John Cheville

Mayo Foundation for Medical Education and Research | MMS · Department of Laboratory Medicine

Molecular investigations have led to increased therapeutic options for prostatic adenocarcinoma. A single case report of a PRPSAP1:: NTRK3 gene fusion occurring in prostate cancer was previously reported. A review of the literature revealed that NTRK gene rearrangements are exceedingly rare molecular events in prostate cancer. NTRK gene fusions can...

The histologic heterogeneity of human Muscle Invasive Bladder Cancer (MIBC) is one of the main contributing factors to poor treatment outcomes. Recent reports on MIBC histological variants have highlighted increased levels of transcription factors (TF) associated with epithelial-mesenchymal transformation (EMT) and epigenetic regulation in the sarc...

Background Only 20 percent of renal and bladder cancer patients will show a significant response to immune checkpoint inhibitor (ICI) therapy, and no test currently available accurately predicts ICI response. Methods We developed an “immunotumoroid” cell model system that recapitulates the tumor, its microenvironment, and necessary immune system c...

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC...

381 Background: Venous tumor thrombus (VTT) is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). It is unknown if VTT and pulmonary embolism (PE) predispose patients to pulmonary metastasis. Methods: We queried our institutional registry for ccRCC patients undergoing radical nephrectomy (1970-2019). Cox proportion...

Background: Approximately 30% of renal cell carcinoma (RCC) cases present with de novo metastatic disease, while 20% to 30% of those with localized disease will develop metastases following surgical resection. Various drug classes have been investigated to treat RCC, including cytokine-based therapies, small molecule Vascular Endothelial Growth Fac...

Sequencing efforts have identified key oncogenic drivers and transcriptomic subtypes of high-grade gliomas (HGGs), but this knowledge has not resulted in individualized therapy or improved patient outcomes. Here, we used a functional genomics approach combining integrated genomic/transcriptomic analyses with patient-derived 3D micro-cancers (mCance...

Spermatocytic tumor (ST) is a rare type of germ cell tumor that occurs exclusively in the postpubertal testis and typically affects elderly men. Most STs are benign, but rare cases exhibit aggressive clinical behavior, often in association with transition to sarcomatoid histology. Limited molecular analyses have been performed on STs; therefore, th...

Background While both seminal vesicle (SVI) and lymph-node invasion (LNI) have been identified as adverse prognostic variables among men undergoing radical prostatectomy (RP), the relative impact of each of these features on subsequent oncologic outcomes has not been well defined. We assessed the impact of LNI on long-term oncologic outcomes among...

Background Bladder cancer is a significant malignancy in humans and canines, with high death rates and devastating clinical symptoms. Despite significant advances in therapeutic management over the years, only a small fraction of bladder cancer patients respond to immunotherapies as a second line of treatment. Since immunotherapies act on various c...

Chemical imaging, especially mid-infrared spectroscopic microscopy, enables label-free biomedical analyses while achieving expansive molecular sensitivity. However, its slow speed and poor image quality impede widespread adoption. We present a microscope that provides high-throughput recording, low noise, and high spatial resolution where the botto...

Histopathology has remained a cornerstone for biomedical tissue assessment for over a century, with a resource-intensive workflow involving biopsy or excision, gross examination, sampling, tissue processing to snap frozen or formalin-fixed paraffin-embedded blocks, sectioning, staining, optical imaging, and microscopic assessment. Emerging chemical...

Introduction: Systemic immunotherapy has changed the paradigm of treatment of advanced renal cell carcinoma, but nephrectomy continues to benefit selected patients. While we continue to identify mechanisms behind drug resistance, the effect of surgery on natural anti-tumor immunity is poorly understood. Specifically, peripheral blood mononuclear c...

Purpose: Multiple prognostic models exist to assess survival among patients with metastatic clear cell renal cell carcinoma (m-ccRCC). However, the relative contribution of histopathologic features of the metastasis has not been extensively studied. Herein, we compared models using clinical, primary tumor, and metastatic features to predict cancer...

Background: Immune checkpoint inhibitors (ICIs) are now a first-line treatment option for patients with pleural mesothelioma with the recent approval of ipilimumab and nivolumab. Mesothelioma has a low tumor mutation burden and no robust predictors of survival with ICI. Since ICIs enable adaptive antitumor immune responses, we investigated T-cell...

This work examines differences in chromatin accessibility, methylation, and response to DNA hypomethylating agents between mismatch repair-deficient and non-mismatch repair-deficient endometrial cancer. Next-generation sequencing of a stage 1B, grade 2 endometrioid endometrial cancer tumor revealed microsatellite instability and a variant of unknow...

