Medicine and Health Sciences Commons^™

Mustang: Multi-Sample Spatial Transcriptomics Data Analysis With Cross-Sample Transcriptional Similarity Guidance, Seyednami Niyakan, Jianting Sheng, Yuliang Cao, Xiang Zhang, Zhan Xu, Ling Wu, Stephen T C Wong, Xiaoning Qian

Faculty, Staff and Students Publications

Spatially resolved transcriptomics has revolutionized genome-scale transcriptomic profiling by providing high-resolution characterization of transcriptional patterns. Here, we present our spatial transcriptomics analysis framework, MUSTANG (MUlti-sample Spatial Transcriptomics data ANalysis with cross-sample transcriptional similarity Guidance), which is capable of performing multi-sample spatial transcriptomics spot cellular deconvolution by allowing both cross-sample expression-based similarity information sharing as well as spatial correlation in gene expression patterns within samples. Experiments on a semi-synthetic spatial transcriptomics dataset and three real-world spatial transcriptomics datasets demonstrate the effectiveness of MUSTANG in revealing biological insights inherent in the cellular characterization of tissue samples under study.

Clinical Significance Of Pno1 As A Novel Biomarker And Therapeutic Target Of Hepatocellular Carcinoma, Sanjit K. Roy, Shivam Srivastava, Caroline Mccance, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

The RNA-binding protein PNO1 plays an essential role in ribosome biogenesis. Recent studies have shown that it is involved in tumorigenesis; however, its role in hepatocellular carcinoma (HCC) is not well understood. The purpose of this study was to examine whether PNO1 can be used as a biomarker of HCC and also examine the therapeutic potential of PNO1 knockout for the treatment of HCC. PNO1 expression was upregulated in HCC and associated with poor prognosis. PNO1 expression was positively associated with tumour stage, lymph node metastasis and poor survival. PNO1 expression was significantly higher in HCC compared to that in …

Casi: A Framework For Cross-Timepoint Analysis Of Single-Cell Rna Sequencing Data, Yizhuo Wang, Christopher R Flowers, Michael Wang, Xuelin Huang, Ziyi Li

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) technology has been widely used to study the differences in gene expression at the single cell level, providing insights into the research of cell development, differentiation, and functional heterogeneity. Various pipelines and workflows of scRNA-seq analysis have been developed but few considered multi-timepoint data specifically. In this study, we develop CASi, a comprehensive framework for analyzing multiple timepoints' scRNA-seq data, which provides users with: (1) cross-timepoint cell annotation, (2) detection of potentially novel cell types emerged over time, (3) visualization of cell population evolution, and (4) identification of temporal differentially expressed genes (tDEGs). Through comprehensive simulation …

Imaging Features Of Primary Intracranial Sarcoma With Dicer1 Mutation: A Multicenter Case Series, Rami W Eldaya, Richard J Fagan, Samir A Dagher, Angshumoy Roy, Sonika Dahyia, Gregory N Fuller, Max Wintermark, Matthew S Parsons, Thierry A G M Huisman

Faculty, Staff and Student Publications

Primary intracranial sarcoma, DICER1-mutant, is a rare, recently described entity in the fifth edition of the WHO Classification of CNS Tumors. Given the entity's rarity and recent description, imaging data on primary intracranial sarcoma, DICER1-mutant, remains scarce. In this multicenter case series, we present detailed multimodality imaging features of primary intracranial sarcoma, DICER1-mutant, with emphasis on the appearance of the entity on MR imaging. In total, 8 patients were included. In all 8 patients, the lesion demonstrated blood products on T1WI. In 7 patients, susceptibility-weighted imaging was obtained and demonstrated blood products. Primary intracranial sarcoma, DICER1-mutant, …

Undifferentiated Pleomorphic Sarcoma Of The Face, Erin Brown, Cheyenne Rahimi, Neel D. Gupta, Jagan D. Gupta, Triet M. Do, Mae Igi, Enrique Palacios

School of Medicine Faculty Publications

No abstract provided.

