Histiocytic and dendritic cell neoplasms: Reappraisal of a Japanese series based on t(14;18) and neoplastic PD-L1 expression.

Histiocytic and dendritic cell (H/DC) neoplasms are heterogeneous, originating from myeloid- or stromal-derived cells. Multiple reports describe the cross-lineage transdifferentiation of neoplastic B cells into H/DC neoplasms. Most such cases are from Western countries, and rarely from Japan or East Asia. Here we report 17 cases of H/DC neoplasms in Japanese patients, with analysis of t(14;18) by fluorescence in situ hybridization, and of neoplastic programmed death-ligand 1 (PD-L1) expression by immunostaining (clones SP142, E1J2J, and 28-8). These 17 cases were diagnosed according to the 2017 World Health Organization (WHO) classification, and included two histiocytic sarcomas (HS), two interdigitating cell (IDC) sarcomas, one Langerhans cell sarcoma, two dendritic cell sarcomas, and 10 follicular dendritic cell (FDC) sarcomas. No case had any past history of follicular lymphoma (FL). Two cases of HS and one IDC sarcoma, all of which were myeloid-driven, were found to exhibit t(14;18). In the latter case, at 30 months after IDC sarcoma diagnosis, FL development was detected. Three (30%) FDC sarcoma cases exhibited neoplastic PD-L1 expression with all the three PD-L1 antibody clones. This is the first report of t(14;18) and neoplastic PD-L1 expression on H/DC neoplasms among Japanese patients, each of which appeared to be associated with HS and FDC sarcoma, respectively.

Follicular Dendritic Cell Sarcoma With Indolent T-Lymphoblastic Proliferation Is Associated With Paraneoplastic Autoimmune Multiorgan Syndrome.

Nonclonal expansions of immature T cells outside of the thymus, termed indolent T-lymphoblastic proliferation (iT-LBP), have been identified in rare lymphoproliferative disorders. We report that iT-LBP is a frequent finding in cases of follicular dendritic cell sarcoma (FDCS), and shows an association with paraneoplastic autoimmune multiorgan syndrome (PAMS). We studied 31 cases of FDCS by paraffin immunohistochemistry using antibodies to CD21, CD23, CD35, clusterin, CXCL13, podoplanin, CD3, CD4, CD8, CD20, CD1a, and TdT. Chart review was performed to characterize the clinical behavior including evidence of autoimmune disease. FDCS occurred in a wide variety of nodal and extranodal sites. Fourteen of 31 (45%) cases contained immature TdT-positive T cells; in 5 cases these cells were numerous and present throughout the tumor. Four of these 5 patients with numerous immature T cells developed autoimmune disease, clinically categorized as PAMS and/or myasthenia gravis. PAMS persisted after tumor resection, causing severe morbidity and mortality. These findings suggest that the neoplastic follicular dendritic cells can recruit or foster the proliferation of immature T cells and that these cells may play a role in mediating PAMS. Recognition of iT-LBP in FDCS is important to avoid misdiagnosis as thymoma or T-lymphoblastic lymphoma, and may predict serious autoimmune complications in some patients.

Distinctive Histogenesis and Immunological Microenvironment Based on Transcriptional Profiles of Follicular Dendritic Cell Sarcomas.

Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors with variable clinical, morphologic, and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared with other mesenchymal tumors, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other mesenchymal tumors and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n = 1,289) between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other mesenchymal tumors identified 370 and 2,927 differentially expressed transcripts, respectively, and on the basis of pathway enrichment analysis ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. As the transcriptome of FDC sarcomas retained similarity with FDCs, the immune landscape of FDC sarcoma was investigated by applying the CIBERSORT algorithm to FDC sarcomas and non-FDC mesenchymal tumors and demonstrated that FDC sarcomas were enriched in T follicular helper (TFH) and T regulatory (TREG) cell populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and its ligands PD-L1 and PD-L2, which were found to be significantly upregulated in FDC sarcomas as compared with other mesenchymal tumors, a finding also confirmed in situ Here, it is demonstrated for the first time the transcriptional relationship of FDC sarcomas with nonmalignant FDCs and their distinction from other mesenchymal tumors.Implications: The current study provides evidence of a peculiar immune microenvironment associated with FDC sarcomas that may have clinical utility. Mol Cancer Res; 15(5); 541-52. ©2017 AACR.

High frequency of clonal IG and T-cell receptor gene rearrangements in histiocytic and dendritic cell neoplasms.

