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Verrucous esophageal carcinoma is a unique indolent subtype of squamous cell carcinoma: a systematic review and individual patient regression analysis

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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A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol).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.

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Abbreviations

AJCC/UICC:

American Joint Committee of Cancer/Union for International Cancer Control

EMR:

Endoscopic mucosal resection

ESCC:

Esophageal squamous cell carcinoma

ESD:

Endoscopic submucosal dissection

EUS:

Endoscopic ultrasound

JAMAS:

Japan Medical Abstracts

MGH:

Massachusetts General Hospital

TCGA:

The Cancer Genome Atlas

VEC:

Verrucous esophageal carcinoma

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Acknowledgements

The authors thank Prof. Dr. Louis M. Wong Kee Song for valuable clinical information regarding the diagnosis and management of verrucous esophageal carcinoma. The results shown here are in part based upon data generated by the TCGA Research Network: https://www.cancer.gov/tcga.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA

    Darrick K. Li & Kavel H. Visrodia

  2. Digestive Center for Diagnosis and Treatment, Damascus, Syrian Arab Republic

    Samir Haffar

  3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinjuku, Tokyo, Japan

    Masayasu Horibe

  4. School of Public Health, University of Waterloo, Waterloo, ON, Canada

    Haya A. Homsi

  5. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    Lawrence Zukerberg

  6. Evidence-Based Practice Center, Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA

    Mohammad H. Murad

  7. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA

    Manish Gala

  8. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

    Masayasu Horibe & David A. Katzka

  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

    Manish Gala & Fateh Bazerbachi

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  1. Darrick K. Li
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Correspondence to Manish Gala or Fateh Bazerbachi.

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Li, D.K., Haffar, S., Horibe, M. et al. Verrucous esophageal carcinoma is a unique indolent subtype of squamous cell carcinoma: a systematic review and individual patient regression analysis. J Gastroenterol 56, 12–24 (2021). https://doi.org/10.1007/s00535-020-01736-1

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  • DOI: https://doi.org/10.1007/s00535-020-01736-1

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