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Encephalic Leukocytoclastic Vasculitis During Treatment with Sunitinib for Renal Cell Carcinoma: a Case Report

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Encephalic Leukocytoclastic Vasculitis During Treatment with Sunitinib for Renal Cell Carcinoma: a Case Report medicines Case Report Encephalic Leukocytoclastic Vasculitis during Treatment with Sunitinib for Renal Cell Carcinoma: A Case Report Maria Massucci 1, Veronica Mollica 1, Alessandro Rizzo 1,* , Laura Ventrella 2, Ilaria Maggio 1, Lisa Manuzzi 1, Lidia Gatto 3, Giovanni Brandi 4 and Francesco Massari 1 1 Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni—15, 40138 Bologna, Italy; [email protected] (M.M.); [email protected] (V.M.); [email protected] (I.M.); [email protected] (L.M.); [email protected] (F.M.) 2 Maria Cecilia Hospital, Cotignola (RA), 48033 Ravenna, Italy; [email protected] 3 Medical Oncology Department, Bellaria Hospital, Azienda USL of Bologna, Via Altura n.3, 40139 Bologna, Italy; [email protected] 4 Oncology Unit, Department of Experimental, Diagnostic and Specialty Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy; [email protected] * Correspondence: [email protected] Abstract: Renal cell carcinoma is a malignant tumor that arises in the kidney parenchyma. For many years, sunitinib has represented the mainstay of medical treatment for metastatic renal cell carcinoma. Herein, we present the case of a 66-year-old woman with metastatic clear cell renal carcinoma under- going treatment with sunitinib for two years that developed encephalic leukocytoclastic vasculitis, probably due to a paraneoplastic syndrome. Keywords: encephalic vasculitis; sunitinib; renal cell carcinoma (RCC); leukocytoclastic vasculitis; paraneoplastic syndrome Citation: Massucci, M.; Mollica, V.; Rizzo, A.; Ventrella, L.; Maggio, I.; Manuzzi, L.; Gatto, L.; Brandi, G.; 1. Introduction Massari, F. Encephalic Leukocytoclastic Vasculitis during Renal cell carcinoma (RCC) is a malignant tumor arising in the kidney parenchyma [1]; Treatment with Sunitinib for Renal from the histological point of view, clear cell renal cell carcinoma (ccRCC) is the most Cell Carcinoma: A Case Report. frequent histological type of renal malignancy, accounting for approximately 75–80% of Medicines 2021, 8, 5. https:// cases [2]. RCC currently represents the seventh most common type of cancer in men and the doi.org/10.3390/medicines8010005 tenth in women in Western countries, with about 25–30% of patients presenting metastatic disease at diagnosis [3]. Received: 8 December 2020 The prognosis and treatment of metastatic RCC depends on prognostic scores based Accepted: 8 January 2021 on clinical, laboratory, and pathological parameters [4]. For many years, the mainstay Published: 11 January 2021 of medical treatment for advanced RCC was represented by interferon alfa (IFN α) and interleukin 2 (IL2) [5]; subsequently, other two categories of drugs proved to be more Publisher’s Note: MDPI stays neu- effective: anti-angiogenic agents and mammalian target of rapamycin (mTOR) inhibitors [6]. tral with regard to jurisdictional clai- In recent years, immune checkpoint inhibitors (ICIs) have been used, at first as second-line ms in published maps and institutio- treatment, and subsequently as front-line treatment options in metastatic RCC (mRCC), nal affiliations. where immune-based combinations have profoundly modified the therapeutic algorithm of this malignancy [7]. Sunitinib is an oral, multi-target tyrosine kinase inhibitor (TKI) which has an anti- Copyright: © 2021 by the authors. Li- angiogenic effect through the inhibition of vascular endothelial growth factor (VEGF) and censee MDPI, Basel, Switzerland. platelet-derived growth factor (PDGF) receptors; for many years, sunitinib has been one This article is an open access article of the standard first-line treatments for mRCC [8]. As in the case of other multi-kinase distributed under the terms and con- inhibitors, sunitinib has been associated with a wide range of grade 1 to 4 adverse events— ditions of the Creative Commons At- including skin disorders, hand–foot syndrome, periorbital edema, hair depigmentation, tribution (CC BY) license (https:// skin discoloration, subungual splinter hemorrhages, and genital rash [9]. Other manifesta- creativecommons.org/licenses/by/ tions, such as vasculitis, have been rarely reported in patients receiving sunitinib [10,11]. 