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Diagnostic Pathology

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Open Access 01-12-2021 | NSCLC | Case Report

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

Authors: Huanli Duan, Wei Gao, Leiming Wang, Feng Cao, Lianghong Teng

Published in: Diagnostic Pathology | Issue 1/2021

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.

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Xue Y, Meehan B, Fu Z, Wang XQD, Fiset PO, Rieker R, et al. SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in non-small cell lung cancer. Nat Commun. 2019;10(1):557. https://doi.org/10.1038/s41467-019-08380-1.CrossRefPubMedPubMedCentral

Muppala R, Donenberg T, Huang MS, Schlumbrecht MP. SMARCA4 germline gene mutation in a patient with epithelial ovarian: a case report. Gynecol Oncol Rep. 2017;22:45–7. https://doi.org/10.1016/j.gore.2017.09.010.CrossRefPubMedPubMedCentral

Stewart BD, Kaye F, Machuca T, Mehta HJ, Mohammed TL, Newsom KJ, et al. SMARCA4-deficient thoracic sarcoma: a case report and review of literature. Int J Surg Pathol. 2020;28(1):102–8. https://doi.org/10.1177/1066896919865944.CrossRefPubMed

Witkowski L, Carrot-Zhang J, Albrecht S, Fahiminiya S, Hamel N, Tomiak E, et al. Germline and somatic SMARCA4 mutations characterize small cell carcinoma of the ovary, hypercalcemic type. Nat Genet. 2014;46(5):438–43. https://doi.org/10.1038/ng.2931.CrossRefPubMed

Agaimy A, Daum O, Markl B, Lichtmannegger I, Michal M, Hartmann A. SWI/SNF complex-deficient undifferentiated/Rhabdoid carcinomas of the gastrointestinal tract: a series of 13 cases highlighting mutually exclusive loss of SMARCA4 and SMARCA2 and frequent co-inactivation of SMARCB1 and SMARCA2. Am J Surg Pathol. 2016;40(4):544–53. https://doi.org/10.1097/PAS.0000000000000554.CrossRefPubMed

Naito T, Umemura S, Nakamura H, Zenke Y, Udagawa H, Kirita K, et al. Successful treatment with nivolumab for SMARCA4-deficient non-small cell lung carcinoma with a high tumor mutation burden: a case report. Thorac Cancer. 2019;10(5):1285–8. https://doi.org/10.1111/1759-7714.13070.CrossRefPubMedPubMedCentral

Lin DI, Allen JM, Hecht JL, Killian JK, Ngo NT, Edgerly C, et al. SMARCA4 inactivation defines a subset of undifferentiated uterine sarcomas with rhabdoid and small cell features and germline mutation association. Mod Pathol. 2019;32(11):1675–87. https://doi.org/10.1038/s41379-019-0303-z.CrossRefPubMed

Kolin DL, Dong F, Baltay M, Lindeman N, MacConaill L, Nucci MR, et al. SMARCA4-deficient undifferentiated uterine sarcoma (malignant rhabdoid tumor of the uterus): a clinicopathologic entity distinct from undifferentiated carcinoma. Mod Pathol. 2018;31(9):1442–56. https://doi.org/10.1038/s41379-018-0049-z.CrossRefPubMed

Perret R, Chalabreysse L, Watson S, Serre I, Garcia S, Forest F, et al. SMARCA4-deficient thoracic sarcomas: Clinicopathologic study of 30 cases with an emphasis on their nosology and differential diagnoses. Am J Surg Pathol. 2019;43(4):455–65. https://doi.org/10.1097/PAS.0000000000001188.CrossRefPubMed

10.

Early CA, Wangsiricharoen S, Jones RM, VandenBussche CJ. Review of SMARCA4 (BRG1)-deficient carcinomas following a malignant pleural effusion specimen confounded by reduced claudin-4 expression. J Am Soc Cytopathol. 2020;10(2):197–207. https://doi.org/10.1016/j.jasc.2020.08.002.CrossRefPubMed

11.

Herpel E, Rieker RJ, Dienemann H, Muley T, Meister M, Hartmann A, et al. SMARCA4 and SMARCA2 deficiency in non-small cell lung cancer: immunohistochemical survey of 316 consecutive specimens. Ann Diagn Pathol. 2017;26:47–51. https://doi.org/10.1016/j.anndiagpath.2016.10.006.CrossRefPubMed

12.

