Journal of Kidney Cancer and VHL <p>Journal of Kidney Cancer and VHL (ISSN: 2203-5826) is indexed in <strong>PubMed</strong>,&nbsp;Emerging Sources Citation Index&nbsp;of <strong>Web of Science</strong>, and the Directory of Open Access Journals (<strong>DOAJ</strong>). Journal is dedicated for the dissemination of research findings in kidney cancer and VHL.</p> Codon Publications en-US Journal of Kidney Cancer and VHL 2203-5826 High Levels of PD-L1+ and Hyal2+ Myeloid-derived Suppressor Cells in Renal Cell Carcinoma <p>Renal cell carcinoma (RCC) patients frequently have increased number of immunosuppressive myeloid cells in circulation. High number of myeloid-derived suppressor cells (MDSCs) in the blood are associated with immune suppression as well as with cancer-related inflammation which drives the mobilization of myeloid cells to tumor tissue. Here, we show that peripheral blood from a previously untreated RCC patient has increased the number of monocytic CD33<sup>+</sup>CD11b<sup>+</sup> MDSCs, which also co-expressed PD-L1 and membrane-bound enzyme hyaluronidase 2 (Hyal2). PD-L1 expression is associated with immune suppression, whereas expression of Hyal2 is associated with inflammation, because Hyal2<sup>+</sup> myeloid cells can degrade the extracellular hyaluronan (HA), leading to the accumulation of pro-inflammatory HA fragments with low molecular weight. These findings implicate the potential involvement of monocytic MDSCs in both tumor-associated immune suppression and cancer-related inflammation. Analysis of organotypic tumor-tissue slice cultures prepared from cancer tissue of the same patient revealed the significant presence of PD-L1<sup>+</sup> HLA-DR<sup>+</sup> macrophage-like or dendritic cell-like antigen-presenting cells in tumor stroma. Interestingly, stroma-associated PD-L1<sup>+</sup> cells frequently have intracellular hyaluronan. Collectively, data presented in this study suggest that the interplay between tumor-recruited myeloid cells and stromal HA may contribute to the inflammation and immune tolerance in kidney cancer.</p> Sergei Kusmartsev Elizabeth Kwenda Paul R. Dominguez-Gutierrez Paul L. Crispen Padraic O’Malley Copyright (c) 2022 Sergei Kusmartsev, Elizabeth Kwenda, Paul R. Dominguez-Gutierrez, Paul L. Crispen, Padraic O'Malley 2022-04-16 2022-04-16 9 2 1 6 10.15586/jkcvhl.v9i2.208 Massive Malignant Epithelioid Angiomyolipoma of the Kidney <p>Renal angiomyolipomas (AMLs) are a subset of perivascular epithelioid cell neoplasms (PEComas) that are associated with tuberous sclerosis complex (TSC). Epithelioid angiomyolipomas (EAMLs) are a rare variant of AML with more aggressive propensities. EAMLs with malignant potential can be difficult to distinguish from relatively benign AMLs and other renal tumors. Although there are no established criteria for predicting EAML malignancy, there are proposed histologic parameters that are associated with higher tumor risk. EAML can be treated with surgical resection as well as mTOR inhibitors. Here, we present a unique case of a patient with a 36-cm renal EAML metastatic to the lungs that was treated with complete surgical resection of the primary lesion and mTOR inhibition.</p> Isaac M. Tessone Benjamin Lichtbroun Arnav Srivastava Alexandra L. Tabakin Charles F. Polotti Roman Groisberg Evita Sadimin Eric A. Singer Miral S. Grandhi Copyright (c) 2022 Isaac M. Tessone, Benjamin Lichtbroun, Arnav Srivastava, Alexandra L. Tabakin, Charles F. Polotti, Roman Groisberg, Evita Sadimin, Eric A. Singer, Miral S. Grandhi 2022-04-22 2022-04-22 9 2 13 18 10.15586/jkcvhl.v9i2.210 Simultaneous Bilateral Testicular Metastases from Renal Clear Cell Carcinoma: A Rare Presentation in Von Hippel–Lindau disease <p>In this article, we present a Von Hippel–Lindau (VHL) patient with synchoronus bilateral testicular metastasis from renal cell carcinoma (RCC). A 50 year-old man, a known case of VHL syndrome was referred with palpable masses in both the testes. His medical history demonstrated that he had undergone the brain surgery for cerebellar hemangioblastoma. He had undergone simultaneous Whipple’s pancreatectomy and left radical nephrectomy becuase of well-differentiated neuroendocrine tumors in head and body of the pancreas and a 6-cm clear cell-type grade-3 RCC in the left kidney. Scrotal sonography demonstrated vascular and heteroechogen masses measuring 19×14 mm in lower pole of the right testicle, 19×16 mm in upper pole of the right testicle, and 23×16.5 mm in upper pole of the left testicle. After having patient’s consent, bilateral orchiectomy was performed by inguinal incision. Histopathologic examination and immunohistochemistry staining revealed metastasis from RCC. The most common neoplasm of reproductive system in VHL patients is epididymal papillary cystadenoma. Owing to it’s benign nature, the management is conservative with routine physical examination and ultrasonography. Our patient indicated that every scrotal mass in patients with VHL is not to be considered as epididymal papillary cystadenoma.