Fig. 1: Comparison of primary and metastatic lesions in Patient 1.

A Histologic examination of the primary ovarian neoplasm (top panel) demonstrates complex branching glands composed of the pseudostratified back-to-back columnar epithelium (shown at 10X and 40X magnification) positive for ER and PAX8 (shown at 20X magnification) consistent with low-grade endometrioid carcinoma, while the spinal metastasis (middle panel) consists of sheets of poorly differentiated cells with high nuclear-to-cytoplasmic ratio and nuclear molding (10 and 40X magnification), negative for ER and PAX8 and (lower panel) with variable positivity for CK7, chromogranin, synaptophysin, and INSM1 indicating neuroendocrine differentiation (all at 20X magnification). B Next-generation sequencing demonstrates the overlap of several copy alterations with a notable divergence between the specimens, consistent with tumor heterogeneity and/or clonal evolution. C Comparison of the single nucleotide variants and indels (and their variant allele fractions, VAFs) between the primary ovarian neoplasm, pelvic recurrence, and neuroendocrine spinal metastasis reveals multiple shared somatic findings, confirming their clonal relationship (shared variants are highlighted in yellow).