Neurofibromatosis type 1 associated with pheochromocytoma and gastrointestinal stromal tumors: A case report and literature review

Pan,Dongfeng; Liang,Peifeng; Xiao,Hongyan

doi:10.3892/ol.2016.4670

Neurofibromatosis type 1 associated with pheochromocytoma and gastrointestinal stromal tumors: A case report and literature review

Authors:
- Dongfeng Pan
- Peifeng Liang
- Hongyan Xiao
View Affiliations

Affiliations: Emergency Department, The People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China, Department of Medical Statistics, The People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China, Department of Pathology, The People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region 750002, P.R. China
Published online on: June 1, 2016 https://doi.org/10.3892/ol.2016.4670
Pages: 637-643

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

Neurofibromatosis type 1 (NF1) is a genetic disorder associated with neurofibromin 1 (NF1) gene mutation, which generates an increased risk of variety of tumor types. The current study reports a case involving NF1, pheochromocytoma (PHEO) and gastrointestinal stromal tumors (GIST). A 56‑year‑old man presented with abdominal pain and polypnea. Clinical investigation revealed multiple diffuse soft‑tissue lesions throughout his body, and pigmented macules on the skin. Imaging analyses revealed thoracic scoliosis, multiple subcutaneous nodules in the abdomen and trunk, and a 7.0x7.7x8.9‑cm oval‑shaped, cystic mass in the left upper abdominal cavity. Immunohistochemical staining indicated that S‑100 protein and synaptophysin were highly expressed in adrenal gland neoplasm, whilst CD117 and CD34 were highly expressed in small intestine tumors. The overall clinical and pathological finding suggested a diagnosis of NF1, giant PHEO and small intestinal stromal tumor. In addition, a literature review was conducted to identify the specific clinical features of patients with this condition. Only 11 similar cases have been reported worldwide. In the present study, paroxysmal hypertension occurred in the majority of patients, and GISTs tended to be located in the small intestine. In addition, the present study demonstrated that many of the patients had a poor prognosis. Therefore, the present study indicates that NF1‑PHEO‑GIST is a special type tumor with varied clinical symptoms, which may be associated with an increased risk for poor prognosis; however, more studies are required to confirm this.

