FOXL2 Mutational Analysis in the Differential Diagnosis of Ovarian Spindled Sex-Cord Stromal Tumors.
Joema F Lima, Long Jin, Amy C Clayton, Michael R Henry, Gary L Keeney, Debra A Bell, Bobbie S Gostout, Andre M Oliveira, Fabiola Medeiros. Mayo Clinic, Rochester, MN
Background: Sex cord-stromal tumors (SCSTs) of the ovary comprise less than 10% of all ovarian tumors. The majority are ordinary fibromas, others types being uncommon or rare. The differential diagnosis of the predominantly spindled and cellular SCSTs, particularly sarcomatoid granulosa cell tumors (GCTs), cellular fibromas (CFs) and thecomas (THs), is often difficult due to their close histologic resemblance and absence of reliable ancillary tests. Recently, the single somatic mutation FOXL2 402C→G (C134W) was reported in approximately 95% of adult-type granulosa cell tumors and in 15% of thecomas, but was absent in other ovarian tumors. However, the morphologic subtypes evaluated in these studies were not specified. Most GCTs are easily diagnosed based on morphologic and immunohistochemical features, and the challenge resides in the differentiation of the sarcomatoid variant from other SCSTs. This study evaluates the potential diagnostic application of FOXL2 mutational analysis, specifically in the setting of spindled and cellular SCSTs.
Design: A total of 86 ovarian tumors, including 12 sarcomatoid GCTs, 27 GCTs of other subtypes, 30 CFs, 9 THs and 8 SCSTs of other categories (4 Sertoli-Leydig cell tumors, 2 steroid cell tumors, and 2 unclassified SCSTs) were retrieved from the archives of the Mayo Clinic. Reticulin, inhibin and calretinin were performed in all cases. The diagnoses were based on blind review of the HE slides and the aforesaid stains by two pathologists with expertise in gynecologic pathology. DNA was extracted from formalin-fixed, paraffin-embedded tissue sections followed by polymerase chain reaction and direct sequencing of the FOXL2 gene.
Results: The median age of the patients was 55 years old (range 14 to 69). Tumor size ranged from 0.5 to 39 cm. FOXL2 402C→G (C134W) was detected in 23 of 27 non-sarcomatoid GCTs (85.2%), 6 of 12 of sarcomatoid GCTs (50%) and 2 of 9 THs (22.2%). The mutation was not detected in any of the CFs and SCSTs of other categories. Mutational analysis was repeated in all GCTs lacking the mutation and the results were confirmed.
Conclusions: The frequency of FOXL2 402C→G (C134W) in similar to that reported in the literature for non-sarcomatoid GCTs and THs. However, it is significantly lower for sarcomatoid GCTs, which had detectable FOXL2 mutations in only half of the cases. Therefore, mutational analysis may prompt re-evaluation of the tumor classification criteria for sarcomatoid SCSTs. Additional studies are warranted to establish the application of molecular testing in the diagnosis of GCTs.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 122, Tuesday Afternoon