A Rat-Based Preclinical Platform Facilitating Transcatheter Hepatic Arterial Infusion In Immunodeficient Rats With Liver Xenografts Of Patient-Derived Pancreatic Ductal Adenocarcinoma, Masanori Ozaki, Ken Kageyama, Kenjiro Kimura, Shinpei Eguchi, Akira Yamamoto, Ryota Tanaka, Takehito Nota, Hiroki Yonezawa, Hideyuki Nishiofuku, Yuki Sakai, Naoki Tani, Atsushi Jogo, Mizue Terai, Takami Sato, Takeaki Ishizawa, Yukio Miki

Department of Medical Oncology Faculty Papers

Liver metastases from pancreatic ductal adenocarcinoma (PDAC) are highly fatal. A rat-based patient-derived tumor xenograft (PDX) model is available for transcatheter therapy. This study aimed to create an immunodeficient rat model with liver xenografts of patient-derived primary PDAC and evaluate efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived PDACs were transplanted into the livers of 21 rats each (totally, 63 rats), randomly assigned into hepatic arterial infusion, systemic venous infusion, and control groups (n = 7 each) four weeks post-implantation. Computed tomography evaluated tumor volumes before and four weeks after treatment. Post-euthanasia, resected tumor specimens …

Emotion Regulation Strategies And Perceived Emotional Intelligence: The Effect Of Age., Iwanna Sepiadou

Adultspan Journal

The aim of this study was to investigate the relationship between perceived emotional intelligence and the reported use of cognitive reappraisal and expressive suppression. We also investigated the possible effects of age on the aforementioned variables. The total sample consisted of 379 people (158 men, 220 women, 1 unreported). Across participants, 273 were young (20-39 years old) and 106 were middle-aged (40-65 years old). We found statistically significant positive correlations between the dimensions of perceived emotional intelligence and the reported use of cognitive reappraisal and negative primarily correlations between the dimensions of perceived emotional intelligence and the reported use of …

Risks Of Depression, Anxiety, And Suicide In Partners Of Men With Prostate Cancer: A National Cohort Study, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Alexis C Edwards, Kristina Sundquist, Weiva Sieh

Faculty, Staff and Student Publications

BACKGROUND: A diagnosis of prostate cancer (PC) may cause psychosocial distress not only in a man but also in his intimate partner. However, long-term risks of depression, anxiety, or suicide in partners of men with PC are largely unknown.

METHODS: A national cohort study was conducted of 121 530 partners of men diagnosed with PC during 1998-2017 and 1 093 304 population-based controls in Sweden. Major depression, anxiety disorder, and suicide death were ascertained through 2018. Cox regression was used to compute hazard ratios (HRs) while adjusting for sociodemographic factors.

RESULTS: Partners of men with high-risk PC had increased risks …

Correction: Horne Et Al White Matter Correlates Of Domain-Specific Working Memory, Autumn Horne, Junhua Ding, Tatiana T Schnur, Randi C Martin

Faculty, Staff and Student Publications

In the original publication [...].

Response To Lao, Guan, Wang, Et Al, Casey Crump, Pär Stattin, James D Brooks, Jan Sundquist, Alexis C Edwards, Kristina Sundquist, Weiva Sieh

Faculty, Staff and Student Publications

No abstract provided.

Role Of Integrase-Pp2a Interaction In Human T-Cell Leukemia Virus Type-1 Replication And Pathogenesis, Shayna Turbin

Senior Honors Papers / Undergraduate Theses

Human T-cell leukemia virus type-1 (HTLV-1) is an oncogenic retrovirus that causes multiple disorders, including adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. HTLV-1 retroviral integrase binds to the regulatory B’56γ subunit of the host cell Protein Phosphatase 2A (PP2A). Integrase contains a highly conserved LxxIxE motif that is essential for binding, which increases integration efficiency and facilitates HTLV-1 hijack of host cell machinery. We aim to understand how mutations introduced in the highly conserved binding site can affect viral particle production and infectivity. We transfected 729B human lymphoblastoid cells and 293T cells with mutant and wildtype virus. Mutations L213A, …

