Synchronous Triple Primary Gastrointestinal Tract Malignancies: A Case Report

Article information

Korean J Helicobacter Up Gastrointest Res. 2025;25(4):381-384

Publication date (electronic) : 2025 December 4

doi : https://doi.org/10.7704/kjhugr.2025.0058

Hyeon Min Rim, Young Min Rah, Ju Seok Kim

Department of Internal Medicine, Chungnam National University Sejong Hospital, Sejong, Korea

Corresponding author Ju Seok Kim, MD, PhD Department of Internal Medicine, Chungnam National University Sejong Hospital, 20 Bodeum 7-ro, Sejong 30099, Korea E-mail: showsik@cnuh.co.kr

Received 2025 August 14; Revised 2025 September 3; Accepted 2025 September 16.

Abstract

INTRODUCTION

The incidence of multiple primary malignant tumors, defined as the occurrence of two or more distinct malignant neoplasms in a single patient, has been increasing [1]. Although a few cases of double or triple primary malignancies have been reported both domestically and internationally, their numbers remain limited. Herein, we report a rare case of synchronous triple primary gastrointestinal malignancy involving the stomach, esophagus, and colon, accompanied by a review of the relevant literature.

CASE REPORT

A 54-year-old male patient visited our outpatient clinic with abnormal findings detected on upper gastrointestinal endoscopy performed at a local clinic. The patient had been residing in a nursing facility for financial reasons and had a 20-year history of smoking approximately one pack of cigarettes per day prior to admission, along with occasional social alcohol consumption. At the time of presentation, he denied any symptoms, such as abdominal pain, changes in bowel habits, or weight loss. This was his first endoscopic examination, and he was referred for the evaluation of a superficially elevated lesion of approximately 1.5-cm on the lesser curvature of the lower gastric body (Fig. 1A). Repeat endoscopic examination and biopsy of the gastric lesion were performed at our clinic, and histopathological evaluation revealed a tubular adenoma with high-grade dysplasia. Additionally, during the same examination, a mucosal lesion with a shallow depression and an irregular surface approximately 1 cm in size was incidentally identified in the upper esophagus, 25 cm distal to the incisor teeth (Fig. 2A). Biopsy of the esophageal lesion revealed high-grade squamous epithelial dysplasia.

Fig. 1.

Gastric cancer findings. A: Endoscopic findings: a raised lesion approximately 1.5 cm in size on the lesser curvature of the gastric body. B: Histopathologic findings: moderately differentiated adenocarcinoma (intestinal type) with invasion into the submucosa (2.5 mm) (H&E stain, ×100). C: A surgical specimen: subtotal gastrectomy with gastrojejunostomy.

Fig. 2.

Esophageal cancer findings. A: Endoscopic findings: a shallow, irregularly depressed lesion approximately 1 cm in size with a nodular surface, located 25 cm from the incisor teeth in the upper esophagus. B: Histopathologic findings: esophageal squamous dysplasia, high-grade (H&E stain, ×100).

For staging purposes, computed tomography (CT) of the chest and abdomen was performed, which showed no evidence of masses, lymphadenopathy, or distant metastases. Endoscopic resection was planned for both gastric and esophageal lesions. Endoscopic submucosal dissection (ESD) was first performed for the elevated lesion on the lesser curvature of the lower gastric body. Histological examination of the resected specimen revealed moderately differentiated adenocarcinoma of the intestinal type. The tumor measured 1.4×0.9 cm and exhibited deep invasion into the submucosal layer (2.5 mm), but no involvement of the basal or lateral resection margins, and no lymphovascular invasion, was identified (Fig. 1B).

Following recovery, ESD was performed for the esophageal lesions with high-grade dysplasia. Histopathologic analysis confirmed high-grade esophageal squamous dysplasia, with a lesion size of 1.2×0.6 cm and clear resection margins both laterally and vertically (Fig. 2B).

Although endoscopic resections of the gastric and esophageal lesions were successfully completed, additional surgical intervention was planned for the early gastric cancer located on the lesser curvature of the lower body, given its deep submucosal invasion (2.5 mm). In collaboration with the surgical team through a multidisciplinary consultation, a preoperative staging evaluation was performed using positron emission tomography-computed tomography (PET-CT). This revealed an abnormal hypermetabolic uptake in the sigmoid colon that had not been detected on the previous CT scan (Fig. 3).

Fig. 3.

Positron emission tomography findings: hypermetabolic lesion with increased fluorodeoxyglucose uptake in the sigmoid colon (indicated by the red arrow).

