Follicular dendritic cells are a specialized type of dendritic cells that are largely restricted to lymphoid follicles. They form dense three-dimensional meshworks within benign follicles, which maintain the follicular architecture [4]. FDC sarcoma is a neoplastic proliferation of cells showing morphologic and immunophenotypic features of follicular dendritic cells [5]. The etiology of that neoplastic transformation is unknown although it may evolve in situations in which there is FDC hyperplasia and overgrowth [4]. It usually occurs de novo; however, it can sometimes occur in association with hyaline vascular Castleman disease, whether simultaneously or as a succeeding event [4]. It presents as a painless solid mass, usually nodal (mainly cervical lymph nodes) but it can also involve extra nodal sites, such as tonsils, spleen, skin, and gastrointestinal tract [4, 6, 7]. A new variant has been recently described: EBV-positive inflammatory follicular dendritic cell tumor and is reported to occur exclusively in the liver and spleen, exhibit more interspersed lymphoplasmacytic infiltrate, and express EBV by in situ hybridization [8]. Overall, FDC sarcoma is considered a low-grade sarcoma that has a significant recurrence rate in nearly half the cases, and it also can metastasize [3]. Surgical resection remains the best treatment for these tumors.

Histologically, these tumors can be difficult to diagnose, as the morphological spectrum is broad and often causes confusion. Cytological atypia is present only in a subset of cases and mitotic figures are common but highly variable in number. By immunohistochemistry, FDCs express CD21, CD23, CD35, CXCL13, and clusterin. They also usually express vimentin, fascin, HLA-DR, and EMA and variably positive for CD68, S100, and CD45 [1, 4]. Clusterin staining is reported to be highly sensitive (100%) and specific (93%) and along with CD21 and CD23, constitute the essential stains required to establish a definitive diagnosis [9]. PRAME stain exhibits diffuse positivity in most melanomas, while typically presenting as negative or showing limited and focal immunoreactivity in nevi [10]. Variable degrees of PRAME staining have been sporadically observed in other malignant tumors, including most synovial sarcomas, myxoid liposarcomas, and malignant peripheral nerve sheath tumors (MPNST) [10]. Other neoplasms such as seminomas and carcinomas of various origins including endometrial, serous ovarian, mammary ductal, lung, and renal showed an intermediate proportion of cases and variable extent of tumor cells positive for PRAME protein expression [10]. To our knowledge, PRAME positivity has not been reported in FDC sarcoma before. In our case, PRAME is positive but all other melanoma markers (S100, HMB45, Melan A, and SOX10) are negative. Few FDC sarcoma cases with aberrant phenotype have been reported before including a case of intra-abdominal FDC sarcoma with pleomorphic features and aberrant expression of neuroendocrine markers [11], an unusual case of FDC sarcoma of the omentum with pleomorphic morphology and aberrant cytokeratin expression [12], another case with aberrant T-cell antigen expression [13], and a clinicopathologic study of 15 FDC cases with expression of MDM2, somatostatin receptor 2A, and PD-L1 [14].

Although genetic drivers for tumorigenesis in FDC are largely unknown, recent genomic profiling studies have revealed several recurrent gene alterations in FDC sarcoma, including BRAF V600E mutation [15] and loss-of-function variants in tumor suppressor genes involved in the regulation of NF-κB pathway and cell cycle, such as NFKBIA, CYLD, CDKN2A, and RB1 genes [16]. In addition, genomic profiling for one patient with primary esophageal follicular dendritic cell sarcoma revealed pathogenic variants in multiple genes, including CHEK2, FAT1, TP53, DPYD, ERBB2IP, FBXW7, KMT2D, PPP2R1A, and TSC2 [17]. The NGS results for this patient identified loss-of-function pathogenic variants in RB1 (p.W516*), TP53 (p.G187D), and FBXW7 (p.S294fs), which have been reported previously in FDC sarcoma patients, supporting the FDC sarcoma diagnosis.

In conclusion, we report a case of FDC sarcoma with an unusual extranodal localization in the parotid gland. Furthermore, the aberrant positive expression of the melanocytic marker PRAME has not been reported before. All other melanocytic markers were negative in our case and the characteristic FDC markers are positive.