Exuberant squamous metaplasia of the gastric mucosa in a patient with gastric adenocarcinoma
Diagnostic Pathology volume 10, Article number: 46 (2015)
The presence of squamous epithelium in the stomach is only occasionally encountered and is associated with prolonged mucosal injury. Squamous metaplasia in patients with cancer is relatively rare and only four cases have been reported in the stomach, all of which have been associated with squamous cell carcinomas. We present the first case of exuberant squamous metaplasia in a patient with gastric adenocarcinoma of the cardia.
A 56-year-old woman presented with epigastric pain and weight loss. Endoscopy showed an irregular depressed hyperemic lesion covered with a whitish plaque on the cardia. A total gastrectomy was performed and the tumor in the subcardia was found to extend up to the proximal stomach with diffuse squamous metaplasia in the surface of the tumor and proximal gastric mucosa in contiguity with the esophageal squamous epithelium. It is believed that the squamous extension from the esophagus to the proximal stomach and the gastric adenocarcinoma occurred at the same time.
Synchronous squamous metaplasia and underlying adenocarcinoma in the stomach is extremely rare. Recognition of this entity would be beneficial for clinicians to avoid unnecessary treatment.
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The presence of squamous epithelium in the stomach is only occasionally encountered and is associated with prolonged mucosal injury [1,2]. However, squamous metaplasia with the coexistence of a neoplasm is relatively rare and only 4 cases have been reported in the English literature—4 cases of squamous cell carcinomas (SCC) and 1 case of SCC in situ [3-7]. However, squamous metaplasia associated with gastric adenocarcinoma has not been reported. We present the first case of exuberant squamous metaplasia in a patient with gastric adenocarcinoma of the cardia.
A 56-year-old Korean woman presenting with epigastric pain and weight loss visited a local clinic and was transferred to our hospital for further treatment. The medical history of the patient did not include any significant prior illness. No significant positive signs were found on physical examination. Endoscopy showed an irregular depressed hyperemic lesion covered with a whitish plaque on the cardia (Figure 1). The lesion was approximately 4 cm in diameter and the whitish plaque was partly contiguous with the esophageal mucosa at the gastroesophageal junction. The biopsy specimen revealed infiltrating neoplastic single cells with benign squamous epithelium (Figure 2). Laboratory results were within normal limits, and serum carcinoembryonic antigen (CEA) levels and carbohydrate antigen 19–9 (CA 19–9) levels were normal. A total gastrectomy was performed without any surgical complications.
On gross examination, an irregular depressed lesion with a whitish plaque was detected in the high body (Figure 3A). Entire tumor was sampled for histologic examinations. Histological examination revealed poorly differentiated tubular adenocarcinoma that was diffuse-type. The tumor was centered in the subcardia extending up to the proximal stomach without involvement of the gastroesophageal junction (type III by the Siewert classification)  (Figure 3B). Diffuse squamous metaplasia was present in the surface of the tumor and the proximal gastric mucosa in contiguity with the esophageal squamous epithelium (Figure 4). We performed EBER in situ hybridization and the entire tumor was negative. The tumor infiltrated into the muscularis propria although none of the 54 regional lymph nodes showed metastasis (pT2N0M0, stage IB by the 7th edition of the AJCC/TNM classification). The patient is alive without recurrence 3 month after gastrectomy.
Although the pathophysiology of squamous metaplasia in the stomach remains obscure, prolonged injury appears to be a prerequisite for this mucosal abnormality. The presence of squamous epithelium in the gastric mucosa has been described in patients with underlying diseases such as peptic ulcer , tuberculosis , syphilis , corrosive gastritis , pernicious anemia , and aberrant pancreatic tissue . These cases support the hypothesized relationship between injurious stimuli and the development of squamous metaplasia. In animal studies, gastric squamous metaplasia has been induced by the injection of pyrogallic acid  and methylcholanthere . Squamous metaplasia following chronic irritation occurs elsewhere in the body, for example in the lower respiratory tract, bladder, salivary duct, pancreatic duct, cecum, uterus, and in the mucosa of the prolapsed rectum.
The four patients with squamous metaplasia in the stomach and concurrent carcinoma who have been recorded in the literature are tabulated in Table 1 along with pertinent details given by the authors [3-6]. The stomach from all four patients contained areas of squamous metaplasia transitioning to SCC, corroborating the development of SCC from the squamous metaplasia. The patients in cases 1 to 3 had prior a history of prolonged gastritis provoked by sustained mucosal injuries. The gastric mucosa of the patient in case 1  was damaged by acid and the entirety of the stomach was lined by squamous epithelium. The patient in case 2  was diagnosed with congenital syphilis, progressed to chronic syphilitic gastritis, and had squamous metaplasia in the antrum. The stomach of the patient in case 3 showed diffuse gastritis due to prior cytotoxic chemotherapy for malignant lymphoma .
In contrast to these previously reported cases, our case was unique in that the benign squamous epithelium covering the tumor surface was in continuity with the esophageal epithelium without any transition area. Endoscopic and microscopic findings revealed diffuse mucosal atrophy with intestinal metaplasia, which is considered to be a risk factor for gastric adenocarcinoma . Based on the above observations, we hypothesize that the squamous extension from the esophagus to the proximal stomach and the adenocarcinoma occurred at the same time, which is an exceedingly rare event.
The tumor topography of the border between the esophagus and stomach affects the treatment strategy that for patients with type II tumors by the Siewert classification, with esophagectomy offering no advantages over extended gastrectomy . The biopsy specimen in our case showed infiltrating cancer cells beneath the benign squamous epithelium, which could be misinterpreted as adenocarcinoma at the esophagogastric junction or invasion into the esophagus. The endoscopic findings showed gastric extension of whitish plaque in contiguity with the esophagus. Microscopically, the proximal gastric mucosa showed diffuse squamous metaplasia with no evidence of carcinoma. Therefore, the possibility of squamous metaplasia in the stomach should be considered to avoid unnecessary treatment such as proximal esophagectomy. If the squamous metaplasia is too small to recognize, Lugol’s iodine solution would be helpful for staining the metaplastic area .
Synchronous squamous metaplasia and underlying adenocarcinoma in the stomach is extremely rare. Here, we describe the first case with unique endoscopic findings.
Written informed consent was obtained from the patient for the publication of this report and any accompanying images.
Squamous cell carcinomas
- CA 19–9:
Carbohydrate antigen 19–9
American Joint Committee on Cancer
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This study was supported by a grant from the 20 by 20 project of Samsung Medical Center (GF01140111).
The authors declare that they have no competing interests.
KEB first identified this case and participated in providing the clinical information, KMK contributed to the concept and design and approved the final version of the manuscript and SA wrote the manuscript and performed the literature review. All authors read and approved the final manuscript.
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Ahn, S., Bae, G.E. & Kim, KM. Exuberant squamous metaplasia of the gastric mucosa in a patient with gastric adenocarcinoma. Diagn Pathol 10, 46 (2015). https://doi.org/10.1186/s13000-015-0281-5