Case Of Follicular Dendritic Cell Sarcoma Research Articles

Smooth Muscle Myosin Heavy Chain Expression in Nodal and Extranodal Follicular Dendritic Cell Sarcoma.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm requiring a high index of suspicion, especially on small biopsies. Smooth muscle myosin heavy chain (SMMHC) is a common immunohistochemical (IHC) stain that has been reported to mark normal nodal follicular dendritic cells (FDCs). We hypothesize that SMMHC can be a sensitive marker for FDCS and aim to compare its performance with established markers of FDCS. The archive of a large academic center was searched for cases of FDCS. Clinical features, including age, sex, and site at diagnosis, were reviewed. A hematoxylin and eosin-stained slide was evaluated to assess for morphology and presence of hyaline vascular Castleman disease. The established FDC markers CD21, CD23, fascin, clusterin, and D2-40 were reviewed and compared with SMMHC for all cases. The staining pattern was classified as positive (strong or weak) or negative. Seven unique cases of nodal and extranodal FDCS were collected. SMMHC was positive in most cases (n=5) and performed similarly to established FDC markers, including clusterin, CD21, and CD23 (n=7 each), and fascin and D2-40 (n=4 each). SMMHC was also negative in all 14 examined cases among 5 common differential diagnoses. We demonstrate that the common IHC marker SMMHC has high specificity and similar sensitivity as established FDC markers in nodal and extranodal FDCS, and is useful in the evaluation of common neoplastic mimics.

Cytological diagnosis of follicular dendritic cell sarcoma with a unique pattern of D2-40 immunoexpression.

Fine needle aspiration procedure is routinely used for cytological diagnosis of nodal or extra nodal lesions. Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm arising from follicular dendritic cells of lymphoid follicles at nodal and extranodal sites. Multimodal therapies have emerged for FDCS, necessitating its accurate pathologic diagnosis with additional ancillary testing for directing clinical management. By immunohistochemical analysis, FDCS is positive for the complement receptors CD21, CD23, and CD35. In addition, D2-40 is reported to be highly sensitive for FDCS with a strong membranous pattern of expression. In this study, we present the cytological diagnosis of a case of FDCS in retroperitoneal lymph nodes with an emphasis on a unique staining pattern of D2-40 which showed a strong nuclear pattern in tumor cells comparable to the membranous pattern of D2-40 on the control tissue and other surgical cases of FDCS in our comparative study.

Clinical profile and response to adjuvant treatments in patients with follicular dendritic cell sarcoma in the United States: Insights from SEER analysis.

e23537 Background: Follicular Dendritic Cell Sarcoma (FDCS) is a rare, indolent, low-grade sarcoma known for local recurrences managed primarily by surgery. The role for adjuvant therapy has not been established for either radiation or chemotherapy. We aimed to comprehensively analyze clinical and epidemiological profiles and responses to treatment in these patients. Methods: This is a retrospective study using the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Result (SEER) database. Cases of FDCS between 2001 to 2022 were identified utilizing the International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9758/3. Only adults > 18 years of age and diagnosed by positive histology or cytology were included. Descriptive statistics were used to describe demographic and tumor characteristics. Logistic regression was used to identify the factors influencing survival. Kaplan-Meier method was used to plot survival based on different treatment regimens and stages. Results: A total of 168 patients with FDCS were identified, with more than 50% of the patients ≥ 50 years of age. The mean age at diagnosis was 52.6 years, 56% were female, and 74.4% were white. Most of the patients had localized disease (63.7%), 17.9% had distant disease, and the remaining had unknown stages. About 90% of the patients underwent surgery, with 41% receiving local tumor excision. In Univariate analysis, older age, and distant disease were found to have poor outcomes. Surgery, irrespective of stage, was found to improve overall Survival (Table 1). While chemotherapy and distant disease had poor outcomes in univariate analysis, they were not statistically significant in multivariate analysis. The majority of the patients who received chemotherapy alone without surgical intervention had distant disease, explaining the poor outcome seen in univariate analysis. Among 107 patients with localized disease, 41 patients (41.1%) underwent only surgery and 43 patients (40.1%) received adjuvant therapy (either chemotherapy or radiation vs both) along with surgery. 5-year overall survival was significantly lower in patients who received adjuvant therapy. (88.4% vs 68.4%, p = 0.001). Conclusions: In conclusion, FDCS has a fair overall 5-year survival with surgery alone. Patients with localized disease, who received adjuvant therapies had poor survival outcomes as compared to the surgery-only group owing to disease burden. Large prospective studies are required to properly evaluate the benefit of adding chemotherapy or radiotherapy in resectable disease.

