[1131] The Role of Reticulum, Inhibin and Calretinin Staining and FOXL2 Mutational Analysis in the Diagnosis of Sarcomatoid Granulosa Cell Tumors, Cellular Fibromas and Thecomas

Joema Felipe Lima, Fabiola Medeiros, Debra Bell. Mayo Clinic, Rochester, MN

Background: Typical adult granulosa cell tumors are generally easily and reproducibly diagnosed on morphology alone. It has been recently documented that adult granulosa cell tumors presumably of typical type, contain the single somatic mutation FOXL2 402C→G (C134W) in approximately 95% of cases whereas it is detected in only about 15% of thecomas. We recently demonstrated a lower rate of FOXL2 mutations among spindled or sarcomatoid adult granulosa cell tumors (GCT), diagnosed by pathologist consensus. This study aims to investigate the role the reticulin pattern, the immunoexpression of alpha-inhibin and calretinin, and the presence of FOXL2 mutation, in the diagnosis of diffuse GCT, cellular fibroma (CF) and thecoma (Th), based on a consensus histological diagnosis.
Design: A total of 60 ovarian SCST of spindle pattern, including 32 GCT of diffuse type, 20 CF and 8 Th were retrieved from archives of Mayo Clinic. Reticulin, inhibin and calretinin stains were performed in all cases. The final diagnosis was established based on a consensus between 5 of 8 experienced pathologists. DNA was extracted from formalin-fixed, paraffin-embedded tissue sections followed by polymerase chain reaction and direct sequencing of FOXL2 gene.
Results: The median age of the patients was 53 years old (range 20 to 87). Tumor size ranged from 0.6 to 23 cm. The results of reticulin, alpha-inhibin and calretinin are detailed on the table below.

Relation between diagnosis, FOXL2 mutation, Calretinin, Inhibin and Reticulin.
Consensus diagnosisFOXL2(%)Calretinin (%)Alpha-InhibinReticulin
GCT (n=32)17 positive (53)30 positive (94)31 positive (97)24 nested (75)
Cellular Fibroma1 positive (5)10 positive (50)19 positive (95)-
Thecoma (n=8)2 positive (13)4 positive (50)7 positive (88)1 nested (13)
Sensitivity839410075
Specificity3656893


The presence of a nested pattern on reticulum had a sensitivity of 78% and specificity of 74 % for detection of a FOXL2 mutation.
Conclusions: These data demonstrate the difficulty in establishing a diagnosis of diffuse or sarcomatoid GCT. Neither the presence of the FOXL2 mutation, calretinin or inhibin immunostaining or the presence of nests on reticulum stain easily confirmed the morphologic consensus diagnosis. Distinguishing between spindled sex cord stromal tumors remains difficult. Perhaps determining the best methods for their diagnosis may be established only by correlation with biologic behavior in long tern follow-up studies.
Category: Gynecologic & Obstetrics

Tuesday, March 20, 2012 9:30 AM

Poster Session III # 200, Tuesday Morning

 

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