Synchronous presentation of intra‐nodal follicular dendritic cell sarcoma and Castleman disease
Authors: Preetesh Jain, Victor G. Prieto, John T. Manning, Nathan Fowler, L. Jeffrey Medeiros, Rashmi Kanagal‐Shamanna
Journal: American Journal of Hematology (2016)

A 53-year-old woman presented with a three-week history of progressive epigastric and right lower abdominal pain. She also had a history of skin rash, arthralgias, alopecia aerata, and bilateral hearing loss. Family history was significant for schwannoma, neurofibromatosis, Hashimoto thyroiditis, and Graves' disease. Physical examination revealed café-au-lait spots on her left shoulder and epigastric tenderness. Laboratory studies showed a normal complete blood cell count, normal renal and liver function tests, and elevated plasma levels of dopamine, norepinephrine, and free normetanephrine. Her colonoscopy and upper GI endoscopy were unremarkable. Magnetic resonance imaging of the abdomen showed a 4.2 cm × 2.5 cm, well circumscribed, T2 hyper-intense retroperitoneal mass abutting the pancreatic body. Octreotide and MIBG (metaiodobenzylguanidine) scans were negative. The patient underwent a complete surgical resection of the retroperitoneal mass. Histologic sections showed lymph nodes with multi-focal areas of atypical follicular dendritic cell (FDC) proliferation in intra-follicular and inter-follicular regions. In one focus, these formed a 7.5 mm expansile nodular mass with a storiform pattern of arrangement (Image 1A). The FDCs had plump eosinophilic cytoplasm, with cytologic atypia characterized by large, hyperchromatic nuclei, and without necrosis. The mitotic rate was 3–5/10 high power fields (Image 1B). This nodule was entirely contained within the lymph node. In the remainder of the lymph node, multi-focal areas of atypical FDC proliferation did not form discrete masses. Few areas of the lymph node showed follicles with "onion skin"-like proliferation in the mantle zone (solid arrows), hyaline vascular changes (asterisk), and penetrating vessels (empty arrow), interfollicular areas showing thin fascicles (arrow) are shown (Image 1C,D). By immunohistochemical studies, the areas of FDC proliferation, including the expansile nodule, were positive for CD21 (Image 1E), CD23, CD35, fascin, and D2-40 or podoplanin (Image 1F); and negative for CD30, S100, and ALK. CD3 highlighted T-cells, mostly surrounding the follicles. TdT was positive in rare scattered cells. A diagnosis of intra-nodal FDC sarcoma associated with stroma-rich hyaline-vascular variant of Castleman disease was made. Repeat imaging was negative for residual tumor. Radiotherapy was initially considered due to the presence of multi-focal atypical FDC proliferation throughout the lymph node. However, based on the relatively small size, intranodal location and favorable histologic findings of FDC sarcoma, a decision was made to follow the patient with observation alone. Diagnosis of FDCS can be challenging. In about 20% of cases, FDCS is associated with Castleman disease, commonly of hyaline vascular type, that is diagnosed either concurrently or prior to FDCS 1-3. The presence of background histologic features of CD is often a clue to the diagnosis of FDCS. While a definitive clonal relationship between these two entities has not been established, sequential histological evaluation has suggested progression of FDC proliferation in CD to FDCS 1. The spectrum of histologic changes ranging from Castleman disease, multi-focal areas of abnormal FDC proliferation, and focal FDCS observed in this case further supports the causative relationship between CD and FDCS. FDCS and CD are managed by surgical resection, followed by radiation or chemotherapy if residual disease is present 4. A: Low-power view of the expansile nodule within a large lymph node (central area of clear cells surrounded by dark, small lymphocytes. B: High-power view of spindle cells with large nuclei, abundant cytoplasm, and interspersed lymphocytes. C: Few areas of the lymph node showing changes of Castleman disease such as follicles with "onion skin"-like proliferation in the mantle zone (solid arrows), hyaline vascular changes (asterisk), and penetrating vessels (empty arrow). D: Perifollicular and interfollicular areas showing thin fascicles (arrow) of spindle cells similar to those seen in panel (B). The dendritic cells in both the nodule and the interspersed areas express CD21 (E), fascin, and D2-40 (F). (E,F: anti-CD21 and D2-40 respectively; diaminobencidine with light hematoxylin as counterstain). P.J., R.K-S., V.G.P., J.T.M, and L.J.M. collected and analyzed pathology and wrote the paper. N.F. managed the patient. All Authors have reviewed and approved the manuscript. All authors do not have any disclosures/conflicts of interest.