Esophageal Paget’s Disease Secondary to Hypopharyngeal Carcinoma: a Case Report
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Paget’s disease is defined as neoplastic cells of glandular differentiation infiltrating squamous epithelium . In essence, it represents a population of malignant mucin-producing cells which sit in amongst benign squamous cells within skin or mucosa. These cells can arise secondary to a primary carcinoma, which may have so called ‘Pagetoid spread’ of malignant cells at the periphery of the lesion, or more rarely, Paget’s cells can arise de novo within the squamous epithelium, the pathogenesis of which is not yet understood. Having been first described in the breast by Sir James Paget in 1874, extramammary Paget’s disease is an entity most commonly seen in the vulva and anus but it is known to occur rarely in the esophagus, almost exclusively in the context of invasive esophageal adenocarcinoma. Paget’s cells within esophageal squamous epithelium are found in 4.9% of invasive adenocarcinoma cases and are most commonly associated with diffuse, poorly differentiated adenocarcinoma with dyscohesive malignant cells [2, 3, 4, 5]. Few case reports are present in the literature to describe Paget’s cells within the esophagus but those that exist include cases involving mucous gland carcinoma, adenosquamous carcinoma and adenocarcinoma arising on a background of Barrett’s esophagus [2, 3, 4, 5].
We present a case in which widespread esophageal Paget’s disease arises secondary to poorly differentiated carcinoma of the hypopharynx. A literature search did not yield any similar cases.
Upper gastrointestinal endoscopy and esophageal biopsies were carried out following the excision of the primary lesion and the Paget’s disease was found to extend into the esophagus, prompting regular follow-up endoscopies and biopsies.
We feel that this is a rare case of Paget’s disease extending from a primary lesion site within the hypopharynx into the distal part of the esophagus.
Paget’s disease is a recognized, although rare, entity in the esophagus, almost exclusively seen in the presence of co-existing esophageal adenocarcinoma. A study of esophageal adenocarcinoma cases carried out in 2007 by Abraham et al. found that Paget’s disease is present in 4.9% of such cases . Amongst the eight patients in the study identified as having esophageal Paget’s disease, seven were male and one was female, with a mean age of 62.4 years, demographics which mirror those of esophageal adenocarcinoma. The study found that five of these eight cases had not previously been reported as showing Paget’s cells, which was only noted on subsequent review as part of the study. This might suggest that Paget’s cells can be overlooked during the initial assessment of esophageal adenocarcinoma specimens. The same study also found that the most useful special stain for highlighting the intracellular mucin associated with Paget’s disease was PAS-diastase . The glandular differentiation of Paget’s cells can be revealed by positive immunohistochemical staining for glandular cytokeratins (CK7), EMA and CEA. Notably, EMA (also called MUC1) is universally expressed by nearly all cases of extramammary Paget’s disease and it is comparable with CK7 as a universal cytokeratin marker for Paget’s cells .
Our case of esophageal Paget’s disease arises in the absence of a primary esophageal lesion, but secondary to a poorly differentiated hypopharyngeal tumour, with the pagetoid spread of malignant cells extending the entire length of the esophagus. A literature search did not find any other similar cases, although there are two cases reported of primary Paget’s disease of the esophagus, in which the Paget’s cells were thought to have arisen de novo within the squamous epithelium [2, 3]. These cases, similarly to ours, arose in the absence of a primary esophageal lesion, although there was no mention of a primary pharyngeal tumor in these reports.
An important, although extremely rare, differential in cases of Paget’s disease of the esophagus is melanoma. The dyscohesive, large, atypical cells distributed throughout the squamous epithelium is typical of pagetoid spread by malignant melanoma which accounts for 0.1–0.2% of primary esophageal malignancies . For this reason, melanocytic markers are an important component of the assessment of these cases.
In light of this case, it may be prudent to perform regular upper gastrointestinal endoscopy and esophageal biopsies in patients who are found to have Paget’s disease of the epithelium adjacent to a primary pharyngeal lesion.
The authors would like to thank Professor Neil Shepherd, Gloucestershire Hospitals NHS Foundation Trust, for his expert opinion. Mrs. Janine Zylstra, Research Coordinator at St Thomas’ Hospital has helped in obtaining a written consent from the patient.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
Informed consent was obtained from the patient for this case report.
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