Complete Pathologic Response To Gemcitabine And Oxaliplatin Chemotherapy After Prior Therapies In A Patient With Hepatocellular Carcinoma And Peritoneal Metastases Undergoing Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy, Amry Majeed, Sneha Alaparthi, Dina Halegoua-De Marzio, Jaime Eberle-Singh, Wei Jiang, Pramila Rani Anne, Ashesh P. Shah, Wilbur B. Bowne, Daniel Lin

Jefferson Hospital Staff Papers and Presentations

Hepatocellular carcinoma (HCC) is often diagnosed at a late stage and frequently recurs despite curative intervention, leading to poor survival outcomes. Frontline systemic therapies include combination immunotherapy regimens and tyrosine kinase inhibitors. We report a case of a 38-year-old woman with chronic hepatitis B and C coinfection-associated non-cirrhotic HCC, which recurred in the peritoneum after initial resection of her primary tumor. Disease progression occurred on both atezolizumab/bevacizumab and lenvatinib, and she was subsequently treated with gemcitabine and oxaliplatin (GEMOX) chemotherapy and exhibited a profound clinical response on imaging with normalization of alpha fetoprotein (AFP) after several months. Following extensive multidisciplinary …

Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate …

Predicting The Pathway Involvement Of Metabolites Based On Combined Metabolite And Pathway Features, Erik D. Huckvale, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

A major limitation of most metabolomics datasets is the sparsity of pathway annotations for detected metabolites. It is common for less than half of the identified metabolites in these datasets to have a known metabolic pathway involvement. Trying to address this limitation, machine learning models have been developed to predict the association of a metabolite with a “pathway category”, as defined by a metabolic knowledge base like KEGG. Past models were implemented as a single binary classifier specific to a single pathway category, requiring a set of binary classifiers for generating the predictions for multiple pathway categories. This past approach …

Single Extracellular Vesicle Imaging And Computational Analysis Identifies Inherent Architectural Heterogeneity, Kshipra S Kapoor, Seoyun Kong, Hikaru Sugimoto, Wenhua Guo, Vivek Boominathan, Yi-Lin Chen, Sibani Lisa Biswal, Tanguy Terlier, Kathleen M Mcandrews, Raghu Kalluri

Faculty, Staff and Student Publications

Evaluating the heterogeneity of extracellular vesicles (EVs) is crucial for unraveling their complex actions and biodistribution. Here, we identify consistent architectural heterogeneity of EVs using cryogenic transmission electron microscopy (cryo-TEM), which has an inherent ability to image biological samples without harsh labeling methods while preserving their native conformation. Imaging EVs isolated using different methodologies from distinct sources, such as cancer cells, normal cells, immortalized cells, and body fluids, we identify a structural atlas of their dominantly consistent shapes. We identify EV architectural attributes by utilizing a segmentation neural network model. In total, 7,576 individual EVs were imaged and quantified by …

Histone Demethylase Kdm5 Regulates Cardiomyocyte Maturation By Promoting Fatty Acid Oxidation, Oxidative Phosphorylation, And Myofibrillar Organization, Manisha Deogharia, Leslye Venegas-Zamora, Akanksha Agrawal, Miusi Shi, Abhinav K Jain, Kevin J Mchugh, Francisco Altamirano, Ali J Marian, Priyatansh Gurha

Faculty, Staff and Student Publications

Aims: Human pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) provide a platform to identify and characterize factors that regulate the maturation of CMs. The transition from an immature foetal to an adult CM state entails coordinated regulation of the expression of genes involved in myofibril formation and oxidative phosphorylation (OXPHOS) among others. Lysine demethylase 5 (KDM5) specifically demethylates H3K4me1/2/3 and has emerged as potential regulators of expression of genes involved in cardiac development and mitochondrial function. The purpose of this study is to determine the role of KDM5 in iPSC-CM maturation.