The 2008 World Health Organization (WHO) diagnostic criteria of histiocytic and dendritic cell neoplasms from hematopoietic and lymphoid tissues no longer required the absence of clonal B-cell/T-cell receptor gene rearrangements. It is true that the clonal B-cell/T-cell receptor gene rearrangements have been identified in rare cases of histiocytic and dendritic cell neoplasms, such as those with or following lymphoma/leukemia or in some sporadic histiocytic/dendritic cell sarcomas, but the clonal features of such group of tumor are still not clear. Here we investigated the clonal status of 33 samples including Langerhans cell histiocytosis (LCH), Langerhans cell sarcoma (LCS), follicular dendritic cell sarcoma (FDCS), interdigitating dendritic cell sarcoma (IDCS) and histiocytic sarcoma (HS). Among them, twenty-eight cases were sporadic without current or past lymphoma/leukemia. Three cases were found with a past history of T-cell lymphoma, one case was followed by extraosseous plasmacytoma, and one case was found with diffuse large B-cell lymphoma (DLBCL). Our results showed that there was a high frequency of clonal IG and T-cell receptor gene rearrangements in these cases. Notably, 4 cases of LCH and 2 cases of FDCS showed both B and T cell receptor gene rearrangements concurrently. One case of FDCS synchronous with DLBCL showed identical clonal IGH in both tumor populations and clonal TCRß in FDCS alone. No matter if the presence of clonal receptor gene rearrangements was associated with the tumor origin or tumorigenesis, it might serve as a novel tumor marker for developing target therapy.

Inflammatory pseudotumor-like follicular dendritic cell sarcoma of the spleen: a report of six cases with increased IgG4-positive plasma cells.

Inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a rare neoplasm typically occurring in the spleen or liver. We present six cases of EBV(+) IPT-like FDC sarcoma of the spleen among Koreans along with their clinicopathologic features and IHC results. Most patients presented with an asymptomatic, incidentally detected single splenic mass and were successfully managed by splenectomy alone. Concomitant disease was found in one case, showing EBV(+) gastric carcinoma with lymphoid-rich stroma. Histologic features showed fibro-inflammatory lesions that were often accompanied by necrosis and epithelioid histiocytic collection, which are barely distinguishable from IPT. Tumor cells did not frequently express conventional FDC markers, including CD21 (3/6 positive cases), clusterin (4/6), and D2-40 (2/6), but showed uniform positivity for smooth muscle actin (SMA). Noticeably, significant numbers of IgG4(+) plasma cells were found within all six tumors. We suggest that the diagnosis of IPT-like FDC sarcoma should be made by the application of a panel of FDC markers, and CD21 negativity or SMA positivity cannot be the criterion for exclusion of IPT-like FDC sarcoma. Relationship of IPT-like FDC sarcoma of the spleen and IgG4-related sclerosing disease should be investigated in further studies.

Follicular dendritic cell sarcoma of the liver: unusual presentation of a rare tumor and literature review.

BACKGROUND: Hepatic follicular dendritic cell (FDC) sarcoma is an extremely rare neoplasm. Most commonly, FDC sarcoma presents as a solitary mass in lymph nodes, however, several extra-nodal locations have been identified. METHODS: We report a case of a 53-year-old female who presented with symptoms of abdominal pain, fever, anemia, and jaundice. After an extensive review of the literature, we have found only 12 cases of hepatic FDC sarcoma. RESULTS: The tumor was 11.5 cm in diameter and composed of spindle and epithelioid cells with ovoid nuclei and associated with mixed inflammatory infiltrate. Immunohistochemical stains were positive for CD35 and CD21. The patient underwent a left hepatic lobectomy. CONCLUSIONS: Liver follicular dendritic cell sarcoma is a very rare tumor. Most cases present with abdominal pain and weight loss, and most of them can be managed by hepatic resection with excellent short-term outcomes.

Cervical follicular dendritic cell sarcoma: a case report and review of the literature.

Follicular dendritic cell (FDC) sarcoma is a rare tumour with a low-to-intermediate grade of malignancy. It frequently occurs in cervical, mediastinal and axillary lymph nodes. In approximately 30% of cases an extranodal localization has been reported (tonsils, oral cavity, mediastinum, liver, and spleen). Very little is known about possible treatment options and overall prognosis. This case reports a 66 year-old patient, who underwent surgical removal of a persistently enlarged right cervical lymph node. The histopathological examination revealed a spindle cell tumour with lymphocyte and plasma cell infiltrates. Neoplastic cells stained positive for CD21, CD23 and CD35, thus confirming the diagnosis of FDC sarcoma. The neoplasm recurred two years later and partial regression was achieved by IGEV rescue therapy. We briefly discuss clinical history, histopathological differential diagnosis and treatment options of FDC sarcoma.

Follicular dendritic cell sarcoma: a report of six cases and a review of the Chinese literature.

