Abstract
Primary hepatic carcinoma with inhibin positivity is a rare aggressive liver tumor with seven cases described. The tumor presents at a younger age than primary hepatic carcinoma with all cases being females. RNA albumin ISH positivity suggests the tumor to be a primary hepatic carcinoma. The tumor is different from hepatocellular carcinoma as well as intrahepatic cholangiocarcinoma because of its distinct morphology, lack of hepatocellular differentiation, strong inhibin staining, and lack of typical mutations. A 26-year-old male presented with a 20-cm liver mass. The tumor progressed on therapy with development of multiple lung metastasis. Currently, the patient is enrolled in phase II clinical trial utilizing nivolumab and ipilumumab. While the tumor has a female preponderance, it is not exclusively found in females. Additional studies are necessary to determine the cause of inhibin staining, driving molecular alterations, natural history of this rare tumor, and to come up with consensus nomenclature.
References
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424
Vrettou E, Hytiroglou P, Sikas N, Soultoyannis I, Goodman ZD (2005) Hepatic adenocarcinoma expressing inhibin in a young patient on oral contraceptives. Virchows Arch 446:560–565. https://doi.org/10.1007/s00428-005-1241-3
Braxton DR, Saxe D, Damjanov N, Stashek K, Shroff S, Morrissette JD, Tondon R, Furth EE (2017) Molecular and cytogenomic profiling of hepatic adenocarcinoma expressing inhibinA, a mimicker of neuroendocrine tumors: proposal to reclassify as “cholangioblastic variant of intrahepatic cholangiocarcinoma”. Hum Pathol 62:232–241. https://doi.org/10.1016/j.humpath.2017.02.001
Wen KW, Srivastava A, Joseph N, Saunders T, Kakar S (2019) “Sex Cord-Like” hepatic carcinoma: a rare variant of intrahepatic cholangiocarcinoma? Abstract 1537. Page 54. Laboratory Investigation. Volume 99, Supplement 1
Ong CK, Subimerb C, Pairojkul C, Wongkham S, Cutcutache I, Yu W, McPherson JR, Allen GE, Ng CCY, Wong BH, Myint SS, Rajasegaran V, Heng HL, Gan A, Zang ZJ, Wu Y, Wu J, Lee MH, Huang DC, Ong P, Chan-on W, Cao Y, Qian CN, Lim KH, Ooi A, Dykema K, Furge K, Kukongviriyapan V, Sripa B, Wongkham C, Yongvanit P, Futreal PA, Bhudhisawasdi V, Rozen S, Tan P, Teh BT (2012) Exome sequencing of liver fluke-associated cholangiocarcinoma. Nat Genet 44:690–693
Nault JC, Fabre M, Couchy G, Pilati C, Jeannot E, Tran Van Nhieu J (2012) GNAS-activating mutations define a rare subgroup of inflammatory liver tumors characterized by STAT3 activation. J Hepatol. 56(1):184–191
Basturk O, Berger MF, Yamaguchi H, Adsay V, Askan G, Bhanot UK (2017) Pancreatic intraductal tubulopapillary neoplasm is genetically distinct from intraductal papillary mucinous neoplasm and ductal adenoca. Mod Pathol. 30(12):1760–1772
Wu J, Matthaei H, Maitra A, Wood MDMLD, Eshleman JR et al (2011) Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med 3:92ra66
Saâda-Bouzid E et al (2015) Prognostic value of HMGA2, CDK4, and JUN amplification in well-differentiated and dedifferentiated liposarcomas. Modern Pathology 28.11:1404
Franchi A, Calzolari A, Zampi G (1998) Immunohistochemical detection of c-fos and c-Jun expression in osseous and cartilaginous tumours of the skeleton. Virchows Arch 432(6):515–519
Yokoyama Y, Sagara M, Sato S, Saito Y (1998) Value of glutathiones-transferase π and the oncogene products c-Jun, c-Fos, cH-Ras, and c-Myc as a prognostic indicator in endometrial carcinomas. Gynecol Oncol 68(3):280–287
Gupta S et al (2015) Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer. Scientific Reports 5:16811
Decaens T, Godard C, de Reyniès A, Rickman DS, Tronche F, Couty JP, Perret C, Colnot S (2008) Stabilization of β-catenin affects mouse embryonic liver growth and hepatoblast fate. Hepatology 47(1):247–258
Clotman F, Jacquemin P, Plumb-Rudewiez N, Pierreux CE, van der Smissen P, Dietz HC, Courtoy PJ, Rousseau GG, Lemaigre FP (2005) Control of liver cell fate decision by a gradient of TGFβ signaling modulated by Onecut transcription factors. Genes Dev 19(16):1849–1854
Rodgarkia-Dara C, Vejda S, Erlach N, Losert A, Bursch W, Berger W, Schulte-Hermann R, Grusch M (2006) The activin axis in liver biology and disease. Mutation Research/Reviews in Mutation Research 613(2–3):123–137
Lowery MA, Ptashkin R, Jordan E, Berger MF, Zehir A, Capanu M, Kemeny NE, O'Reilly EM, el-Dika I, Jarnagin WR, Harding JJ, D'Angelica MI, Cercek A, Hechtman JF, Solit DB, Schultz N, Hyman DM, Klimstra DS, Saltz LB, Abou-Alfa GK (2018) Comprehensive molecular profiling of intrahepatic and extrahepatic cholangiocarcinomas: potential targets for intervention. Clin Cancer Res 24:4154–4161. https://doi.org/10.1158/1078-0432.ccr-18-0078
Churi CR, Shroff R, Wang Y, Rashid A, Kang HSC, Weatherly J, Zuo M, Zinner R, Hong D, Meric-Bernstam F, Janku F, Crane CH, Mishra L, Vauthey JN, Wolff RA, Mills G, Javle M (2014) Mutation profiling in cholangiocarcinoma: prognostic and therapeutic implications. PLoS One 9:e115383. https://doi.org/10.1371/journal.pone.0115383
Frost K, Seir K, Lackner A, Grusch M, Grasl-Kraupp B, Schulte-Hermann R, Rodgarkia-Dara C (2011) Inhibin/activin expression in human and rodent liver: subunits α and βB as new players in human hepatocellular carcinoma? Br J Cancer 104(8):1303–1312
Nasir A, Lehrke HD, Mounajjed T, Said S, Zhang L, Yasir S, Shah SS, Chandan VS, Smyrk TC, Moreira RK, Boland Froemming JM, Herrera Hernandez LP, Wu T-T, Graham RP (2019) Albumin in situ hybridization can be positive in adenocarcinomas and other tumors from diverse sites. Am J Clin Pathol 152(2):190–199
Author information
Authors and Affiliations
Contributions
Tom Z Liang: literature review, material collection and writing, and editing the manuscript.
Gilbert Whang: collection of radiology findings and editing the radiology portion of the manuscript.
Shefali Chopra: conception and design, literature review, material collection, writing and editing the manuscript.
All authors have agreed with submission of this manuscript in the present and subsequent form.
Corresponding author
Ethics declarations
Yes, all the ethical standards have been complied with.
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Quality in Pathology
Rights and permissions
About this article
Cite this article
Liang, T.Z., Whang, G. & Chopra, S. Primary hepatic carcinoma with inhibin positivity in a young male patient: a rare tumor previously only reported in females—case report and review of literature. Virchows Arch 478, 605–610 (2021). https://doi.org/10.1007/s00428-020-02864-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-020-02864-y