4.0/). Medicines 2021, 8, 5. https://doi.org/10.3390/medicines8010005 https://www.mdpi.com/journal/medicines Medicines 2021, 8, 5 2 of 4 Medicines 2021, 8, x FOR PEER REVIEW 2 of 4 Paraneoplastic syndromes, that are correlated to the production of specific molecules byOther tumor manifestations, cells or by such the as immune vasculitis, response have been to rarely the tumor,reported have in patients been receiving described in about 10–40%sunitinib of [10,11]. patients with mRCC [12]. Herein, we present a case of encephalic vasculitis in a patientParaneoplastic undergoing syndromes, first-line that treatment are correlated with to sunitinib the production for metastaticof specific molecules ccRCC. by tumor cells or by the immune response to the tumor, have been described in about 10–40% of 2.patients Cases with and mRCC Methods [12]. Herein, we present a case of encephalic vasculitis in a patient undergoing first-line treatment with sunitinib for metastatic ccRCC. In January 2015, a 66-year-old woman underwent left nephrectomy for localized ccRCC2. Cases without and Methods distant metastases. A computed tomography (CT) scan performed during follow-upIn January in September 2015, a 66-year-old 2017 showed woman adrenal underwent metastases; left nephrectomy thus, sunitinib for localized 50 mg daily on accRCC 4 weeks without on/2 distant weeks metastases. off schedule A computed was started tomography as first-line (CT) scan therapy. performed With during this treatment, thefollow-up patient in achievedSeptember a 2017 partial showed response adrenal without metastases; experiencing thus, sunitinib important 50 mg daily toxicities. on a 4 weeksA total on/2 weeks body CToff schedule scan performed was started two as first-line years after therapy. the startWith ofthis treatment treatment, showedthe the ap- patient achieved a partial response without experiencing important toxicities. pearance of a hypodense area of two centimeters in the left rolandic area. Given the unclear A total body CT scan performed two years after the start of treatment showed the natureappearance of this of a lesion, hypodense brain area magnetic of two centimeters resonance in imaging the left rolandic (MRI) wasarea. performed,Given the with the radiologicalunclear nature images of this lesion, showing brain the magnetic probable resonance vasculitic imaging nature (MRI) of was the performed, lesion (Figure with 1) . The pa- tientthe radiological was asymptomatic images showing and, the in probable particular, vasculitic did nature not present of the lesion any neurological(Figure 1). The symptoms. Topatient exclude was asymptomatic that vasculitis and, could in particular be correlated, did not to present a paraneoplastic any neurological syndrome, symptoms. we evaluated anti-neutrophilTo exclude that vasculitis cytoplasmic could be antibodies correlated to (ANCAs) a paraneoplastic in the syndrome, blood, which we evaluated were negative—a findinganti-neutrophil which cytoplasmic supported antibodies the hypothesis (ANCAs) that in the the vasculitis blood, which could were be negative—a due to a paraneoplas- finding which supported the hypothesis that the vasculitis could be due to a parane- tic syndrome. oplastic syndrome. Figure 1. First brain magnetic resonance imaging showing encephalic vasculitis during sunitinib Figure 1. First brain magnetic resonance imaging showing encephalic vasculitis during sunitinib treatment. treatment. The patient patient discontinued discontinued sunitinib sunitinib treatment treatment and was started and was on steroid started therapy. on steroid A therapy. Asubsequent subsequent brain brain MRI demonstrated MRI demonstrated a small reduction a small of reductionthe known brain of the lesion, known proba- brain lesion, probablybly due to duethe use to theof steroids use of (Figure steroids 2). A (Figure total body2). ACT total scan bodyshowed CT the scan stability showed of the sta- previous findings in the other metastatic sites; thus, the patient continued the suspension Medicines 2021, 8, x FOR PEER REVIEWbility of previous findings in the other metastatic sites; thus, the patient3 of continued 4 the suspensionof sunitinib with of sunitinib a programmed with tumor a programmed imaging assessment tumor imaging after two assessment months. after two months. Figure 2. Second brain magnetic resonance imaging performed after discontinuation of sunitinib Figure 2. Second brain magnetic resonance imaging performed after discontinuation of sunitinib and steroid therapy. and steroid therapy. 3. Discussion Leukocytoclastic vasculitis (LCV) represents a small vessel vasculitis with inflamma- tory infiltrate composed of neutrophils. The development of LCV is associated with both immune complex deposition and hypersensitivity to a suspected drug. LCV represents a rare complication during anticancer treatments and it can be associated with chronic in- fection, drugs, and paraneoplastic syndrome. When LCV is diagnosed during cancer treatment, it is very important to determine if the vasculitis is associated with the ongoing therapy to evaluate whether to continue such treatment safely [12]. One hypothesis is that the abnormal production of antibodies and tumor neoantigens lead to the formation of immune complexes that are deposited
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