Paraneoplastic Cerebellar Degeneration with Anti-CV2/CRMP5 Antibodies in Ovarian Cancer: Case Report and Review of the Literature

Paraneoplastic neurological syndromes (PNS) are rare presentations of an underlying oncological disease and more unusual during an oncological disease. They most likely present in small-cell lung carcinomas and thymomas, but present in <1% of the gynecological neoplasms. Acknowledging the pathophysiology is essential for management, explaining its clinical presentation, and future research. We present a patient with an underlying gynecological cancer that during her disease developed a PNS with an unusual autoantibody (anti-CV2/CRMP5) mediating the disease. We report a case of a 62-year-old female diagnosed with ovarian cancer who in the course of her disease developed neurological symptoms associated with cerebellar degeneration. After ruling out differential diagnoses such as metastases, a PNS was suspected and studied, in which anti-CV2/CRMP5 antibodies were positive. With her clinical presentation, radiological features, autoantibody positivity on cerebrospinal fluid, and an underlying oncological disease, cerebellar degeneration was diagnosed. The pathophysiology of PNS is not fully understood; therefore, its diagnosis and management are complex. Diagnosis is based on clinical presentation and specific antibodies associated. Unfortunately, patients have a bad prognosis and diminished quality of life, and therefore a multidisciplinary approach is needed. It is important to mention that the presentation of PNS does not mandatorily appear before the diagnosis of cancer, and multiple cases have been reported in which patients with an underlying oncological disease develop these syndromes. As medical oncologists and neurologists, we must consider and study these syndromes as a possible etiology in cases with an underlying cancer who develop neurological symptoms in the course of their disease.

Immune Thrombocytopenia Induced by Immune Checkpoint Inhibitrs in Lung Cancer: Case Report and Literature Review

Immune checkpoint inhibitors (ICIs), including antibodies targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1), are being extensively used on advanced human malignancies therapy. The treatment with ICIs have acquired durable tumor inhibition and changed the treatment landscape in lung cancer. Immune-related adverse events including pneumonitis and thyroiditis have been well described, but less frequent events, such as ICIs-induced thrombocytopenia, are now emerging and may sometimes be severe or fatal. Since early detection and prompt intervention are crucial to prevent fatal consequences, it is of outmost importance that medical staff is aware of these potential toxicities and learn to recognize and treat them adequately. This review focuses on the epidemiology, clinical presentation, mechanisms, and clinical management of ICIs-induced thrombocytopenia in patients with lung cancer. We also present a patient with advanced lung adenocarcinoma who received the PD-L1 inhibitor atezolizumab and eventually developed severe thrombocytopenia. The case indirectly suggests that cytokine changes might contribute to immune dysregulation in ICIs-induced thrombocytopenia.

Effectiveness of combination with eribulin in third line of chemotherapy for triple negative breast cancer (case report)

In most cases triple negative breast cancer is characterized by an aggressive course of disease and early development of resistance to chemotherapy. Thereafter, the late-line treatment choice, usually after anthracyclines and taxanes, is problematic due to the limited amount of effective and low-toxic cytostatics. In our opinion, in this situation the use of eribulin which possesses unique antitumor action mechanisms is a good option. An illustrative case of a pronounced antitumor effect of eribulin in metastatic breast cancer with triple negative phenotype resistant to previous lines of chemotherapy is presented.

Identification of Recessively Inherited Genetic Variants Potentially Linked to Pancreatic Cancer Risk

Although 21 pancreatic cancer susceptibility loci have been identified in individuals of European ancestry through genome-wide association studies (GWASs), much of the heritability of pancreatic cancer risk remains unidentified. A recessive genetic model could be a powerful tool for identifying additional risk variants. To discover recessively inherited pancreatic cancer risk loci, we performed a re-analysis of the largest pancreatic cancer GWAS, the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including 8,769 cases and 7,055 controls of European ancestry. Six single nucleotide polymorphisms (SNPs) showed associations with pancreatic cancer risk according to a recessive model of inheritance. We replicated these variants in 3,212 cases and 3,470 controls collected from the PANcreatic Disease ReseArch (PANDoRA) consortium. The results of the meta-analyses confirmed that rs4626538 (7q32.2), rs7008921 (8p23.2) and rs147904962 (17q21.31) showed specific recessive effects (p<10−5) compared with the additive effects (p>10−3), although none of the six SNPs reached the conventional threshold for genome-wide significance (p < 5×10−8). Additional bioinformatic analysis explored the functional annotations of the SNPs and indicated a possible relationship between rs36018702 and expression of the BCL2L11 and BUB1 genes, which are known to be involved in pancreatic biology. Our findings, while not conclusive, indicate the importance of considering non-additive genetic models when performing GWAS analysis. The SNPs associated with pancreatic cancer in this study could be used for further meta-analysis for recessive association of SNPs and pancreatic cancer risk and might be a useful addiction to improve the performance of polygenic risk scores.

