Supplementary Material for: Adenosquamous carcinoma in Barrett’s esophagus – a rare entity

A 34-year-old man, with a personal history of non-dysplastic Barrett’s Esophagus C14M14 (on annual endoscopic surveillance for 7 years) and past smoking (10 cigarettes/day between the ages of 18 and 30), underwent a surveillance esophagogastroduodenoscopy. The squamocolumnar junction was located at 21cm from the incisors. On white light endoscopy, a 20mm Paris 0-IIa+IIb lesion located at 25cm from the incisors was identified, presenting irregular vascular and glandular patterns on virtual chromoendoscopy (shown in Fig. 1), and loss of aceto-whitening. As the biopsy showed extensive low- and high-grade dysplasia and focal desmoplastic reaction in relation to invasive carcinoma, the lesion was resected en bloc by endoscopic submucosal dissection. The dissection was performed using an insulated-tip knife (ITknife Nano®) and the clip-and-thread traction method (shown in Fig. 2). The final scar occupied 75% of the esophageal circumference. Full specimen’ pathology revealed adenosquamous carcinoma with a predominant glandular component and a smaller epidermoid component (approximately 20% of the tumoral area) (shown in Fig. 3). The lesion measured 17.5mm in total, and 7mm the invasive component. The carcinoma invaded the muscularis mucosae, there was no evidence of lymphovascular and perineural invasion and the resection margins were free (R0; vertical margin distancing less than 1mm from the lesion, horizontal margin distancing at least 2mm from the lesion). Immunohistochemical analysis showed positivity for AE1/AE3, CK5/6 and p40 (shown in Fig. 4 – left panel) on the epidermoid component, and positivity for CEA (shown in Fig. 4 – right panel) on the glandular component. A staging contrast-enhanced computed tomography did not show regional or distant spread. This lesion’s resection met curative criteria except for the histological subtype. The case was discussed on multidisciplinary team meeting together with the patient, and given the more aggressive behavior of this entity, patient’s age and Barrett’s esophagus length, the patient underwent esophagectomy with lymphadenectomy, uneventfully, without residual disease on the surgical specimen.
Adenosquamous carcinoma of the esophagus is rare, comprising <1% of all esophageal neoplasias [1,2], with only six cases described in the background of Barrett’s mucosa. Adenosquamous carcinoma has an incidence peak in the 7th decade of life, and more commonly affects men (ratios of 4:1 to 8:1) [3]. Misdiagnosis rates on preoperative biopsies are high, ranging between 61% and 100% [3]. It seems to behave aggressively, with worse overall survival than adenocarcinoma [2,4], but due to its rarity, prognosis is not precisely defined and there are no guidelines regarding its management.
This case supports an aggressive behaviour of esophageal adenosquamous carcinoma, as the the patient had an upper endoscopy performed the previous year by an expert endoscopist complying to quality standards, without any visible lesion and no dysplasia on random biopsies per Seattle protocol, and developed an invasive carcinoma within one year. Multidisciplinary team discussion is important in situations like this, as endoscopic resection would be considered curative treatment in an otherwise unremarkable squamous cell carcinoma or adenocarcinoma. Large series of superficial esophageal adenosquamous carcinoma are needed to better define prognosis in the early stages of this entity.