GOALS: The main purpose of this study is to broaden the clinicopathological spectrum and increase recognition of follicular dendritic cell sarcoma (FDCS) through analysis of the clinical and pathological features of 50 cases. METHODS: The clinicopathological features of total 50 cases of FDCS were analyzed including a review of 44 cases reported in Chinese literature before October 2009 and six original cases from the pathology files conducted by the authors. RESULTS: The youngest patient came under observation in this study is only seven years old. Including the cases contributed by the authors, our literary review indicated that male dominated the tumor cases (M: F = 3: 2). 28 cases (56%) present with this disease in extranodal sites. Tumor cells demonstrated positive staining for the follicular dendritic cell markers CD21 (47/49), CD35 (43/45), CD23 (20/23) and CD68 (23/25). In situ hybridization for Epstein-Barr virus-encoded RNA was performed in 10 cases. Nevertheless, EBV expression was absent in all these cases. The follow-up analysis of all cases shows that 26 (81.2%) patients were alive and disease free; 6 (18.8%) patients were alive with recurrent disease or metastasis; and nobody had died of this disease at the time of last follow-up. CONCLUSIONS: The diagnosis of the FDCS is based on the findings of morphology and immunohistochemistry. The FDCS occurred in China should be viewed and treated as a low-grade sarcoma, and the role of the EBV in the pathogenesis of this tumor is still uncertain. There is a possibility that the tumor might be racial or geographic correlated, because most cases were reported from Eastern Asia area; it's particular the case of the liver or spleen tumor.

Follicular dendritic cell sarcoma with immature T-cell proliferation.

Follicular dendritic cell sarcoma is characterized by proliferation of spindled to ovoid cells reminiscent of follicular dendritic cells. However, the association of follicular dendritic cell sarcoma with a dense infiltration of immature T cells has not hitherto been reported. We report an unusual case of follicular dendritic cell sarcoma of the mesentery with immature T-cell proliferation in a 68-year-old man. The infiltrating immature T cells demonstrated expression of CD3, CD1a, TdT, and coexpression of CD4 and CD8 by immunohistochemistry. In addition, the patient was subsequently diagnosed with myasthenia gravis and paraneoplastic pemphigus and died of distant metastasis within 2 years after initial diagnosis of follicular dendritic cell sarcoma. The aggressive clinical course of this case contrasts with the indolent course of follicular dendritic cell sarcomas, and thus, the prognostic implications of follicular dendritic cell sarcoma with immature T-cell proliferation require clarification. The complication of myasthenia gravis and paraneoplastic pemphigus may suggest that immature T-cell proliferation has an autoimmunity-related systemic influence.

Follicular dendritic cell sarcoma of small intestine with aberrant T-cell marker expression.

Follicular dendritic cell sarcoma (FDCS) is an uncommon neoplasia usually occurring in lymphoid tissue. Herein is presented a case of FDCS of the small intestine with positivity for T-cell antigen, simulating T-cell lymphoma. An 82-year-old man consulted a doctor for a 1 week history of epigastric pain. Imaging indicated a mass in the small intestine. Malignant lymphoma was suspected because of high serum levels of soluble interleukin-2 receptor, and resection of the tumor was performed. Microscopically the tumor consisted of large pleomorphic cells with reactive small lymphocytes. Most of the nuclei of the tumor cells were round or ovoid, and some of the tumor cells also had spindle-shaped nuclei. Although the tumor cells were diffusely positive for CD45RO and CD4 on immunohistochemistry, negativity for pan-T-cell markers and CD56 was unusual for T-cell lymphoma of intestinal origin. Additional immunohistochemistry demonstrated that the tumor cells were positive for follicular dendritic cell markers including CD23, CD35 and CAN.42, and diagnosis of FDCS was made. To the authors' knowledge this is the first case of FDCS aberrantly expressing CD45RO; FDCS expressing T-cell markers can be a pitfall for diagnosis of FDCS.

Follicular dendritic cell sarcoma/tumor: 2 cases of a rare tumor of difficult clinical and pathological diagnosis.

The follicular dendritic cell sarcoma/tumor is a neoplasic proliferation of fusiform and ovoid cells with characteristic morphology and immunohistochemical pattern. The sarcoma/tumor term is designated due to the variability of the cytological status and, in many cases, its indeterminate clinical course. This report presents the 2 first cases seen at the Hospital General de México, OD (General Hospital of Mexico). The aim of this study is to contribute to the morphology and immunophenotype of this infrequent neoplasm, as well as discuss its differential diagnosis and clinical evolution.

Follicular dendritic cell sarcoma: a case report.

BACKGROUND: Follicular dendritic cell (FDC) sarcoma is a neoplastic proliferation of spindled to ovoid cells showing morphologic and phenotypic features of follicular dendritic cells. It is a rare tumor that can present in nodal and extranodal sites. CASE: A 41-year-old woman presented with a 6-week history of an enlarging lump in her neck. Fine needle aspiration (FNA) was performed. FNA findings led to the diagnosis of malignant tumor. We suggested that it was an FDC sarcoma. The tumor was excised. On microscopic examination, the tumor largely replaced the lymph node. It was composed of oval to spindle cells arranged in sheets and interlacing fascicles with a storiform pattern. The tumor cells showed widespread immunopositivity for CD21. Based on these findings the diagnosis of FDC sarcoma was made. Two years later local recurrence occurred. CONCLUSION: FDC sarcoma has characteristic FNA findings. Once FDC sarcoma is suspected cytologically or histologically, immunohistochemical stains must be performed for reaching the correct diagnosis. Awareness of this rare entity is necessary to avoid its underrecognition.