Follicular Dendritic Cell Sarcoma With Co-Expression of CD4 and CD30 Mimics Anaplastic Large Cell Lymphoma

Follicular dendritic cell sarcoma (FDCS) is a low-grade malignant neoplasm that tends to be under-recognized owing to its rarity and wide pathologic spectrum. Knowledge of the atypical morphology and immunophenotype of FDCS is critical to avoid misdiagnosis. Here we presented a case of extranodal FDCS with an unusual morphology and a previously unreported immunophenotype leading to misdiagnosis. A 32-years-old man presented with a tonsilar mass that showed epithelioid cells in nested and alveolar patterns. Immunohistochemistry study revealed that the tumor cells were positive for CD4 and CD30, and were negative for cytokeratin, CD3, CD20, CD68, CD163, lysozyme, ALK, S-100, and desmin. Multiple outside expert consultations rendered a consensus diagnosis of ALK-negative anaplastic large cell lymphoma (ALCL). The patient received multiple lines of chemotherapy and radiotherapy. However, the residual tumor progressively enlarged eight months later and a more complex morphology was presented in the re-excised tumor: including spindle cells with vesicular nuclei and nuclear pseudoinclusions in fascicles or a whorled pattern, and plump ovoid cells arranged in meningioma-like whorls as well as epithelioid tumor cells similar to the initial biopsy. All these three components were positive for CD4, CD21, CD23, and CD35. The diagnosis was revised to FDCS after a positive immunostaining for CD21, CD23, and CD35 on the initial specimen was confirmed retrospectively. A literature review identified 57 cases of FDCS published from 2009 through 2019, and 13 (22.8%) of them were misdiagnosed at initial presentation. Among these misdiagnosed cases, all except one case were extranodal, and the incorrect initial diagnosis was mostly location-related. These cases expand the pathologic spectrum of FDCS, and further emphasize the necessity for pathologists to stay alert for this rare entity, bringing FDCS into the differentials for any spindle cell tumors, undifferentiated epithelioid cell tumors, and ALCL to avoid misdiagnosis.