Diagnosis and management of a rare case of esophageal epidermoid metaplasia: A case report

Abstract

BACKGROUND

Esophageal epidermoid metaplasia (EEM) is a rare potentially premalignant oesophageal lesion characterized by a dense granular layer with overlying hyperorthokeratosis resembling the epidermis of skin. Given the low prevalence, data to guide management also remains sparse.

CASE SUMMARY

We highlight a case of a 60-year-old male who presented with gastroesophageal reflux disease symptoms 2 years after an index gastroscopy which showed C0M1 Barrett’s oesophagus. The repeat gastroscopy detected a 15 mm oesophageal epidermoid metaplasia on a background of stable Barrett’s esophagus. This was rather peculiar as the images form his index gastroscopy 2 years prior did not reveal any suspicious oesophageal mucosal abnormality. He underwent a successful endoscopic mucosal resection within 3 months with a surveillance gastroscopy scheduled 6 months later. The cases of confirmed EEM are very low. One study demonstrated out of 1048 consecutive oesophageal biopsies and resections for any indication, only two were EEM (0.19%). It was also noted that the prevalence of epidermoid metaplasia was significantly higher (P < 0.05) in the 58 patients with oesophageal squamous neoplasms, two of whom (3.5%) had concurrent epidermoid metaplasia.

CONCLUSION

This association necessitates careful consideration when determining resection vs surveillance-based management of EEM.

Key Words: Esophageal epidermoid metaplasia; Barrett's esophagus; Endoscopic mucosal resection; Gastroesophageal reflux disease; Gastroscopy; Surveillance; Premalignant; Case report

Core Tip: Is there any role as premalignant: A precursor to esophageal squamous cell carcinoma and dysplasia? Esophageal epidermoid metaplasia (EEM) is a rare but potentially premalignant oesophageal lesion. There remains a paucity of data on the formal management of EEM, likely due to the heterogeneity in the presentation, characterisation and detection of EEM. The decision for endoscopic resection vs conservative management is highly individualised. We highlight this case with the aim to increase awareness and detection rate.

INTRODUCTION

Esophageal epidermoid metaplasia (EEM) is a rare but potentially premalignant oesophageal lesion which has got a distinct dense granular layer with overlying hyperorthokeratosis that resembles the epidermis of skin[1,2]. Given the low prevalence[1], data to guide management also remains sparse. Characterisation of EEM and their relationship to squamous dysplasia and squamous cell carcinoma (SCC) is thus important to determine management. We highlight this case with the aim to increase awareness which will impact endoscopic detection rate and further management.

CASE PRESENTATION

Chief complaints

A 60-year-old male presented with ongoing symptoms of gastroesophageal reflux disease (GORD) which includes heartburn, left upper quadrant pain, post prandial bloating and belching.

History of present illness

The patient had been diagnosed with C0M1 Barrett’s Oesophagus, on his previous gastroscopy 2 years earlier.

History of past illness

The patient had unremarkable personal and familial health history. His alcohol intake is minimal and he is a non-smoker.

Personal and family history

No family history of the disease.

Physical examination

Physical examination was unremarkable without any red flags.

Laboratory examinations

No abnormalities on routine blood test.

Imaging examinations

Endoscopic imaging was performed by repeat gastroscopy, which revealed a white patch about 10-15 mm in size adjacent to the stable Barrett's segment in the lower oesophagus at 39 cm (Figures 1 and 2). Biopsy revealed oesophageal squamous mucosa with a papillary architecture, small amount of subepithelial stroma with the epithelium showing a granular layer and overlying hyperkeratosis in keeping with epidermoid metaplasia (Figures 2, 3 and 4).

Figure 1 Endoscopic images of the white patch. A: Endoscopic image; B: Near focus endoscopic image.

Figure 2 High-power view of biopsy fragments of oesophageal squamous epithelium with hyperkeratosis and granular layer (dark purple layer and cells with cytoplasmic granules) in keeping with epidermoid metaplasia.

Figure 3 Section of endoscopic mucosal resection with squamous mucosa, splayed muscularis mucosa and superficial submucosa. The epithelium shows epidermoid metaplasia (between arrows).

Figure 4 Closer view of endoscopic mucosal resection specimen with transition between normal and metaplastic epithelium.

