Malignant paraganglioma of the posterior mediastinum: A case report with genetic analysis

Adachi,Yasushi; Mita,Hiroaki; Sasaki,Yasushi; Himori,Ryogo; Onodera,Kei; Nakamura,Masahiro; Kikuchi,Takefumi; Yamashita,Kentaro; Yoshida,Yukinari; Ishii,Yoshifumi; Endo,Takao

doi:10.3892/mco.2018.1758

Malignant paraganglioma of the posterior mediastinum: A case report with genetic analysis

Authors:
- Yasushi Adachi
- Hiroaki Mita
- Yasushi Sasaki
- Ryogo Himori
- Kei Onodera
- Masahiro Nakamura
- Takefumi Kikuchi
- Kentaro Yamashita
- Yukinari Yoshida
- Yoshifumi Ishii
- Takao Endo
View Affiliations

Affiliations: Division of Gastroenterology, Department of Internal Medicine, Sapporo Shirakaba‑dai Hospital, Sapporo, Hokkaido 062‑0052, Japan, Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Hokkaido 060‑8556, Japan, Department of Gastroenterology, Sapporo Medical University, Sapporo, Hokkaido 060‑8543, Japan, Department of Pathology, Sapporo Shirakaba‑dai Hospital, Sapporo, Hokkaido 062‑0052, Japan
Published online on: November 8, 2018 https://doi.org/10.3892/mco.2018.1758
Pages: 10-16
Copyright: © Adachi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Paraganglioma and pheochromocytoma are rare neuroendocrine neoplasms that originate from chromaffin cells. In many of these tumors, several mutations are reported to occur in the genes of germline and/or somatic cells. A case of paraganglioma in the posterior mediastinum with highly malignant potential is reported. The patient had a rapid clinical course, and it was difficult to reach the final diagnosis. The initial diagnosis on fine‑needle aspiration biopsy was a gastrointestinal stromal tumor (GIST) arising from the esophagus. Although radiation therapy was effective for the main tumor, the lung metastases did not respond sufficiently to several tyrosine kinase inhibitors. Autopsy and immunohistochemical examination using a battery of different markers resulted in a final diagnosis of malignant paraganglioma. Next‑generation sequencing revealed several gene mutations and copy number variations, including of fumarate hydratase (FH), neurofibromatosis type‑1 (NF1) and RET. Those gene alterations may contribute to the pathogenesis of this malignant phenotype to a certain extent. To confirm this, further cases and studies are required. In addition, it should be noted that histological examination of a small piece of tumor might have sampling bias and could cause misdiagnosis.