Fine needle aspiration cytology of follicular dendritic cell sarcoma of the stomach masquerading as gastrointestinal stromal tumor: A case report of a unique entity with emphasis on cytomorphology.

Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm, postulated to arise from follicular dendritic cells, with approximately 343 reported cases. Less than 100 cases of FDCS were in the gastrointestinal tract, with only four cases described in the stomach, none of them diagnosed on fine needle aspiration (FNA) cytology. We report here the first case of FDCS of the stomach diagnosed on FNA. Our patient is a 31-year-old male who presented with several years history of intermittent abdominal pain prompting occasional emergency-room visits. Imaging showed a 10.6 cm mass arising from the stomach, concerning for gastrointestinal stromal tumor. FNA cytology was performed using five passes with a 22-gauge needle. The smears were moderately cellular consisting of sheets and large, loosely cohesive clusters of ovoid to spindle cells with indistinct cytoplasmic borders and abundant cytoplasm, peppered with numerous small mature lymphocytes. The nuclei of the tumor cells were oval with finely granular chromatin with frequent nuclear grooves, pseudoinclusions, and easily recognizable mitotic figures. The tumor cells were positive for FDCS markers (CD21, CD23, and CD35).

Next Generation Sequencing of Castleman Disease and Follicular Dendritic Cell Sarcomas Associated with Castleman Disease

