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Short Communications: Gastroenterology

Esophageal Squamous Papilloma in Children: A Single-center Case Series

Tou, Andrea M.; Al-Nimr, Amer O.

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Journal of Pediatric Gastroenterology and Nutrition: May 2021 - Volume 72 - Issue 5 - p 690-692
doi: 10.1097/MPG.0000000000003066
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Abstract

What Is Known/What Is New

What Is Known

  • Esophageal squamous papilloma is a rare condition seen primarily in adults, with limited pediatric data available to provide an estimated prevalence in children.
  • Its etiology is still unclear, with human papilloma virus proposed as a possible factor in the development of these lesions.

What Is New

  • This article provides an estimated pediatric prevalence of esophageal squamous papilloma, with data suggesting that it is possibly increasing over time.
  • Reflex testing for human papilloma virus status is likely unnecessary, as no patients were found human papilloma virus-positive.
  • Further long-term studies are needed to demonstrate esophageal squamous papilloma's benign nature and to help develop management guidelines.

Esophageal squamous papilloma (ESP) is a rare epithelial lesion occurring most commonly in the adult population but has also recently been described in children. Its prevalence has previously been reported as ranging from 0.01% to 0.45% (1–4) in adults, but there is insufficient data to provide an estimate in children. The etiology of ESP is not well understood, although chronic inflammation, direct trauma, and human papilloma virus (HPV) infection have been proposed to contribute to the development of these lesions (5,6). The aim of this study was to provide an estimated prevalence of this lesion in our pediatric population, as well as to identify any demographic, clinical, or pathologic associations—including HPV infection, which has been linked with ESP in adult literature.

An ESP lesion appears as a small sessile or pedunculated, multilobulated, and verrucous polyp with finger-like projections (Fig. 1). Biopsy reveals an uninflamed fibrovascular core, with conserved cellular orientation lined by squamous epithelium with normal differentiation and absent cytological atypia (Fig. 2). These lesions are typically found to be benign (4). Few studies describe ESP lesions in children, with a majority presented as single case reports. In this single-center case series, we present 10 patients with ESP. This will consequently be the largest reported case series of ESP in the pediatric population.

F1
FIGURE 1:
Esophageal squamous papilloma lesion from patient no. 3. Endoscopic image of an ESP lesion in the distal esophagus of a 14-year-old girl who underwent an EGD for abdominal pain and gastrointestinal reflux. The lesion appears as a small sessile, multilobulated polyp with finger-like projections. ESP = esophageal squamous papilloma.
F2
FIGURE 2:
Microscopic appearance of ESP: uninflamed fibrovascular core, with conserved cellular orientation lined by squamous epithelium with normal differentiation and absent cytological atypia. Data from (7). EGD = esophagogastroduodenoscopy; ESP = esophageal squamous papilloma.

METHODS

The study was undertaken after obtaining appropriate Institutional Review Board (IRB) and departmental approval by the Pediatric Clinical Research Review Committee on April 10, 2015. Patient data was secured in a password-protected hospital computer managed by the study team. All known ESP cases at University Hospitals Rainbow Babies & Children's Hospital in Cleveland, Ohio were identified using the Pathology Database Search Natural Language II Processor. The search was conducted on histopathology reports over a study period of 15 years, from January 1, 2000 to December 31, 2014. We included patients under the age of 18 years who had undergone an esophagogastroduodenoscopy (EGD) and had a diagnosis of ESP confirmed and reported on histopathology. All histology reports were reviewed confirming this diagnosis. Once patients with ESP were identified, a chart review was performed within the electronic medical record to obtain demographic information including age, race, and gender. We also obtained information surrounding the indication for the EGD, the location of the lesion, and the HPV status of the lesion by Fluorescence In Situ Hybridization (FISH) analysis. Lastly, we gathered the total number of pediatric EGDs performed during this 15-year study period at the institution to estimate the prevalence of ESP in our population. Due to the rarity of this lesion and small number of cases, we have presented a descriptive study.

RESULTS

The total number of EGDs performed at this institution during the 15-year study period was 12,459. It is not known how many of these patients underwent more than 1 EGD. We identified 10 unique patients who were found to have ESP on biopsy. Two of the patients had 2 lesions reported. Ages ranged from 2 to 17 years old. The most common indication for undergoing an EGD was abdominal pain, which was reported in 7 patients (70%), followed by gastrointestinal reflux, which was described in 4 patients (40%). Four patients presented with a combination of symptoms, as further detailed in Table 1. Six lesions were reported as proximal, 4 were distal, and 2 did not have a location reported. Most patients had solitary lesions, although 2 patients had 2 lesions identified. Regarding our patient demographics, 80% of patients were 13 years or older, 70% were girls, and 70% were of white race. Two of the patients had a previous EGD reported earlier with no evidence of prior papilloma.

