PMC4699873_01
Pathologic features of the primary ovarian sarcoma in Patient #1 with DICER1 mutation. a. Low power view shows epithelial lined cysts, solid sarcoma and focal necrosis. b. Higher power view shows spindled and stellate cells in a pale mucoid matrix. c,d. Higher power views highlight areas with significant nuclear pleomorphism. (Hematoxylin and eosin; x100 (a), x200 (b,c,d)).
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F1
Pathology showed an undifferentiated sarcoma with limited myogenic phenotype (Fig. 1).
Sertoli-Leydig cell tumor in the contralateral ovary of Patient #1.. a. Low power view showing Leydig cells with abundant pink cytoplasm in upper left adjacent to nests of small Sertoli cells. b. Elongated tubules of Sertoli cells. c. Spindle cell pattern seen focally. d. Ribbons of Sertoli cells with hyperchromatic nuclei. (Hematoxylin and eosin; x100 (a), x400 (b,c,d))
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F2
SLCT (Fig. 2).
Pathologic features of the Sertoli-Leydig tumor in patient #2. a.Tubular structures and nests of Sertoli cells. b. Epithelial lined cyst with nest of Sertoli cells and rare anaplastic cells. c. Cystic structure within the SLCT. d. Focal mucinous gland. (Hematoxylin and eosin; x200 (a,b), x100 (c,d)).
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SLCT (Fig. 3) and 2 other DICER1-related conditions: a lung cyst and thyroid nodule. Sequencing of this individual's SLCT showed the germline
Unique intronic mutation in DICER1 resulting in duplication of splice site. a. Germline DICER1 sequencing results from Patient #1 (Lanes 5 and 6) compared with reference genome (Lanes 1-4). Intron-exon boundary indicated by vertical blue line with six base pairs of the splice site in the blue box. Mutated base NM_177438.2:c.5096-12 G>A in blue highlight. Putative new intron-exon boundary indicated by vertical red line. b. Sanger sequence chromatogram from Patient 1. Red arrow indicates heterozygous mutation site. c. Next generation sequence data as displayed with Integrative Genome Viewer. Red arrow highlights the mutated base.
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F4
The NM_177438.2:c.5096-12 G>A germline mutation seen in these two patients results in an exact duplication of the six bases at the splice site at the intron 23 and exon 24 junction (Fig. 4).