Follicular Dendritic Cell Sarcoma.
Upon gross examination, FDCS is a relatively well-circumscribed tumor with a tan, solid-appearing cut surface with pushing borders (2) and variable areas of hemorrhage and necrosis (Figure 1).
HISTOPATHOLOGY, IMMUNOHISTOCHEMISTRY, AND DIFFERENTIAL DIAGNOSIS
Histologically, FDCS is composed of uniform, spindle and ovoid cells, with eosinophilic cytoplasm and nuclei with a vesicular chromatin pattern, nuclear pseudoinclusions, and distinct nucleoli (Figure 2). The neoplastic cells are usually arranged in fascicular, somewhat syncytial sheets, with whorled or storiform patterns in some areas, sometimes reminiscent of meningioma, (2,5) often with intermixed, small lymphocytes (4) (Figure 3). The mitotic rate is typically low, but pleomorphic cases can have higher mitotic rates.
Follicular dendritic cell sarcoma is frequently misdiagnosed, primarily because it is rare and often not considered in the differential diagnosis of a spindle cell neoplasm. Depending on location and presentation, the differential diagnosis of FDCS can include inflammatory myofibroblasts tumor, inflammatory pseudotumor, interdigitating dendritic cell sarcoma, Langerhans cell histiocytosis, sarcomatoid carcinoma, undifferentiated pleomorphic sarcoma, thymoma, lymphoma, Schwannoma, and gastrointestinal stromal tumor.
Immunohistochemical markers assist in arriving at the diagnosis of FDCS if the appropriate immunohistochemical markers specific for follicular dendritic cell differentiation/FDCS are applied. The neoplastic spindle cells of FDCS are typically immunohistochemically positive for CD21 (Figure 4), CD35 (Figure 5), and CD23. Clusterin is also highly sensitive and specific for FDCS when strongly and diffusely positive. (13,14) Although the neoplastic cells of FDCS cells can have variable immunohistochemical expression of vimentin (positive in several soft tissue tumors), CD68 (typically positive in undifferentiated pleomorphic sarcoma and Langerhans cell histiocytosis), and S100 (typically positive in Schwannoma), none of these markers are specific for FDCS. Because of the lack of specificity of these markers for FDCS, a misdiagnosis can occur if FDCS is not considered in the differential diagnosis, and dendritic cell immunohistochemical markers described above are not applied. The neoplastic cells of FDCS are consistently negative for cytokeratins, CD31, CD34, and CD1a, making sarcomatoid carcinoma, angiosarcoma, and Langerhans cell histiocytosis less likely.
INFLAMMATORY PSEUDOTUMOR-LIKE VARIANT OF FOLLICULAR DENDRITIC CELL SARCOMA
An inflammatory pseudotumor-like variant of FDCS has been described, with areas that are histologically similar to conventional inflammatory pseudotumors, differentiating it from conventional FDCS. (3) The inflammatory pseudotumorlike variant of FDCS occurs most commonly in the liver and spleen. Aside from the differences in histology and location from conventional FDCS, the 2 entities also differ in clinical presentation (15); the inflammatory pseudotumor variant of FDCS has a marked female predominance (15-17) and often presents with systemic symptoms. The inflammatory pseudotumor-like variant of FDCS is associated with Epstein-Barr virus (EBV), with Epstein-Barr virus-encoded RNA found in most cases. (16,18) Ge et al (19) found Epstein-Barr virus-encoded RNA in situ hybridization was positive in 92.1% of the neoplastic spindle cells. Most cases also expressed conventional FDCS markers, including CD21, CD35, CD23, and clusterin. In addition to the differential diagnosis for conventional FDCS, the differential diagnosis of the inflammatory pseudotumor-like variant could also include Hodgkin lymphoma because the inflammatory pseudotumor-like variant of FDCS can occasionally show Reed-Sternberg-like cells in a background of predominantly spindle cell morphology. (20)
MOLECULAR PATHOLOGY AND CYTOGENETICS
Several recent studies have evaluated molecular and cytogenetic abnormalities that may be linked to FDCS. Griffin et al (21) found recurrent loss-of-function alterations in nuclear factor [kappa]B regulatory genes NFKBIA and CYLD, cell cycle progression genes (CDKN2A and RBI), and genes involved in immune evasion, including CD274 and PDCD1LG2, which resulted in the activation of the nuclear factor [kappa]B genes. Go et al (22) showed BRAF mutations were present in 18.5% of FDCS and 40% of inflammatory pseudotumor-like variants of FDCS cases. Increased knowledge about the molecular genetic profile of FDCS can potentially translate to targeted therapy in the future.
