An immunohistochemical and molecular analysis of problematic and unclassified ovarian sex cord–stromal tumors

• Published in: Human pathology 2013-12, Vol.44 (12), p.2774-2781
• Main Authors: Stewart, Colin J.R., FRCPA, Alexiadis, Maria, BSc, Crook, Maxine L., BSc, Fuller, Peter J., PhD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; DICER1; Female; FOXL2; Humans; Immunohistochemistry; Medical research; Middle Aged; Molecular; Mutation; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Ovary; Pathology; Sex Cord-Gonadal Stromal Tumors - genetics; Sex Cord-Gonadal Stromal Tumors - metabolism; Sex Cord-Gonadal Stromal Tumors - pathology; Sex cord–stromal tumor; Tumors; Unclassified
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2013.07.028

Summary Most ovarian sex cord–stromal tumors (SCSTs) can be categorized on the basis of conventional histology, but approximately 10% of cases are unclassified because they present indeterminate or overlapping morphologic features. Immunohistochemical and molecular studies of unclassified ovarian SCST are very limited, but recently, it has been demonstrated that 2 major subgroups of SCST, adult-type granulosa cell tumor and Sertoli-Leydig cell tumor, are characterized by somatic mutations in FOXL2 and DICER1 , respectively. In this study, 12 diagnostically problematic ovarian SCST, including 9 unclassified tumors, were investigated for FOXL2 and DICER1 mutations and for immunohistochemical expression of calretinin, CD56, CD99, estrogen receptor α , estrogen receptor β , FOXL2, inhibin, progesterone receptor, and steroidogenic factor-1. Four of 11 tumors with satisfactory analysis showed a FOXL2 mutation; 3 of these cases were reported initially as unclassified SCST and 1 as Sertoli-Leydig cell tumor. Conversely, 3 cases with an original diagnosis of granulosa cell tumor were FOXL2 mutation–negative, and none of 7 tumors with satisfactory analysis demonstrated a DICER1 mutation. All tumors expressed at least 4 of the immunomarkers examined, although staining was often focal and there was no consistent correlation with tumor morphology. In conclusion, molecular analysis is useful in the assessment of diagnostically challenging ovarian SCST. The absence of FOXL2 and DICER1 mutations in most unclassified SCST suggests that these could represent a distinct tumor subgroup with different molecular pathogenesis. Immunohistochemical profiles overlap with those of better categorized SCST, but staining may be focal or negative emphasizing the requirement for antibody panels in diagnostic assessment.