Rituximab, a chimeric mouse/human monoclonal antibody that binds to the CD20 antigen, is part of current treatment of many B-cell malignancies and several autoimmune diseases. Very few cases of rituximab administration during pregnancy have been described. We report here the case of rituximab administration during the first trimester of pregnancy in a woman with autoimmune hemolytic anemia. No significant effects were observed in B-cell counts or the immune status of the newborn.

Clear cell renal cell carcinoma (ccRCC) is an aggressive tumor that is characterized in most cases by inactivation of the tumor suppressor gene VHL. The VHL/HIF/VEGF pathway thus plays a major role in angiogenesis and is currently targeted by antiangiogenic therapy. The emergence of resistance is leading to the use of targeted immunotherapy against immune checkpoint PD1/PDL1 that restores antitumor immune response. The correlation between VHL status and PD-L1 expression has been little investigated. In this study, we retrospectively reviewed 98 consecutive cases of ccRCC and correlated PD-L1 expression by immunohistochemistry (IHC) with clinical data (up to 10-year follow-up), pathological criteria, VEGF, PAR-3, CAIX and PD-1 expressions by IHC and complete VHL status (deletion, mutation and promoter hypermethylation). PD-L1 expression was observed in 69 ccRCC (70.4%) and the corresponding patients had a worse prognosis, with a median specific survival of 52 months (p 5 0.03). PD-L1 expression was significantly associated with poor prognostic factors such as a higher ISUP nucleolar grade (p 5 0.01), metastases at diagnosis (p 5 0.01), a sarcomatoid component (p 5 0.04), overexpression of VEGF (p 5 0.006), and cytoplasmic PAR-3 expression (p 5 0.01). PD-L1 expression was also associated with dense PD-1 expression (p 5 0.007) and with ccRCC with 0 or 1 alteration(s) (non-inactivated VHL tumors; p 5 0.007) that remained significant after multivariate analysis (p 5 0.004 and p 5 0.024, respectively). Interestingly, all wild-type VHL tumors (no VHL gene alteration, 11.2%) expressed PD-L1. In this study, we found PD-L1 expression to be associated with noninactivated VHL tumors and in particular wild-type VHL ccRCC, which may benefit from therapies inhibiting PD-L1/PD-1.Clear cell renal cell carcinoma (ccRCC) accounts for 3% of adult cancers and is a very aggressive tumor with a 50% risk of metastases at initial diagnosis or follow-up. 1 The VHL (von Hippel-Lindau) gene, located on chromosome 3p25, is a major tumor suppressor gene involved in ccRCC oncogenesis. 2 Alterations of this gene occur in the majority of ccRCC through mutations or deletions and/or hypermethylation of its promoter. 3 VHL gene inactivation necessarily involves biallelic alterations in tumor cells, as both first and second "hits" must occur to be inactivated. However, a minority of ccRCC exhibit no or a single allele alteration on the VHL gene. 4 The protein, pVHL, is a component of an E3 ubiquitinligase, which targets the transcription factor: hypoxia-

Hepatocellular carcinoma (HCC) is the second most common cause of death by cancer in the world. Due to the delayed HCC development in hepatitis C carriers and nonalcoholic fatty liver disease, the incidence of HCC in the elderly is increasing and is becoming a global health issue. Elderly patients with HCC should be assessed through proper oncologic approach, namely, screening tools for frailty (Geriatric-8 or Vulnerable Elders Survey-13) and comprehensive geriatric assessment. This review of the literature supports the same treatment options for elderly patients as for younger patients, in elderly patients selected as fit following proper oncogeriatric assessment. Unfit patients should be managed through a multidisciplinary team involving both oncological and geriatrician professionals. Specific studies and recommendations for HCC in the elderly should be encouraged.

This long-term study is the first to support the notion that synchronous m-ccRCC has a distinct phenotype. This is probably linked to the occurrence of oncogenic events that could explain the worse prognosis. These particular patients with metastases could benefit from specific therapy.

Among activated VHL tumors, the wild-type subgroup defines an aggressive phenotype with worse survival rates, suggesting that these tumors must be more thoroughly screened.