A study by Perry et al (23) demonstrated cytogenetic abnormalities of a near diploid clone with loss of chromosomes 3 and 14 in one FDCS case and a hypodiploid clone with loss of chromosomes 5, 6, 9, 14, 16, and 22 in another FDCS case. However, FDCS is often associated with a complex karyotype.
PROGNOSIS AND TREATMENT
Although FDCS typically has an indolent course, local recurrence is very common, with a recurrence rate of 40% to 50%, and an aggressive clinical course, including metastases to lung, liver, or lymph nodes, is possible. (15) Overall, FDCS should be considered at least an intermediate-grade tumor. (5) Poor prognostic factors for FDCS include a size of 6 cm or larger, an intra-abdominal location, coagulative necrosis, 5 mitoses/10 high-power fields or more, and prominent nuclear atypia/pleomorphism. (5) The inflammatory pseudotumor-like variant of FDCS is thought to have a more indolent clinical course when compared with conventional FDCS. (20,24)
Prospective data, comparing treatment regimens for FDCS, are not available, likely because of the low incidence of FDCS; therefore, optimal treatment recommendations for these patients are not well-defined. For localized FDCS, most cases are treated by surgical resection, with or without adjuvant chemotherapy and/or radiation. Although Gounder and colleagues (12) reported no significant difference in 5-year survival rates between those who received adjuvant or neoadjuvant therapy (n = 11) and those who underwent surgical resection alone (n = 12), Soriano et al (25) found longer disease-free survival in patients with FDCS who received a combination of surgery, chemotherapy, and radiation. For patients with more-widespread FDCS or those in whom surgical resection is otherwise not possible, lymphoma-type regimens or sarcoma regimens may be used.
Follicular dendritic cell sarcoma is a rare neoplasm with follicular dendritic cell differentiation, which typically has an indolent course, but should be considered at least an intermediate-grade tumor given its metastatic potential. The histologic appearance and typical immunohistochemical staining pattern are often sufficiently sensitive and specific to help make the diagnosis. However, it can easily be misdiagnosed in clinical practice if not considered in the differential diagnosis; therefore, a high level of clinical suspicion is needed in appropriate cases.
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(18.) Li XQ, Cheuk W, Lam PW, et al. Inflammatory pseudotumor-like follicular dendritic cell tumor of liver and spleen: granulomatous and eosinophil-rich variants mimicking inflammatory or infective lesions. Am J Surg Pathol. 2014; 38(5):646-653.
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Please Note: Illustration(s) are not available due to copyright restrictions
Caption: Figure 1. Abdominal, extranodal follicular dendritic cell sarcoma with smooth, tan cut surface and relatively well-circumscribed border.
Caption: Figure 2. Follicular dendritic cell sarcoma composed of uniform spindle and oval cells with eosinophilic cytoplasm, nuclei with a vesicular chromatin pattern, occasional intracellular inclusions, distinct nucleoli, and admixed chronic inflammatory cells (hematoxylin-eosin, original magnification X40).
Caption: Figure 3. Follicular dendritic cell sarcoma with spindle cells arranged in fascicular sheets with whorled/storiform pattern and admixed chronic inflammatory cells (hematoxylin-eosin, original magnification X10).
Caption: Figure 4. CD21 immunohistochemical stain highlighting follicular dendritic cell sarcoma spindle cells (original magnification X20).
Caption: Figure 5. CD35 immunohistochemical stain highlighting follicular dendritic cell sarcoma spindle cells (original magnification X20).
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|Title Annotation:||Resident Short Reviews|
|Author:||Chen, Tiffany; Gopal, Purva|
|Publication:||Archives of Pathology & Laboratory Medicine|
|Date:||Apr 1, 2017|
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