Subsequently, colonoscopy was performed to evaluate this lesion. A friable, spontaneously bleeding mass measuring approximately 4 cm in diameter was identified 20 cm proximal to the anal verge in the sigmoid colon, and biopsies were obtained (Fig. 4A). Histopathological analysis confirmed the presence of a moderately differentiated adenocarcinoma. Consequently, the patient underwent a simultaneous laparoscopic subtotal gastrectomy with gastrojejunostomy (Fig. 1C) and low anterior resection of the sigmoid colon (Fig. 4B).

Fig. 4.

Sigmoid colon cancer findings. A: Colonoscopy findings: a mass lesion approximately 4 cm in size located 20 cm above the anal verge in the sigmoid colon. B: A surgical specimen: low anterior resection of the sigmoid colon. C: Surgical histopathologic findings: moderately differentiated adenocarcinoma of the sigmoid colon with invasion into the pericolorectal tissue (H&E stain, ×100).

Histological examination of the subtotal gastrectomy speci-men revealed no residual carcinoma, which was consistent with complete removal by the prior ESD. All the 21 dissected lymph nodes were free of metastatic involvement. The low anterior resection specimen showed a moderately differentiated adenocarcinoma measuring 4.8×2.6 cm, with invasion extending beyond the muscularis propria into the pericolorectal tissue. The proximal (6.5 cm) and distal (6.0 cm) resection margins were clear, and no evidence of vascular invasion was observed (Fig. 4C).

Thus, the patient was diagnosed with synchronous triple primary malignancies involving the stomach, esophagus, and colon. The pathological stages of each tumor were as follows: early gastric cancer, stage IA (pT1aN0M0); sigmoid colon cancer, stage IIA (pT3N0M0); and early esophageal cancer, stage 0 (carcinoma in situ). Curative resections were achieved through ESD and subtotal gastrectomy for the gastric lesion, low anterior resection for the sigmoid colon cancer, and ESD for the early esophageal lesion.

The patient was followed up for approximately one year with periodic endoscopic and radiological evaluations, showing no evidence of recurrence or metastasis during the follow-up period.

DISCUSSION

Although the incidence of multiple primary malignant tumors has been increasing in recent years, case reports and epidemiological studies remain relatively limited. According to earlier data from the Mayo Clinic in 1975, the incidence of multiple primary malignancies among more than 3700 patients was 5.1%. In Korea, a 2006 study conducted by the National Cancer Center found that the prevalence of synchronous malignancies among patients with gastric cancer was approximately 3.3%, while synchronous triple primary cancers were extremely rare, occurring in only two cases among 2200 patients [1-3].

Although several reports of multiple primary malignancies have been published in Japan, the United States, China, and Korea, the number of documented cases remains limited. Therefore, the present report holds clinical significance because of the rarity of synchronous triple primary gastrointestinal malignancies.

Multiple primary malignant tumors can be distinguished from metastatic lesions according to the following criteria: 1) each tumor must be histologically confirmed as malignant; 2) each tumor must possess distinct pathological char-acteristics; 3) the tumors must be anatomically separate and discontinuous from one another; and 4) the second tumor must not represent the recurrence or metastasis of the first malignancy [4]. In addition, multiple primary malignancies are classified as either synchronous or metachronous depending on the interval between diagnoses, with six months generally used as the cutoff point.

In the present case, the patient was diagnosed with independent primary malignancies of the esophagus, stomach, and sigmoid colon. Because two additional primary cancers were identified within six months of the first diagnosis, the condition was classified as a synchronous triple primary malignancy [5,6]. The patient was treated with a combination of endoscopic and surgical resections and recovered uneventfully without major complications.

Synchronous malignancies, such as colorectal cancer accompanying primary gastric carcinoma, are generally associated with a poorer prognosis than metachronous lesions. Therefore, the early detection of synchronous tumors is crucial for improving patient survival [7,8]. In this case, the patient was relatively young (54 years old), and the initial endoscopic examination led to the discovery of multiple primary malignancies within a short period. The absence of prior routine screening examinations likely contributed to the delayed detection. Hence, regardless of age, clinicians should maintain a high index of suspicion for multiple primary cancers and conduct comprehensive evaluations, including regular endoscopic surveillance, CT, and PET-CT to enable early diagnosis.

Microsatellite instability testing in this case revealed microsatellite stability, effectively excluding hereditary etiologies such as Lynch syndrome (hereditary nonpolyposis colorectal cancer). For similar future cases, supplementary genetic analyses may provide valuable insights into potential hereditary predispositions.

Article information Continued