Esophageal verrucous carcinoma arising from hyperkeratotic plaques associated with human papilloma virus type 51

Abstract

Esophageal verrucous carcinoma is a rare variant of esophageal squamous cell carcinoma. We report a case of esophageal verrucous carcinoma associated with human papilloma virus (HPV) type 51. The patient had long-standing dysphagia and odynophagia, and white esophageal plaques showing hyperkeratosis on biopsy. At repeat endoscopy, the esophagus was covered with verrucous white plaques and areas of nodular mucosa with white fronds, with a distal 10-cm smooth mass protruding into the lumen. Biopsies demonstrated an atypical squamoproliferative lesion but no frank malignancy. HPV type 51 DNA was detected in endoscopic biopsy specimens by polymerase chain reaction. Because the size of the lesion favored an underlying verrucous carcinoma, our patient underwent minimally invasive esophagectomy with gastric pull-up and cervical anastomosis. The pathologic diagnosis was a well-differentiated esophageal verrucous carcinoma. One year after esophagectomy, the patient feels well and is free of disease. Although HPV DNA was not detected in the cancer tissue obtained at surgery, our case suggests an association between HPV type 51 and esophageal verrucous carcinoma. The clinical evolution in this case highlights the importance of endoscopic surveillance in patients with exuberant esophageal hyperkeratosis, and of definitive surgical resection when malignancy is suspected even if frank malignancy is not demonstrated on superficial biopsies.

Semiquantitative histologic evaluation improves diagnosis of esophageal carcinoma cuniculatum on biopsy

“…9 Intraepithelial neutrophilic infiltration and intraepithelial neutrophilic microabscess are consistent findings in our current study, in both the resected and endoscopic mucosal biopsies with carcinoma cuniculatum. The presence of neutrophilic inflammation and Candida organisms in endoscopic mucosal biopsies taken from an obvious esophageal mass should prompt a search for evidence of a well-differentiated squamous cell carcinoma such as carcinoma cuniculatum or verrucous carcinoma, as supported by our current series and the report by Tonna et al 8 The neutrophilic inflammation in the esophageal carcinoma cuniculatum may be due to superimposed Candida infection, bacterial overgrowth, local irritation/trauma secondary to obstruction, or an inflammatory response associated with the neoplastic process per se as it is also present in cases of carcinoma cuniculatum without Candida infection or bacterial overgrowth. While the exact mechanism of this intraepithelial neutrophilic infiltration remains unclear, a few previous studies appear to support that overexpression of transforming growth factor-b1 (TGFb1) in squamous cell neoplasm/ carcinoma may lead to neutrophilic inflammation via an interleukin 17 (IL-17)-dependent signaling pathway.…”

“…Our results are in line with a previous study, which showed that nonpapillary squamous high-grade dysplasia was only present in the deep portion of the tumor but not the superficial endoscopic mucosal biopsy from verrucous carcinoma of the esophagus, a closely related variant of well-differentiated squamous cell carcinoma. 8 Conventional diagnostic criteria of Esophageal carcinoma cuniculatum esophageal squamous cell carcinoma used by pathologists for endoscopic mucosal biopsy are heavily based on the presence of deep keratinization and atypia, particularly marked nuclear atypia, which may explain the low sensitivity of 9% observed in our study prior to our semiquantitative histologic assessment. In this study, the original endoscopic biopsies were diagnosed as esophagitis or non-specific inflammation on 17 occasions including eight diagnoses of fungal esophagitis or changes suggestive of fungal esophagitis.…”

“…It may be impossible to differentiate these entities on endoscopic mucosal biopsies as both entities pose enormous diagnostic difficulties as shown in our current studies as well as in the previous reports. 8,13 As esophageal squamous mucosa can undergo marked reactive changes, we caution that a diagnosis of carcinoma cuniculatum should not be solely based on the histologic assessment, even with the semiquantitative approach described here. Rather, the diagnosis should only be made with a strict clinicopathologic correlation.…”

“…Each feature, if present, was given 1 point, and the final histologic score was calculated for each biopsy by summing up the points. The mean scores for carcinoma cuniculatum in the resected specimens, endoscopic mucosal biopsies, and control esophageal biopsies were 8 The biopsies with a score of 6 were erosive esophagitis (from a patient with end-stage renal disease), active esophagitis (from patients with stricture at the esophagogastric junction (n ¼ 1) or of the entire esophagus (n ¼ 1)), and Candida esophagitis from a patient with radiation-induced stricture of the cervical esophagus for the treatment of laryngeal squamous cell carcinoma. Follow-up endoscopic mucosal biopsy showed improved histologic score to 0 in the patient who had erosive esophagitis (from 6 to 0) and in the patient with active esophagitis with stricture at the EGJ (from 6 to 3).…”

Papilomavírus humano e sua associação com o carcinoma colorretal

“…Nos últimos anos, entretanto, artigos da literatura especializada vêm mostrando a presença do DNA do HPV em amostras de tecido de carcinomas do esôfa-go 13 , estômago 14,15 , pulmão 14 , mama 16 e colorretal [17][18][19] . O HPV foi detectado em até 37,5% dos adenocarcinomas gástricos 15 , e em 27,8% dos CEC esofágicos 20 , havendo diferença em áreas de alta e de baixa prevalência para esse tumor maligno (65 e 6%, respectivamente) 21 .…”