Top

Diagnostic Pathology

Published in:

Open Access 01-12-2019 | Case Report

Targeted sequencing identifies the mutational signature of double primary and metastatic malignancies: a case report

Authors: Chuangzhou Rao, Liangqin Nie, Xiaobo Miao, Analyn Lizaso, Guofang Zhao

Published in: Diagnostic Pathology | Issue 1/2019

Abstract

Background

The accurate identification of the tissue of origin is critical for optimal management of cancer patients particularly those who develop multiple malignancies; however, conventional diagnostic methods at times may fail to provide conclusive diagnosis of the origin of the malignancy. Herein, we describe the use of targeted sequencing in distinguishing the primary and metastatic tumors in a patient with metachronous malignancies in the lung, colon and kidney.

Case presentation

In December 2016, a 55-year-old Chinese male was diagnosed with stage IB lung adenosquamous carcinoma and treated with left lower lobectomy and 4 cycles of platinum-based chemotherapy. After being disease-free for 3.5 months, three colonic polyps were discovered and were diagnosed as invasive adenocarcinoma after polypectomy. Within 5.4 months from the polypectomy, squamous cell renal carcinoma was identified and was managed by radical nephrectomy. Immunohistochemistry results were inconclusive on the origin of the kidney tumor. Hence, the three archived surgical tissue samples were sequenced using a targeted panel with 520 cancer-related genes. Analysis revealed similar mutational signature between the lung and kidney tumors and a distinct mutational profile for the colon tumor, suggesting that the lung and colon malignancies were primary tumors, while the kidney tumor originated from the lung, revealing a diagnosis of metastatic double primary cancer – lung carcinoma with renal cell metastasis and second primary colon carcinoma.

Conclusion

Mutational profiling using targeted sequencing is valuable not only for the detection of actionable mutations, but also in the identification of the origin of tumors. This diagnostic approach should be considered in similar scenarios.

Available only for authorised users

Monzon FA, Lyons-Weiler M, Buturovic LJ, Rigl CT, Henner WD, Sciulli C, et al. Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin. J Clin Oncol. 2009;27(15):2503–8. https://doi.org/10.1200/JCO.2008.17.9762.CrossRefPubMed

Greco FA, Spigel DR, Yardley DA, Erlander MG, Ma X-J, Hainsworth JD. Molecular profiling in unknown primary cancer: accuracy of tissue of origin prediction. Oncologist. 2010;15(5):500–6. https://doi.org/10.1634/theoncologist.2009-0328.CrossRefPubMedPubMedCentral

Kulkarni A, Pillai R, Ezekiel AM, Henner WD, Handorf CR. Comparison of histopathology to gene expression profiling for the diagnosis of metastatic cancer. Diagn Pathol. 2012;7:110. https://doi.org/10.1186/1746-1596-7-110.CrossRefPubMedPubMedCentral

Wu F, Huang D, Wang L, Xu Q, Liu F, Ye X, et al. 92-gene molecular profiling in identification of Cancer origin: a retrospective study in Chinese population and performance within different subgroups. PLoS One. 2012;7(6):e39320. https://doi.org/10.1371/journal.pone.0039320.CrossRefPubMedPubMedCentral

Greco FA, Lennington WJ, Spigel DR, Hainsworth JD. Molecular profiling diagnosis in unknown primary cancer: accuracy and ability to complement standard pathology. J Natl Cancer Inst. 2013;105(11):782–90. https://doi.org/10.1093/jnci/djt099.CrossRefPubMed

Weiss LM, Chu P, Schroeder BE, Singh V, Zhang Y, Erlander MG, et al. Blinded comparator study of Immunohistochemical analysis versus a 92-gene Cancer classifier in the diagnosis of the primary site in metastatic tumors. J Mol Diagn. 2013;15(2):263–9. https://doi.org/10.1016/j.jmoldx.2012.10.001.CrossRefPubMed

Handorf CR, Kulkarni A, Grenert JP, Weiss LM, Rogers WM, Kim OS, et al. A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors. Am J Surg Pathol. 2013;37(7):1067–75. https://doi.org/10.1097/PAS.0b013e31828309c4.CrossRefPubMedPubMedCentral

Hafner C, Knuechel R, Stoehr R, Hartmann A. Clonality of multifocal urothelial carcinomas: 10 years of molecular genetic studies. Int J Cancer. 2002;101(1):1–6. https://doi.org/10.1002/ijc.10544.CrossRefPubMed

Orlow I, Tommasi DV, Bloom B, Ostrovnaya I, Cotignola J, Mujumdar U, et al. Evaluation of the clonal origin of multiple primary melanomas using molecular profiling. J Invest Dermatol. 2009;129(8):1972–82. https://doi.org/10.1038/jid.2009.4.CrossRefPubMedPubMedCentral

10.

Wang Y, Lang MR, Pin CL, Izawa JI. Comparison of the clonality of urothelial carcinoma developing in the upper urinary tract and those developing in the bladder. SpringerPlus. 2013;2:412. https://doi.org/10.1186/2193-1801-2-412.CrossRefPubMedPubMedCentral

11.

