TITLE

Benign clear cell "sugar" tumor of the lung in a patient with Birt-Hogg-Dubé syndrome: a case report

AUTHOR(S)
Yoko Gunji-Niitsu; Toshio Kumasaka; Shigehiro Kitamura; Yoshito Hoshika; Takuo Hayashi; Hitoshi Tokuda; Riichiro Morita; Etsuko Kobayashi; Keiko Mitani; Mika Kikkawa; Kazuhisa Takahashi; Kuniaki Seyama
PUB. DATE
November 2016
SOURCE
BMC Medical Genetics;11/21/2016, Vol. 17, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Case Study
ABSTRACT
Background: Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a tumor suppressor gene of which protein product is involved in mechanistic target of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism. Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome, although the condition is due to deleterious sequence variants in a tumor suppressor gene. Here we report, for the first time to our knowledge, a patient with BHD syndrome who was complicated with a clear cell "sugar" tumor (CCST) of the lung, a benign tumor belonging to perivascular epithelioid cell tumors (PEComas) with frequent causative relation to tuberous sclerosis complex 1 (TSC1) or 2 (TSC2) gene. Case presentation: In a 38-year-old Asian woman, two well-circumscribed nodules in the left lung and multiple thin-walled, irregularly shaped cysts on the basal and medial area of the lungs were disclosed by chest roentgenogram and computer-assisted tomography (CT) during a preoperative survey for a bilateral faucial tonsillectomy. Analysis of the resected tumor showed large polygonal cells with clear cytoplasm proliferating in a solid pattern. Immunohistochemistry revealed that these tumor cells were positive for microphthalmia-transcription factor, S100, and CD1a but negative for HMB45, indicating that the tumor was a CCST. Genetic testing indicated that the patient had a germline mutation on exon 12 of the FLCN gene, i.e., insertion of 7 nucleotides (CCACCCT) (c.1347_1353dupCCACCCT). Direct sequencing of the FLCN exon 12 using genomic DNA obtained from her microdissected CCST cells clearly revealed loss of the wild-type FLCN sequence, which confirmed complete functional loss of the FLCN gene. On the other hand, no loss of heterozygosity around TCS1- or TSC2-associated genetic region was demonstrated. Conclusion: To our knowledge, this is the first report of CCST of the lung in a patient with BHDS, indicating that CCST should be added to the spectrum of pulmonary manifestations of BHDS.
ACCESSION #
119711164

 

Related Articles

  • Dermatology Clinic.  // Clinical Advisor;Aug2013, Vol. 16 Issue 8, p82 

    The article offers information on the diagnosis and treatment of Birt-Hogg-Dubé (BHD) syndrome. It notes the clinical constellation of BHD which includes renal tumors, fibrofolliculomas, and pneumothorax. It mentions renal cancer as the most dangerous consequence of BHD and suggests annual...

  • Birt Hogg Dubé Sendromlu Bir Olgu. Akay, Bengü Nisa; Parlak, Nehir; Akyol, Aynur; Heper, Aylin Okçu // Turkish Journal of Dermatology / Turk Dermatoloji Dergisis;Dec2013, Vol. 7 Issue 4, p245 

    Birt- Hogg- Dubé syndrome associated with benign tu morsof the hairfollicle (fi brofolliculoma, trichodiscoma), a large number of lung cysts and renal tumor is an autosomal dominant genodermatosis. In these patients, benign tumors of the hair follicle is often seen after the age of 20, lung...

  • Isolated familial pneumothorax in a Taiwanese family with Birt-Hogg-Dubé syndrome. C. Y. Yang; H. C. Wang; J. S. Chen; C. J. Yu // Journal of Postgraduate Medicine;Oct-Dec2013, Vol. 59 Issue 4, p321 

    Primary spontaneous pneumothorax usually occurs as a sporadic event, but may be clustered in certain families with an underlying inherited disorder. Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disease accounting for familial pneumothorax. BHD syndrome, caused by mutation of the...