Dysplasia in Papilloma at the Tip of the Tongue; A Rare Entity-Importance of on Time Prevention

Background: Oral papilloma is benign lesion while there is concern about high-risk types of Human Papilloma Virus (HPV) for cancer. Case Presentation: The patient was a 30-year-old woman who presented to the School of Dentistry, Semnan University of Medical Sciences for orthodontic treatment. Intraoral examinations revealed a prominent white papule on the tip of the tongue. Histopathologic exanimation revealed the proliferation of hyper keratinized stratified squamous epithelium arranged in projections with fibrovascular connective tissue cores, cell irregularity with hyperchromatic nucleus and koilocytes within the epithelium which confirmed the diagnosis of squamous papilloma (SP) with mild to moderate dysplasia. The patient was instructed to take care of the sexual behaviors and the injection of Gardasil vaccine was recommended. A month later, there was no evidence of a lesion. Conclusion: Though SPs are common lesions in the oral cavity, occurrence of dysplasia on SPs on the anterior part of the mouth is rare. Surgical removal supplemented by administration of Gardasil vaccine can be the treatment of choice in these cases. The significance of close attention to the oral lesions and consultation with an Oral and Maxillofacial Medicine Specialist is highly recommended in order to accurate diagnosis and timely treatment.

Association of three micro-RNA gene polymorphisms with the risk of cervical cancer: a meta-analysis and systematic review

Objective Regulation of single nucleotide polymorphisms (SNP) in micro-RNA (miRNA) on the host cells may be one of the most important factors influencing the occurrence of cervical cancer based on the prevalence of HPV infection and the development of cervical cancer. In order to explore the contribution of miRNA polymorphism to the occurrence and development of cervical cancer, we conducted an analytical study. Methods We selected the polymorphisms of three widely studied miRNAs (miRNA-146a rs2910164, miRNA-499 rs3746444, and miRNA-196a2 rs11614913). Then, we conducted a meta-analysis (for the first time) to investigate their susceptibility to cervical cancer. Case control studies on the correlation between these three miRNAs and cervical cancer susceptibility were investigated by searching on from Pubmed, The Cochrane Library, Embase, CBM, CNKI, Wanfang database, and VIP database. Basic characteristics were recorded and meta-analysis of the case studies was performed using the STATA 15.1 software. Results The miRNA-146a rs2910164 mutation significantly reduced the risk of cervical cancer in both recessive model (OR = 0.804, 95% CI = 0.652-0.992, P = 0.042; CC vs. CG+GG) and allelic model (OR = 0.845, 95% CI = 0.721-0.991, P = 0.038; C vs. G). There was no significant correlation between miRNA-499 rs3746444 and the risk of cervical cancer. The miRNA-196a2 rs11614913 mutation was significantly associated with a reduced risk of cervical cancer in homozygous model (OR = 0.641, 95% CI = 0.447-0.919, P = 0.016; TT vs. CC), dominant model (OR = 0.795, 95% CI = 0.636-0.994, P = 0.045; CT+TT vs. CC), recessive model (OR = 0.698, 95% CI = 0.532-0.917, P = 0.01; TT vs. CC+CT), and allelic models (OR = 0.783, 95% CI = 0.643-0.954, P = 0.015, T vs. C). Conclusion In summary, this meta-analysis shows that the mutant genotypes of miRNA-146a rs2910164 and miRNA-196a2 rs11614913 are associated with a reduced risk of cervical cancer. Therefore, they may be two gene regulatory points for the prevention of cervical cancer. Systematic review registration PROSPERO registration number CRD42021270079.