World Journal of Urology

, Volume 28, Issue 3, pp 329–334 | Cite as

Improvement of histopathological classification of adrenal gland tumors by genetic differentiation

  • Torsten GruschwitzEmail author
  • Jan Breza
  • Heiko Wunderlich
  • Kerstin Junker
Topic Paper



There are often problems in differentiating between benign and malignant adrenal gland tumors by imaging and histopathology. Fine-needle biopsy is possible but not used owing to problems in histopathological differentiation. On account of considerable differences in the therapy and aftercare of benign and malignant adrenal tumors, correct classification of tumor type is of greatest importance. The purpose of this study was to define specific genetic alterations differentiating between adenomas and carcinomas.


DNA was isolated from tumor areas in paraffin sections and amplified by a modified protocol for DOP-PCR. After labeling of tumor-DNA and normal DNA with biotin-dUTP and digoxigenin-dUTP, respectively, comparative genomic hybridization (CGH) was carried out according to standard protocols. Retrospectively, 26 (16 adenomas and 10 carcinomas) tumors of the adrenal cortex were analyzed.


Genetic alterations were found in 5/16 adenomas (31.25%) and in all adrenocortical carcinomas. The mean number of genetic changes per tumor was 8.7 (range 6–12) in carcinomas. The benign cortical tumors present 1.6 changes (range 0–3) per tumor. Only a moderate correlation between number of alterations and size of tumor was seen. Furthermore, specific chromosomal alterations of carcinomas were identified.


Genetic evaluation facilitates differentiation between adrenal gland tumors. Genetic tests should be used in routine diagnostics of adrenal specimens. Potentially, fine-needle biopsy can be established as standard diagnostics of adrenal tumors with unknown genesis.


Adrenal tumor Tumor-type differentiation Genetic evaluation Fine-needle biopsy 


Conflict of interest statement



  1. 1.
    Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B (1995) Incidentally discovered adrenal masses. Endocrine rev 16:460–484Google Scholar
  2. 2.
    Barzon L, Sonino N, Fallo F, Palù G, Boscaro M (2003) 315 Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol 149(4):273–285CrossRefPubMedGoogle Scholar
  3. 3.
    Third National Cancer Survey: Incidence Data, National Cancer Institute Monograph (1975) United States Department of Health, Education and Welfare, Public Health Service, National Institute of Health, National Cancer InstituteGoogle Scholar
  4. 4.
    Ng L, Libertino JM (2003) Adrenocortical carcinoma: diagnosis, evaluation and treatment. J Urol 169(1):5–11CrossRefPubMedGoogle Scholar
  5. 5.
    Blake MA, Holakere NS, Boland GW (2008) Imaging techniques for adrenal lesion characterization. Radiol Clin North Am 46(1):65–78CrossRefPubMedGoogle Scholar
  6. 6.
    Cerfolio RJ, Vaughan ED Jr, Brennan TG Jr, Hirvela ER (1993) Accuracy of computed tomography in predicting adrenal tumor size. Surg Gynecol Obstet 176(4):307–309PubMedGoogle Scholar
  7. 7.
    Weiss LM (1984) Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 8(3):163–169PubMedCrossRefGoogle Scholar
  8. 8.
    Weiss LM, Medeiros LJ, Vickery AL Jr (1989) Pathologic features of prognostic significance in adrenocortical carcinoma. Am J Surg Pathol 13(3):202–206PubMedGoogle Scholar
  9. 9.
    Hough AJ, Hollifield JW, Page DL, Hartmann WH (1979) Prognostic factors in adrenal cortical tumors. A mathematical analysis of clinical and morphologic data. Am J Clin Pathol 72(3):390–399PubMedGoogle Scholar
  10. 10.
    Van Slooten H, Schaberg A, Smeenk D, Moolenaar AJ (1985) Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer 55(4):766–773CrossRefPubMedGoogle Scholar
  11. 11.
    Saeger W (2000) Histopathological classification of adrenal tumours. Eur J Clin Invest 30(Suppl. 3):58–62CrossRefPubMedGoogle Scholar
  12. 12.
    Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR (2004) The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev 25(2):309–340CrossRefPubMedGoogle Scholar
  13. 13.
    Stojadinovic A, Ghossein RA, Hoos A et al (2002) Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol 20(4):941–950CrossRefPubMedGoogle Scholar
  14. 14.
    NIH (2002) NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”). NIH Consens State Sci Statements 19(2):1–25Google Scholar
  15. 15.
    Lumachi F, Borsato S, Tregnaghi A et al (2003) CT-scan, MRI and image-guided FNA cytology of incidental adrenal masses. Eur J Surg Oncol 29(8):689–692CrossRefPubMedGoogle Scholar
  16. 16.
    Telenius H, Carter NP, Bebb CE, Nordenskjold M, Ponder BA, Tunnacliffe A (1992) Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics 13(3):718–725CrossRefPubMedGoogle Scholar
  17. 17.
    Dackiw AP, Lee JE, Gagel RF, Evans DB (2001) Adrenal cortical carcinoma. World J Surg 25(7):914–926CrossRefPubMedGoogle Scholar
  18. 18.
    Zhao J, Speel EJ, Muletta-Feurer S et al (1999) Analysis of genomic alterations in sporadic adrenocortical lesions. Gain of chromosome 17 is an early event in adrenocortical tumorigenesis. Am J Pathol 155(4):1039–1045PubMedGoogle Scholar
  19. 19.
    Sidhu S, Marsh DJ, Theodosopoulos G et al (2002) Comparative genomic hybridization analysis of adrenocortical tumors. J Clin Endocrinol Metab 87(7):3467–3474CrossRefPubMedGoogle Scholar
  20. 20.
    Kjellman M, Kallioniemi OP, Karhu R et al (1996) Genetic aberrations in adrenocortical tumors detected using comparative genomic hybridization correlate with tumor size and malignancy. Cancer Res 56(18):4219–4223PubMedGoogle Scholar
  21. 21.
    Dohna M, Reincke M, Mincheva A, Allolio B, Solinas-Toldo S, Lichter P (2000) Adrenocortical carcinoma is characterized by a high frequency of chromosomal gains and high-level amplifications. Genes Chromosomes Cancer 28(2):145–152CrossRefPubMedGoogle Scholar
  22. 22.
    Bernard MH, Sidhu S, Berger N et al (2003) A case report in favor of a multistep adrenocortical tumorigenesis. J Clin Endocrinol Metab 88(3):998–1001CrossRefPubMedGoogle Scholar
  23. 23.
    Kjellman M, Larsson C, Backdahl M (2001) Genetic background of adrenocortical tumor development. World J Surg 25(7):948–956CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Torsten Gruschwitz
    • 1
    Email author
  • Jan Breza
    • 2
  • Heiko Wunderlich
    • 1
  • Kerstin Junker
    • 1
  1. 1.Department of UrologyUniversity Medical CenterJenaGermany
  2. 2.Department of UrologyUniversity of BratislavaBratislavaSlovakia

Personalised recommendations