Wu A, He S, Li J, Liu L, Liu C, Wang Q, et al. Colorectal cancer in cases of multiple primary cancers: clinical features of 59 cases and point mutation analyses. Oncol Lett. 2017;13(6):4720–6. https://doi.org/10.3892/ol.2017.6097.CrossRefPubMedPubMedCentral

12.

Becerra MF, Reznik E, Redzematovic A, Tennenbaum DM, Kashan M, Ghanaat M, et al. Comparative genomic profiling of matched primary and metastatic tumors in renal cell carcinoma. Eur Urol Focus. 2018;4(6):986–94. https://doi.org/10.1016/j.euf.2017.09.016.CrossRefPubMed

13.

Ueno M, Muto T, Oya M, Ota H, Azekura K, Yamaguchi T. Multiple primary cancer: an experience at the Cancer institute hospital with special reference to colorectal cancer. Int J Clin Oncol. 2003;8(3):162–7. https://doi.org/10.1007/s10147-003-0322-z.CrossRefPubMed

14.

Vogt A, Schmid S, Heinimann K, Frick H, Herrmann C, Cerny T, et al. Multiple primary tumours: challenges and approaches, a review. ESMO open. 2017;2(2):e000172. https://doi.org/10.1136/esmoopen-2017-000172.CrossRefPubMedPubMedCentral

15.

Li F, Zhong W-Z, Niu F-Y, Zhao N, Yang J-J, Yan H-H, et al. Multiple primary malignancies involving lung cancer. BMC Cancer. 2015;15:696. https://doi.org/10.1186/s12885-015-1733-8.CrossRefPubMedPubMedCentral

16.

Chen H, Zhang S, Wu Z. Fanconi anemia pathway defects in inherited and sporadic cancers. Transl Pediatr. 2014;3(4):300–4. https://doi.org/10.3978/j.issn.2224-4336.2014.07.05.CrossRefPubMedPubMedCentral

17.

van der Heijden MS, Yeo CJ, Hruban RH, Kern SE. Fanconi anemia gene mutations in young-onset pancreatic cancer. Cancer Res. 2003;63(10):2585–8.PubMed

18.

Couch FJ, Johnson MR, Rabe K, Boardman L, McWilliams R, de Andrade M, et al. Germ line Fanconi anemia complementation group C mutations and pancreatic cancer. Cancer Res. 2005;65(2):383–6.PubMed

19.

Berwick M, Satagopan JM, Ben-Porat L, Carlson A, Mah K, Henry R, et al. Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer. Cancer Res. 2007;67(19):9591–6. https://doi.org/10.1158/0008-5472.CAN-07-1501.CrossRefPubMedPubMedCentral

20.

Thompson ER, Doyle MA, Ryland GL, Rowley SM, Choong DYH, Tothill RW, et al. Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. PLoS Genet. 2012;8(9):e1002894. https://doi.org/10.1371/journal.pgen.1002894.CrossRefPubMedPubMedCentral

21.

Esteban-Jurado C, Franch-Exposito S, Munoz J, Ocana T, Carballal S, Lopez-Ceron M, et al. The Fanconi anemia DNA damage repair pathway in the spotlight for germline predisposition to colorectal cancer. Eur J Hum Genet. 2016;24(10):1501–5. https://doi.org/10.1038/ejhg.2016.44.CrossRefPubMedPubMedCentral

22.

Yang S-Y, Hsiung C-N, Li Y-J, Chang G-C, Tsai Y-H, Chen K-Y, et al. Fanconi anemia genes in lung adenocarcinoma- a pathway-wide study on cancer susceptibility. J Biomed Sci. 2016;23(1):23. https://doi.org/10.1186/s12929-016-0240-9. CrossRefPubMedPubMedCentral

23.

Moldvay J, Jackel M, Bogos K, Soltész I, Agócs L, Kovács G, et al. The role of TTF-1 in differentiating primary and metastatic lung adenocarcinomas. Pathol Oncol Res. 2004;10(2):85–8. https://doi.org/10.1007/BF02893461.CrossRefPubMed

24.

Bayrak R, Yenidunya S, Haltas H. Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas. Pathol Res Pract. 2011;207(3):156–60. https://doi.org/10.1016/j.prp.2010.12.005.CrossRefPubMed

Title: Targeted sequencing identifies the mutational signature of double primary and metastatic malignancies: a case report
Authors: Chuangzhou Rao
Liangqin Nie
Xiaobo Miao
Analyn Lizaso
Guofang Zhao
Publication date: 01-12-2019
Publisher: BioMed Central
Published in: Diagnostic Pathology / Issue 1/2019
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-019-0874-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Targeted sequencing identifies the mutational signature of double primary and metastatic malignancies: a case report

Abstract

Background

Case presentation

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Case presentation

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2019

Stromal osseous metaplasia in urothelial carcinoma of the bladder: a rare case report and literature review

A rare simultaneous coexistence of epithelioid gastrointestinal stromal tumors and schwannoma in the stomach: a case report

Melanoma arising in a Giant congenital melanocytic nevus: two case reports

MicroRNA-1298 is downregulated in non-small cell lung cancer and suppresses tumor progression in tumor cells

Leiomyoma with KAT6B-KANSL1 fusion: case report of a rapidly enlarging uterine mass in a postmenopausal woman

Primary renal well-differentiated neuroendocrine tumors: report of six cases with an emphasis on the Ki-67 index and mitosis