FINAL DIAGNOSIS

Endoscopically and histologically, the diagnosis was EEM.

TREATMENT

Despite biopsy specimen showing no dysplasia, he underwent a successful endoscopic mucosal resection (EMR) within 3 months with a surveillance gastroscopy scheduled 6 months later (Video).

OUTCOME AND FOLLOW-UP

Decision was made based on the size of the lesion, potential for premalignancy as well as patient preference.

DISCUSSION

EEM (or esophageal leukoplakia) appears to share some similarities with a more common condition known as oral leukoplakia which is an oral, potentially premalignant condition associated with tobacco use, alcohol intake and human papillomavirus infection. The cases of confirmed EEM are very low. One study demonstrated out of 1048 consecutive oesophageal biopsies and resections for any indication, only two were EEM (0.19%). It was also noted that significantly higher prevalence (P < 0.05) of epidermoid metaplasia was noted in the 58 patients with oesophageal squamous neoplasms, of which two (3.5%) had concurrent epidermoid metaplasia[1]. EEM is a preneoplastic condition associated with squamous dysplasia and esophageal SCC (ESCC). One study highlighted squamous neoplasia occurring before, concordant with or after EEM[2]. Genetic alterations in oesophageal epidermoid metaplasia specimens that predispose them to oesophageal SCC have been reported. Targeted next-generation sequencing revealed EEM specimens harboured alterations in genes often associated with ESCC and the most common genes implicated are TP53, PIK3CA, EGFR, MYCN, HRAS, and the TERT promoter. TP53 mutation in EEM specimens sow correlation with concurrent or progression to high-grade squamous dysplasia/ESCC which may serve as an early detection biomarker to guide management[3]. Other associated conditions include Lichen Planus, Barrett’s oesophagus, GORD, tobacco and alcohol use[2]. Singhi et al[3] demonstrated that in 18 patients with biopsy proven EEM, tobacco smoking or long history of second-hand smoke was prevalent in 11 (61%) patients and alcohol intake in 7 (39%). The most likely mechanism being chronic irritation and defective healing of tissues which is a well-known effect of alcohol and tobacco. There is also an association with oesophageal dysmotility, distal constriction, and stasis[4]. Another study demonstrated that the majority of patients do not have predilection for alcohol abuse and are non-smokers[5]. These characteristics were clearly seen in our patient who is a non-smoker without significant alcohol intake but had a long-term history of GORD with Barrett’s oesophagus. EEM appears sharply demarcated on endoscopy and is defined histologically by epithelial hyperplasia, a distinct granular cell layer, and superficial hyperorthokeratosis. Orthokeratosis is a subtype of hyperkeratosis referring to the thickening of the stratum corneum of the esophageal squamous epithelium cells and when paired with hypergranulosis leads to the ‘epidermisation’ of the esophageal mucosa. Although histological features of hyperorthokeratosis and hypergranulosis are both unique and distinct, these findings may be mistaken for injury-related tissue changes, such as those due to chemical or physical agents. The differential diagnosis would include corrosive damage, pill-induced esophagitis, and sloughing esophagitis[5,6]. It is also important to consider pseudoepitheliomatous hyperplasia, which is a benign self-limiting condition related to chronic inflammation, infection and/or neoplasia. Given the pre neoplastic potential, endoscopic resection and close follow may be warranted[7,8]. Larger lesions with dysplasia may benefit from endoscopic resection and or ablation such as with radiofrequency ablation[3]. Lesions that are not easily resectable or diffusely panoesophageal and do not harbor dysplasia, surveillance with repeat gastroscopy with 4-quadrant biopsies every 1-2 cm in 6 months and then yearly if no dysplasia or disease progression is suggested[6]. In our patient who had a 15-20 mm EEM with a background history of Barrett’s, EMR was performed as per patient preference after careful discussion on the risks of the procedure vs the risks of premalignant and malignant progression, with a plan for short term surveillance.

CONCLUSION

In summary, EEM is a precursor to ESCC and the need for vigilant recognition is important to ensure early detection. Management should address the underlying risk factors and focus on individualised endoscopic surveillance on the area of leukoplakia as well the surrounding background mucosa given the close correlation between precursor lesions such as EEM and, oesophageal dysplasia and carcinoma.