TABLE 1 - Patient demographics and characteristics of their esophageal squamous papilloma lesion
Patient No. Age Race Gender Indication for EGD Location Number of lesions HPV status of the lesion Year of diagnosis
1 17 Unknown Female Abdominal pain Unknown 1 FISH not sent 2014
2 16 White Male Abdominal pain and weight loss Distal 2 FISH negative for HPV 2014
3 14 White Female Abdominal pain and reflux Distal 1 FISH negative for HPV 2014
4 13 White Male Abdominal pain and reflux Proximal 1 FISH negative for high- and low-risk HPV 2014
5 2 Hispanic Female Suspected GVHD Unknown 1 FISH negative for HPV 2014
6 14 White Male Abdominal pain Proximal 2 FISH negative for high- and low-risk HPV 2013
7 17 White Female Reflux Proximal 1 FISH negative for high- and low-risk HPV 2012
8 9 Black Female Reflux and EoE Proximal 1 FISH negative for HPV 2012
9 15 White Female Abdominal pain Distal 1 No viral cytopathic effect or HPV-related architecture 2010
10 14 White Female Abdominal pain Proximal 1 FISH negative for HPV, possible insufficient sample 2006
EGD = esophagogastroduodenoscopy; EoE = eosinophilic esophagitis; FISH = Fluorescence In Situ Hybridization; GVHD = graft-versus-host disease; HPV = human papilloma virus.

None of the 12 lesions obtained had evidence for HPV via FISH analysis, or viral cytopathic effect on histopathology. Three lesions had an analysis with FISH specifically differentiating for high- versus low-risk HPV but of all them were negative for both. HPV studies were unfortunately not sent for 2 of the lesions.

This discovery of 10 patients with ESP at our institution provides an estimated prevalence of 0.08% over the entire study period. Nine of the 10 patients were, however, identified within the last 5 years of the study (2009–2014). If we stratify for this time period, there were 9 patients with ESP identified among 5251 EGDs. This suggests that the prevalence of ESP in children may be closer to 0.17%.

DISCUSSION

This study represents the largest case series of ESP in the pediatric population to the best of our knowledge. Nonetheless, this is still a relatively small cohort of patients and it is difficult to say whether our clinical and demographic data represent the true predispositions of this lesion. This will require more cases to be reported nationally and around the world, which will also help answer the question of whether there is a true increase in prevalence over time, as our data may suggest. Overall, our prevalence mirrors previously reported figures in adults, although the range remains wide (1–4). We also did not include long-term follow-up or repeat endoscopies, which limits our ability to report information on recurrence, development of papillomatosis, or long-term malignant potential (8). Future directions may include searching for data on our patients’ final diagnoses, and assessing if symptoms improved after removal of the ESP. This may be beneficial to determine if these were truly incidental findings. There is also the possibility that our study underestimates the prevalence of ESPs in children at our center as there may have been variable provider decision-making regarding biopsy or polypectomy. We, however, still believe that this analysis gives a compelling estimate of ESP prevalence in children because of the large number of EGDs performed at our center, and the 15-year duration of the study.

Although definite etiology of this entity is still unclear, there are 2 theories proposed in adult literature, which have gained the most recognition but both of which are still largely debated. Firstly, is that ESP may be caused by chronic inflammation from conditions, such as gastroesophageal reflux or esophagitis (9), or direct trauma from mechanical irritation with nasogastric tubes or esophageal dilation (10). The second theory suggests that HPV can be causative or associated with the development of ESP lesions (6). Contrary to this theory, no patients were found to have HPV in our presented data, and this is consistent with the majority of other reported pediatric cases, and many adult cases as well. Even when HPV has been found in ESP lesions, these were primarily linked to low-risk genotypes. This may suggest that future reflex testing via FISH for HPV may not be beneficial nor cost effective in children.

There is no clear consensus for management currently but most cases report no recurrence of the lesion following removal. Majority of studies have found that ESP is a benign lesion, and there have been no malignancies associated with ESP found in the pediatric population to date to the best of our knowledge. Surveillance is, thus largely considered unnecessary. There are, however, reports in adult literature that suggest ESP can progress to squamous carcinoma (2). Further studies are required to clarify any association (11,12). At present, endoscopic removal of the lesion is the safest treatment modality if found, even though the probability for malignancy for isolated ESP without diffuse papillomatosis is low.

Conclusion

Our study described 10 unique pediatric patients with ESP, which is a rare esophageal lesion and when found, is more commonly seen in adults. Most notably, we found that none of our specimens tested positive for HPV, and that there may be an increasing prevalence of ESP in the pediatric population. There is a continued need for further pediatric data to help establish clearer demographic and clinical associations of this lesion, and also to determine if there is any associated malignant potential.

REFERENCES

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    Keywords:

    endoscopy; esophagogastroduodenoscopy; esophagus; human papilloma virus

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