EoE is an antigen-driven allergic condition with both genetic and environmental contributions [15–16]. Although EoE occurs in most racial and ethnic groups, there is a predominance in non-Hispanic whites . EoE is more common in patients from rural regions and cold climate zones; it is inversely associated with Helicobacter pylori infection both in adult and pediatric studies . In our study we attempted to control for inherent differences in patient population and geographical region by collating data from multiple tertiary care centers located in different regions of the country.
Recent studies have reported the concurrence of eGCT and significant esophageal intraepithelial eosinophilia, most frequently in the pediatric population [9, 11–12]. In our multicenter retrospective study of eGCT from 294,855 EGD procedures, 40% of cases had gastroesophageal reflux disease or Barrett esophagus, but only one case in our series of 45 adults had concomitant EoE and eGCT (2%). The apparent rate of concomitant EoE and eGCT in our adult cohort is considerably less than that observed in prior studies, both of which included pediatric patients. Riffle et al. reported an overall rate of 33% from > 30,000 esophageal cases. They identified 18 patients with eGCT, 6 of whom had both EoE and eGCT. Four of these patients were adults and two were adolescents . Nojkov et al, reported an overall rate of 31% from 167,434 EGD procedures, including 5 of 16 cases of eGCT that were associated with EoE. Four of these were identified in adults, while 1 was diagnosed in an adolescent . Interesting, although the absence of pediatric patients in our multi-institutional cohort likely affected our observed rate of concomitant EoE and eGCT, this does not completely account for the differences between our study and those of prior retrospective studies. A larger multicenter prospective study may be warranted to further investigate the reported association and to determine the underlying pathophysiology of EoE and eGCT.
In addition to the single case of EoE in our eGCT group, there were two other cases with significant intraepithelial eosinophilic infiltrates. One was a resection specimen from squamous cell carcinoma status post neoadjuvant therapy with complete response. The other was in biopsies from the distal esophagus, suggesting a closer relationship to severe reflux esophagitis. Reflux disease or heart burn was the presenting symptom in 28% of our patients. The eGCTs found in these patients were in the distal segment of the esophagus (66%), ranging in size from 0.3 to 2.0 cm, in greatest dimension. These findings raise the possibility that the eGCT, by potentially impairing function of the gastroesophageal junction, may have contributed to the onset or severity of reflux esophagitis in these patients. In addition, a case report of an esophageal leiomyoma that apparently caused reflux esophagitis in a patient emphasizes this point . It is tempting, with these observations in mind, to suggest the inclusion of mass lesions including eGCT in the different diagnosis of new onset reflux esophagitis.
There are reports of concomitant presentation of eGCT and other neoplasms, both benign and malignant, including leiomyoma, squamous cell carcinoma and intramucosal adenocarcinoma in the setting of Barrett esophagus [18–20]. The latter illuminates one of the more interesting and novel findings of our study: the presence of eGCT in patients with an established diagnosis of Barrett esophagus or histologic evidence of goblet cell metaplasia having eGCT. It is also of interest that these cases of eGCT with background goblet cell metaplasia showed more atypical features, along with significantly increased intratumoral eosinophils.
Neither Nojkov et al., nor Riffle et al. identified eGCT patients with Barrett esophagus/goblet cell metaplasia. Nonetheless, the latter report included observations similar to those in our study, including a high number of eGCTs (67%) with increased intratumoral eosinophilia and a disproportionately high number of eosinophils in eGCT with atypical features . In our study, 76% of eGCT cases had increased intralesional eosinophils and 47% of the cases had eosinophils in the lamina propria of the overlying esophageal mucosa. Given the reproducibility of these findings, we postulate that eosinophilia within the eGCT and adjacent stroma may be driving the observed the atypical/reactive histologic features.
Although eGCT is commonly considered a benign entity; there are rare cases that presented with lung and liver metastases [21–23]. There is a single report of eGCT secreting a serum tumor marker (carbohydrate antigen 19 − 9) . Notably, we had no cases of metastatic eGCT in our patient cohort.
Although our study of eGCT is the largest to date, drawing on patient populations from three tertiary care medical centers located in different geographic regions of the country, our retrospective study nonetheless has limitations. Most significantly, our patient cohort consists of only adults and no pediatric patients. We had two eGCT that were diagnosed incidentally by histology. The standard esophageal biopsies encountered in daily practice are limited, containing only the esophageal epithelium that is immediately superficial to the lesion. With the lack of submucosa in these biopsy specimens, our sample set likely underestimates the prevalence of eGCT in these populations. Also of note, 9 patients in our cohort were diagnosed within the 2001–2007 year period, before the consensus guidelines for EoE was established [6–7]. If EoE was widely recognized as a disease entity earlier, more diagnostic and follow up material would have been available for histologic evaluation and we may have diagnosed additional cases of eGCT.