Immunochemistry

 melan-A+ (MLANA+) (#9422316#)
 alpha-inhibin+ (INHA+)

Predisposition

 Beckwith-Wiedemann syndrome
 germ-line P53 mutations

• Li-Fraumeni syndrome
• inherited R337H p53 mutation without Li-Fraumeni syndrome (#11481490#)

 Carney complex
 multiple endocrine neoplasia type 1
 congenital adrenal hyperplasia
 McCune-Albright syndrome

Associations

 ganglioneuroblastoma (P53 germline mutations) (#9598730#)

Cytogenetics

 CGH: #10514385#

Molecular biology

> Multistep adrenocortical tumorigenesis (#12629075#)

 Locus TP53 (17p13)

• TP53 mutations (30-50%) (#11454518#)

 Locus 11p15.5

• LOH at 11p15.5 (28.5%)
• Uniparental disomy at 11p15.5 (24%) (#7911125#)
• IGF2 overexpression (#10843195#, #7911125#)
• loss of function of p57KIP2 (#10634406#)
• Structural and functional abnormalities at 11p15 are associated with the malignant phenotype (#9253334#)

 LOH at 11q13: significantly higher in adrenocortical carcinomas (60%) than in benign lesions (11%) (#9935177#)

 high expression of cyclin E and G1 CDK
 altered expression of novH (#11502835#)

 allelotype: #9596277#

Differential diagnosis

 islet cell carcinoma
 pulmonary large cell undifferentiated carcinoma
 hepatocellular carcinoma (HCC)
 renal cell carcinoma
 bronchogenic carcinoma
 pheochromocytoma and paraganglioma
 alveolar soft part sarcoma

CGH

Losses

 1p21-31
 2q
 3p
 3q
 6q
 9p
 11q14-qter

Gains and amplifications

 5q12
 9q34
 12q
 17q
 17p
 20q

LOH

 1p (22%)
 3p (22%)
 9p (26%)

References

 Stratakis CA. Genetics of adrenocortical tumors: gatekeepers, landscapers and conductors in symphony. Trends Endocrinol Metab. 2003 Nov;14(9):404-10. PMID: #14580759#

 Reincke M, Beuschlein F, Slawik M, Borm K. Molecular adrenocortical tumourigenesis. Eur J Clin Invest. 2000 Dec;30 Suppl 3:63-8. PMID: #11281372#