Birt-Hogg-Dubé syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature.
Birt-Hogg-Dube Syndrome
/ complications
Diagnosis, Differential
Gastrointestinal Neoplasms
/ complications
Gastrointestinal Tract
/ pathology
Humans
Hyperplasia
/ complications
Intestinal Polyps
/ complications
Male
Middle Aged
Neoplasms, Multiple Primary
/ diagnosis
Polyps
/ complications
Proto-Oncogene Proteins
/ genetics
Tumor Suppressor Proteins
/ genetics
Birt-Hogg-Dubé syndrome
FLCN gene
Pneumothorax
Polyps
Skin neoplasms
Journal
BMC medical genetics
ISSN: 1471-2350
Titre abrégé: BMC Med Genet
Pays: England
ID NLM: 100968552
Informations de publication
Date de publication:
14 03 2020
14 03 2020
Historique:
received:
24
10
2018
accepted:
04
03
2020
entrez:
16
3
2020
pubmed:
17
3
2020
medline:
6
5
2020
Statut:
epublish
Résumé
Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis characterized by benign growth of the hair follicles, the presence of pulmonary cysts, spontaneous pneumothorax, and bilateral renal tumors that are usually hybrid oncocytic or multifocal chromophobe renal cell carcinoma. The diagnosis is confirmed by the presence of a pathogenic variant in the tumor suppressor folliculin (FLCN) gene mapped at 17p11.2. Although the dermatological lesions typical of BHDS are benign and only cause aesthetic concerns, and the pulmonary manifestations are controllable, the greater tendency of patients with this syndrome to present benign or malignant renal tumors, often bilateral and multifocal, makes the diagnosis of this syndrome important for the prognosis of the patients. The objective was to report the case of a patient with BHDS, without pulmonary manifestations and with hyperplastic polyposis of the gastrointestinal tract, and to perform a literature review. A 60-year-old man complained of abdominal pain and diarrhoea for 2 months. Physical examination was normal except for the presence of normochromic papules in the frontal region of the face associated with hyperkeratotic and hyperchromic papules in the dorsal region. The excisional biopsies of the skin lesions indicated trichodiscomas. Esophagogastroduodenoscopy, enteroscopy, and colonoscopy showed the presence of hyperplastic polyps in the stomach, duodenum, jejunum, colon, and rectum. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed multiple expansive solid lesions in both kidneys, with necrotic and calcified areas. Renal magnetic resonance angiography also showed a solid lesion in the right kidney measuring 5 cm in diameter and another solid lesion in the left kidney measuring 8 cm in diameter, both suggestive of renal angiomyolipoma. CT scans of the skull, chest, and temporal bones were normal. The genetic study revealed the presence of a variant of FLCN in the intron 13. To the best of our knowledge, this is the first reported case of BHDS with the simultaneous finding of gastrointestinal hyperplastic polyposis, which may represent a possible phenotypic expression of this syndrome that has not yet been described.
Sections du résumé
BACKGROUND
Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis characterized by benign growth of the hair follicles, the presence of pulmonary cysts, spontaneous pneumothorax, and bilateral renal tumors that are usually hybrid oncocytic or multifocal chromophobe renal cell carcinoma. The diagnosis is confirmed by the presence of a pathogenic variant in the tumor suppressor folliculin (FLCN) gene mapped at 17p11.2. Although the dermatological lesions typical of BHDS are benign and only cause aesthetic concerns, and the pulmonary manifestations are controllable, the greater tendency of patients with this syndrome to present benign or malignant renal tumors, often bilateral and multifocal, makes the diagnosis of this syndrome important for the prognosis of the patients. The objective was to report the case of a patient with BHDS, without pulmonary manifestations and with hyperplastic polyposis of the gastrointestinal tract, and to perform a literature review.
CASE PRESENTATION
A 60-year-old man complained of abdominal pain and diarrhoea for 2 months. Physical examination was normal except for the presence of normochromic papules in the frontal region of the face associated with hyperkeratotic and hyperchromic papules in the dorsal region. The excisional biopsies of the skin lesions indicated trichodiscomas. Esophagogastroduodenoscopy, enteroscopy, and colonoscopy showed the presence of hyperplastic polyps in the stomach, duodenum, jejunum, colon, and rectum. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed multiple expansive solid lesions in both kidneys, with necrotic and calcified areas. Renal magnetic resonance angiography also showed a solid lesion in the right kidney measuring 5 cm in diameter and another solid lesion in the left kidney measuring 8 cm in diameter, both suggestive of renal angiomyolipoma. CT scans of the skull, chest, and temporal bones were normal. The genetic study revealed the presence of a variant of FLCN in the intron 13.
