Abstract
Microcystic stromal tumors (MCST), first described in 2009 by Irving et al., are rare ovarian neoplasms. The entity was introduced into the 2014 WHO classification of tumors of female reproductive organs in the group of sex cord-stromal tumors, which is rather heterogeneous. We studied three cases of ovarian tumor with the characteristic morphological features and immunohistochemical marker profiles of MCST. The three tumors showed micro, and macrocystic patterns with solid areas, and were composed of small round to spindle-shaped cells, without atypia. The tumors diffusely and strongly expressed CD10, FOXL2, and nuclear β-catenin, but without immmunoreactivity for hormone receptors, calretinin, or inhibin. Genome analyses showed no somatic mutation of exon 1 of the FOXL2 gene and of exons 24 and 25 of DICER1 gene, the latter not having been reported previously. The patients are well, without evidence of tumor progression 1 to 10 years after diagnosis.
The absence of FOXL2 and DICER1 gene mutation, along with strong FOXL2 immunoreactivity provides additional evidence to place MCST within pure gonadal stromal rather than sex cord ovarian tumors.
This is a preview of subscription content, log in via an institution to check access.
References
Irving JA, Young RH (2009) Microcystic stromal tumor of the ovary: report of 16 cases of a hitherto uncharacterized distinctive ovarian neoplasm. Am J Surg Pathol 33:367–375
Maeda D, Shibahara J, Sakuma T et al (2011) β-catenin (CTNNB1) S33C mutation in ovarian microcystic stromal tumors. Am J Surg Pathol 35:1429–1440
Yang M, Bhattacharjee MB (2014) Ovarian microcystic stromal tumor: report of a new entity with immunohistochemical and ultrastructural studies. Ultrastruct Pathol 38:261–267
Kang YN, Cho CH, Kwon SY (2015) Microcystic stromal tumor of the ovary with mutation in exon 3 of β-catenin: a case report. Int J Gynecol Pathol Off J Int Soc Gynecol Pathol 34:121–125
Lee SH, Koh YW, Roh HJ et al (2015) Ovarian microcystic stromal tumor: a novel extracolonic tumor in familial adenomatous polyposis. Genes Chromosomes Cancer 54:353–360
Bi R, Bai Q-M, Yang F et al (2015) Microcystic stromal tumour of the ovary: frequent mutations of β-catenin (CTNNB1) in six cases. Histopathology 67:872–879
Lee JH, Kim H-S, Cho NH et al (2016) Genetic analysis of ovarian microcystic stromal tumor. Obstet Gynecol Sci 59:157–162
Podduturi V, Tran T, Champion KJ et al (2015) Microcystic stromal tumor of the ovary: a case report of a newly described ovarian neoplasm with a β-catenin (CTNNB1) G34E mutation. Int J Gynecol Pathol Off J Int Soc Gynecol Pathol 34:541–545
Kurman RJ, Carcangiu ML, Herrington CS WHO Classification of Tumours of Female Reproductive Organs, 2014th ed. International Agençy for Research on Cancer, Lyon
Shah SP, Köbel M, Senz J et al (2009) Mutation of FOXL2 in granulosa-cell tumors of the ovary. N Engl J Med 360:2719–2729
Heravi-Moussavi A, Anglesio MS, Cheng S-WG et al (2012) Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med 366:234–242
Irving JA, Lee C-H, Yip S et al (2015) Microcystic stromal tumor: a distinctive ovarian sex cord-stromal neoplasm characterized by FOXL2, SF-1, WT-1, cyclin D1, and β-catenin nuclear expression and CTNNB1 mutations. Am J Surg Pathol 39:1420–1426
Costa MJ, Ames PF, Walls J, Roth LM (1997) Inhibin immunohistochemistry applied to ovarian neoplasms: a novel, effective, diagnostic tool. Hum Pathol 28:1247–1254
McCluggage WG, Maxwell P (2001) Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cord-stromal tumours. Histopathology 38:403–408
Movahedi-Lankarani S, Kurman RJ (2002) Calretinin, a more sensitive but less specific marker than alpha-inhibin for ovarian sex cord-stromal neoplasms: an immunohistochemical study of 215 cases. Am J Surg Pathol 26:1477–1483
Al-Agha OM, Huwait HF, Chow C et al (2011) FOXL2 is a sensitive and specific marker for sex cord-stromal tumors of the ovary. Am J Surg Pathol 35:484–494
Stewart CJR, Alexiadis M, Crook ML, Fuller PJ (2013) An immunohistochemical and molecular analysis of problematic and unclassified ovarian sex cord-stromal tumors. Hum Pathol 44:2774–2781
Schmidt D, Ovitt CE, Anlag K et al (2004) The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Dev Camb Engl 131:933–942
Weng Q, Wang H, Medan S et al (2006) Expression of inhibin/activin subunits in the ovaries of fetal and neonatal mice. J Reprod Dev 52:607–616
McCluggage WG, Singh N, Kommoss S et al (2013) Ovarian cellular fibromas lack FOXL2 mutations: a useful diagnostic adjunct in the distinction from diffuse adult granulosa cell tumor. Am J Surg Pathol 37:1450–1455
Goulvent T, Ray-Coquard I, Borel S et al (2016) DICER1 and FOXL2 mutations in ovarian sex cord–stromal tumours: a GINECO Group study. Histopathology 68:279–285
Deshpande V, Oliva E, Young RH (2010) Solid pseudopapillary neoplasm of the ovary: are report of 3 primary ovarian tumors resembling those of the pancreas. Am J Surg Pathol 34:1514-20
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study was conducted according to the rules of Declaration of Helsinki and the Ethics Committee of the Medical Board (CHU Lyon) agreed to these investigations. Consent for genetic investigations, was obtained from the three patients.
Funding
There is no funding for this study.
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Meurgey, A., Descotes, F., Mery-Lamarche, E. et al. Lack of mutation of DICER1 and FOXL2 genes in microcystic stromal tumor of the ovary. Virchows Arch 470, 225–229 (2017). https://doi.org/10.1007/s00428-016-2038-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-016-2038-2