Science et thérapie du cancer

COVID-19 Hepatic Prodromal Syndrome in Patient with Non-Clear Cell Metastatic Renal Cell Carcinoma: A Case Report

Abstract

Giovanni Lo Re, Paolo Doretto, Massimiliano Balbi and Sandro Sulfaro

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.