Primary jejunal follicular dendritic cell sarcoma: a case report with clinicopathological, immunophenotypic, and genetic characterization and literature review

Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm; jejunal involvement accounts for <5% of extranodal cases, with fewer than 20 published reports. We present a case of jejunal FDCS with an aggressive clinical course. Targeted DNA and RNA next-generation sequencing (NGS) was performed. A 62-year-old woman presented with left lower quadrant pain; CT revealed an 8.7 × 9.4 cm jejunal mass, and staging evaluation showed no enlarged regional lymph nodes or hepatic/splenic lesions; no separate lymph node sampling was performed, and pathological nodal status was not assessable. The resected tumor measured 13.5 × 9.8 × 7.7 cm. Resection confirmed classic-type FDCS on the basis of morphology and follicular dendritic cell marker immunohistochemistry (CD21 + /CD35 + /CXCL13 + /SSTR2 + , EBER-negative) with more than 5 mitoses per 10 high-power fields (HPFs) and geographic necrosis. NGS showed copy-number loss of CYLD (a negative regulator of NF-κB activation), amplification of chromosome 15q involving MAP2K1 , SRSF3 :: MTCH1 and VIRMA :: HOXA13 fusions, a heterozygous germline pathogenic EXT2 mutation, and missense mutations in AXIN1 and CYP2A6 . These molecular findings were supportive but not diagnostic. CYLD loss is consistent with the NF-κB pathway dysregulation described in FDCS. The MAP2K1 alteration was a copy-number amplification without an activating point mutation. The novel fusions and the AXIN1 and CYP2A6 missense variants are of uncertain significance. The germline EXT2 variant is an incidental finding unrelated to FDCS pathogenesis. Despite adjuvant CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), the tumor recurred 3 months after surgery, and the patient died of disease 8 months after resection. The patient had an aggressive clinical course of classic-type FDCS associated with CYLD loss and MAP2K1 amplification. The high mitotic rate, large tumor size, and adverse copy-number alterations were consistent with the rapid progression observed. These findings suggest that intensive surveillance and consideration of targeted therapy directed at the MEK or NF-κB signaling pathway may be reasonable in similar cases.