Gastric extremely well differentiated adenocarcinoma of gastric phenotype: as a gastric counterpart of adenoma malignum of the uterine cervix
© Ae Lee; licensee BioMed Central Ltd. 2005
Received: 09 March 2005
Accepted: 23 May 2005
Published: 23 May 2005
Most of gastric adenocarcinoma can be simply diagnosed by microscopic examination of biopsy specimen. Rarely the structural and cellular atypia of tumor cells is too insignificant to discriminate from benign foveolar epithelium.
A 67-year-old male presented with a gastric mass incidentally found on the abdominal computed tomography (CT) for routine medical examination. Gastric endoscopic examination revealed a huge fungating mass at the cardia and mucosal biopsy was performed. Microscopically the biopsy specimen showed proliferation of bland looking foveolar epithelia in the inflammatory background and diagnosed as foveolar epithelial hyperplasia. Because the clinical and endoscopic features of this patient were strongly suggestive of malignancy, the patient underwent radical total gastrectomy. The resected stomach revealed a huge fungating tumor at the cardia. The cut surface of the tumor was whitish gelatinous. Microscopically the tumor was sharply demarcated from surrounding mucosa and composed of very well formed glandular structures without significant cellular atypia, which invaded into the whole layer of the gastric wall. Tumor glands were occasionally complicated or dilated, and glandular lumina were filled with abundant mucin. Immunohistochemically the tumor cells revealed no overexpression of p53 protein but high Ki-67 labeling index. The tumor cells and intraluminal mucin were diffusely expressed MUC1 and MUC5AC and only focally expressed MUC2. On abdominal CT taken after 12 months demonstrated peritoneal carcinomatosis and multiple metastatic foci in the lung.
The clinicopathologic profiles of gastric extremely well differentiated adenocarcinoma of gastric phenotype include cardiac location, fungating gross type, very similar histology to foveolar epithelial hyperplasia, foveolar mucin phenotype, lack of p53 overexpressoin and high proliferative index.
Most of gastric adenocarcinoma can be simply diagnosed by microscopic examination of biopsy specimen. Extremely well differentiated adenocarcinoma (EWDA) of the stomach is histologically too bland and too similar to benign foveolar epithelium to make a diagnosis as malignancy. Till date, several cases of EWDA of the stomach were reported by Japanese authors. But the cases reported as EWDA were heterogeneous groups histologically and phenotypically. Most of reported cases revealed well differentiated adenocarcinoma mimicking complete type intestinal metaplasia with intestinal mucin phenotype [1, 2]. Only few cases corresponded to EWDA of the stomach mimicking reactive foveolar epithelia with gastric mucin phenotype . Recently I experienced a case of EWDA of the stomach which was very similar to benign foveolar epithelia histologically and phenotypically and reminiscent of gastric counterpart of adenoma malignum of the uterine cervix .
Traditionally, gastric carcinomas have been classified into two main types, the so-called intestinal and diffuse, based on the tendency toward gland-formation . Recently using immunohistochemical staining techniques specific for gastric- and intestinal type mucins, the phenotype of each tumor was histologically reclassified [5, 6]. Of these, MUC1 and MUC5AC are expressed in the superficial foveolar epithelium of gastric mucosa, and MUC2 is expressed in goblet cells of intestinal mucosa or intestinal metaplastic cells of stomach. Up to date several cases of EWDA of the stomach have been reported in literatures [1–3]. The reports described histologically and phenotypically heterogeneous groups of EWDA and their results were not inconsistent with the present case. Niimi et al, described the usefulness of p53 and Ki-67 immunohistochemical analysis for preoperative diagnosis of EWDA of the stomach. However, in the present case as well as Nokubi et al 's case which was very similar to the present case in all respects, p53 overexpression was not observed in the EWDA. These two cases were equally associated with predominant gastric phenotype, which reflect the fact that gastric type adenocarcinoma of the stomach is less likely associated with p53 mutation pathway . The immunostaining for high KI-67 was helpful to distinguish EWDA from benign foveolar epithelia in the present case.
EWDA of the stomach is a rare highly differentiated adenocarcinoma in which most of the glands are impossible to distinguish from benign foveolar glands, particularly in biopsy specimen . In the present case the resected specimen EWDA showed variable histologic features area by area. Although most of tumor glands were lined by deceptively bland, mucin-rich columnar cells with basal nuclei, more atypical areas were also detected at least focally. The more atypical areas were composed of complex or haphazard arrangement of the glands as well as increased nuclei with loss of polarity and prominent nucleoli. Because the most reliable diagnostic criteria of EWDA of the stomach like adenoma malignum of uterine cervix are deeper invasion and/or metastasis, it is difficult to make a correct diagnosis in biopsy specimen. However, multifocal and repeat biopsies and careful microscopic examination can elicit the recognition of more atypical areas suggesting malignancy. The present case was misinterpreted as benign foveolar epithelial hyperplasia for the biopsy specimen, but the radiological and endoscopic findings suggested malignancy strongly. The clinicopathologic correlation is also mandatory in cases of EWDA of the stomach. First of all, to keep in mind of the entity of EWDA is essential to reach to a correct diagnosis.
The clinicopathologic profiles of gastric extremely well differentiated adenocarcinoma of gastric phenotype include cardiac location, fungating gross type, very similar histology to foveolar epithelial hyperplasia, foveolar mucin phenotype, lack of p53 over expressoin and high proliferative index. In gastric EWDA of gastric phenotype, the unique criterion of malignancy is an evidence of deeper invasion. It is good reason for considering this tumor as gastric counterpart of adenoma malignum of the uterine cervix.
Permission of the patient was obtained for publication of his case records. This research was conducted by the research fund of Dankook University in 2003.
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