Darrick K Li1, Samir Haffar2, Masayasu Horibe3,4, Haya A Homsi5, Lawrence Zukerberg6, Mohammad H Murad7, Kavel H Visrodia1, Manish Gala8,9, David A Katzka4, Fateh Bazerbachi10. 1. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. 2. Digestive Center for Diagnosis and Treatment, Damascus, Syrian Arab Republic. 3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan. 4. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. 5. School of Public Health, University of Waterloo, Waterloo, ON, Canada. 6. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. 7. Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA. 8. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA. mgala@mgh.harvard.edu. 9. Assistant in Medicine, Instructor in Medicine, Harvard Medical School, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, GRJ 825D, Boston, MA, 02114, USA. mgala@mgh.harvard.edu. 10. Assistant in Medicine, Instructor in Medicine, Harvard Medical School, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, GRJ 825D, Boston, MA, 02114, USA. fbazerbachi@mgh.harvard.edu.
Abstract
BACKGROUND AND AIMS: Verrucous esophageal carcinoma (VEC) is a rare malignancy that presents a diagnostic challenge. We aim to characterize the clinical and genomic features, tumor behavior, and treatment outcomes of VEC to guide clinical practice. METHODS: We performed a systematic review of the literature and identified additional cases from Massachusetts General Hospital records and The Cancer Genome Atlas (TCGA). We obtained individual VEC patient data and analyzed publicly available clinicogenomic data from TCGA. We performed a regression analysis comparing cases of VEC to esophageal squamous cell carcinoma (ESCC) to identify factors influencing survival. RESULTS: A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol). Symptoms were present at diagnosis in 95% of patients, most commonly dysphagia and weight loss. Median symptom onset to diagnosis time was 11.5 months with frequent misdiagnosis as Candida esophagitis. Among VEC cases with pathologic staging, lymph node metastases were rare (5%) compared to ESCC (40%). VEC was genomically characterized by enrichment of SMARCA4 missense mutations and a lack of pathogenic TP53 mutations. Despite its diagnostic elusiveness, in a multivariate regression analysis, VEC was detected at earlier stages (p = < 0.001) compared to ESCC, and advanced stage was the only significant factor affecting survival (p = 0.013). CONCLUSIONS: VEC is a rare, clinically and genomically distinct subtype of ESCC. Recognition and diagnosis of this lesion may allow the pursuit of curative and less morbid treatment strategies.
BACKGROUND AND AIMS: Verrucous esophageal carcinoma (VEC) is a rare malignancy that presents a diagnostic challenge. We aim to characterize the clinical and genomic features, tumor behavior, and treatment outcomes of VEC to guide clinical practice. METHODS: We performed a systematic review of the literature and identified additional cases from Massachusetts General Hospital records and The Cancer Genome Atlas (TCGA). We obtained individual VEC patient data and analyzed publicly available clinicogenomic data from TCGA. We performed a regression analysis comparing cases of VEC to esophageal squamous cell carcinoma (ESCC) to identify factors influencing survival. RESULTS: A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol). Symptoms were present at diagnosis in 95% of patients, most commonly dysphagia and weight loss. Median symptom onset to diagnosis time was 11.5 months with frequent misdiagnosis as Candida esophagitis. Among VEC cases with pathologic staging, lymph node metastases were rare (5%) compared to ESCC (40%). VEC was genomically characterized by enrichment of SMARCA4 missense mutations and a lack of pathogenic TP53 mutations. Despite its diagnostic elusiveness, in a multivariate regression analysis, VEC was detected at earlier stages (p = < 0.001) compared to ESCC, and advanced stage was the only significant factor affecting survival (p = 0.013). CONCLUSIONS: VEC is a rare, clinically and genomically distinct subtype of ESCC. Recognition and diagnosis of this lesion may allow the pursuit of curative and less morbid treatment strategies.
Authors: Pradeep K Siddappa; Fadi Hawa; Larry J Prokop; M Hassan Murad; Barham K Abu Dayyeh; Vinay Chandrasekhara; Mark D Topazian; Fateh Bazerbachi Journal: Gastroenterol Rep (Oxf) Date: 2021-02-03
Authors: Robert Lam; Nicholas Tarangelo; Rong Wang; Masayasu Horibe; Alyssa A Grimshaw; Dhanpat Jain; Samir Haffar; Fateh Bazerbachi; Pamela L Kunz; Darrick K Li Journal: Oncologist Date: 2022-09-02 Impact factor: 5.837