CONCLUSIONS
To the best of our knowledge, this is the first reported case of BHDS with the simultaneous finding of gastrointestinal hyperplastic polyposis, which may represent a possible phenotypic expression of this syndrome that has not yet been described.
Identifiants
pubmed: 32171268
doi: 10.1186/s12881-020-0991-8
pii: 10.1186/s12881-020-0991-8
pmc: PMC7071710
doi:
Substances chimiques
FLCN protein, human
0
Proto-Oncogene Proteins
0
Tumor Suppressor Proteins
0
Types de publication
Case Reports
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
52Références
Ponti G, Pellacani G, Seidenari S, Pollio A, Muscatello U, Tomasi A. Cancer associated genodermatoses: skin neoplasms as clues to hereditary tumor syndromes. Crit Rev Oncol Hematol. 2013;85:239–56.
doi: 10.1016/j.critrevonc.2012.07.001
Stamatakis L, Metwalli AR, Middelton LA, Linehan M. Diagnosis and management of BHD-associated kidney cancer. Familial Cancer. 2013;12:397–402.
doi: 10.1007/s10689-013-9657-4
Toro JR, Wei MH, Glenn GM, Weinreich M, Toure O, Vocke C, Turner M, Choyke P, Merino MJ, Pinto PA, Steinberg SM, Schmidt LS, Linehan WM. BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports. J Med Genet. 2008;45:321–31.
doi: 10.1136/jmg.2007.054304
Sasso AAD, Belém LC, Zanetti G, Souza CA, Escuissato DL, Irion KL, Guimarães MD, Marchiori E. Birt-Hogg-Dubé syndrome. State-of-the-art review with emphasis on pulmonary involvement. Resp Med. 2015;109:289–96.
doi: 10.1016/j.rmed.2014.11.008
Nishii T, Tanabe M, Tanaka R, Matsuzawa T, Okudela K, Nozawa A, Nakatani Y, Furuya M. Unique mutation, accelerated mTOR signaling and angiogenesis in the pulmonary cysts of Birt-Hogg-Dubé syndrome. Pathol Int. 2013;63:45–55.
doi: 10.1111/pin.12028
Schmidt LS, Linehan WM. Molecular genetics and clinical features of Birt-Hogg-Dubé syndrome. Nat Rev Urol. 2015;12:558–69.
doi: 10.1038/nrurol.2015.206
Iribe Y, Yao M, Tanaka R, Kuroda N, Nagashima Y, Nakatani Y, Furuya M. Genome-wide uniparental disomy and copy number variations in renal cell carcinomas associated with Birt-Hogg-Dubé syndrome. Am J Pathol. 2016;186:337–46.
doi: 10.1016/j.ajpath.2015.10.013
Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, Turner ML, Choyke PL, Sharma N, Peterson J, Morrison P, Maher ER, Walther MM, Zbar B, Linehan WM. Germline BHD mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome. Am J Hum Genet. 2005;76:1023–33.
doi: 10.1086/430842
Benusiglio PR, Giraud S, Deveaux S, Méjean A, Correas JM, Joly D, Timsit MO, Ferlicot S, Verkarre V, Abadie C, Chauveau D, Leroux D, Avril MF, Cordier JF, Richard S, French National Cancer Institute Inherited Predisposition to Kidney Cancer Network. Renal cell tumor characteristics in patients with the Birt-Hogg-Dubé cancer susceptibility syndrome: a retrospective, multicentre study. Orphanet J Rare Dis. 2014;9:163–8.
doi: 10.1186/s13023-014-0163-z
Vocke CD, Yang Y, Pavlovich CP, et al. High frequency of somatic frameshift BHD gene mutations in Birt-Hogg-Dube associated renal tumors. J Natl Cancer Inst. 2005;97:931–5.
doi: 10.1093/jnci/dji154
Leiden Open Variation Database. European Birt-Hogg-Dubé Consortium LOVD Gene homepage for FLCN. https://grenada.lumc.nl/LOVD2/shared1/home.phd? Select db=FLCN (2015).
