From hyperplasia to carcinoma: a molecular driven adrenal disease

Area of Science:

• Endocrinology
• Oncology
• Genetics

Background:

• Bilateral Macronodular Adrenocortical Disease (BMAD) involves bilateral benign adrenal nodules, often with autonomous cortisol secretion.
• Germline mutations in tumor suppressor genes, notably ARMC5, are found in about 30% of BMAD cases.
• The progression from BMAD to adrenal cortical carcinoma (ACC) is rare, with limited functional evidence linking the two.

Purpose of the Study:

• To investigate the potential link between BMAD and the development of ACC.
• To analyze the molecular alterations in a case of ACC arising within a background of BMAD.
• To hypothesize BMAD as a potential precursor lesion for ACC.

Main Methods:

• Case report of a patient with Cushing's syndrome on BMAD who later developed ACC.
• Germline genotyping for known tumor suppressor genes (CDKN1B, KDM1A, PRKACA, PRKAR1A, MEN1, APC, ARMC5, TP53).
• Next-generation sequencing of both the ACC and adjacent macronodular adrenal tissue.

Main Results:

• The patient developed ACC over 20 years after initial BMAD diagnosis.
• Germline genotyping revealed no pathogenic variants in the screened genes.
• Somatic molecular profiling demonstrated a progressive accumulation of alterations from benign nodules to ACC.

Conclusions:

• BMAD may represent an early stage in the development of ACC.
• The findings suggest a potential pathway from benign adrenal nodules to malignancy.
• Increased radiological monitoring for patients with BMAD is recommended to detect early signs of ACC.