FINAL DIAGNOSIS: FOLLICULAR DENDRITIC CELL SARCOMA
Follicular dendritic cell (FDC) sarcoma is a rare neoplasm of follicular dendritic cells that are antigen-presenting cells of the B-cell follicles in lymph nodes and extranodal lymphoid tissue. Most patients are adults with an equal sex distribution. More than half the cases are nodal in origin, with cervical lymph nodes as the most common site of involvement. Approximately 30% of the cases have been located at extranodal sites. The tonsil, nasopharynx, pancreas, peripancreatic and peritoneal tissues are the most common extranodal sites. One case of FDC sarcoma involving the breast has also been reported.
Systemic symptoms are rare. Patients most often present with a slow growing painless mass. Castleman disease is one clinical setting where hyperplasia and dysplasia of follicular dendritic cells has been implicated as precursor lesions to this neoplasm. Nearly 10-20% of cases are associated with Castleman disease (of hyaline vascular type). EBV genome has been identified in several putative FDC sarcomas that show morphologic resemblance to inflammatory pseudotumor.
Gross appearance is similar to that of other sarcomas with a well-circumscribed tan grey cut surface. Necrosis and cystic change may be seen in larger tumors. Histologic appearance is that of a spindled and ovoid cell proliferation forming fascicles and a storiform pattern with whirling, reminiscent of a meningioma. Tumor cells have plump eosinophilic cytoplasm and indistinct cell borders. Nuclei are elongated with vesicular or finely granular chromatin and distinct nucleoli. Although most cases are cytologically bland with a low mitotic rate (0-10/10 HPF), cases with greater cytologic atypia and higher mitotic rates may be seen. Often there is a sparse infiltrate of mature lymphocytes and plasma cells, predominantly in a perivascular distribution. In cases involving the liver and spleen, the tumor cells often do not demonstrate a cohesive proliferation of spindled cells, and have a greater degree of inflammatory infiltrate causing diagnostic confusion with inflammatory pseudotumor.
Awareness of FDC sarcoma is important, as the tumor closely mimics other tumors and tumor-like conditions. Even with immunohistochemical work-up, diagnosis may be missed as FDC markers are often not included in the routine panel of antibodies used for investigation of undifferentiated neoplasms. At least 7 cases of extranodal FDC sarcomas of the head and neck were initially misdiagnosed as inflammatory pseudotumor, ectopic meningioma, malignant schwannoma, poorly differentiated carcinoma, fibrous histiocytoma, carcinoma showing thymus like elements (CASTLE), and acinic cell carcinoma. The key histologic feature suggestive of FDC sarcoma is the perivascular distribution of small lymphocytes within the tumor. All cases need confirmation by immunohistochemistry.
Immunohistochemical profile shows immunoreactivity for markers specific for follicular dendritic cell differentiation: CD21, CD23 and CD35. The cells are also usually positive for vimentin, fascin, HLA-DR and EMA (the latter causing confusion with meningioma and carcinoma). They are variably positive for S100 and CD68. Staining for CD1a, lysozyme, CD34, CD3, CD79a, CD30, HMB45 and cytokeratin is consistently negative. The small lymphocytes have been variably demonstrated to be predominantly T or B cells. Tumors arising in the liver and spleen often show only weak and focal positivity for follicular dendritic cell markers. Ultrastructural examination shows complex interdigitating cytoplasmic processes joined by desmosomes.
The behavior is typically indolent. Patients are treated with surgical excision, with and without adjuvant chemotherapy. Local recurrences occur in about 40-50% of cases and metastases occur in 25%. Cases with intra-abdominal presentation, greater cytologic atypia or increased mitotic activity follow a more aggressive clinical course. One case of FDC sarcoma of the breast that demonstrated high-grade features histologic features (necrosis, mitoses) followed an uneventful clinical course up to 19 years following initial treatment. At least 10-20% of patients die of their disease, often after a long period of time.
Contributed by Hina Sheikh, MD and Fiona Craig MD