Castleman disease (CD) is a rare lymphoproliferative disorder, that can transform into malignant lymphomas during clinical progress. Histologically CD can be subdivided into a hyaline-vascular variant (CD-HVV), a plasma cell variant (CD-PCV) and an intermediate variant (CD-IV) and further sub-classified into localized unicentric CD (U-CD), and multicentric CD (M-CD). An association with human herpes virus 8 (HHV8) and human immunodeficiency associated virus (HIV) in some CD cases is well documented, though the pathogenesis of CD still remains to be understood (Casper et al. Br J Haematol 2005). In recent years, cytogenetic and molecular studies have demonstrated clonal abnormalities in CD (Fajgenbaum et al. Blood 2017) as well as somatic mutations in follicular dendritic cell sarcoma (FDCS) - a rare clinically aggressive mesenchymal tumor associated with CD-HVV (Griffin et al. Mod Pathol 2015). However, an understanding of the genetic and epigenetic landscape of these rare diseases is lacking. To the best of our knowledge, our study is the first to analyze the genetic and epigenetic features of CD and FDCS associated with CD.We analyzed 18 cases of CD and 3 cases of FDCS associated with CD by whole exome and/or targeted next generation deep sequencing (NGS). Hybrid-capture NGS [FoundationOne (F1), Foundation Medicine Inc. (FMI), Cambridge, MA] of 343 genes was performed on our 18 CD cases as previously described (Lee et al. Cancer Discov 2016). 100 base-pair paired end whole exome sequencing was performed on our 3 FDCS cases using Sureselect whole exome V5 kit (Agilent Technologies) at an average depth of coverage of 180-fold. Alignment was performed using BWA-MEM with further analysis performed using GATK (version 3), Varscan2, and SNNPET (Agilent Technologies). Annotation of variants was performed using Surecall (version 3.5.1.46, Agilent Technologies) and Seattleseq (University of Washington, Seattle WA; Version 9.10). Variants were additionally curated using Exome Aggregation Consortium (EXAC), Clinvar, 1000 genomes, and Exome Variant Server (EVS). Copy number variation (CNV) analysis was performed with Surecall and CNVSeq, both run with default parameters, and analysis was performed on the “hits” file.Of our 18 CD cases, 13 were CD-HVV, 3 were CD-PCV and 2 were CD-IV. 14 cases were unicentric and 4 were multicentric. All cases were negative for HHV8 and HIV. A single case of multicentric CD, CD-PVC, showed a somatic DNMT3A L295Q mutation; a gene frequently mutated in hematopoietic neoplasms and possibly related to clonal hematopoiesis of indeterminant potential (Zhang et al. Biomark Res 2017; Yang et al. Nat Rev Cancer 2015). Two other cases of multicentric CD showed common amplification of PTPN6 , ETS1 and TGFBR2 . These genes are known to interface in oncogenesis or critical biologic processes: deletion of PTPN6 results in alteration in dendritic cell function and autoimmunity (Clare et et al. Nano 2013), overexpression of ETS1 is seen in other instances such as breast carcinoma, and leukemia (Dittmer et al. Mol Cancer 2013) and relatively increased expression of TGFBR2 is seen in stromal/vascular tissues. Only one CD-HVV case, presenting clinically untypically aggressive, showed amplifications of HIST genes. These findings could be consistent with a clonal, neoplastic nature to at least a subset of CD cases.To understand the possible association between CD-HVV and FDCS we also analyzed the mutational landscape of FDCS associated with CD. Our FDCS cases had 3-5 somatic mutations and CNVs in oncogenes and genes known to be critical in tumorigenesis, such as: ZBTB7a - playing a key role in the development from lymphoid progenitors into B-cell lineage, and STAT3 - a transcription factor mutated in NK, T-cell and B-cell disorders (Yu et al. Nat Publ Gr 2014). Given the diverse clinical presentation of FDCS it is not surprising, that previously published mutations seen in FDCS not arising from CD were missing in our study. However, previously described CNVs in FDCS such as NFKBI , and JAK2 were present, next to overlapping CNVs in BRAF and FANCB in two of our cases. In one of our FDCS cases loss of several HISTH genes were further seen. No Translocations or recurrent mutations were seen. [Display omitted] DisclosuresMughal:Foundation Medicine, Inc: Employment, Other: Stock. Ali:Foundation Medicine, Inc: Employment, Other: Stock.

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.

A Rare Aggressive Case of Follicular Dendritic Cell Sarcoma

Follicular dendritic cell sarcoma (FDCS) is a rare lymphoid neoplasm with indolent clinical process. However, we presented here a rare case of FDCS in aggressive pace. The case was a 48-year-old female complaining of dysphagia for half a year. She was found gastric fundus bulge under gastroscopy and diagnosed as low-differentiated gastric adenocarcinoma in the local hospital. After three courses of chemotherapy with paclitaxel combined with oxaliplatin and 5-fluorouracil, PET-CT showed progressive disease (PD) with not only gastric bulk but also invasion to the liver and multiple lymph nodes in the abdomen. The patient was admitted to the Department of Surgery of our hospital. Total gastrectomy and liver tumor resection were performed and postoperative pathology demonstrated FDCS. The patient was transferred to our department for chemotherapy. After three courses of CHOP, PET-CT showed tumor in the anastomotic site, partial liver resection margin and left adrenal gland. The patient was sent for radiotherapy. After radiation, PET-CT demonstrated PD and the puncture of left supraclavicular lymph node confirmed FDCs. Thalidomide and prednisone were given orally. At the same time, the whole exome sequencing (WES) was performed, based on which therapy response index (TRI) was analyzed by Cellworks software. According to TRI, the regimen of etoposide, carboplatin, bendamustine and chidamide was chosen for the patient. After the chemotherapy, the patient developed repeated vomiting and diarrhea. Abdominal CT showed intussusception and intestinal obstruction. She was sent for gastrointestinal surgery to relieve obstruction and postoperative pathology again confirmed FDCS. However, her abdominal pain and diarrhea occurred again one month after operation. The patient was discharged voluntarily and went to local hospital for supportive care. During a year from the onset to abandon of tumor therapy, the case was administered operation, radiotherapy and chemotherapy. The regimens of chemotherapy included paclitaxel-based chemotherapy for solid tumors, CHOP for lymphoma, and formulated regimen according to the analysis of WES. However, all of these therapeutic strategies were unable to control the progress of her disease. Hitherto, there is no guideline or consensus to guide the treatment of FDCS. The diagnosis and treatment process of this relapsed and refractory case can provide reference for clinicians to manage FDCS. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: FDCS of this case was in the aggressive manner. Routine therapeutic strategies, including operation, radiotherapy and chemotherapy based on paclitaxel or CHOP, were not able to control the progress. Therefore, the whole exome sequencing (WES) was performed, based on which therapy response index (TRI) was analyzed by Cellworks software. According to TRI, the regimen of etoposide, carboplatin, bendamustine and chidamide was chosen for the patient under the consent of her and her family for off-label use.