View Figures

View References

1	Riccardi VM: Von Recklinghausen neurofibromatosis. N Engl J Med. 305:1617–1627. 1981. View Article : Google Scholar : PubMed/NCBI
2	Friedman JM: Epidemiology of neurofibromatosis type 1. Am J Med Genet. 89:1–6. 1999. View Article : Google Scholar : PubMed/NCBI
3	Gutmann DH, Aylsworth A, Carey JC, Korf B, Marks J, Pyeritz RE, Rubenstein A and Viskochil D: The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. Jama. 278:51–57. 1997. View Article : Google Scholar : PubMed/NCBI
4	Walther MM, Herring J, Enquist E, Keiser HR and Linehan WM: von Recklinghausen's disease and pheochromocytomas. J Urol. 162:1582–1586. 1999. View Article : Google Scholar : PubMed/NCBI
5	Fung MM, Viveros OH and O'Connor DT: Diseases of the adrenal medulla. Acta Physiol. 192:325–335. 2008. View Article : Google Scholar
6	Miettinen M, Fetsch JF, Sobin LH and Lasota J: Gastrointestinal stromal tumors in patients with neurofibromatosis 1: A clinicopathologic and molecular genetic study of 45 cases. Am J Surg Pathol. 30:90–96. 2006. View Article : Google Scholar : PubMed/NCBI
7	Yantiss RK, Rosenberg AE, Sarran L, Besmer P and Antonescu CR: Multiple gastrointestinal stromal tumors in type I neurofibromatosis: A pathologic and molecular study. Mod Pathol. 18:475–484. 2005. View Article : Google Scholar : PubMed/NCBI
8	Cichoz-Lach H, Kasztelan-Szczerbińska B and Słomka M: Gastrointestinal stromal tumors: Epidemiology, clinical picture, diagnosis, prognosis and treatment. Pol Arch Med Wewn. 118:216–221. 2008.PubMed/NCBI
9	Vlenterie M, Flucke U, Hofbauer LC, Timmers HJ, Gastmeier J, Aust DE, van der Graaf WT, Wesseling P, Eisenhofer G and Lenders JW: Pheochromocytoma and gastrointestinal stromal tumors in patients with neurofibromatosis type I. Am J Med. 126:174–180. 2013. View Article : Google Scholar : PubMed/NCBI
10	Ozcinar B, Aksakal N, Agcaoglu O, Tukenmez M, Ozemir IA, Barbaros U, Colak N and Erbil Y: Multiple gastrointestinal stromal tumors and pheochromocytoma in a patient with von Recklinghausen's disease. Int J Surg Case Rep. 4:216–218. 2013. View Article : Google Scholar : PubMed/NCBI
11	Kramer K, Hasel C, Aschoff AJ, Henne-Bruns D and Wuerl P: Multiple gastrointestinal stromal tumors and bilateral pheochromocytoma in neurofibromatosis. World J Gastroenterol. 13:3384–3387. 2007. View Article : Google Scholar : PubMed/NCBI
12	Teramoto S, Ota T, Maniwa A, Matsui T, Itaya N, Aoyagi K, Kusanagi H and Narita M: Two von Recklinghausen's disease cases with pheochromocytomas and gastrointestinal stromal tumors (GIST) in combination. Int J Urol. 14:73–74. 2007. View Article : Google Scholar : PubMed/NCBI
13	Bümming P, Nilsson B, Sörensen J, Nilsson O and Ahlman H: Use of 2-tracer PET to diagnose gastrointestinal stromal tumour and pheochromocytoma in patients with Carney triad and neurofibromatosis type 1. Scand J Gastroenterol. 41:626–630. 2006. View Article : Google Scholar : PubMed/NCBI
14	Luo ZM, Jin XL and Teng HH: Neurofibromatosis type I complicating interstitialoma and pheochromocytoma: A case of report. Chin J Diag Pathol. 36:140–141. 2006.
15	Jeong CY, Hong SC, Lee YJ, Jung EJ, Choi SK, Joo YT, Ha WS, Park ST and Lee JS: Multiple duodeno-jejunal GIST associated with pheochromocytoma in patients with von Recklinghausen disease. J Korean Surg Soc. 69:74–78. 2005.(In Korean).
16	Rizzo S, Bonomo S, Moser A, Bottura D, Castellini C, Mazzola F, Lauro E, Vicenzi L, Betresini B, Angeli G, et al: Bilateral pheochromocytoma associated with duodeno-jejunal GIST in patient with von Recklinghausen disease: Report of a clinical case. Chir Ital. 53:243–246. 2001.(In Italian). PubMed/NCBI
17	Sakaguchi N, Sano K, Ito M, Baba T, Fukuzawa M and Hotchi M: A case of von Recklinghausen's disease with bilateral pheochromocytoma-malignant peripheral nerve sheath tumors of the adrenal and gastrointestinal autonomic nerve tumors. Am J Surg Pathol. 20:889–897. 1996. View Article : Google Scholar : PubMed/NCBI
18	Oguzkan S, Terzi YK, Cinbis M, Anlar B, Aysun S and Ayter S: Molecular genetic analyses in neurofibromatosis type 1 patients with tumors. Cancer Genet Cytogenet. 165:167–171. 2006. View Article : Google Scholar : PubMed/NCBI
