Molecular Characterization of Biphasic Follicular Dendritic Cell Sarcoma

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm commonly found in extranodal sites with unclear pathogenesis. Tumor cells typically exhibit a spindled morphology, whereas epithelioid morphology is rarely reported. Here, we have presented a rare biphasic FDCS with distinct immunophenotypic and molecular characteristics. A 63-year-old female presented with constipation and rectal bleeding. Imaging revealed an 11.4 cm lobulated enhancing soft tissue mass in the posterior pelvis. H&E sections revealed 2 sharply demarcated biphasic neoplastic populations: one population comprised spindled cells expressing CD21, CD23, CD35, clusterin, EMA, and D2-40; the other population consisted of epithelioid cells lacking CD21 and other FDC-associated markers except for focal weak clusterin expression. Both populations tested negative for CD163, CD68, S-100, langerin, CD1a, ALK-1, CD30, CD117, HMB45, Pan-CK, and EBER. The tumor was initially misdiagnosed as a collision (FDCS and perivascular epithelioid cell tumor) tumor. Molecular studies revealed a nearly identical mutational profile in both components confirming clonal identity and ruling out a composite tumor. In addition, low-level pathogenic mutations (variant allele frequency <10%) were found in GABRA6, ICOSLG, and VEGFA, alongside altered transcript expression in PDGFRB in both populations. Although no RNA fusions were detected, we demonstrated a significant increase in PDGFRB expression using the RNA Salah Targeted Expression panel, with a log 2 ratio > 2, indicating a more than 4-fold increase compared with a pooled normal control. Here, we have provided molecular characterization of biphasic FDCS. Prior such characterization seems to be unavailable in the literature.