Rosty C, Buchanan DD, Walters RJ, Carr NJ, Bothman JW, Young JP, Brown IS. Hyperplastic polyp of the duodenum: a report of 9 cases with immunohistochemical and molecular findings. Hum Pathol. 2011;42:1953–9.
doi: 10.1016/j.humpath.2011.02.018
Rubio CA. Traditional serrated adenomas of the upper digestive tract. J Clin Pathol. 2016;69:1–5.
doi: 10.1136/jclinpath-2015-203258
Horpaopan S, Kirfel J, Peters S, Kloth M, Hüneburg R, Altmüller J, Drichel D, Odenthal M, Kristiansen G, Strassburg C, Nattermann J, Hoffmann P, Nürnberg P, Büttner R, Thiele H, Kahl P, Spier I, Aretz S. Exome sequencing characterizes the somatic mutation spectrum of early serrated lesions in a patient with serrated polyposis syndrome (SPS). Hered Cancer Clin Pract. 2017;15:22.
doi: 10.1186/s13053-017-0082-9
Salomao M, Luna AM, Sepulveda JL, Sepulveda AR. Mutational analysis by next generation sequencing of gastric type dysplasia occurring in hyperplastic polyps of the stomach: mutations in gastric hyperplastic polyps. Exp Mol Pathol. 2015;99:468–73.
doi: 10.1016/j.yexmp.2015.08.014
Terada T. Malignant transformation of foveolar hyperplastic polyp of the stomach: a histopathological study. Med Oncol. 2011;28:941–4.
doi: 10.1007/s12032-010-9556-6
Roche HJ, Carr NJ, Laing H, Bateman AC. Hyperplastic polyps of the duodenum: an unusual histological finding. J Clin Pathol. 2006;59:1305–6.
doi: 10.1136/jcp.2005.035022
Franzin G, Novelli P, Fratton A. Hyperplastic and metaplastic polyps of the duodenum. Gastrointest Endosc. 1983;29:140–2.
doi: 10.1016/S0016-5107(83)72560-5
den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, Roux AF, Smith T, Antonarakis SE, Taschner PE. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat. 2016;37(6):564–9. https://doi.org/10.1002/humu.22981 .
doi: 10.1002/humu.22981
Nahorski MS, Lim DH, Martin L, Gille JJ, McKay K, Rehal PK, Ploeger HM, van Steensel M, Tomlinson IP, Latif F, Menko FH, Maher ER. Investigation of the Birt-Hogg-Dubé tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer. J Med Genet. 2010;47:385–90.
doi: 10.1136/jmg.2009.073304
Lencastre A, Ponte P, Apetato M, Nunes L, Lestra S. Birt-Hogg-Dubé syndrome. An Bras Dermatol. 2013;88:203–5.
doi: 10.1590/abd1806-4841.20132199
Tobino K, Seyama K. Birt-Hogg-Dubé syndrome with renal angiomyolipoma. Intern Med. 2012;51:1279–80.
doi: 10.2169/internalmedicine.51.7211
Spring P, Fellmann F, Giraud S, Clayton H, Hohl D. Syndrome of Birt-Hogg-Dubé, a histopathological pitfall with similarities to tuberous sclerosis: a report of three cases. Am J Dermatopathol. 2013;35(2):241–5.
doi: 10.1097/DAD.0b013e318259b593
Menko FH, van Steensel MA, Giraud S, et al. Birt-Hogg-Dubé syndrome: diagnosis and management. Lancet Oncol. 2009;10:1199–206.
doi: 10.1016/S1470-2045(09)70188-3
Byrne M, Mallipeddi R, Pichert G, Whittaker S. Birt-Hogg-Dubé syndrome with a renal angiomyolipoma: further evidence of a relationship between Birt-Hogg-Dubé syndrome and tuberous sclerosis complex. Australas J Dermatol. 2012;53:151–4.
doi: 10.1111/j.1440-0960.2011.00738.x
Bhatt JR, Richard PO, Kim NS, Finelli A, Manickavachagam K, Legere L, Evans A, Pei Y, Sykes J, Jhaveri K, Jewett MA. Natural history of renal Angiomyolipoma (AML): Most patients with large AMLs >4cm can be offered active surveillance as an initial management strategy. Eur Urol. 2016;70:85–90.
doi: 10.1016/j.eururo.2016.01.048
Bissler JJ, Kingswood JC, Radzikowska E, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicenter, randomized, double-blind, placebocontrolled trial. Lancet. 2013;381:817e824.