Clinicopathological Features of Follicular Dendritic Cell Sarcoma

Objective To explore the clinicopathological and immunohistochemical characteristics of follicular dendritic cell sarcoma(FDCS)and the expressions of IgG and IgG4. Methods We retrospectively analyzed the clinicopathological and immunohistochemical data of 9 pathologically confirmed FDCS cases in Peking Union Medical College Hospital from January 2005 to December 2018.Immunohistochemical staining of IgG and IgG4 were performed,and Epstein-Barr virus(EBV)-encoded RNA(EBER)in situ hybridization were carried out. Results Nine cases of FDCS included 4 men and 5 women aged 16-53 years [mean(38.2±9.7)years].The clinical manifestations included masses,lymph node enlargement,rash,and fever.The tumors were located in lymph node,retroperitoneal region,adrenal gland,neck,axillary region,and liver,respectively.Ultrasound showed clear boundary cystic or solid mass with maximum diameters of 1.5-15.0 cm.Microscopically,the spindle tumor cells were arranged in solid and storiform patterns with abundant and slightly stained cytoplasm,vacuolated nuclei,and small nucleoli.The mitosis was 1-3/10 high power fields,and necrosis was found in 5 cases.Immunohistochemically,the tumor cells were positive for CD21(6/9),CD35(6/9),and CD23(7/9). Conclusions FDCS is a rare malignant tumor,which is easy to be missed.The combination of CD21,CD35,and CD23 is helpful for diagnosis.Hyaline-vascular type Castleman's disease may be the precursor of FDCS,and there may be only a small number of IgG4-positive plasma cells in FDCS.Surgical resection remains the main treatment for FDCS.

Follicular Dendritic Cell Sarcoma of the Tonsil: A Multimodality Approach

Follicular dendritic cell sarcoma (FDCS) accounts for < 0.4% of soft tissue sarcomas. Only 35 cases of tonsillar FDCS have been reported, and majority had localized presentation. We present a case of FDCS of the tonsil, wherein a well-coordinated trimodality approach provided good disease control in advanced disease. A 53-year-old man presented with a painless and enlarging neck mass of 11-month duration, with no other symptoms. Close examination revealed a 10 × 5 cm mass at the left carotid triangle, and a 3.2 × 2.2 cm mass at the left tonsillar fossa. Imaging revealed the tumor to be unresectable due to its attachment to the great vessels. There were no distant metastases. Biopsy and immunohistochemistry were initially deemed consistent with an undifferentiated sarcoma. Palliative chemotherapy was given using single agent doxorubicin and subsequent dacarbazine, resulting in partial response and stable disease, respectively. Pathological re-evaluation was pursued because of the uncharacteristic slow progression of the tumor, revealing diffuse positivity for CD21 and negative for CD1A and CD34, consistent with FDCS. The patient underwent three cycles of gemcitabine plus docetaxel resulting in 50% regression. This allowed dissection of level IB-V lymph nodes and subsequent radiotherapy for the neck and tonsillar mass, with weekly gemcitabine as a radiosensitizer. Evaluation 8 months post-treatment showed no signs of disease progression. Treatment-related complications included radiation dermatitis and swallowing dysfunction, which both resolved on follow-up. This case highlights the multidisciplinary management of a rare type of sarcoma in an uncommon anatomic location. Precise pathologic diagnosis is important in soft tissue sarcoma because of its therapeutic implications. For FDCS, effective response may still be achieved in the third-line setting. J Med Cases. 2020;11(10):309-316 doi: https://doi.org/10.14740/jmc3551

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.