Objectives: There is a paucity of data on penile amyloidosis. We aimed to assess the frequency of different amyloid types in surgical specimens from the penis involved by amyloidosis and correlate relevant clinicopathologic parameters with proteomic findings. Methods: Since 2008, our reference laboratory has performed liquid chromatography/tande...

Introduction: Muscle-Invasive Bladder Cancer (MIBC) is associated with a poor overall survival rate. One important factor that contributes to poor treatment outcomes is the histologic heterogeneity of MIBC tumors, which limits the translational value of some rodent models. As opposed to mice, dogs with spontaneously occurring bladder cancer have be...

Background: Mutations in RAS is reported in embryonal rhabdomyosarcoma (ERMS). Upregulation of IGF2/IGF1R axis and IGF2 overexpression is a common finding. Targeting RAS downstream is associated with high toxicity. Combination therapies targeting parallel pathways is necessary to overcome treatment resistance. Dual inhibition of RAS downstream and...

Objective: Upper tract urothelial cancers (UTUC) can be difficult to characterize, and non-invasive surveillance tools are lacking. UTUC are often treated with nephroureterectomy (NU). To address these gaps, we sought to discover and validate methylated DNA markers (MDMs) for detection of UTUC. Methods: Archival formalin fixed paraffin embedded (FF...

Renal manifestations in patients with tuberous sclerosis complex (TSC) include cysts, angiomyolipoma, and renal cell carcinoma. Unlike many hereditary predisposition syndromes, the spectrum of renal tumors in TSC patients (including both angiomyolipoma and renal cell carcinoma) is broad, with significant morphologic heterogeneity. An improved under...

Intraluminal crystalloids are a common finding within malignant prostatic acini and are infrequently identified within benign glands. The proteomic composition of these crystalloids remains poorly understood and may provide insight regarding prostate cancer pathogenesis. Laser microdissection assisted liquid chromatography tandem mass spectrometry...

674 Background: Metastasis directed therapy (MDT) is associated with improved cancer-specific survival and delay in use of systemic therapy for metastatic clear cell RCC (mccRCC). Although the benefits of MDT may differ based on organ site of metastasis due to differences in disease biology, survival based on site of metastasis remain underexplored...

548 Background: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study ai...

Renal cell carcinoma (RCC) is among the top 10 most common cancers in both men and women with an estimated 75 000 cases each year in the US. Over the last decade, the therapeutic landscape for patients with metastatic RCC has significantly evolved, with immunotherapy emerging as the new front-line therapy. Despite significant improvement in toxicit...

A pathologist's optical microscopic examination of thinly cut, stained tissue on glass slides prepared from a formalin-fixed paraffin-embedded tissue blocks is the gold standard for tissue diagnostics. In addition, the diagnostic abilities and expertise of pathologists is dependent on their direct experience with common and rarer variant morphologi...

Penile squamous cell carcinomas (SCC) originating in the shaft are rare. pT1/pT2 categories in the American Joint Committee on Cancer (AJCC) staging manual (8th edition) are poorly defined for SCCs arising in the dorsal shaft as anatomic structures differ between the glans and dorsal shaft (corpus spongiosum vs dartos/Buck's fascia, respectively)....

Machine learning has been leveraged for image analysis applications throughout a multitude of subspecialties. This position paper provides a perspective on the evolutionary trajectory of practical deep learning tools for genitourinary pathology through evaluating the most recent iterations of such algorithmic devices. Deep learning tools for genito...

Diffuse gliomas are aggressive brain tumors that lack effective therapies. Despite advances in the molecular characterization of gliomas, targeted treatments have failed to improve patient outcomes to date. Here, we employed a functional genomics approach to rapidly identify therapeutic vulnerabilities and provide a strategy to individualize patien...

Context.—: Epithelioid angiomyolipomas (eAMLs) are rare tumors of the kidney that occur in patients with tuberous sclerosis complex or in a sporadic setting; a subset of these tumors exhibit metastatic behavior. Objective.—: To analyze molecular profiling data to identify pathogenic alterations in rare cases of metastatic eAML, and to identify i...

Introduction/Background We sought to compare in-vitro mis- match-repair deficient endometrial cancer (EC) methylation and responses to DNA-hypomethylating agents using spheroid- based microcancer 3D tumor cell viability assay. Methodology Study tumor was prospectively collected from a patient with stage 1B, grade 2 endometrioid EC. Characteriza- ti...