</p> Asaad Moradi Delaram Farhoumand Behnaz Bouzari Behnam Shakiba Copyright (c) 2022 Asaad Moradi, Delaram Farhoumand, Behnaz Bouzari, Behnam Shakiba 2022-05-05 2022-05-05 9 2 19 21 10.15586/jkcvhl.v9i2.211 Renal Cell Carcinoma with Testicular Metastases: A Case Report and Review of the Literature <p>Renal cell carcinoma (RCC) metastases to the testicle are an extremely rare clinical entity. Here, we describe the case of a man with metastatic RCC who developed a new testicular mass. Pathologic analysis after surgical removal of this testicle confirmed the diagnosis of metastatic RCC. This report highlights the unique diagnostic and therapeutic challenges associated with such a disease process.</p> Sho Yoshitake Brian M. Shinder Kevin Dazen Colton Smith Tina M. Mayer Evita Sadimin Eric A. Singer Copyright (c) 2022 Sho Yoshitake, Brian Shinder, Kevin Dazen, Tina Mayer, Colton Smith, Eric Singer, Evita Sadimin 2022-05-06 2022-05-06 9 2 22 26 10.15586/jkcvhl.v9i2.212 Hereditary Leiomyomatosis and Renal Cell Cancer-Recognizing Patterns May Save Lives <p>In 2001, Finish investigators described a rare familiar syndrome characterized by an inherited susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). Hereditary leiomyomatosis and renal cell cancer (HLRCC) is now linked to a germline mutation in the <em>fumarate hydratase</em> (<em>FH</em>) gene that encodes a Krebs cycle enzyme, transforming fumarate to malate. The accumulation of fumarate, an oncometabolite, promotes tumorigenesis. We present a case of a 41-year-old female diagnosed with HLRCC after a radical nephrectomy due to renal cell cancer. Genetic analyses confirmed a novel <em>FH</em> mutation. Close follow-up allowed for a precocious diagnosis of a metachronous renal tumor and later a hepatic metastasis. Her family was also counseled and offered genetic testing. As observed in this case, the diagnosis of HLRCC is of paramount importance for patients and their families: there is a 15% cumulative lifetime risk of developing RCC, which frequently occurs in young patients and metastasizes at an early stage. Implementing a regular follow-up with adequate imaging examinations may help save lives.</p> Catarina Tavares Maria Sofia Quental José Ricardo Brandão Miguel Silva-Ramos Copyright (c) 2022 Catarina Machado, Maria Sofia Quental, José Ricardo Brandão, Miguel Silva-Ramos 2022-05-26 2022-05-26 9 2 27 31 10.15586/jkcvhl.v9i2.222 Renal Cell Carcinoma with Cardiac Metastases: A Case Report and Review of the Literature <p>Cardiac metastases from renal cell carcinoma (RCC) are very rare. We describe the case of a woman with RCC with cardiac metastases involving the entire right atrium, penetrating through the myocardium, with extension into the tricuspid valve and right ventricle. This report highlights the unique challenge of the diagnosis and treatment of cardiac metastases in RCC.</p> Ellen M. Cahill Alexandra Tabakin Brian Shinder Mark Bramwit Biren Saraiya Xinyang Xu Cristo G. Salazar Zhongren Zhou Eric A. Singer Copyright (c) 2022 Ellen M. Cahill, Alexandra L. Tabakin, Brian Shinder, Mark Bramwit, Biren Saraiya, Eric A. Singer 2022-05-25 2022-05-25 9 2 32 38 10.15586/jkcvhl.v9i2.229 Incidence and Distribution of New Renal Cell Carcinoma Cases: 27-Year Trends from a Statewide Cancer Registry <p>Nationwide databases have implicated an increased incidence of renal cell carcinoma (RCC). The Pennsylvania (PA) Cancer Registry was queried to better define incidence, geographic distribution, and statewide trends of new RCC cases over a 27-year period. JoinPoint Trend Analysis Software modeled average annual percent changes (APCs) in age-adjusted rates (AAR). Maps plotting county-level incidence rates and stage distribution of disease across the state in 5-year time intervals were created using R 4.0.2 software. Overall, 59,628 cases of RCC were recorded in PA from 1990 to 2017. Eighty six percent of patients were &gt;50 years of age, 61% were males, and 89% were Caucasian. Stage distribution using the SEER staging system included 64% local, 17% regional, and 16% distant. Over the study interval, AAR of all RCC cases increased from 9.9 to 18.0 patients per 100,000 population with an APC of 2.3% (p &lt; 0.01). AAR of local disease increased from 5.4 to 12.7 patients per 100,000 population with an APC of 3.2% (p &lt; 0.01). AAR of regional disease also increased from 1.9 to 2.9 patients per 100,000 population with an APC of 1.0% (p = 0.01). Younger patients (&lt;50 years) had a greater rate of increase than older counterparts (APC 3.8% vs. 2.0%, p &lt; 0.05). Geospatial investigation of new RCC cases noted certain geographic concentrations of greater disease incidence. The incidence of RCC in PA has increased over the past 27 years in PA. One-third of the cases are regional or metastatic at presentation and rates of increase were most notable in younger patients.</p> Ahmad N. Alzubaidi Stephen Sekoulopoulos Jonathan Pham Vonn Walter Jay G. Fuletra Jay D. Raman Copyright (c) 2022 Ahmad N. Alzubaidi, Stephen Sekoulopoulos, Jonathan Pham, Vonn Walter, Jay G. Fuletra, Jay D. Raman 2022-04-18 2022-04-18 9 2 7 12 10.15586/jkcvhl.v9i2.219