Open Access Journal of Cancer Science & Therapy Case Report Volume 13:6, 2021 Abstract Introduction: diagnostic and therapeutic difficulties for cancer are emerging in COVID-19 pandemic. In addition to interstitial pneumonia, disseminated intravascular coagulation and sepsis, liver injury (LI) is a fairly frequent occurrence, with significant weight on evolution and prognosis of COVID-19. Its involvement is linked to cholangiocytes ACE2. Excluded other pathogenesis, LI could represent prodromal phase of COVID-19, if initial diagnostic negativity will be followed by COVID-19 positivity. Clinical case: A 59-year-old male patient has diagnosis of metastatic papillary non-clear cell renal cell carcinoma (nccRCC). After neoadjuvant Sunitinib he was submitted to right nephrectomy with caval-atrial thrombectomy in extra-corporeal circulation. Thereafter he continues Sunitinib until disease progression (PD) to bone followed by Axitinib from December 2015 to December 2015 and left femoral radiotherapy (RT) with disease control (DC). After lung and liver PD he was treated with Nivolumab from December 2015 to June 2016 with liver response and overall DC. After liver and caval thrombosis PD, Sorafenib, administered from June 2016 to December 2017, quarterly Zoledronic acid and bone RT obtained DC. Subsequent RT and Cabozantinib from February 2018 to September 2019, during which he reported pathological fracture of left femur, he underwent a surgical reduction and synthesis. From January 2020 to September 2020 Everolimus was administered with DC. Subsequently, in light of PD related to immunosuppression, after proven COVID-19 negativity, he started therapy with intravenous low doses Cyclophosphamide, Fluorouracil and subcutaneous Interleukin-2 with moderate toxicity. Following the onset of dyspnea, confirmation of COVID-19 negativity, he was hospitalized and chest CT scan demonstrated size reduction of largest lung lesion. After antibiotic and steroid therapy with clinical improvement and discharge, patient complained symptoms worsening and biochemistry showed cholestatic hepatitis signs and INR lengthening. During subsequent hospitalization, he experienced rectorrhagia and biohumoral tests shown negativity for COVID-19, hypo-albumin, and persistence of coagulative and hepatic disorders. Change of immunological parameters, from which lymphocyte immunophenotype with initial increase of Treg counts followed by decrease during chemo-immunotherapy were observed. Despite support care, patient died with nasopharyngeal swab COVID-19 positivity. Conclusion: This prodromal hepatic picture in heavy treated nccRCC could be an expression of increase of T lymphocytes and Treg counts, stimulated by IL-2, with negative feedback on hyper-inflammation, linked to hyper-cytokinemia, with attempt to control viral infection. It result in the delaying of the disease course whereas failure with lymphocyte and Treg reduction count culminates with final worsening until COVID-19 positivity. Keywords: Renal carcinoma • COVID-19 • Interleukin-2 • Immune homeostasis • Liver injury COVID-19 Hepatic Prodromal Syndrome in Patient with Non-Clear Cell Metastatic Renal Cell Carcinoma: A Case Report Giovanni Lo Re 1* , Paolo Doretto 2 , Massimiliano Balbi 3 and Sandro Sulfaro 4 1 Department of Medical Oncology and Immune-Related Tumors, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, PN 33081, Italy. 2 Clinical Pathology Unit, Azienda sanitaria Friuli Occidentale (AS FO), Via Montereale 24, Pordenone, PN 33170, Italy 3 Internal Medicine Unit, Azienda Sanitaria Friuli Occidentale (AS FO), Via Savorgnano 2, San Vito al Tagliamento, PN 33078, Italy 4 Department of Pathology, Azienda Sanitaria Friuli Occidentale (AS FO), Via Montereale 24, Pordenone, PN 33170, Italy *Address for Correspondence: Giovanni Lo Re, Department of Medical Oncology and Immune-Related Tumors, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Via Gallini 2 Aviano, (PN), 33081, Italy, Tel: 0039434399788; E-mail: Giovanni.lore@cro.it Copyright: © 2021 Lo Re, G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received 01 June 2021; Accepted 15 June 2021; Published 22 June 2021 Introduction After one year from the first case of COVID-19 reported in Wuhan, the capital of Hubei (China), on December 2019, on April 9th 2021 global cases and deaths are 133.146.550 and 2.888.530 respectively. We are currently going through the third pandemic wave and from COVID-19 vaccination campaign 669.248.795 vaccine doses are administered. Excluding the majority of cases presenting a mild SARS-CoV-2 infection, moderate and severe forms occur in 10%-20% of cases, symptomatic mainly following up into pneumonia which causes hypoxia and requires hospitalization. Severe forms are linked to hyper- inflammation and mainly result in acute respiratory distress syndrome (ARDS). It can be complicated by Disseminated Intravascular Coagulation (DIC) phenomena and septic shock, which require hospitalization in an intensive care unit, with a poor prognosis in about 2% of cases [1-3]. However from other organ injury, liver involvement is frequent in patients who are COVID-19 positive. Liver injury (LI) is mostly often mild or moderate, whereas severe grade is present on among the 6.4% of patients, which is predictive of unfavorable disease course [4,5]. The frequent hepatic injury is related to the presence of ACE2 receptors, functional host receptor for SARS-CoV-2, especially in 60% of cholangiocytes whereas it has a minimal extent in hepatocytes and it is absent in Kuppfer cell [6]. In addition to hepatic toxicity linked to the drug administration for COVID-19 [7,8]. Varying degrees of hepatic involvement may present a higher rate of serum elevations of alanine aminotransferse (ALT). Mild liver involvement occurs in more than one-third of infected patients who can show elevated ALT or aspartate aminotransferase (AST), abnormal prothrombin time and low albumin level [9-11]. These serologic abnormalities are more frequent in COVID-19 positive patients than in negative patient ones [12,13]. Furthermore in positive patients, especially in those who have undergone auto transplantation or with primary liver cancer, their grade is related to the disease outcome, risk of complications, clinical worsening and the need for hospitalization in an intensive care unit and intubation [14]. Furthermore, a correlation between LI, use of drugs and its p possible negative impact on COVID-19 was found [15,16]. From the anatomo-pathological point of view, in the context of multi- organ involvement, LI is characterized by the presence of thrombi and neutrophilic plugs in the advanced stage of the disease, an expression of hyper-inflammation linked to IL-6 [17]. In the cancer patient, elevation of hepatic function indices can mainly be an expression of drug-related toxicity or hepatic progression. If these occurrences are excluded, this picture could