Normal Cowper glands and ducts are imperceptible at imaging. However, abnormalities of the Cowper glands and ducts are increasingly seen owing to increasing use of cross-sectional imaging. In this article, the authors present a comprehensive review of the normal anatomy of the Cowper glands and ducts and the clinical and imaging findings of conditi...

Introduction: Pediatric rhabdomyosarcoma (RMS) is the most common soft tissue tumor in children, with nearly 20% of children presenting with locally aggressive and/or metastatic disease. Despite aggressive chemotherapy and radiotherapy, the 5-year overall survival rate is still less than 40%. In addition, resistance to chemotherapy remains the majo...

Introduction: Hepatocyte growth factor receptor, more commonly referred to as MET, is a known oncogenic driver in multiple malignancies. Recently the tyrosine kinase inhibitors capmatinib and tepotinib have been approved by the United States Food and Drug Administration for the treatment of patients with non-small cell lung cancers that harbor MET...

Renal manifestations in patients with tuberous sclerosis complex (TSC) include cysts, angiomyolipoma, and renal cell carcinoma. Unlike many hereditary predisposition syndromes, the spectrum of renal tumors in TSC patients (including both angiomyolipoma and renal cell carcinoma) is broad, with significant morphologic heterogeneity. An improved under...

Intratumoral heterogeneity arising from tumor evolution poses significant challenges biologically and clinically. Dissecting this complexity may benefit from deep learning (DL) algorithms, which can infer molecular features from ubiquitous hematoxylin and eosin (H&E)–stained tissue sections. Although DL algorithms have been developed to predict som...

Juxtaglomerular cell tumors and glomus tumors both arise from perivascular mesenchymal cells. Juxtaglomerular cells are specialized renin-secreting myoendocrine cells in the afferent arterioles adjacent to glomeruli, and juxtaglomerular tumors derived from these cells are therefore unique to the kidney. In contrast, glomus tumors have been describe...

As there is limited literature on paratesticular tumors of müllerian and mesothelial origin, we reviewed archived cases of serous borderline tumors (n = 15), low-grade serous carcinoma (n = 1), well-differentiated papillary mesothelial tumors (WDPMTs; n = 2), and mesothelioma (n = 12), for relevant clinicopathologic features. Molecular profiling da...

Background: We hypothesized full-thickness chest wall resection (FTCWR) with advanced surgical techniques and modern systemic therapy is safe, provides local control, and good overall survival. Methods: Retrospective review of FTCWR (including rib or part of sternum) for breast cancer between 2000 and 2020. Primary endpoints included 90-day morb...

Objectives To compare renal functional outcomes, as determined by percent decline in estimated glomerular filtration rate (eGFR) and CKD stage progression following radical (RN) and partial nephrectomy (PN) stratified by preoperative CKD stage. Materials and Methods We retrospectively evaluated adults treated with RN or PN between 1980 and 2018 fo...

Introduction and objectives PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. T...

An optical microscopic examination of thinly cut stained tissue on glass slides prepared from a FFPE tissue blocks is the gold standard for tissue diagnostics. In addition, the diagnostic abilities and expertise of any pathologist is dependent on their direct experience with common as well as rarer variant morphologies. Recently, deep learning appr...

Muscle-invasive bladder cancer (MIBC) is associated with a poor survival rate of 40% at 5 years follow-up. Current standard-of-care in the management of bladder cancer relies on platinum-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy. However, even with this aggressive course of treatment, up to 50% of patients with MIBC fail t...

The outcome of patients with Muscle Invasive Bladder Cancer (MIBC) is highly variable with many patients experiencing progressive disease despite multimodal therapy. A key variable that contributes to poor patient outcomes lies in our inability to predict therapeutic response due to the molecular heterogeneity of MIBC tumors. There is, therefore, a...

Context.— In women, radical cystectomy includes removal of bladder, uterus, fallopian tubes, ovaries, and anterior vaginal wall, yet contiguous extension of urothelial carcinoma to all pelvic organs is rare and routine removal may be unnecessary. Objective.— To study pelvic organ involvement in women at radical cystectomy and investigate oncologic...

Purpose The aim of the present study is to identify predictive imaging findings and construct a diagnostic model for differentiating renal cell carcinoma (RCC) with and without sarcomatoid dedifferentiation (sRCC and non-sRCC). Methods This study is a single-center retrospective study. All patients had magnetic resonance imaging (MRI) with gradien...

Objective: To profile juxtaglomerular cell tumors (JXG) and histologic mimics by analyzing renin expression; to identify non-JXG renin-producing tumors in The Cancer Genome Atlas (TCGA) data sets; and to define the prevalence of hypertension (HTN) and patient outcomes with angiotensin signaling inhibitor (ASI) use in tumors of interest. Patients...

