BRCA2-Related Hereditary Cancer Syndrome-Associated Small Bowel Adenocarcinoma With Multiple BRCA2 Mutations: A Case Report and Review of the Literature

Abstract

Background: Small bowel adenocarcinomas (SBAs) are rare and aggressive cancers. About one-fifth of SBA patients have predisposing conditions; among them, there are also genetic tumor syndromes, including Lynch syndrome, familial adenomatous polyposis, and Peutz-Jeghers syndrome. Although BRCA2 mutations, both somatic and germline, have been recently described in SBAs, direct evidence of BRCA2 inactivation in SBA tumor tissue of patients with BRCA2-related hereditary cancer syndrome is still very limited.

Case presentation: Herein, we described a case of a 51-year-old woman with a history of breast cancer who developed an adenocarcinoma of the duodeno-jejunal flexure causing persistent vomiting. After clinical staging, the patient underwent surgical resection, and histologic examination of the specimen confirmed a poorly differentiated adenocarcinoma infiltrating the visceral peritoneum and showing lymph node metastases (stage III, pT4N1). Two years later, the SBA relapsed, and next generation sequencing was performed in matched tumor and normal tissues. In addition to KRAS and TP53 mutations in the tumor, both somatic and germline BRCA2 mutations were identified, indicating biallelic BRCA2 alterations.

Conclusion: BRCA2-associated hereditary tumor syndrome could have an etio-pathogenetic role in SBA development; thus, we suggest that this syndrome should be considered in patients with an SBA diagnosis below the age of 50 years, especially when a personal or family history of breast cancer is present.

Keywords: BRCA2; genetic tumor syndrome; small intestinal adenocarcinoma.

FIGURE 1

(A) Low power view of the small bowel adenocarcinoma (hematoxylin and eosin staining). (B–D) Tumor cells are diffusely positive for cytokeratin 20 (B, cytokeratin 20 immunostaining) and for CDX2 (D, CDX2 immunostaining), while the immunoreactivity for cytokeratin 7 is restricted to the deeper invasive portion (arrow) of the tumor (C, cytokeratin 7 immunostaining). Original magnification: 0.5× (A–D).

FIGURE 2

(A) High power view of the small bowel adenocarcinoma showing poor differentiation (hematoxylin and eosin). (B) Cytokeratin 20‐positive tumor cells perforating the serosa (cytokeratin 20 immunostaining). Note the black ink indicating the serosa surface. (C) Lymph node metastasis (arrow) of the cytokeratin 20‐positive small bowel adenocarcinoma (cytokeratin 20 immunostaining). (D) Tumor cells at the invasive front are also positive for cytokeratin 7 (cytokeratin 7 immunostaining). (E) The intestinal transcription factors CDX2 is diffusely positive (CDX2 immunostaining). (F) Several tumor cells are also weakly positive for the transcription factor SATB2 (SATB2 immunostaining). Original magnification: 10× (A); 10× (B); 5× (C); 15× (D); 15× (E); 13× (F).