19	Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference. Arch Neurol. 45:575–578. 1988.PubMed/NCBI
20	Friedman J and Birch PH: Type 1 neurofibromatosis: A descriptive analysis of the disorder in 1,728 patients. Am J Med Genet. 70:138–143. 1997. View Article : Google Scholar : PubMed/NCBI
21	Zinnamosca L, Petramala L, Cotesta D, Marinelli C, Schina M, Cianci R, Giustini S, Sciomer S, Anastasi E, Calvieri S, et al: Neurofibromatosis type 1 (NF1) and pheochromocytoma: Prevalence, clinical and cardiovascular aspects. Arch Dermatol Res. 303:317–325. 2011. View Article : Google Scholar : PubMed/NCBI
22	Opocher G, Conton P, Schiavi F, Macino B and Mantero F: Pheochromocytoma in von Hippel-Lindau disease and neurofibromatosis type 1. Fam Cancer. 4:13–16. 2005. View Article : Google Scholar : PubMed/NCBI
23	Erem C, Onder Ersöz H, Ukinç K, Hacihasanoglu A, Alhan E, Cobanoğlu U, Koçak M and Erdöl H: Neurofibromatosis type 1 associated with pheochromocytoma: A case report and a review of the literature. J Endocrinol Invest. 30:59–64. 2007. View Article : Google Scholar : PubMed/NCBI
24	March Rocchietti M: Type 1 neurofibromatosis and pheochromocytoma: Focus on hypertension. J Neurosci Rural Pract. 3:107–108. 2012. View Article : Google Scholar : PubMed/NCBI
25	Gutmann DH, Geist RT, Rose K, Wallin G and Moley JF: Loss of neurofibromatosis type I (NFI) gene expression in pheochromocytomas from patients without NFI. Genes Chromosomes Cancer. 13:104–109. 1995. View Article : Google Scholar : PubMed/NCBI
26	Singer S, Rubin BP, Lux ML, Chen CJ, Demetri GD, Fletcher CD and Fletcher JA: Prognostic value of KIT mutation type, mitotic activity and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol. 20:3898–3905. 2002. View Article : Google Scholar : PubMed/NCBI
27	Pinsk I, Dukhno O, Ovnat A and Levy I: Gastrointestinal complications of von Recklinghausen's disease: Two case reports and a review of the literature. Scand J Gastroenterol. 38:1275–1278. 2003. View Article : Google Scholar : PubMed/NCBI
28	Caterino S, Lorenzon L, Petrucciani N, Iannicelli E, Pilozzi E, Romiti A, Cavallini M and Ziparo V: Gastrointestinal stromal tumors: Correlation between symptoms at presentation, tumor location and prognostic factors in 47 consecutive patients. World J Surg Oncol. 9:132011. View Article : Google Scholar : PubMed/NCBI
29	Maertens O, Prenen H, Debiec-Rychter M, Wozniak A, Sciot R, Pauwels P, De Wever I, Vermeesch JR, de Raedt T, De Paepe A, et al: Molecular pathogenesis of multiple gastrointestinal stromal tumors in NF1 patients. Hum Mol Genet. 15:1015–1023. 2006. View Article : Google Scholar : PubMed/NCBI
30	Yamamoto H, Tobo T, Nakamori M, Imamura M, Kojima A, Oda Y, Nakamura N, Takahira T, Yao T and Tsuneyoshi M: Neurofibromatosis type 1-related gastrointestinal stromal tumors: A special reference to loss of heterozygosity at 14q and 22q. J Cancer Res Clin Oncol. 35:791–798. 2009. View Article : Google Scholar
31	Novelli M, Rossi S, Rodriguez-Justo M, Taniere P, Seddon B, Toffolatti L, Sartor C, Hogendoorn PC, Sciot R, Van Glabbeke M, et al: DOG1 and CD117 are the antibodies of choice in the diagnosis of gastrointestinal stromal tumours. Histopathology. 57:259–270. 2010. View Article : Google Scholar : PubMed/NCBI
32	Miettinen M, Majidi M and Lasota J: Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs): A review. Eur J Cancer. 38:S39–S51. 2002. View Article : Google Scholar : PubMed/NCBI
33	Bruynzeel H, Feelders RA, Groenland THN, van den Meiracker AH, van Eijck CH, Lange JF, de Herder WW and Kazemier G: Risk factors for hemodynamic instability during surgery for pheochromocytoma. J Clin Endocrinol Metab. 95:678–685. 2010. View Article : Google Scholar : PubMed/NCBI
34	ESMO/European Sarcoma Network Working Group: Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 23(Suppl 7): 23. vii49–vii55. 2012.PubMed/NCBI
35	Shinomura Y, Kinoshita K, Tsutsui S and Hirota S: Pathophysiology, diagnosis and treatment of gastrointestinal stromal tumors. J Gastroenterol. 40:775–780. 2005. View Article : Google Scholar : PubMed/NCBI