Undifferentiated colonic neoplasm with SMARCA4 germline gene mutation and loss of SMARCA4 protein expression: a case report and literature review

Abstract

Background Nonsense mutation or inactivation of SMARCA4 (BRG1) is associated with a monomorphic undifferentiated histological appearance in tumors at different sites. The association between SMARCA4 alteration and undifferentiated colonic carcinoma needs to be further elucidated. Methods A 61-year-old male patient presented to the hospital with intermittent epigastric pain in the right upper abdomen and abdominal distension. The enhanced computed tomography detected a mass in the hepatic flexure of the colon and multiple liver metastases. Results The right hemicolectomy contained a 4.5-cm undifferentiated malignancy with cells arranged in sheets, abundant necrosis, and areas showing rhabdoid morphology. The immunohistochemistry result showed that these tumor cells were focally positive for cytokeratin (CK), CK8, and CK18; however, diffusely positive for vimentin, P53, Fli-1, and SALL-4. Notably, tumor cells showed a heterogeneous loss of SMARCA4 expression pattern and intact SMARCB1 expression. Next-generation sequencing showed a germline SMARCA4 c.3277C>T(p.R1093*)mutation, somatic APC mutation, and no abnormal SMARCB1 gene. The tumor exhibited microsatellite stability, negative PD-L1 expression, and few infiltrating CD8 + T cells. The patient died a month later after surgery. Conclusions We presented a rare case of undifferentiated colonic neoplasm with loss of SMARCA4 protein expression and germline SMARCA4 mutation. Moreover, the role of SMARCA4 alterations in tumor diagnosis and treatment was also summarized.

Case Series of SMARCA4-Deficient Undifferentiated Esophageal Carcinoma

“…The second patient had risk factors for esophageal carcinoma while the first patient had a positive family history, which highlights the possibility of a germline mutation. Duan et al reported a patient with SMARCA4-deficient undifferentiated colonic carcinoma due to a germline SMARCA4 gene mutation, who had a second-degree relative with colon cancer at age 50 [ 11 ].…”

A Novel DNA Variant in SMARCA4 Gene Found in a Patient Affected by Early Onset Colon Cancer

“…Therefore, germline pathogenic variants in SMARCA4 have been reported to be related to the predisposition of several types of cancers, namely Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT), early onset Ovarian Cancer (OC), neuroblastoma, and rhabdoid tumor predisposition syndrome [ 34 , 35 , 36 ]. Germline mutations at SMARCA4 that cause a truncated protein are reported to be the key genetic event because a decrease in functional BRG1 protein is expected and has often been related to such cancer pathologies as SMARCA4-deficient Non-Small-Cell-Lung Cancer (NSCLC) and rhabdoid tumor predisposition syndrome [ 35 , 37 , 38 , 39 ]. Indeed, pathogenic variants in the SMARCA4 gene are mainly associated with early onset (≤40 years) OC [ 36 ].…”

“…In contrast to what has been examined so far in the association between pathogenic mutations in SMARCA4 and early onset in SCCOHT and NSCLC, there are currently no close correlations in the literature with this gene and CRC, particularly in young people (EOCRC), therefore necessitating further investigation to find potential linkages [ 37 ]. However, variants in genes not closely related to colon cancer are instead to be considered with more interest in patients with early onset, as different studies are being conducted to better understand the molecular basis of juvenile forms of CRC [ 5 ], which is important knowledge for therapeutic assets.…”

Cytomorphology of metastatic colonic MXD4::NUTM1‐rearranged sarcoma

“…Our patient on the most recent clinical follow-up is 1) is extremely broad and includes NUT carcinoma, melanoma, neuroendocrine neoplasm, myoepithelial carcinoma, SMARCA4-deficient neoplasms, synovial sarcoma, and plasma cell neoplasm. [19][20][21][22][23][24][25][26][27][28][29][30] Immunohistochemical stains and/or molecular testing will be essential. That said, the tumor immunoreactivity with NUT comes with a caveat.…”

“…The differential diagnosis based on the epithelioid and rhabdoid/plasmacytoid morphology (Table 1) is extremely broad and includes NUT carcinoma, melanoma, neuroendocrine neoplasm, myoepithelial carcinoma, SMARCA4‐deficient neoplasms, synovial sarcoma, and plasma cell neoplasm 19–30 . Immunohistochemical stains and/or molecular testing will be essential.…”