Methods and results: KDM5A, B, and C proteins were mainly expressed …

Data Normalization For Addressing The Challenges In The Analysis Of Single-Cell Transcriptomic Datasets, Raquel Cuevas-Diaz Duran, Haichao Wei, Jiaqian Wu

Faculty, Staff and Student Publications

BACKGROUND: Normalization is a critical step in the analysis of single-cell RNA-sequencing (scRNA-seq) datasets. Its main goal is to make gene counts comparable within and between cells. To do so, normalization methods must account for technical and biological variability. Numerous normalization methods have been developed addressing different sources of dispersion and making specific assumptions about the count data.

MAIN BODY: The selection of a normalization method has a direct impact on downstream analysis, for example differential gene expression and cluster identification. Thus, the objective of this review is to guide the reader in making an informed decision on the most …

Hormonal Basis Of Brain Fog In Cancer Treatment, Yuan Pan, Jian Hu

Faculty, Staff and Student Publications

The cognitive side effects of cancer treatment are common, but no targeted therapy exists yet to treat or prevent such neurological sequelae. We explore the role of hormones as mediators between cancer therapy and cognitive impairment, discussing potential future directions.

Ras G-Domains Allosterically Contribute To The Recognition Of Lipid Headgroups And Acyl Chains, Neha Arora, Huanwen Mu, Hong Liang, Wenting Zhao, Yong Zhou

Faculty, Staff and Student Publications

Mutant RAS are major contributors to cancer and signal primarily from nanoclusters on the plasma membrane (PM). Their C-terminal membrane anchors are main features of membrane association. However, the same RAS isoform bound to different guanine nucleotides spatially segregate. Different RAS nanoclusters all enrich a phospholipid, phosphatidylserine (PS). These findings suggest more complex membrane interactions. Our electron microscopy-spatial analysis shows that wild-types, G12V mutants, and membrane anchors of isoforms HRAS, KRAS4A, and KRAS4B prefer distinct PS species. Mechanistically, reorientation of KRAS4B G-domain exposes distinct residues, such as Arg 135 in orientation state 1 (OS1) and Arg 73/Arg 102 in OS2, …

Efficacy Of Intravesical Nadofaragene Firadenovec For Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From A Phase 3 Trial, Vikram M. Narayan, Stephen A. Boorjian, Mehrdad Alemozaffar, Badrinath R. Konety, Neal D. Shore, Leonard G. Gomella, Ashish M. Kamat, Trinity J. Bivalacqua, Jeffrey S. Montgomery, Seth P. Lerner, Joseph E. Busby, Michael Poch, Paul L. Crispen, Gary D. Steinberg, Anne K. Schuckman, Tracy M. Downs, Joseph Mashni, Brian R. Lane, Thomas J. Guzzo, Gennady Bratslavsky, Lawrence I. Karsh, Michael E. Woods, Gordon Brown, Daniel Canter, Adam Luchey, Yair Lotan, Brant A. Inman, Michael B. Williams, Michael S. Cookson, Sam S. Chang, Alexander I. Sankin, Michael A. O'Donnell, David Sawutz, Richard Philipson, Nigel R. Parker, Seppo Yla-Herttuala, Dorte Rehm, Jørn S. Jakobsen, Kristian Juul, Colin P.N. Dinney

Department of Urology Faculty Papers

Purpose: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector–based gene therapy for bacillus Calmette-Guérin (BCG)–unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up.

Materials and Methods: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence–free (HGRF).