Most spermatocytic tumors (ST) have an excellent prognosis. In rare instances metastatic disease has been documented. However, it is unclear if aggressive tumors have specific molecular alterations. Herein, we have studied primary ST with (n=4) and without (n=3) “anaplastic” features, including single nucleotide polymorphism microarrays for 5 ST (n...

Large genome-wide association studies have identified hundreds of single-nucleotide polymorphisms associated with increased risk of prostate cancer (PrCa), and many of these risk loci is presumed to confer regulatory effects on gene expression. While eQTL studies of long RNAs has yielded many potential risk genes, the relationship between PrCa risk...

In this report, we present a case of penile calciphylaxis, an extremely rare and serious condition occurring in association with dysregulation of systemic calcium metabolism in the setting of chronic renal impairment. Calciphylaxis can occur at various body sites and is associated with diffuse vascular calcifications in small and medium-sized arter...

To determine the incidence of renal neoplasia among patients undergoing nephrectomy for polycystic kidney disease (PKD), we queried our institutional nephrectomy registry (years 2000–2020). Approximately 4% (231 of 5757) of patients who underwent nephrectomy had PKD, and 26 of these 231 patients (11.3%) had renal neoplasia. Tumors from an additiona...

Importance In BAP1 tumor predisposition syndrome, clear cell renal cell carcinoma (RCC) is frequently associated with melanoma and/or mesothelioma, while germline MITF p.E318K alterations are being increasingly reported in melanoma/RCC. Limited data exist on the co-occurrence of melanoma and/or mesothelioma with renal neoplasia and the prevalence o...

Objectives ERBB pathway alterations present therapeutic targets in high grade endometrial cancer (EC), but efficacy can be limited by persistent co-activation of other ERBB binding partners. The efficacy of dual-inhibition MEK+pan-ERBB or BET+pan-ERBB in an ERBB2/ERBB3 amplified EC was investigated via 3D microcancer ex-vivo cell assay. Methods Tu...

Purpose Collecting duct carcinoma is a rare pathologic entity with a paucity of clinical data in the literature. We aim to evaluate our institutional experience with the management of this disease. Materials and methods All renal tumors in the Mayo Clinic Nephrectomy Registry were re-reviewed retrospectively by an expert urologic pathologist. Case...

Aims Large cell calcifying Sertoli cell tumour (LCCSCT) is a rare testicular sex cord-stromal tumour that primarily affects young patients and is associated with Carney complex. We sought to characterize the clinicopathological features of a series of LCCSCT and evaluate the diagnostic utility of PRKAR1A immunohistochemistry (IHC). Methods and res...

Introduction The favorable outcomes with immunotherapy for mesothelioma were somewhat unexpected since this tumor has a low tumor mutation burden which has been associated with benefit in other cancers. Since chromosomal rearrangements are common in mesothelioma and have neoantigenic potential, we sought to determine whether they are associated wit...

Novel therapeutic strategies are needed for the treatment of rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. By using a combination of cell surface proteomics and transcriptomic profiling of RMS and normal muscle, we generated a catalog of targetable cell surface proteins enriched in RMS tumors. Among the top candidates, we...

Accurate diagnosis of cribriform Gleason pattern 4 (CrP4) prostate adenocarcinoma (PCa) is important due to its independent association with adverse clinical outcomes and as a growing body of evidence suggests that it impacts clinical decision making in PCa management. To identify reproducible features for diagnosis of CrP4, we assessed interobserv...

Background: Immune checkpoint inhibitors are an important therapeutic option for urothelial carcinoma, but durable responses are achieved in a minority of patients. Identifying pre-treatment biomarkers that may predict response to these therapies or who exhibit intrinsic resistance, is of paramount importance. Objective: To explore the prevalenc...

Background: Bim (BCL-2-interacting mediator of cell death) is a downstream pro-apoptotic signaling molecule activated by the PD-1 pathway. Objective: We sought to determine if Bim expression in peritumoral T-lymphocytes (PTLs) is associated with survival in patients with metastatic clear cell renal cell carcinoma (ccRCC). Methods: Immunohistochemis...

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder cancer focusing on important topics of high interest for the practicing surgical pathologist and urologist. This review represents the second of 2 manuscripts ensuing from this effort. Herein, we address the effective reporting of bladder cancer...

The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder neoplasia with a focus on issues relevant to the practicing surgical pathologist for the understanding and effective reporting of bladder cancer, emphasizing particularly on the newly accumulated evidence post-2016 World Health Organization (WHO...