Small Cell Carcinoma Hypercalcemic Type: Consistent Clinico-Pathologic Features and Lack of Molecular Markers
Emanuela D'Angelo, Cristina Rivera, Belen Canet, Ana Mozos, Jaime Prat. Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau). Autonomous University of Barcelona, Barcelona, Spain
Background: Small cell carcinoma hypercalcemic type (SCC-HT) is a unique ovarian cancer of unknown histogenesis with highly consistent clinicopathologic features and aggressive behaviour. Consistent immunohistochemical markers, other than weak expression of cytokeratins and a strong vimentin immunoreaction, are lacking. We tried to identify genetic alterations in 21 of these rare neoplasms.
Design: Twenty cases were seen in consultation over a 19-years period and one was from the hospital files. Twenty juvenile granulosa cell tumors (JGCT) were used as controls. A tissue microarray (TMA) was stained with AE1/AE3, vimentin, p53, WT1, and FOXL2. We also investigated mutation of the TP53 gene (exons 5-8) and the KRAS gene (exon 2, codons 12 and 13) by direct sequencing.
Results: The mean age of the patients was 22 years (range 10-39) and the tumor size 15 cm (range 7-20 cm). Nine cases were confined to the ovary (stage I) and 12 had widespread tumor (stage III). Necrosis was found in 14 cases and the average mitotic rate was 15 (range: 4-27 MF x 10HPF). Twelve patients died of their disease within 2 years, and 5 were alive with disease 1-2 postoperatively. Three patients were alive and well at 2, 4, and 6 years. Tumor stage was a strong prognostic factor. All 21 tumors were focally immunoreactive for cytokeratins AE1/AE3, and 14 tumors exhibited diffuse immunoreaction for vimentin. Tumor cells showed low to moderate immunohistochemical expression of p53 in a mean of 36.25% of cells (range 5-68%). Eighteen cases exhibited WT1 positivity, 9 with 3+ intensity. FOXL2 immunostaining was expressed in 14 of 19 JGCTs, but in none of the SCC-HTs. Neither p53 nor K-RAS mutations were found in any case.
Conclusions: Although the diagnosis of SCC-HT was easily made by H&E stained sections, there was a striking lack of reliable molecular markers. Focal positivity with AE1/AE3 and diffuse WT1 immunoreaction suggests an epithelial origin. In difficult cases, negative staining with FOXL2 may aid in the differential diagnosis with JGCT. p53 immunoreaction was not supported by p53 gene mutation. The absence of both, p53 and K-RAS mutations, suggest that SCC-HT follow alternative carcinogenic pathways.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 158, Wednesday Morning