Oncocytoma of the adrenal gland in Birt-Hogg-Dube syndrome

Ramsingh, Jason; Watson, Carol

doi:10.1136/bcr-2018-224283

Cited by 7 publications

(3 citation statements)

References 7 publications

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“…15 A 3.7 cm oncocytoma of the adrenal gland was reported in a 32-year-old BHD syndrome man with c.1285 dupC confirmed by genetic test. 16 Our case is an ACC occurring in a BHD syndrome patient with suspicious radiologic evidence of bilateral pulmonary metastases, which harbored IDH2 c.5332C>T, PRKAR1A c.1074del, PDGFRB c.3282C>A, in addition to FLCN c.1285dup and had VEGFA overexpression by transcriptomic analysis. A comprehensive genomic characterization of ACC lead by The Cancer Genome Atlas (TCGA) using a dataset of 91 ACCs expanded ACC driver genes including TP53 , ZNFR3 , CTNNB1 , PRKAR1A , CCNE1 , and TERF2.…”

Section: Discussionmentioning

confidence: 78%

Adrenal Cortical Carcinoma and Additional Rare Pathologic Findings in Multi-Organs in a Birt-Hogg-Dubé Syndrome Patient: With an Emphasis on the Molecular Characteristics of Adrenal Cortical Carcinoma

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 78%

Adrenal Cortical Carcinoma and Additional Rare Pathologic Findings in Multi-Organs in a Birt-Hogg-Dubé Syndrome Patient: With an Emphasis on the Molecular Characteristics of Adrenal Cortical Carcinoma

et al. 2022

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“…6 A histopathological finding of oncocytic tumour of the left adrenal in a man in his 30s with a prior diagnosis of BHD syndrome was published by Ramsingh and Watson. 7 …”

Section: Discussionmentioning

confidence: 99%

Phaeochromocytoma in a patient with a Birt-Hogg-Dubé syndrome phenotype

Alkundi

Momoh

2023

BMJ Case Rep

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A case of phaeochromocytoma in a female patient in her 50s with phenotypical expressions for the rare Birt-Hogg-Dubé (BHD) syndrome is presented. Whether this is an incidental finding or that there is a composite relationship between these two entities remains to be fully described. Less than 10 cases reporting likely association of BHD syndrome with adrenal tumours have been reported in the literature to date.

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“…Oncocytomas are epithelia-derived human neoplasms characterized by an aberrant accumulation of swollen and deranged mitochondria within the cytoplasm. These tumors, found in endocrine and exocrine tissues [ 14 ], mainly occur in sporadic forms, albeit rare familial cases have been reported within the phenotypic spectrum of Birt-Hogg-Dubè (BHD; OMIM:135150) [ 15 , 16 ] or Cowden syndrome (CS, OMIM:158350) [ 17 , 18 ], and of Familial Non-medullary Thyroid Carcinoma (OMIM: 188470) [ 19 , 20 ]. Even though oncogenic drivers are known in these syndromes, i.e., the Folliculin ( FLCN ) gene for BHD and Phosphatase and Tensin Homolog ( PTEN ) for CS, the search for a role of such nuclear genes in triggering oncocytic transformation has failed to date, and it is likely therefore that other modifiers impinge on the phenotypic change that occurs in a few, but not all syndromic individuals.…”

Section: Introductionmentioning

confidence: 99%

Pathogenic Mitochondrial DNA Mutation Load Inversely Correlates with Malignant Features in Familial Oncocytic Parathyroid Tumors Associated with Hyperparathyroidism-Jaw Tumor Syndrome

Luise

Iommarini

Marchio

et al. 2021

Cells

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While somatic disruptive mitochondrial DNA (mtDNA) mutations that severely affect the respiratory chain are counter-selected in most human neoplasms, they are the genetic hallmark of indolent oncocytomas, where they appear to contribute to reduce tumorigenic potential. A correlation between mtDNA mutation type and load, and the clinical outcome of a tumor, corroborated by functional studies, is currently lacking. Recurrent familial oncocytomas are extremely rare entities, and they offer the chance to investigate the determinants of oncocytic transformation and the role of both germline and somatic mtDNA mutations in cancer. We here report the first family with Hyperparathyroidism-Jaw Tumor (HPT-JT) syndrome showing the inherited predisposition of four individuals to develop parathyroid oncocytic tumors. MtDNA sequencing revealed a rare ribosomal RNA mutation in the germline of all HPT-JT affected individuals whose pathogenicity was functionally evaluated via cybridization technique, and which was counter-selected in the most aggressive infiltrating carcinoma, but positively selected in adenomas. In all tumors different somatic mutations accumulated on this genetic background, with an inverse clear-cut correlation between the load of pathogenic mtDNA mutations and the indolent behavior of neoplasms, highlighting the importance of the former both as modifiers of cancer fate and as prognostic markers.

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Oncocytoma of the adrenal gland in Birt-Hogg-Dube syndrome

Cited by 7 publications

References 7 publications

Adrenal Cortical Carcinoma and Additional Rare Pathologic Findings in Multi-Organs in a Birt-Hogg-Dubé Syndrome Patient: With an Emphasis on the Molecular Characteristics of Adrenal Cortical Carcinoma

Adrenal Cortical Carcinoma and Additional Rare Pathologic Findings in Multi-Organs in a Birt-Hogg-Dubé Syndrome Patient: With an Emphasis on the Molecular Characteristics of Adrenal Cortical Carcinoma

Phaeochromocytoma in a patient with a Birt-Hogg-Dubé syndrome phenotype

Pathogenic Mitochondrial DNA Mutation Load Inversely Correlates with Malignant Features in Familial Oncocytic Parathyroid Tumors Associated with Hyperparathyroidism-Jaw Tumor Syndrome

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