Auburn Research Day 2022

Cl i n i ca l Case Repor t | Med i ca l St udent Ebv-Associated Nasopharyngeal Carcinoma in a Caucasion Male Smoker: A Case Report

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Julian Aguilar, OMS III; Kenneth Appel, OMS III; Cristina Negoescu, OMS III; Chinyere C. Mbaeri, MD VCOM – Auburn Campus; Wellington Regional Medical Center, Wellington, FL

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma is a malignancy of squamous origin with distinct distribution in Northern Africa and Southeast Asia. It is particularly uncommon in the United States. We report a case of a 50-year-old Caucasian male with a long-standing history of tobacco use that presented with a left sided neck mass. CT scan of the neck showed a 3.8 cm enhancing mass or node in the left side of neck and a 2.4 cm soft tissue density mass in the cavernous sinus on the right. MRI of the face/ neck/orbit with and without contrast showed an enlarged lymph node just posterior to the left submandibular gland measuring approximately 2.4 x 1.8 cm, a large posterior cervical triangle nodal mass measuring 2.7 x 3.2 cm, and mild right sided adenopathy not

as prominent as on the left. Left nasopharyngeal mass biopsies and fine needle aspiration of the left sided neck mass were all consistent with squamous cell carcinoma. Immunohistochemistry stains revealed cytokeratin AE1/AE3, p63, HLA-DR, CK56, and EBV were all positive in the neoplastic epithelial cells, supporting the diagnosis of nonkeratinizing nasopharyngeal carcinoma. In situ hybridization analysis resulted in HPV negative and EBV positive testing. Patient has completed three cycles of induction chemotherapy followed by concurrent chemoradiation as well as nine weeks of radiation. This case report demonstrates the possibility of an uncommon malignancy presenting in a patient of differing demographics than those typically affected.

4 Nosha Farhadfar; Raad Z. Gharaibeh; Wendy J. Dahl; Lacey Mead; Michael Weaver; Zeina Al-Mansour; Christian Jobin; Debra Lyon; John R. Wingard; Debra Lynch Kelly Department of Medicine, Division of Hematology & Oncology, University of Florida; (2) Department of Medicine, Division of Gastroenterology, University of Florida; (3) Food Science and Human Nutrition, University of Florida; (4) College of Nursing, University of Florida Cl i n i ca l Case Repor t | Med i ca l St udent Gut Microbiota Dysbiosis and Persistent Fatigue in Hematopoietic Cell Transplant Survivors

Introduction: Fatigue is a prevalent and distressing complication among hematopoietic stem cell transplant (HCT) survivors, negatively affecting physical, social, and emotional quality of life domains. Evidence links chronic inflammation to alterations in nervous system activity and distressing symptoms such as fatigue. Gut mucosa damage due to alteration in gut microbiota (GM) and microbial translocation likely increase systemic pro-inflammatory cytokines. The aim of this study was to evaluate the relationship between GM and persistent fatigue post HCT. Methods: This study included 30 adults who had HCT for a hematologic disease and were at least one-year post-HCT. Patients with chronic GVHD were excluded. Fatigue was assessed using the Brief Fatigue Inventory (BFI). A cut-off score of four for fatigue on a scale of 0-10 was used to indicate clinically significant fatigue. Patients were grouped into two categories: BFI 0–3 (without fatigue) and BFI ≥ 4 (with fatigue). The V1-V3 region of the 16S rRNA gene from fecal specimens was sequenced using Illumina MiSeq. Sequencing reads were processed, dereplicated, chimeras filtered, amplicon sequence variants (ASVs) generated and assigned taxonomy using DADA2. Beta diversity analysis through Principal Coordinate Analysis (PCoA) was generated using Bray-Curtis dissimilarity matrix and the difference was tested using linear model with generalized least squares (gls) in R. Alpha diversity analysis was done using Chao1. Linear discriminant analysis effect size (LEfSe) was used to find markers that differentiate between the two groups.

Results: Patient were categorized into two cohorts; 1) with fatigue (n= 14) 2) without fatigue (n=16). The two cohorts were similar in demographic, disease, or transplant (Table 1). There was a significant difference in GM composition (beta diversity) between the two cohorts (Figure A, P = 0.001). Alpha diversity (richness) was also significantly lower in survivors with fatigue (Figure B, P =0.002). LEfSe analysis identified 46 discriminative features (p< 0.05, LDA score >2) whose relative abundance varied significantly among individuals with and without fatigue. Ten ASVs were associated with fatigue and 36 ASVs were associated with those without fatigue. Several ASVs enriched in survivors with fatigue included organisms such as Klebsiella and Enterococcus, which have been implicated in inflammatory bowel diseases. The ASVs enriched in the cohort without fatigue were members of the Ruminococcaceae family (Oscillospira spp) and Lachnospiraceae family (Fusicatenibacter, Coprococcus spp) which are known to have the ability to ferment complex plant carbohydrates. Conclusion: These findings show an association between GM composition and fatigue and suggest a microbial contribution to clinically significant fatigue post-HCT which may guide new approaches for treatment of fatigue based on GM manipulation.

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