Intestinal, intestinal-type and intestine-localized metastatic adenocarcinoma. Immunohistochemical approach to the differential diagnosis.

The pathologist is often called to define the origin of tumors through the help of ancillary studies, mainly immunohistochemical stainings. In this setting, the differential diagnosis between intestinal adenocarcinomas, other tumors with intestinal-type morphology, and adenocarcinomas metastatic to the bowel can be particularly difficult. In such cases, an accurate assessment of the disease is required to address the patients to the optimal treatment. Immunohistochemistry offers the use of multiple antibodies: the integrated evaluation of specific stainings can lead to a correct diagnosis. Particularly, the use of cytokeratins, mucins, and ß-catenin could be of great help in most cases. In addition, recently, novel specific markers such as SATB2 and AMACR have been introduced, improving the utility of immunohistochemistry in the differential diagnosis of intestinal-type and intestinal adenocarcinomas.

Features of microvessel density (MVD) and angiogenesis inhibitors in therapeutic approach of hepatocellular carcinoma (HCC).

OBJECTIVE: The curative hepatocellular carcinoma (HCC) therapy was traditionally based on surgical or loco-regional ablation approach. However, HCC is a solid tumor characterized by a highest level of vascularization; therefore, angiogenesis inhibitor could play a pivotal role in the pharmacological therapeutic approach. Despite the low number of approved drugs, a wide range of multi-kinase and MET inhibitor is currently being evaluated in phase II and III study. In this review, we described all the drugs that have shown efficacy in recently and ongoing trials. Moreover, the immunotherapy represents a recent challenge in the HCC treatment. The strategy based on the production of multi-epitope, multi-HLA peptide vaccine naturally processed and presented on primary tumor tissues of HCC patients. A further upgrade of cancer vaccine could be represented by the combination of metronomic chemotherapy and checkpoint inhibitors.

Three dimensional primary cultures for selecting human breast cancers that are sensitive to the anti-tumor activity of ipatasertib or taselisib in combination with anti-microtubule cytotoxic drugs.

Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib, targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor, are currently under clinical investigation in breast cancer (BC) patients. We have previously demonstrated the anti-tumor efficacy of these anti-PI3K/AKT-inibitors in combination with anti-microtubule drugs in human BC cell lines, through a complete cytoskeleton disorganization. In this work, we generated ex-vivo three-dimensional (3D) cultures from human BC as a model to test drug efficacy and to identify new molecular biomarkers for selection of BC patients suitable for anti-PI3K/AKT-inibitors treatment. We have established 3D cultures from 25/27 human BC samples, in which the ability of growth in vitro replicates the clinical and biological aggressiveness of the original tumors. According to the results of next generation sequencing analysis, a direct correlation was found between PI3KA mutations and the sensitivity in 3D models in vitro to taselisib and ipatasertib alone and combined with anti-microtubule agents. Moreover, mutations in HER and MAPK families related genes, including EGFR, KRAS and BRAF, were found in resistant samples, suggesting their potential role as negative predictive factors of response to these agents. Thus, we demonstrated that ex vivo 3D cultures from human BC patients allow a rapid and efficient drug screening for chemotherapies and targeted agents in genetically selected patients and represent an innovative model to identify new biomarkers of drug resistance.

Epithelioid angiosarcoma arising in schwannoma of the kidney: report of the first case and review of the literature.

BACKGROUND: Schwannoma and angiosarcoma are infrequent pathologies that have been rarely reported in the kidney. Angiosarcoma is an uncommon malignant tumor presenting a recognizable vascular differentiation. It can develop in any site but the most common locations include the skin, soft tissues, breast, bone, liver, and spleen while renal localization has been very rarely reported in the literature. Schwannoma is a benign peripheral nerve sheath tumor composed of cells with the immunophenotype and ultrastructural features of differentiated Schwann cells. It has a wide anatomical distribution but the most frequent locations include subcutaneous tissues of the extremities and the head and neck region and the retroperitoneal and mediastinal soft tissues. The occurrence of an angiosarcoma in a pre-existing schwannoma is an extremely rare event with <20 cases reported in worldwide literature. In the present study, a renal case of angiosarcoma arising in schwannoma is presented with a detailed review of the pertinent literature. CASE PRESENTATION: A 56-year-old man was admitted with a few days history of lower back pain and hematuria. Abdominal ultrasound showed a mass inside the left renal medulla. Subsequent imaging investigations with computed tomography and magnetic resonance confirmed the presence of the lesion and showed a pulmonary metastasis. CONCLUSIONS: The final histopathological examination led to the diagnosis of epithelioid angiosarcoma arising in a schwannoma. The patient came to death a few months later due to a massive hemothorax. To the best of our knowledge, the present is the first case of an angiosarcoma arising in a schwannoma of the kidney.