  • Primary spontaneous pneumothorax and the Birt-Hogg-Dubé syndrome. Koul, P.A. // Journal of Postgraduate Medicine;Oct-Dec2013, Vol. 59 Issue 4, p324 

    The article offers information on primary spontaneous pneumothorax and Birt-Hogg-Dubé syndrome (BHDS). BHDS is a genodermatosis that is characterized by predisposition to lung cysts and renal neoplasms. Almost 11 percent of spontaneous pneumothorax patients have family history of the disorder...

  • Renal tumor associated with pulmonary cysts: Birt–Hogg–Dubé syndrome. Escuissato, D.L.; de Almeida Teixeira, B.C.; Warszwiak, D.; Zanetti, G.; Marchiori, E. // QJM: An International Journal of Medicine;Oct2014, Vol. 107 Issue 10, p851 

    No abstract available.

  • Knockdown of Slingshot 2 (SSH2) serine phosphatase induces Caspase3 activation in human carcinoma cell lines with the loss of the Birt-Hogg-Dubé tumour suppressor gene (FLCN). Lu, X; Boora, U; Seabra, L; Rabai, E M; Fenton, J; Reiman, A; Nagy, Z; Maher, E R // Oncogene;2/20/2014, Vol. 33 Issue 8, p956 

    Birt-Hogg-Dubé (BHD) syndrome, is a dominantly inherited familial cancer syndrome associated with susceptibility to renal cell carcinoma (RCC) caused by inactivating mutations in the folliculin (FLCN) gene. The precise functions of the FLCN gene product are still under investigation but RCC...

  • Folliculin Regulates Ampk-Dependent Autophagy and Metabolic Stress Survival. Possik, Elite; Jalali, Zahra; Nouët, Yann; Yan, Ming; Gingras, Marie-Claude; Schmeisser, Kathrin; Panaite, Lorena; Dupuy, Fanny; Kharitidi, Dmitri; Chotard, Laëtitia; Jones, Russell G.; Hall, David H.; Pause, Arnim // PLoS Genetics;Apr2014, Vol. 10 Issue 4, p1 

    Dysregulation of AMPK signaling has been implicated in many human diseases, which emphasizes the importance of characterizing AMPK regulators. The tumor suppressor FLCN, responsible for the Birt-Hogg Dubé renal neoplasia syndrome (BHD), is an AMPK-binding partner but the genetic and...

  • The Relevance of Family History Taking in the Detection and Management of Birt-Hogg-Dubé Syndrome. Torricelli, Elena; Occhipinti, Mariaelena; Cavigli, Edoardo; Tancredi, Giorgia; Rosi, Elisabetta; Rossi, Cesare; Bonaguro, Michela; Candita, Luisa; Papi, Laura; Novelli, Luca; Bezzi, Michela; Bargagli, Elena; Voltolini, Luca; Pistolesi, Massimo // Respiration;2019, Vol. 98 Issue 2, p125 

    Background: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant inherited disorder characterized by inactivation of the gene Folliculin (FLCN), pulmonary cysts with recurrent spontaneous pneumothorax, dermatological lesions, and an increased risk of developing renal malignancies....

  • Folliculin Contributes to VHL Tumor Suppressing Activity in Renal Cancer through Regulation of Autophagy. Bastola, Prabhat; Stratton, Yiwen; Kellner, Emily; Mikhaylova, Olga; Yi, Ying; Sartor, Maureen A.; Medvedovic, Mario; Biesiada, Jacek; Meller, Jarek; Czyzyk-Krzeska, Maria F. // PLoS ONE;Jul2013, Vol. 8 Issue 7, p1 

    Von Hippel-Lindau tumor suppressor (VHL) is lost in the majority of clear cell renal cell carcinomas (ccRCC). Folliculin (FLCN) is a tumor suppressor whose function is lost in Birt-Hogg-Dubé syndrome (BHD), a disorder characterized by renal cancer of multiple histological types including...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics