Uveal melanoma (UM) is the most common primary tumor of the eye in adults. There is no standard adjuvant treatment to prevent metastasis and no effective therapy in the metastatic setting. We have established a unique panel of 7 UM cell lines from either patient's tumors or patient‐derived tumor xenografts (PDXs). This panel recapitulates the molecular landscape of the disease in terms of genetic alterations and mutations. All the cell lines display GNAQ or GNA11 activating mutations, and importantly four of them display BAP1 (BRCA1 associated protein‐1) deficiency, a hallmark of aggressive disease. The mTOR pathway was shown to be activated in most of the cell lines independent of AKT signaling. mTOR inhibitor Everolimus reduced the viability of UM cell lines and significantly delayed tumor growth in 4 PDXs. Our data suggest that mTOR inhibition with Everolimus, possibly in combination with other agents, may be considered as a therapeutic option for the management of uveal melanoma.
The recent literature shows that interest in ocular adnexal lymphomas and their biologic and clinical characteristics—along with their possible association with Chlamydia psittaci infection and therapeutic management with rituximab or anti-Chlamydia psittaci antibiotic therapy—is considerable. These new data have modified the previously reported features of this disease and have made an updated review of the literature necessary. The aims of this review are to present the current knowledge on the biology of these lymphomas, their clinical features and prognostic factors, and the panel of all available treatment options.
The aims of this study were to define the initial pathological and clinical characteristics, and prognostic factors of patients with primary breast malignant lymphoma (PBL). All patients treated at the Institut Curie for lymphoma with breast involvement were reviewed. A pathological review of all cases was performed. Forty‐five cases were selected in whom 38 cases were of diffuse large B‐cell lymphoma. A complete analysis was then performed on these 38 patients. Twenty out of 28 cases (71%) of cases were Bcl‐2 positive and four out of 28 (14%) had a CD10 positive staining. Peculiar initial characteristics showed nodal involvement in 58% of the cases and two or more extra‐nodal sites in 31% of the cases. Among the 37 patients for whom all data were available, and according to the International Prognostic Index, 19 patients (51%) were classified in the low‐risk group, 5 cases (14%) in the low‐ to intermediate‐risk group, 6 patients (16%) in the intermediate‐ to high‐risk group, and 7 (19%) case in the high‐risk group. At the end of initial therapy, 34 patients (89%) achieved CR. With a median follow‐up of 96 months, 18 patients (47%) relapsed of whom 3 had a relapse in central nervous system site. The 5‐year disease‐free (DFS) and overall survivals (OS) were 54% and 61%, respectively. In multivariate analysis, the presence of 2 or more extranodal sites was prognostic for lower DFS (P= 0.0008) and OS (P= 0.09), and a performance status ≥1 was prognostic for lower OS (P= 0.005). Finally, when our series was compared with a historical series of 111 patients with aggressive nodal lymphomas, we observed significant lower survival rates in localized PBL (P< 0.03). Initial breast localization has a pejorative impact on the outcome of patients with Non‐Hodgkin's Lymphoma (NHL), with an impressive adverse influence of additional extranodal sites. These results suggest a specific management of NHL with breast involvement. Am. J. Hematol., 2009.