Follicular dendritic cell sarcoma (FDCS) is an extremely rare mesenchymal neoplasm. This tumor was first reported in 1986 by Monda et al. and is classified by the World Health Organization (WHO) under histiocytic and dendritic cell neoplasms.

The cell of origin is the antigen presenting follicular dendritic cell. Normal (Non-neoplastic) follicular dendritic cells process antigen antibody complexes, and present them to B-cells in lymphoid follicles (Wu et al., 2016).

The etiology is unknown. Rare cases have been described in association with the hyaline vascular type of Castleman disease (Youens et al., 2008).

Follicular dendritic cell sarcomas are extremely rare. The number of reported cases are fewer than 100. Patients as young as 9 up to 82 years old have been described, though it occurs predominantly in adults. Mean and median age of disease are in the fifth decade of life. Both sexes are equally affected.

Most cases of follicular dendritic cell sarcoma present with asymptomatic lymphadenopathy. Cervical and axillary lymph nodes are commonly affected. Extra nodal sites that can be involved include spleen, liver, gastrointestinal tract, skin, lung, mediastinum, pharynx, tonsils and soft tissue. Patients with intra-abdominal tumors may suffer from abdominal pain. Other systemic presentations include fever, night sweats and fatigue. Rarely paraneoplastic myasthenia gravis and pemphigus has been reported in FDCS (Wang et al., 2016). Abnormal levels of alkaline phosphatase as well as anemia are reported with hepatic involvement by FDCS.

The tumor shows various histologic patterns of spindle cells in storiform (the most common form), meningioma -like (whorled), fascicles, bundles or diffuse sheets; heterogenicity in growth patterns can also be seen. Tumor cells are plump with indistinct cell borders (syncytial appearance) and show fibrillary slightly eosinophilic cytoplasm. Tumor cells have vesicular nuclei with fine chromatin, sometimes intranuclear pseudoinclusions, and nucleoli; binucleate cells are present. Perivascular B or T lymphocytes can be seen. In some cases TdT+ T-lymphoblasts can be associated with these tumors (Ohgami et al., 2012, 2013, 2014).
Tumor necrosis is unusual and the mitotic rate can vary from 0 to 10 per 10 high power fields. High mitotic rates are more common in cases with cytologic atypia and clinically aggressive behavior.

Immunohistochemistry: Cells show membranous reaction for CD21, CD23, CD35 (C3d complement receptor). Clusterin is the most sensitive marker which shows diffuse strong cytoplasmic positivity in FDCS. This marker is not positive in other dendritic cell tumors. Podoplanin (D2-40) is another highly sensitive marker that shows a strong membranous reaction. c-Synuclein is another new helpful marker strongly stains follicular dendritic cells and may be useful in diagnosis FDCS. Other markers which are usually positive in the tumor are vimentin, EGFR, fascin, and HLA-DR. MIB-1/Ki-67 index ranges from 1% to 25%. Staining for CD1a, lysozyme, myeloperoxidase, CD34, CD3, CD79a, CD30, HMB-45, desmin, and high-molecular weight cytokeratins are negative on the tumor cells.

Complete surgical excision is the treatment of choice for both primary and recurrent cases. The benefits and advantages of radiotherapy and chemotherapy are not established yet. In cases with a BRAF V600 mutation, a BRAF enzyme inhibitor such as vemurafenib can be a potential choice. Another therapeutic agent are EGFR inhibitors, especially in cases which express moderate to strong EGFR.

Extranodal tumors have a higher risk of metastases than nodal counterparts. Local recurrences are common. Liver, lung and lymph nodes are common metastatic sites. Tumors with larger size (>6cm) significant cellular atypia, coagulative necrosis, intra-abdominal location and high mitotic rate (greater than 5 mitoses in 10 hpf) have unfavorable prognosis.

No specific chromosomal aberration has been established in FDCS. Non-recurrent types of complex cytogenetic abnormalities have been documented (Udayakumar et al., 2015; Perry et al., 2013).

The genetic alterations that drive tumorogenesis are not well understood in FDCS. One recent study that assessed the genetic basis of FDCS reported BRAF V600 mutations in a subset of cases (Go et al., 2014). Another study analyzing somatic alterations, showed loss of function alterations in tumor suppressor genes (NF-kB regulatory genes), including bi-allelic loss of CYLD and frameshift mutations in NFKBIA. Alterations in genes that regulate cell cycle include bi-allelic loss of CDKN2A and RB-1. Finally, focal copy-number gains on chromosome 9p24, a well described mechanism of immune evasion, have been observed in the regions containing CD274 (PD-L1) and PDCD1LG2 (PD-L2) (Griffin et al., 2016).