doi: 10.1016/S0140-6736(12)61767-X
Zöllner JP, Franz DN, Hertzberg C, Nabbout R, Rosenow F, Sauter M, Schubert-Bast S, Wiemer-Kruel A, Strzelczyk A. A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC). Orphanet J Rare Dis. 2020;15(1):23.
doi: 10.1186/s13023-019-1258-3
van Slegtenhorst M, Khabibullin D, Hartman TR, et al. The Birt-Hogg-Dube and tuberous sclerosis complex homologs have opposing roles in amino acid homeostasis in Schizosaccharomyces pombe. J Biol Chem. 2007;282:24583–90.
doi: 10.1074/jbc.M700857200
Misago N, Narisawa Y. Fibrofolliculoma in a patient with tuberous sclerosis complex. Clin Exp Dermatol. 2009;34(8):892–4.
doi: 10.1111/j.1365-2230.2008.03065.x
Hartman TR, Nicolas E, Klein-Szanto A, et al. The role of the Birt-Hogg-Dubé protein in mTOR activation and renal tumorigenesis. Oncogene. 2009;28:1594–604.
doi: 10.1038/onc.2009.14
Kume K, Hirakoba M, Murata I, Yoshikawa I, Otsuki M. Disappearance of both MALT lymphoma and hyperplastic polyps in the stomach after eradication of helicobacter pylori. Am J Gastroenterol. 2001;96(9):2796–7.
doi: 10.1111/j.1572-0241.2001.04143.x
Velázquez-Dohorn ME, López-Durand CF, Gamboa-Domínguez A. Changing Trends in Gastric Polyps. Rev Invest Clin. 2018;70(1):40–5. https://doi.org/10.24875/RIC.17002430 .
doi: 10.24875/RIC.17002430
Hornstein OP, Knickenberg M. Perifolicular fibromatosis cutis with polyp of the colon- a cutaneo-intestinal syndrome suigeneris. Arch Dermatol. 1975;253:161–75.
doi: 10.1007/BF00582068
Daniell J, Plazzer JP, Perera A, Macrae F. An exploration of genotype-phenotype link between Peutz-Jeghers syndrome and STK11: a review. Familial Cancer. 2018;17(3):421–7. https://doi.org/10.1007/s10689-017-0037-3 .
doi: 10.1007/s10689-017-0037-3
Pang M, Liu Y, Hou X, Yang J, He X, Hou N, Liu P, Liang L, Fu J, Wang K, Ye Z, Gong B. A novel APC mutation identified in a large Chinese family with familial adenomatous polyposis and a brief literature review. Mol Med Rep. 2018 Aug;18(2):1423–32. https://doi.org/10.3892/mmr.2018.9130 .
doi: 10.3892/mmr.2018.9130
Vasovčák P, Senkeříková M, Hatlová J, Křepelová A. Multiple primary malignancies and subtle mucocutaneous lesions associated with a novel PTEN gene mutation in a patient with Cowden syndrome: case report. BMC Med Genet. 2011;12:38. https://doi.org/10.1186/1471-2350-12-38 .
doi: 10.1186/1471-2350-12-38
Sager RA, Woodford MR, Shapiro O, Mollapour M, Bratslavsky G. Sporadic renal angiomyolipoma in a patient with Birt-Hogg-Dubé: chaperones in pathogenesis. Oncotarget. 2018;9(31):22220–9. https://doi.org/10.18632/oncotarget.25164 eCollection 2018 Apr 24.
doi: 10.18632/oncotarget.25164
Benhammou JN, Vocke CD. Santani Aet al. Identification ofintragenic deletions and duplication in the FLCN gene in Birt-Hogg-Dube syndrome. Genes Chromosomes Cancer. 2011;50:466–77.26.
doi: 10.1002/gcc.20872
Schmidt LS, Linehan WM. Molecular genetics and clinicalfeatures of Birt-Hogg-Dube syndrome. Nat Rev Urol. 2015;12:558–69.
doi: 10.1038/nrurol.2015.206
Zhang X, Ma D, Zou W, et al. A rapid NGS strategy for comprehensive molecular diagnosis of Birt-Hogg-Dube syn-drome in patients with primary spontaneous pneumothorax. Respir Res. 2016;17:64.
doi: 10.1186/s12931-016-0377-9
Furuya M, Nakatani Y. Pathology of Birt-Hogg-Dubé syndrome: a special reference of pulmonary manifestations in a Japanese population with a comprehensive analysis and review. Pathol Int. 2019;69(1):1–12.
doi: 10.1111/pin.12752