Results: One hundred fifty-seven …

From Survivors To Care Providers: A Multi-Dimensional Study On Physical Activity In Cancer Care, Gaurav Kumar

Theses & Dissertations

As the population of cancer survivors grows, understanding the dynamics of physical activity (PA) engagement is critical due to its potential benefits in reducing adverse health outcomes and mortality associated with cancer. Despite known benefits, both adherence to and promotion of PA among cancer survivors face significant challenges. This comprehensive study examines PA levels, barriers, facilitators, and perceptions among cancer survivors and oncology care providers over a ten-year period. The objectives are to assess adherence levels to PA among cancer survivors, explore the perceived barriers and facilitators to PA engagement from the survivors' perspectives, and understand the barriers, facilitators, and …

Assessment Of In-Vitro And In-Vivo Pre-Clinical Pharmacokinetics Of Epz015666; A Novel Small Molecule For Medulloblastoma Treatment, Pratiksha U. Kshirsagar

Theses & Dissertations

Group 3 medulloblastoma (MB) has the worst prognosis of the MB subgroups associated with elevated MYC expression and a 5-year survival rate of

Quantitation of EPZ was performed on a Shimadzu LC-MS/MS system utilizing electrospray ionization operated in positive mode. The validated assay was linear from 0.2 to 500 ng/mL. Metabolic stability studies demonstrated slow intrinsic clearance of EPZ in mouse and human liver microsomes, suggesting no CYP-mediated metabolism. Additionally, EPZ exhibited low binding affinity to plasma and brain proteins and high apparent permeability across artificial membranes, indicating efficient membrane penetration. Drug transporter studies identified EPZ as a substrate of …

Evaluating Patient Satisfaction Of Medication Education In Oncology, Christina Lew, Pharmd, Bcps, Rose Dimarco, Pharmd, Bcps, Bcop, Maria Hafez, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• Optimization of medication education is important in promoting patient adherence, improving outcomes, and managing toxicities.
• With the increasing complexities of cancer treatments and an aging population, patient understanding is critical. In addition, chemotherapy is associated with toxicities that often require supportive care management.
• Historically, institutions and providers decide upon the type, format, and amount of information provided to patients.
• The aim of the project is to assess patient understanding of information provided in clinic, retention of information after clinic, and patient satisfaction.

Lung Cancer In Immunosuppressed Patients, Garrett Melby, Andrew Bernstein, Md, Matthew Tucker, Md, Julia Palecki, Md, Zoe Begun, Md, Amman Bhasin, Md, Tingting Zhang, Phd, Ida Micaily, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

- Lung cancer is the #1 cause of cancer-related mortality in U.S. adults

- Immune evasion is a key mechanism in tumor cell proliferation

• Immunosuppressed patients have higher lung cancer incidences and worse lung cancer outcomes

- Success of immunotherapies supports the role of host immune function in host tumor response

• Studies have shown immunotherapy to be safe and effective in a variety of immunosuppressed populations
• Immunosuppressed patients are often excluded from immunotherapy trials and under-treated with immunotherapy compared to immunocompetent cohorts

- This study aimed to assess the disease course, PD-L1 expression, and utilized treatment modalities across patients …

Utilizing Inpatient Opportunities To Increase Comprehensive Advanced Care Planning In Oncology Patients, Alexandros Grivas, Md, Brian Schonewald, Md, Sawan Dutta, Md, Matt Bierowski, Md, Chioma Nwonu, Do, Evan Nardone, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

- Advanced Care Planning (ACP) is a high-value intervention that significantly improves end-of-life (EOL) care.

- ACP includes discussion between the patient and a qualified healthcare provider in an appropriate healthcare setting aiming: o To recognize patient’s wishes at end-of-life situations.

• To identify surrogates to act in the patient’s best wishes if they become unable to make such decisions.
• ACPs provide comfort on patients and their families during stressful end-of-life situations and facilitates appropriate use of resources.
• Absence of ACP leads to non-beneficial care, higher financial burden, and family distress.
• Ideal locations to form and document ACP are outpatient …

Oncology Infusion Center Hyperglycemia Protocol, Franklin L. Thelmo, Do Jr., Eric J. Shiffrin, Md, Rose Dimarco, Pharmd, Bcps, Bcop, Emily Brand, Pharmd, Daniel Lin, Md

