Clinicopathological features and diagnosis of Birt-Hogg-Dube syndrome-associated hybrid oncocytic tumor
LIU Yan
WANG Yan
LI Yun-xia
YU Wen-juan
JIANG Yan-xia
LI Yu-jun
ZHANG Wei
Abstract：Objective To investigate the clinicopathological characteristics and diagnosis of Birt-Hogg-Dubé syndrome-associated hybrid oncocytic tumor(BHD-HOT)and to enhance understanding of this type of kidney tumor.Methods Three cases of hybrid oncocytic renal tumors in patients with BHD syndrome were collected.The clinicopathological data of the patients were retrospectively summarized.Morphological observations,immunohistochemical staining,and molecular detection were performed,followed by a literature review.Results All three patients were male,aged 56 to 77 years(average age:66.5 years).One patient presented with double lung cysts accompanied by pneumothorax,skin papules,and renal tumor lesions.For the other two patients,one manifested skin papules in addition to renal tumors,while the other had a history of double lung cysts and pneumothorax.Two cases were identified as bilateral and multifocal.Tumor diameters ranged from 0.8 to 4 cm(average:2.3 cm),with section surfaces appearing gray-red and gray-yellow,and exhibiting clear boundaries.Histological examination revealed a mixed distribution of low-grade eosinophilic and clear cells in a"mosaic-like"arrangement in all three cases.Immunohistochemical analysis indicated that tumor cells in all three cases were negative for Vimentin,while CD117 showed weak to moderate patchy positivity,primarily in eosinophilic cells.In two cases,CK7 displayed scattered positivity,predominantly in clear cells.The Ki-67 proliferation index was less than 3%.Whole-exome sequencing results revealed germline mutations in the FLCN gene in both cases,without the presence of other significant companion mutations such as VHL,TSC1,TSC2,MTOR,or ELOC(TCEB1).The three patients were followed for 38 to 126 months,during which no recurrence or metastasis was observed.Conclusion The multifocal or bilateral occurrence of tumors and the mixed distribution of low-grade eosinophilic and clustered clear cells in a mosaic-like arrangement play a crucial role in diagnosing renal tumors associated with BHD syndrome.Additionally,the presence of extrarenal lesions,such as those in the lungs and skin,can aid in diagnosis,while germline mutations in the FLCN gene remain the gold standard for this diagnosis.
Keywords：Birt-Hogg-Dube syndromeHybrid oncocytic tumorFLCNCarcinomarenal cellDiagnosisdifferential
Publication Date：2024-11-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 1050-1054 )