TY - JOUR
T1 - Adrenal Cortical Carcinoma and Additional Rare Pathologic Findings in Multi-Organs in a Birt-Hogg-Dubé Syndrome Patient
T2 - With an Emphasis on the Molecular Characteristics of Adrenal Cortical Carcinoma
AU - Kim, David
AU - Murvelashvili, Natia
AU - Hamidi, Oksana
AU - Jia, Liwei
N1 - Publisher Copyright:
© The Author(s) 2022.
PY - 2023/8
Y1 - 2023/8
N2 - Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder caused by germline alterations in the FLCN gene. We report a 38-year-old man with BHD syndrome presenting with multiple rare pathologic findings involving various organs, including adrenal cortical carcinoma (ACC). Initially, he presented with severe cholestatic jaundice and was found to have a 25 cm left adrenal mass with radiologic evidence of lung metastases, which was diagnosed as ACC on resection. Concurrently, pigmented, bile-stained granular casts were present within the kidney and diffuse cholestasis of the liver consistent with Stauffer syndrome was identified. Subsequent staging workup detected a 1.2 cm tubulovillous adenoma in the distal ascending colon and an incidental 1.2 cm thyroid nodule. Germline genetic testing revealed a pathogenic FLCN c.1285dup. Targeted DNA next generation sequencing of ACC revealed FLCN c.1285dup, IDH2 c.5332C>T, PRKAR1A c.1074del, and PDGFRB c.3282C>A and concurrent transcriptomic analysis demonstrated VEGFA overexpression. Fourteen months after resection, follow-up computerized tomography (CT) identified the progression of lung metastases and chemotherapy with etoposide doxorubicin and cisplatin was initiated. Here, we report the first ACC with the molecular characteristics in a BHD syndrome patient, although 5 adrenal lesions, including ACC, adenomas or neoplasm with malignant potential due to higher Ki67 labelling index, have been reported in the literature and no somatic analysis in these tumors were performed. Despite the rarity, our case potentially expands the tumor spectrum of BHD patients, helps to solidify possible association with adrenal cortical tumors and reiterates the value of genetic counseling in patients with ACC.
AB - Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant disorder caused by germline alterations in the FLCN gene. We report a 38-year-old man with BHD syndrome presenting with multiple rare pathologic findings involving various organs, including adrenal cortical carcinoma (ACC). Initially, he presented with severe cholestatic jaundice and was found to have a 25 cm left adrenal mass with radiologic evidence of lung metastases, which was diagnosed as ACC on resection. Concurrently, pigmented, bile-stained granular casts were present within the kidney and diffuse cholestasis of the liver consistent with Stauffer syndrome was identified. Subsequent staging workup detected a 1.2 cm tubulovillous adenoma in the distal ascending colon and an incidental 1.2 cm thyroid nodule. Germline genetic testing revealed a pathogenic FLCN c.1285dup. Targeted DNA next generation sequencing of ACC revealed FLCN c.1285dup, IDH2 c.5332C>T, PRKAR1A c.1074del, and PDGFRB c.3282C>A and concurrent transcriptomic analysis demonstrated VEGFA overexpression. Fourteen months after resection, follow-up computerized tomography (CT) identified the progression of lung metastases and chemotherapy with etoposide doxorubicin and cisplatin was initiated. Here, we report the first ACC with the molecular characteristics in a BHD syndrome patient, although 5 adrenal lesions, including ACC, adenomas or neoplasm with malignant potential due to higher Ki67 labelling index, have been reported in the literature and no somatic analysis in these tumors were performed. Despite the rarity, our case potentially expands the tumor spectrum of BHD patients, helps to solidify possible association with adrenal cortical tumors and reiterates the value of genetic counseling in patients with ACC.
KW - Birt-Hogg-Dubé syndrome
KW - FLCN gene
KW - adrenal cortical carcinoma
KW - thyroid nodule
KW - tubulovillous adenoma
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U2 - 10.1177/10668969221117246
DO - 10.1177/10668969221117246
M3 - Article
C2 - 35946080
AN - SCOPUS:85135837545
SN - 1066-8969
VL - 31
SP - 689
EP - 694
JO - International Journal of Surgical Pathology
JF - International Journal of Surgical Pathology
IS - 5
ER -