Health Equity and Quality Improvement (HEQI) Summit

Background

• Problem: Patients receiving chemotherapy for their cancer are often overwhelmed with the stresses of their new diagnoses and other coexistent medical issues may be forgotten or ignored. In the event dysglycemia or diabetes appears during the course of chemotherapy it may difficult for these patients to obtain care in a timely fashion and early literature suggests that dysglycemia may decrease the efficacy of chemotherapy
• Aim: Our goal was a protocol designed to ensure adequate euglycemia in patients at the Oncology Infusion Center (OIC) to eliminate insulin treatment guesswork for hyperglycemia, allow timely care with endocrinology specialists, and create a …

Oncology Treatment Plan Updates In Epic-Beacon, Rose Dimarco, Pharmd, Bcps, Bcop, Gloria Espinosa, Mat, Pharmd, Bcop, Kelly Miskovsky, Pharmd, Bcop, Gina Hemmert, Pharmd

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Background

In Medical Oncology, the utilization of EPIC-Beacon Treatment Plans is integral for prescribing and administering cancer treatments. These treatment plans typically consist of anticancer infusion medications (chemotherapy, immunotherapy, etc.), supportive care medications, required laboratory orders, and other monitoring recommendations to ensure that patients receive safe and effective care. In 2017, TJUH transitioned from Varian’s Aria to EPIC’s electronic medical record system. Since then, there has not been a formal review of existing plans, and there are many inconsistencies between plans in different cancer types.

Problem Statement:

• Currently, there is not a formal process for review of existing treatment plans, …

Comparison Of Hospital Volume And Risk-Standardized Mortality Rate As A Proxy For Hospital Quality In Complex Oncologic Hepatopancreatobiliary Surgery, William T. Julian, John B. Ammori, Jeffrey M. Hardacre, Lee M. Ocuin

Faculty Scholarship

Background: Centralization of hepatopancreatobiliary procedures to more experienced centers has been recommended but remains controversial. Hospital volume and risk-stratified mortality rates (RSMR) are metrics for interhospital comparison. We compared facility operative volume with facility RSMR as a proxy for hospital quality. Patients and Methods: Patients who underwent surgery for liver (LC), biliary tract (BTC), and pancreatic (PDAC) cancer were identified in the National Cancer Database (2004–2018). Hierarchical logistic regression was used to create facility-specific models for RSMR. Volume (high versus low) was determined by quintile. Performance (high versus low) was determined by RSMR tercile. Primary outcomes included median facility RSMR …

A Rare Case Of Primary Sclerosing Pneumocytoma In A Healthy Female, Nitya Batra, Atulya Aman Khosla, Mohammad Muhsin Chisti, Vikash Jaiswal, Ashbita Pokharel

Conference Presentation Abstracts

Introduction: Pulmonary sclerosing pneumocytoma is a rare group of benign pulmonary neoplasms that usually affects older adults over 50 years of age . This neoplasm is more commonly seen in women, with female to male ratio of 5:1 and is predominantly seen in Asian ethnicities. These tumors originate from type II alveolar pneumocytes and are hence classified as adenoma under the 2021 World Health Organization (WHO) classification of tumors . They account for 3-5 percent of total benign lung tumors. One of the striking aspects of PSP is its clinical presentation, or rather the lack thereof in many cases. It …

Aggressive Renal Cell Carcinoma In A Patient With A Rare Genetic Syndrome, Nidhi Navaratna, Nitya Batra, Mohammad Chisti

Conference Presentation Abstracts

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an exceedingly rare genetic disorder characterized by skin and uterine leiomyomas and an increased risk of renal cell cancer. HLRCC follows an autosomal dominant pattern and is due to inactivating germline and somatic mutations in the gene encoding the fumarate hydratase enzyme (FH) involved in the citric acid cycle. The rarity and wide phenotypic variation in the presentation of HLRCC complicates suspicion and testing for this syndrome. We describe the case of a young woman who presented with pathological fracture secondary to bone metastasis from renal cell carcinoma. The patient presented to …