Esophageal papillomatosis: an exceedingly rare disease

Orphanet Journal of Rare Diseases (2023) 18:99 Li et al. Orphanet Journal of Rare Diseases https://doi.org/10.1186/s13023-023-02703-8 Open Access REVIEW Esophageal papillomatosis: an exceedingly rare disease Dandan Li1* , Changfeng Li1, Yuxing Yan1 and Minya Liu1 Abstract If esophageal papilloma (EP) is a rare condition, esophageal papillomatosis (EPS) is a distinct rarity. To date, only 53 well documented cases have been described in English literature. However, the number of reports on EPS significantly increased to over 40 cases during the past 20 years. Perhaps, this is due to the broad use of endoscopy and related research achievements. Most of the cases are individual and it seems that there are no associations between them. And up to now no guidelines can be followed. To further understand this exceedingly rare disease, we had a comprehensive review of the epidemiology, etiology, clinical manifestations, pathogenesis, treatment, and clinical course of EPS. Keywords Esophageal papillomatosis, Human papilloma virus, Endoscopy, Esophageal cancer, Treatment Introduction The criteria of EP were first demonstrated by Stout and Lattes in the 1950s [1, 2]. EP was defined as a coral-like sessile lesion that has a central core of fibrovascular tissue, capped by a squamous epithelium. Adler et al. [3] described the first case of EP that was histologically confirmed. EP prevalence varies from 0.007 to 0.45% [4, 5] and solitary EP is often observed under endoscopy. Occasionally, several EP in one case can also be reported; however, multiple, or extensive EP is extremely rare. In 1977, the first EPS case was inadvertently found in a 3 1/2-yearold boy, who was diagnosed with papilloma of the pyriform sinus, blocking the supraglottis [6]. In this report, multiple EP was first described as EPS. Most studies thought of EPS as multiple and extensive esophageal squamous papillomas. So far, there are only 53 cases that can be found in English literature, and that *Correspondence: Dandan Li 1 Department of Gastrointestinal Medicine (Endoscopy Center), Jilin University, China-Japan Union Hospital, 126 Xiantai Street, Erdao, Changchun 130033, People’s Republic of China are reported in a form of case reports or combined with mini reviews. Although considered as part of EP, EPS has its own characteristics. In this review, we provide an overview of the case studies and summarize the epidemiology, etiology, clinical manifestation and pathology, therapy, and prognosis of EPS. Epidemiology of EPS EPS can be found at any age, from 3.5 months to 91-yearold [7, 8] and the average onset age is approximatively 46.8 years. No significant differences were observed between affected men (24 cases) and women (29 cases). Most of the cases are sporadic and some studies showed that the EP geographic distribution is considerably different [9, 10]. However, based on the literature, there is no evidence that EPS is associated with a geographic origin. Etiology of EPS Although the etiology of EPS is as unclear as EP, it is now thought that several factors are related to EPS incidence, such as chronic mucosal irritation, human papilloma virus (HPV) and genetic factors. It seems similar to EP but has its own characteristics. © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li et al. Orphanet Journal of Rare Diseases (2023) 18:99 Page 2 of 10 Chronic mucosal irritation EPS may result from chronic mucosal irritation which is induced by chemical and mechanical mucosal injuries. Gastroesophageal reflux is the most popular chemical factor that is associated with an underlying esophageal inflammatory process. In animal model studies, gastroesophageal and duodenal reflux have been confirmed to induce EPS [11–13]. Among the EPS cases, more than a quarter of patients had a prolonged chronic reflux disease and repeated heartburn. Chemical induction experiments were also performed using the carcinogen, diethylnitrosamine (DEN) [13] and EPS was detected in approximatively 50% of the rats that were fed with DEN alone and this proportion increased to 61.1% when associated with gastroesophageal reflux. Progressive hyperplasia of the papillae and epithelium led to the formation of papillomas. Other chemical factors, such as tobacco and alcohol abuse are also considered as a lifetime risk of EP [10, 14], which can also be found in EPS cases. Some reports suggested that mechanical injuries, such as previous and repeated esophageal dilatations, a prolonged nasogastric intubation, and metal stent, were associated with the occurrence of EP [10]. It can also been seen in EPS cases [15–17]. For instance, a 78-yearold man with distal esophagus stricture, who had to undergo repeated esophageal dilatations every 6–8 weeks and for more than 4 years, was diagnosed with EPS [16]. Another example was reported by Karras [17] who described the first EPS case following a 6-week placement of a self-expanding metal stent in a patient. All the above conditions support the hypothesis that mucosal injury and regeneration underlie the etiology of EPS formation. A cellular damage-repair response, induced by prolonged chemical and mechanical mucosal irritations could contribute to an hyperregeneration process, associated with EPS development. HPV HPV is now considered to be closely related to EP and esophageal cancer and was suggested as one of the etiological factors [18, 19]. HPV is a non-enveloped double-stranded DNA virus (> 8 kb), that replicates in the nucleus of infected host cells. Until now, more than 100 HPV genotypes have been identified and the ratio of HPV positive EP ranges from 10.5 to 21.3% [10, 20]. In the reports of 53 EPS cases, 29 cases underwent HPV detection, 37.9% (11/29) detected HPV in these patients (Table 1). HPV testing methods vary from immunohistochemistry (IHC), dot blot hybridization (DB), in situ hybridization (ISH), polymerase chain reaction (PCR) to transmission electron microscopy (...truncated)