and molecular exchange: The imaging of tumorous tissue aggressiveness based on tissue perfusion.

Angiogenesis in healthy tissue and within malignant tumors differs on many levels, which may partly be explained by vascular mimicry formation resulting in altered contrast material or different radiopharmaceuticals distributions. Failed remodulation results in changes in the molecular exchange through the capillary wall and those consequences affect the behavior of contrast agents and radiopharmaceuticals. One of the most indicative signs of malignant tissue is the increased permeability and the faster molecular exchange that occurs between the extracellular and intravascular spaces. Dynamic imaging can help to assess the changed microenvironment. The fast-distribution of molecules reflects newly developed conditions in blood-flow redistribution inside a tumor and within the affected organ during the early stages of tumor formation. Tumor development, as well as aggressiveness, can be assessed based on the change to the vascular bed development, the level of molecular exchange within the tissue, and/or indicative distribution within the organ. The study of the vascular network organization and its impact on the distribution of molecules is important to our understanding of the image pattern in several imaging methods, which in turn influences our interpretation of the findings. A hybrid imaging approach (including PET/MRI) allows the quantification of vascularization and/or its pathophysiological impressions in structural and metabolic images. It might optimize the evaluation of the pretreatment imaging, as well as help assess the effect of therapy targeting neovascularization; antiVEGF drugs and embolization-based therapies, for example.