View Figures

View References

1	Jochmanova I and Pacak K: Pheochromocytoma: The first metabolic endocrine cancer. Clin Cancer Res. 22:5001–5011. 2016. View Article : Google Scholar : PubMed/NCBI
2	Hamidi O, Young WF Jr, Gruber L, Smestad J, Yan Q, Ponce OJ, Prokop L, Murad MH and Bancos I: Outcomes of patients with metastatic phaeochromocytoma and paraganglioma: A systematic review and meta-analysis. Clin Endocrinol (Oxf). 87:440–450. 2017. View Article : Google Scholar : PubMed/NCBI
3	Neumann HP, Bausch B, McWhinney SR, Bender BU, Gimm O, Franke G, Schipper J, Klisch J, Altehoefer C, Zerres K, et al: Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med. 346:1459–1466. 2002. View Article : Google Scholar : PubMed/NCBI
4	Currás-Freixes M, Inglada-Pérez L, Mancikova V, Montero-Conde C, Letón R, Comino-Méndez I, Apellániz-Ruiz M, Sánchez-Barroso L, Aguirre Sánchez-Covisa M, Alcázar V, et al: Recommendations for somatic and germline genetic testing of single pheochromocytoma and paraganglioma based on findings from a series of 329 patients. J Med Genet. 52:647–656. 2015. View Article : Google Scholar : PubMed/NCBI
5	Fishbein L, Leshchiner I, Walter V, Danilova L, Robertson AG, Johnson AR, Lichtenberg TM, Murray BA, Ghayee HK, Else T, et al: Comprehensive molecular characterization of pheochromocytoma and paraganglioma. Cancer Cell. 31:181–193. 2017. View Article : Google Scholar : PubMed/NCBI
6	Welander J, Andreasson A, Juhlin CC, Wiseman RW, Backdahl M, Höög A, Larsson C, Gimm O and Söderkvist P: Rare germline mutations identified by targeted next-generation sequencing of susceptibility genes in pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 99:E1352–E1360. 2014. View Article : Google Scholar : PubMed/NCBI
7	Turchini J, Cheung VKY, Tischler AS, De Krijger RR and Gill AJ: Pathology and genetics of phaeochromocytoma and paraganglioma. Histopathology. 72:97–105. 2018. View Article : Google Scholar : PubMed/NCBI
8	Wong NA: Gastrointestinal stromal tumours-an update for histopathologists. Histopathology. 59:807–821. 2011. View Article : Google Scholar : PubMed/NCBI
9	Perry CG, Young WF Jr, McWhinney SR, Bei T, Stergiopoulos S, Knudson RA, Ketterling RP, Eng C, Stratakis CA and Carney JA: Functioning paraganglioma and gastrointestinal stromal tumor of the jejunum in three women: Syndrome or coincidence. Am J Surg Pathol. 30:42–49. 2006. View Article : Google Scholar : PubMed/NCBI
10	Nakagaki T, Tamura M, Kobashi K, Koyama R, Fukushima H, Ohashi T, Idogawa M, Ogi K, Hiratsuka H, Tokino T and Sasaki Y: Profiling cancer-related gene mutations in oral squamous cell carcinoma from Japanese patients by targeted amplicon sequencing. Oncotarget. 8:59113–59122. 2017. View Article : Google Scholar : PubMed/NCBI
11	Castro-Vega LJ, Buffet A, De Cubas AA, Cascón A, Menara M, Khalifa E, Amar L, Azriel S, Bourdeau I, Chabre O, et al: Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet. 23:2440–2446. 2014. View Article : Google Scholar : PubMed/NCBI
12	Azarow KS, Pearl RH, Zurcher R, Edwards FH and Cohen AJ: Primary mediastinal masses. A comparison of adult and pediatric populations. J Thorac Cardiovasc Surg. 106:67–72. 1993.PubMed/NCBI
13	Takeda S, Miyoshi S, Minami M and Matsuda H: Intrathoracic neurogenic tumors-50 years' experience in a Japanese institution. Eur J Cardiothorac Surg. 26:807–812. 2004. View Article : Google Scholar : PubMed/NCBI
14	Reyes MG, Fresco R and Bruetman ME: Mediastinal paraganglioma causing spinal cord compression. J Neurol Neurosurg Psychiatry. 40:276–279. 1977. View Article : Google Scholar : PubMed/NCBI
15	Moran CA, Suster S, Fishback N and Koss MN: Mediastinal paragangliomas. A clinicopathologic and immunohistochemical study of 16 cases. Cancer. 72:2358–2364. 1993. View Article : Google Scholar : PubMed/NCBI
16	Garibaldi E, Bresciani S, Panaia R, Delmastro E, Malinverni G and Gabriele P: Hereditary paraganglioma syndrome associated with SDHD gene mutations: A patient with multicentric presentation treated with radiotherapy. Case report. Tumori. 97:214–220. 2011. View Article : Google Scholar : PubMed/NCBI
17	Baudin E, Habra MA, Deschamps F, Cote G, Dumont F, Cabanillas M, Arfi-Roufe J, Berdelou A, Moon B, Al Ghuzlan A, et al: Therapy of endocrine disease: Treatment of malignant pheochromocytoma and paraganglioma. Eur J Endocrinol. 171:R111–R122. 2014. View Article : Google Scholar : PubMed/NCBI
18	Ayala-Ramirez M, Chougnet CN, Habra MA, Palmer JL, Leboulleux S, Cabanillas ME, Caramella C, Anderson P, Al Ghuzlan A, Waguespack SG, et al: Treatment with sunitinib for patients with progressive metastatic pheochromocytomas and sympathetic paragangliomas. J Clin Endocrinol Metab. 97:4040–4050. 2012. View Article : Google Scholar : PubMed/NCBI
19	Cassol CA, Winer D, Liu W, Guo M, Ezzat S and Asa SL: Tyrosine kinase receptors as molecular targets in pheochromocytomas and paragangliomas. Mod Pathol. 27:1050–1062. 2014. View Article : Google Scholar : PubMed/NCBI