adrenal cortical carcinoma

Images

 Adrenal cortical adenoma and carcinoma

• https://twitter.com/a_sleeping_dog/status/750195822805983232

Digital cases

 JRC:14921 : Lung metastasis of adrenal cortical carcinoma.
 JRC:14613 : Adrenal cortical carcinoma (with Cushing syndrome).
 JRC:18771 : Adrenal cortical carcinoma

Grading systems / Microscopic prognostic parameters

 Weiss score (2004) (21997290)
 The reticulin algorithma (2013)
 The Helsinski score (2015)

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

Variants

 oncocytic adrenocortical carcinoma
 virilizing adrenocortical carcinoma

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)

 TP53 (17p13)

• TP53 mutations (30-50%) (11454518)
• TP53-associated adrenocortical carcinoma

 APC mutations

• APC-associated adrenocortical carcinoma

 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

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

 The weiss score and beyond—histopathology for adrenocortical carcinoma. Papotti M, Libè R, Duregon E, Volante M, Bertherat J, Tissier F. Horm Cancer. 2011 Dec;2(6):333-40. PMID: 21997290

Reviews

 Differences in the molecular mechanisms of adrenocortical tumorigenesis between children and adults. Faria AM, Almeida MQ. Mol Cell Endocrinol. 2012 Mar 31;351(1):52-7. PMID: 22019901

 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