Heterochronic triple primary malignancies with Epstein-Barr virus infection and tumor protein 53 gene mutation: A case report and review of literature

Abstract

Background: The diagnosis and etiology of multiple primary malignant neoplasms (MPMNs) are difficult to establish. Here, we report a case of heterochronic triple primary malignancies with gastric cancer, nasopharyngeal squamous cell cancer, and then rectal cancer.

Case summary: The patient was first diagnosed with gastric cancer at the age of 33 in 2014 and underwent distal gastrectomy and gastrojejunostomy and six cycles of adjuvant chemotherapy. Three years later, he was diagnosed with nasopharyngeal cancer and treated with radical chemoradiotherapy in 2017. Recently, a mass in the middle of the rectum was resected and reported as ulcerative, moderately to poorly differentiated adenocarcinoma. Research on the etiology of MPMNs showed that Epstein-Barr virus (EBV) infection may be the cause of gastric cancer and nasopharyngeal squamous cell cancer since these two primary lesions were positive for transcripts of EBV-encoded ribonucleic acid using an in situ hybridization EBV-encoded ribonucleic acid probe in formalin-fixed, paraffin-embedded tissue. The cause of rectal cancer may be due to a somatic mutation of tumor protein 53 gene in exon 8 (c.844C>T, p.Arg282Trp) through high-throughput sequencing for the rectal cancer. Appropriate standard therapy for each primary cancer was administered, and the patient has no evidence of cancer disease to date.

Conclusion: To our knowledge, this is the first report on heterochronic triple primary malignancies whose cause may be associated with EBV infection and tumor protein 53 genetic mutations. The etiological research may not only elucidate the cause of MPMN but also has implications in clinical management.

Keywords: Case report; Epstein-Barr virus infection; Epstein-Barr virus-encoded RNA; Etiology; Multiple primary malignant neoplasms; TP53 mutation.

Figure 1

Histopathological and immunohistochemical staining of gastric cancer. A: Poorly differentiated carcinoma in the distal stomach with lymphoid interstitial carcinoma; B: Positive staining for Epstein-Barr virus-encoded ribonucleic acid.

Figure 2

Histopathological and immunohistochemical staining of nasopharyngeal cancer. A: Poorly differentiated squamous cell carcinoma of the nasopharynx by pathology of nasal endoscopic biopsy; B: Positive staining for Epstein-Barr virus-encoded RNA.

Figure 3

Axial computed tomography images reveal a rectal mass. A: Axial maximum intensive projection at the same imaging level, and coronal images showed a 40 mm solitary nodule approximately 58 mm away above the anus in the rectum; B: Axial images of positron emission topography-computed tomography at the same imaging level, and rectal image of positron emission topography-computed tomography maximum intensive projection showed a thickened medial rectum wall with homogeneous uptake of 18F-fluorodeoxy-glucose, and the maximum standardized uptake value was 14.6.

Figure 4

Histopathological and immunohistochemical staining of rectal cancer. A: Postoperative pathology revealed ulcerative, moderately to poorly differentiated adenocarcinoma; B: Negative staining for Epstein-Barr virus-encoded ribonucleic acid.

Figure 5

Next-generation sequencing test in rectal cancer specimens. A: Tumor protein 53 (TP53; NM_000546.5) nonsense mutation in exon 9 c.991C>T (p.Gln331*), AF 3.71%; B: TP53 (NM_000546.5) missense mutation in exon 8 c.844C>T (p.Arg282Trp), AF 37.89%.

Figure 6

Mutation of waveform of the tumor protein 53 gene fragment. A and B: There were no base mutations.

Figure 7

The timeline of diagnosis and treatment for multiple primary malignant neoplasms. EBER: Epstein-Barr virus-encoded ribonucleic acid; TP53: Tumor protein 53.