What is the histologic differential diagnosis for Barrett's carcinoma?
H.D. Appelman (Ann Arbor)
The carcinomas that arise in Barrett's mucosa are adenocarcinomas, but they have the entire range of differentiation, from very well differentiated which produces outstanding tubular or glandular structures to miserable differentiated which produces no tubules, but grows as solid masses of various types or as single undifferentiated cells diffusely infiltrating the esophageal wall. However, as long as the carcinoma, no matter its degree of differentiation 1) arises within the esophagus, 2) has a patch of Barrett's mucosa at its margin which, in turn, 3) contains a dysplastic focus, then the diagnosis of Barrett's carcinoma is assured, and for all practical purposes there is no differential diagnosis. When the three conditions listed above are not met, then other carcinomas become part of a differential diagnosis, such as:
1. carcinoma arising from the gastric cardia (cardiac carcinoma) which are histologically indistinguishable from Barrett's carcinomas, probably because they arise from the same type of precursors [1,2];
2. adenosquamous carcinoma arising from squamous cell in situ neoplasia in the esophagus ;
3. endocrine/neuroendocrine or oat cell carcinoma primary in the esophagus ;
4. poorly differentiated squamous cell carcinomas, especially the basaloid squamous variant which grows in cords that may superficially resemble poorly formed tubules of an adenocarcinoma ; and
5. metastatic neoplasms, especially carcinomas from breast, lung and melanomas, which can mimic carcinomas histologically.
Much of the morphology of these tumors are discussed and illustrated in the papers from the O.E.S.O. pathology symposium. Therefore, this discussion will be brief.
Cardiac cancer are separated from Barrett's cancer by site of origin. The bulk of the tumor is situated below the cardioesophageal junction, although cardiac carcinomas often extend into the lower esophagus. There is no Barrett's mucosa at its proximal margin. About 10% of all adenocarcinomas arising in the region of the junction obliterate the junction and do not have Barrett's mucosa above them or dysplasia in cardia below them. These we refer to as "junctional" carcinomas, thereby admitting our ignorance of their site of origin.
Squamous-derived adenosquamous carcinomas may look like comparable carcinomas arising in Barrett's mucosa, so the only way to tell them apart is to find the in situ component, whether dysplastic Barrett's mucosa or in situ high grade squamous intraepithelial neoplasia or dysplasia.
Endocrine malignancies, including oat cell carcinomas, are distinguished by their characteristic cellular constituents and/or by their endocrine markers, such as chromogranin, neuron-specific enolase or synaptophysin, all of which are demonstrated by immunohistochemical technics.
The poorly differentiated squamous variants probably pose the biggest differential diagnostic headache, because they can look very much like equally poorly differentiated adenocarcinomas. Experienced gastrointestinal pathologists probably can tell them apart. For less experienced pathologists, finding the in situ component, the dysplastic Barrett's or the dysplastic squamous, is the best determinant.
Finally, metastatic tumors produce different gross lesions than do primary carcinomas. They tend to be intramural and spread in an expansile fashion, so that there may be only a small mucosal lesion, such as ulcer, while there is a large expansile mass below this.
1. Appelman HD, Kalish RJ, Clancy PE, Orringer MB. Distinguishing features of adenocarcinoma in Barrett's esophagus and in the gastric cardia. In: Spechler SJ, Goyal RK (eds) Barrett's Esophagus: Pathophysiology, Diagnosis and Management. New York: Elsevier, 1985:167-187.
2. Kalish RJ, Clancy PE, Orringer MB, Appelman HD. Clinical, epidemiologic, and morphologic comparison hetween adenocarcinomas arising in Barrett's esophageal mucosa and in the gastric cardia. Gastroenterology 1984;86:461-467.