Experience with endoscopic resection of oesophageal verrucous carcinoma and literature review

Abstract

A 65-year-old male patient with chronic dysphagia was found to have a 2 cm mass at gastro-oesophageal junction on endoscopy. Biopsy showed squamous hyperplasia without malignancy. Controlled radial expansion balloon dilatation and partial resection were performed but the symptoms recurred. He finally underwent endoscopic mucosa resection and histology showed well-differentiated verruciform squamous proliferation limited to the mucosa. Small amounts of tumour remnants were treated during subsequent follow-up endoscopies and the patient has been tumour free since then. Diagnosis of oesophageal verrucous carcinoma can be challenging and could be managed with endoscopic resection. In this report, we review the literature and present our experience with a patient with oesophageal verrucous carcinoma.

Background

Verrucous carcinoma of the oesophagus is a rare type of cancer of squamous cell origin. It has a verrucous or frond-like endoscopic appearance and characteristic histopathological findings of well-differentiated squamous proliferation, variable parakeratosis and hyperkeratosis, and pushing borders with short epithelial projections. The diagnosis can be challenging due to the bland proliferative nature of the disease, and limited small tissue samples obtained by standard forceps biopsies. This can be frequently mistaken for chronic oesophagitis or peptic stricture. Previously, the prognosis was poor and aggressive surgical intervention was recommended, largely due to more extensive local expansion at diagnosis.¹ More recently, particularly with earlier diagnoses, there have been increased reports of less invasive and more effective surgical and endoscopic therapies. Both endoscopic and surgical resections are described in the literature; however, consensus statements are lacking. We describe a case of successful endoscopic resection in a 65-year-old man who presented with dysphagia and was found to have verrucous carcinoma of the oesophagus.

Case presentation

A 65-year-old man was referred to the gastroenterology clinic for a 5-year history of solid food dysphagia without weight loss. Oesophagogastroduodenoscopy (EGD) identified a 2 cm firm, exophytic tumour near the gastro-oesophageal junction. Biopsies showed active inflammation with squamous hyperplasia without evidence of malignancy. CT scan of the abdomen showed no evidence of nodal or distant metastases. Endoscopic ultrasound showed no evidence of submucosal invasion or nodal or distant metastases. Repeat EGD was performed, with identification of this persistent frond-like exophytic tumour (figure 1) and repeat biopsies continued to show active inflammation with reactive squamous hyperplasia. Dilation with a controlled radial expansion (CRE) balloon, and with Savary bougies, and endoscopic mucosal resection (EMR) of a portion of the growth were performed. The pathology specimen showed squamous epithelium with papillary and basal layer hyperplasia, similar to the prior biopsies. Given the recurrent and extensive nature of proliferation, a suspicion for verrucous carcinoma was raised. Subsequently, the tumour was removed via EMR (figure 2). Histology confirmed well-differentiated verruciform squamous proliferation limited to the mucosa with negative peripheral and deep margins (figure 3). Three repeat EGDs done at 3, 6 and 7 months after the initial EMR, showed a small amount of tumour regrowth treated with hot snare polypectomy with argon plasma coagulation, EMR and hot biopsy forceps, respectively.

Figure 1.

Frond-like exophytic tumour.

Figure 2.

Endoscopic mucosal resection of the tumour.

Figure 3.

Well-differentiated verruciform squamous proliferation.

Outcome and follow-up

The fourth EGD that was done 6 months after the last EMR showed no evidence of recurrent/residual tumour (figure 4). The patient is continuing annual surveillance endoscopic exams and the latest EGD did not show any residual lesion.

Figure 4.

Absence of any residual tumour.

Discussion

Oesophageal verrucous carcinoma was first reported in 1967, and about 50 cases have been reported in the literature so far.^{2 3} It is more common in males than females with a ratio of 2:1. It usually presents in the age group of 35–80 years with a mean age of 61 years.^{4 5} Aetiology is not yet clearly defined but chronic inflammatory conditions such as gastro esophageal reflux disease (GERD), cigarette smoking, alcohol, achalasia, oesophageal diverticular disease or caustic injury from ingestions appear to be risk factors.^{1 6} Some cases have also been seen with HPV; however, a clear association is lacking.^7–9 Our patient had male gender and occasional alcohol consumption as risk factors.

Oesophageal verrucous carcinoma usually presents with dysphagia and weight loss, secondary to oesophageal luminal stricture. Other symptoms including haematemesis, coughing and odynophagia may also be seen. Endoscopy classically shows an exophytic, whitish, frond-like mass usually in the lower oesophagus but may involve the upper oesophagus.¹⁰ Superficial biopsies show non-specific acute or chronic inflammation with hyperkeratosis or parakeratosis and are not diagnostic. Previous reports have shown a sensitivity of only 46% for diagnosing verrucous carcinoma on superficial biopsies.⁶ This makes diagnosis challenging requiring repeat procedures with multiple biopsies using large capacity forceps or even complete resection for histopathology.^11–14 In our patient as well, we were able to confirm diagnosis only after EMR was performed and deeper tissue examination was possible by an expert pathologist. Workup should include Endoscopic Ultrasound (EUS) and CT to evaluate for nodal or distant metastasis, both of which are very rare but would alter management. EUS may lead to overstaging of T-stage because of the intense inflammation that can be present around the tumour and should be carefully interpreted. A German review of 15 cases showed that T-staging was overestimated in 2/4 patients who underwent surgical resection.¹⁵ No patients were ultimately found to have lymph node metastasis, including two patients where this was suggested preoperatively.

Distal metastasis has not been reported in the literature although local invasion into bronchi, pleura and pericardium have been reported, and in these cases surgical resection remains the treatment of choice.^{2 6} In most patients however, verrucous carcinomas show more extensive superficial growth rather than deeper penetration or metastasis. With this pattern of local proliferation and limited tendency for invasion and metastases, EMR and endoscopic submucosal dissection (ESD) have been performed with success when the disease is recognised early.³ Tajiri et al reported complete resolution of an 8 mm polypoid verrucous carcinoma, after a single session of endoscopic polypectomy without recurrence on 3 monthly follow-up endoscopies for 3 years.¹⁶ In 2016, Abe et al described ESD as a treatment for verrucous carcinoma for the first time in a 68-year-old man.³ In a case series of 15 patients by Behrens et al, nine patients were treated with local endoscopic therapy, of which four were treated with an intention to cure.¹⁵ Negative surgical margins were not reported in any of these nine patients and further follow-up was largely determined by the endoscopic appearance of the tumour, requiring up to 48 sessions of endoscopic resections in one of the patients. Long-term remission >3 months was only achieved in one of them. This is in contrast to our case, where curative endoscopic treatment was accomplished in four sessions utilising endoscopic resection and ablative techniques. This highlights the importance of achieving negative margins with resection to maintain long-term remission. As endoscopic therapies continue to improve and earlier diagnoses are obtained, these are likely to be viable, and less invasive treatment modalities for this disease, as seen in our case.

Learning points.

• Oesophageal verrucous carcinoma is a rare subtype of oesophageal malignancy with limited tendency for metastases.

• Diagnosis requires more extensive tissue acquisition than standard forceps biopsies and thoughtful recognition by the endoscopist and an expert pathologist.

• Oesophageal verrucous carcinoma can be successfully treated endoscopically in appropriate cases.

• Long-term annual endoscopic surveillance remains reasonable to monitor for recurrence.