Hepatocellular neoplasms arising in association with androgen use

Sounak Gupta, Bita V. Naini, Richard Munoz, Rondell P. Graham, Benjamin R. Kipp, Michael S. Torbenson, Taofic Mounajjed

Research output: Contribution to journalArticle

Abstract

Correlation between androgen use and hepatocellular neoplasia is well established. However, there are no detailed studies of the histopathology and immunohistochemical/molecular profile of these tumors. We studied 9 patients with androgen-associated hepatocellular neoplasms. In addition to histology, immunostains for liver fatty acid-binding protein, b-catenin, glutamine synthetase, C-reactive protein, and serum amyloid A were utilized for tumor subtyping. Molecular testing using Solid Tumor Targeted Cancer Panel was performed on 3 cases. The neoplasms were predominantly seen in male individuals (7/9). Two patients (22%) had multifocal lesions. All lesions had architectural and 4/9 had cytologic atypia. Cholestasis was present in 6/9 cases. Reticulin was focally disrupted in 5/9 cases. Given the clinical setting, all lesions were classified as well-differentiated hepatocellular neoplasms of uncertain malignant potential. In cases with follow-up (6/9 cases, 67%), there were no recurrences or metastases. On the basis of the immunoprofile, 7 (78%) cases were β-catenin activated (including 1 hepatic adenoma with concurrent hepatocyte nuclear factor 1a inactivation) and 2 (22%) had inflammatory phenotype. Somatic mutations in CTNNB1 were detected in all 3 tested cases (all b-catenin activated by immunostain), all involving exon-3. Our data indicate that androgen-associated hepatocellular neoplasms most often develop in male individuals and always show some degree of atypia and/or focal reticulin disruption. Most are b-catenin activated, often harboring CTNNB1 exon-3 mutations, and a minority is inflammatory type. Although b-catenin and inflammatory pathways likely play a role in pathogenesis, the heterogenous molecular profile suggests there are other (yet to be characterized) primary oncogenic mechanisms in this unique tumor type.

Original languageEnglish (US)
Pages (from-to)454-461
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume40
Issue number4
DOIs
StatePublished - 2016
Externally publishedYes

Fingerprint

Androgens
Catenins
Neoplasms
Reticulin
Exons
Hepatocyte Nuclear Factors
Serum Amyloid A Protein
Fatty Acid-Binding Proteins
Glutamate-Ammonia Ligase
Mutation
Cholestasis
Adenoma
C-Reactive Protein
Histology
Neoplasm Metastasis
Phenotype
Recurrence
Liver

Keywords

  • Anabolic steroids
  • Androgen
  • Hepatic adenoma
  • Hepatocellular carcinoma
  • Hepatocellular neoplasm

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Gupta, S., Naini, B. V., Munoz, R., Graham, R. P., Kipp, B. R., Torbenson, M. S., & Mounajjed, T. (2016). Hepatocellular neoplasms arising in association with androgen use. American Journal of Surgical Pathology, 40(4), 454-461. https://doi.org/10.1097/PAS.0000000000000576

Hepatocellular neoplasms arising in association with androgen use. / Gupta, Sounak; Naini, Bita V.; Munoz, Richard; Graham, Rondell P.; Kipp, Benjamin R.; Torbenson, Michael S.; Mounajjed, Taofic.

In: American Journal of Surgical Pathology, Vol. 40, No. 4, 2016, p. 454-461.

Research output: Contribution to journalArticle

Gupta, S, Naini, BV, Munoz, R, Graham, RP, Kipp, BR, Torbenson, MS & Mounajjed, T 2016, 'Hepatocellular neoplasms arising in association with androgen use', American Journal of Surgical Pathology, vol. 40, no. 4, pp. 454-461. https://doi.org/10.1097/PAS.0000000000000576
Gupta, Sounak ; Naini, Bita V. ; Munoz, Richard ; Graham, Rondell P. ; Kipp, Benjamin R. ; Torbenson, Michael S. ; Mounajjed, Taofic. / Hepatocellular neoplasms arising in association with androgen use. In: American Journal of Surgical Pathology. 2016 ; Vol. 40, No. 4. pp. 454-461.
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abstract = "Correlation between androgen use and hepatocellular neoplasia is well established. However, there are no detailed studies of the histopathology and immunohistochemical/molecular profile of these tumors. We studied 9 patients with androgen-associated hepatocellular neoplasms. In addition to histology, immunostains for liver fatty acid-binding protein, b-catenin, glutamine synthetase, C-reactive protein, and serum amyloid A were utilized for tumor subtyping. Molecular testing using Solid Tumor Targeted Cancer Panel was performed on 3 cases. The neoplasms were predominantly seen in male individuals (7/9). Two patients (22{\%}) had multifocal lesions. All lesions had architectural and 4/9 had cytologic atypia. Cholestasis was present in 6/9 cases. Reticulin was focally disrupted in 5/9 cases. Given the clinical setting, all lesions were classified as well-differentiated hepatocellular neoplasms of uncertain malignant potential. In cases with follow-up (6/9 cases, 67{\%}), there were no recurrences or metastases. On the basis of the immunoprofile, 7 (78{\%}) cases were β-catenin activated (including 1 hepatic adenoma with concurrent hepatocyte nuclear factor 1a inactivation) and 2 (22{\%}) had inflammatory phenotype. Somatic mutations in CTNNB1 were detected in all 3 tested cases (all b-catenin activated by immunostain), all involving exon-3. Our data indicate that androgen-associated hepatocellular neoplasms most often develop in male individuals and always show some degree of atypia and/or focal reticulin disruption. Most are b-catenin activated, often harboring CTNNB1 exon-3 mutations, and a minority is inflammatory type. Although b-catenin and inflammatory pathways likely play a role in pathogenesis, the heterogenous molecular profile suggests there are other (yet to be characterized) primary oncogenic mechanisms in this unique tumor type.",
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