Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome

Ann Diagn Pathol. 2014 Jun;18(3):171-6. doi: 10.1016/j.anndiagpath.2014.03.002. Epub 2014 Mar 29.


In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors.

Keywords: Birt-Hogg-Dubé syndrome; Intratumoral peripheral small papillary tufts; Renal tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biopsy
  • Birt-Hogg-Dube Syndrome / genetics
  • Birt-Hogg-Dube Syndrome / pathology*
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / pathology*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology*
  • Female
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Pneumothorax / genetics
  • Pneumothorax / pathology
  • Proto-Oncogene Proteins / genetics
  • Tumor Suppressor Proteins / genetics


  • FLCN protein, human
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins