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Birt-Hogg-Dube syndrome-associated pulmonary cysts

Sunday 25 March 2012

pulmonary cysts of the Birt-Hogg-Dube syndrome

The BHD syndrome-associated pulmonary cyst may be considered a hamartoma-like cystic alveolar formation associated with deranged mTOR signaling.

Multiple pulmonary cysts and pneumothorax are the key signs for diagnosing BHD syndrome.

Birt-Hogg-Dubé (BHD) syndrome

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder characterized by fibrofolliculomas, renal tumors, and pulmonary cysts with recurrent pneumothorax.

This disorder is caused by mutations in the gene that encodes folliculin (FLCN). FLCN is regarded as a tumor suppressor; it mediates cellular activities by interacting with the mammalian target of rapamycin (mTOR).

Synopsis

- pulmonary basilar cysts

  • The inner surface of cysts is lined by epithelial cells, sometimes with a predominance of type II pneumocyte-like cuboidal cells.
  • The cysts occasionally contained internal septa consisting of alveolar walls or showed an "alveoli within an alveolus" pattern.
  • The cells constituting the cysts stained positive for phospho-S6 ribosomal protein expression, suggesting activation of the mTOR pathway.

Other pulmonary lesions

- pleuropulmonary blebs
- spontaneous pneumothorax

Differential diagnosis

- Although BHD pulmonary cysts are frequently misdiagnosed as nonspecific cystic diseases, they are distinctly different in histopathology from other bullous changes.

- Mechanical stress such as rupture and post-rupture remodeling allows mesothelial invagination and fibrosis.

- Such modified BHD pulmonary cysts are virtually indistinguishable from non-specific blebs and bullae.

Etiology

- Birt-Hogg-Dube syndrome (BHD) is caused by mutation in the gene FLCN encoding folliculin (MIM.607273)

See also

- tumor predisposition in Birt-Hogg-Dube syndrome (BHD syndrome)

  • acrochordon (skintag)
  • hair follicle hamartomas
    • fibrofolliculoma
    • trichodiscoma (tumor of the hair disc)
    • perifollicular fibroma
  • colonic polyps
  • renal tumors
    • renal oncocytomas
    • chromophobe renal cell carcinomas

References

- Pulmonary Cysts of Birt-Hogg-Dubé Syndrome: A Clinicopathologic and Immunohistochemical Study of 9 Families. Furuya M, Tanaka R, Koga S, Yatabe Y, Gotoda H, Takagi S, Hsu YH, Fujii T, Okada A, Kuroda N, Moritani S, Mizuno H, Nagashima Y, Nagahama K, Hiroshima K, Yoshino I, Nomura F, Aoki I, Nakatani Y. Am J Surg Pathol. 2012 Apr;36(4):589-600. PMID: #22441547#

- Pleuropulmonary pathology of Birt-Hogg-Dubé syndrome. Butnor KJ, Guinee DG Jr. Am J Surg Pathol. 2006 Mar;30(3):395-9. PMID: #16538061#