A 73-year-old Chinese woman presented with hematochezia without obvious inducement, accompanied by mucus, about twice a day, for 24 days, and she denied the family genetic history. Pelvic magnetic resonance imaging (MRI) scan showed a tumor in the lower rectum. Abdominoperineal combined rectum resection was carried out. The size of the tumor was 3.2cm×6.5cm×1.8cm, and the section was grey-white occupying the entire circumference of the rectum (Fig. 1-A). No other organs were involved by the tumor. Histopathologic evaluation showed a malignant neoplasm is mainly composed of goblet-like cells with rich mucus in the cytoplasm, neuroendocrine cells, and Paneth-like cells. The tumor cells arranged as the nest and sieve shapes (Fig. 1-B). The tumor was located in the lower segment of the rectum and infiltrated into presentational adipose tissue. Histological grade: G3, poorly differentiated. Tumor budding: a high score. Lymph node metastasis: 2/20. These tumor cells showed venous invasion and perineural invasion.
Immunohistochemical staining was performed with the MXB biotechnology kit. The tumor cells were positive for CK20, CDX2, SSTR2, Syn, CD56, E-cad, Ki-67 (60%+), P53(80%+, mutant), and negative for MMR by immunohistochemistry. D-AB/PAS staining showed that PAS was positive for mucus in tumor cells, occasional AB was positive for mucus (Fig. 2). Transmission electron microscopy (TEM) was performed in our work. The neuroendocrine granules and mucous vesicles were observed in the same goblet-like cell of the tumor tissue under TEM. The results confirmed that this tumor is the GCA(Fig. 2).
Paraffin-embedded sections were subjected to comprehensive next-generation sequencing (NGS) analysis with 437 predefined cancer-related genes. Enriched libraries were sequenced on the HiSeq4000 platform (Illumina). Data were analyzed by an effective bioinformatics process. Germline mutations were filtered out by comparing to patient’s whole blood controls. The detection results included point mutation, small fragment insertion-deletion mutation, gene fusion, copy number variation, MSI, and tumor mutational burden. In our case, NGS detected an ERBB2 missense mutation, c.929C > T (p.S310F). The mutation was involved in tumorigenesis, increased susceptibility to ERBB inhibitors, and was likely pathogenic. A TP53 missense mutation, c.581T > G (p.L194R) was detected and it was pathogenic. A CTCF Shearing mutation, c.1999 + 1G > A was detected and it was likely pathogenic. A PBRM1 missense mutation, c.1449G > C (p.K483N), was detected, but the significance was unclear. The significance of BCR missense mutation, c.3361G > A (p.V1121M) was unclear. These results were supportive of the GCA. Our NGS test included the whole transcriptome sequencing, but no mutations were detected in MSI, KRAS, NRAS, BRAFV600E, PDGFRA, KIT, and NTRK. No germline mutation was detected in her family.
The above test results showed that this primary tumor of the rectum was different from the adenocarcinoma and neuroendocrine tumor. The treatment of advanced primary GCA of the rectum is also different from adenocarcinoma and neuroendocrine tumors and affects the prognosis and survival of patients. In our case, the primary GCA of the rectum infiltrated perirectal tissue but did not involve other organs. The tumor stage was pT4bN1bMx in our case. Abdominoperineal combined rectum resection was performed. The patient received radiotherapy and chemotherapy, and her condition was stable in the 6-month follow-up. Therefore, an accurate and standardized pathological diagnosis of the primary GCA of the rectum is very important for the treatment. Our work will help to improve the diagnosis of the primary GCA of the rectum and avoid misdiagnosis and mistreatment.