Matsubara D, Kishaba Y, Ishikawa S, Sakatani T, Oguni S, Tamura T, et al. Lung cancer with loss of BRG1/BRM, shows epithelial mesenchymal transition phenotype and distinct histologic and genetic features. Cancer Sci. 2013;104(2):266–73. https://doi.org/10.1111/cas.12065.CrossRefPubMedPubMedCentral

13.

Wang H, Bierie B, Li AG, Pathania S, Toomire K, Dimitrov SD, et al. BRCA1/FANCD2/BRG1-driven DNA repair stabilizes the differentiation state of human mammary epithelial cells. Mol Cell. 2016;63(2):277–92. https://doi.org/10.1016/j.molcel.2016.05.038.CrossRefPubMedPubMedCentral

14.

Tessier-Cloutier B, Schaeffer DF, Bacani J, Marginean CE, Kalloger S, Köbel M, et al. Loss of switch/sucrose non-fermenting complex protein expression in undifferentiated gastrointestinal and pancreatic carcinomas. Histopathology. 2020;77(1):46–54. https://doi.org/10.1111/his.14096.CrossRefPubMed

15.

Huang SC, Ng KF, Yeh TS, Cheng CT, Chen MC, Chao YC, et al. The clinicopathological and molecular analysis of gastric cancer with altered SMARCA4 expression. Histopathology. 2020;77(2):250–61. https://doi.org/10.1111/his.14117.CrossRefPubMed

16.

Hanninen UA, Katainen R, Tanskanen T, et al. Exome-wide somatic mutation characterization of small bowel adenocarcinoma. PLoS Genet. 2018;14(3):e1007200. https://doi.org/10.1371/journal.pgen.1007200.CrossRefPubMedPubMedCentral

17.

Connor YD, Miao D, Lin DI, Hayne C, Howitt BE, Dalrymple JL, et al. Germline mutations of SMARCA4 in small cell carcinoma of the ovary, hypercalcemic type and in SMARCA4-deficient undifferentiated uterine sarcoma: clinical features of a single family and comparison of large cohorts. Gynecol Oncol. 2020;157(1):106–14. https://doi.org/10.1016/j.ygyno.2019.10.031.CrossRefPubMedPubMedCentral

18.

Dagogo-Jack I, Schrock AB, Kem M, Jessop N, Lee J, Ali SM, et al. Clinicopathologic characteristics of BRG1-deficient NSCLC. J Thorac Oncol. 2020;15(5):766–76. https://doi.org/10.1016/j.jtho.2020.01.002.CrossRefPubMed

19.

Chatzopoulos K, Boland JM. Update on genetically defined lung neoplasms: NUT carcinoma and thoracic SMARCA4-deficient undifferentiated tumors. Virchows Arch. 2021;478(1):21–30. https://doi.org/10.1007/s00428-020-03011-3.CrossRefPubMed

20.

Fruhwald MC, Nemes K, Boztug H, et al. Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE host genome working group. Familial Cancer. 2021. https://doi.org/10.1007/s10689-021-00229-1.

21.

Takada K, Sugita S, Murase K, Kikuchi T, Oomori G, Ito R, et al. Exceptionally rapid response to pembrolizumab in a SMARCA4-deficient thoracic sarcoma overexpressing PD-L1: a case report. Thorac Cancer. 2019;10(12):2312–5. https://doi.org/10.1111/1759-7714.13215.CrossRefPubMedPubMedCentral

22.

Hurkmans DP, Kuipers ME, Smit J, van Marion R, Mathijssen RHJ, Postmus PE, et al. Tumor mutational load, CD8(+) T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients. Cancer Immunol Immunother. 2020;69(5):771–7. https://doi.org/10.1007/s00262-020-02506-x.CrossRefPubMedPubMedCentral

23.

Zhang L, Shay JW. Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer. J Natl Cancer Inst. 2017;109(8):djw332. https://doi.org/10.1093/jnci/djw332.CrossRefPubMedCentral

Title: Undifferentiated colonic neoplasm with SMARCA4 germline gene mutation and loss of SMARCA4 protein expression: a case report and literature review
Authors: Huanli Duan
Wei Gao
Leiming Wang
Feng Cao
Lianghong Teng
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: NSCLC
NSCLC
Published in: Diagnostic Pathology / Issue 1/2021
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-021-01091-6

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Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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