Unusual spindle cell lesion in the gastrointestinal tract: When all else fails

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm affecting patients of a wide age range, typically in the young to middle-aged adult years. The primary lesion may be nodal or extra-nodal in more than half of cases. We present a case of FDCS in a 31-year-old male with a caecal mass and adjacent lymphadenopathy. Endoscopic biopsy of the caecum showed an atypical spindle cell lesion, formed by plump cells with indistinct cell borders, showing a vaguely nodular and whorled architecture. A scattering of lymphocytes were seen in amongst the neoplastic cells. Multiple entities from various cell lineages were considered in the wider differential diagnosis. Based on the morphologic features, the immunohistochemical work-up included CD21 and CD23 which confirmed the lesion to be FDCS. This case highlights the importance of awareness of this rare entity when considering the broader differential diagnosis of unusual spindle cell neoplasms in the GI tract. When recognised, it has a characteristic morphology and immunophenotype which allows for correct diagnosis.

35. Follicular dendritic cell sarcoma of the nasopharynx

Background: Follicular dendritic cell sarcoma (FDCS) is a rare low-grade sarcoma, which presents as intranodal or, more commonly, extranodal disease at a wide variety of sites. To date, only eight cases of FDCS of the nasopharynx are reported.1,2 The morphological spectrum includes fascicular, whorled and sheet-like architecture with bland spindled to ovoid cells and possible nuclear pseudoinclusions. Occasionally, high-grade features including cytological atypia, numerous mitoses and necrosis are seen. Aims: To present the case of a 24-year-old female with a nasopharyngeal mass, subsequently diagnosed as FDCS. Methods: A biopsy was obtained which showed sheets of malignant cells, admixed with lymphocytes and occasional neutrophils. The cells had pale fibrillary cytoplasm, appearing syncytial in some areas. The nuclei were ovoid with fine chromatin, although with significant anisonucleosis, frequent large nuclear pseudoinclusions and occasional nucleoli. Numerous mitoses and areas of necrosis were present. Despite this unusual morphology, immunohistochemistry was positive for CD21, CD23 and CD35, indicative of FDCS. Results and conclusions: FDCS is an uncommon entity which, combined with variant morphology and an unusual site, can lead to a high risk of misdiagnosis; reported in four of six nasopharyngeal cases (67%).2 A high index of suspicion and broad immunohistochemical panel are required for diagnosis, particularly when high-grade features are present.

Special histopathological variants and potential diagnostic traps of classical follicular dendritic cell sarcoma

Objective: To investigate the clinicopathological features, special morphologic variants and potential diagnostic traps of classical follicular dendritic cell sarcoma (FDCS). Methods: A total of 25 cases of classical FDCS diagnosed in the First Hospital Affiliated to Army Medical University from 2006 to 2018 were examined by hematoxylin-eosin staining, immunohistochemistry and in situ hybridization for Epstein-Barr virus-encoded mRNA (EBER). Meanwhile, the types and characteristics of the special variants of FDCS were summarized along with those reported in the literature. Results: The age of patients ranged from 23 to 77 years (mean 52 years), the male to female ratio was 1.5, and the maximum diameter of tumor was 1.5 to 20 cm (mean 7.4 cm). Twelve cases (48%) were misdiagnosed at the initial evaluation. Follow-up information was available for 17 patients, and the follow-up time was 5 to 96 months. The propotion of patients having recurrence, metastasis and mortality was 3/17, 5/17 and 2/17, respectively. Microscopically, besides the typical morphology, 10 cases of FDCS showed special histomorphologies and/or structures, including those mimicking lymphoepithelioma-like carcinoma, desmoplastic infiltrating carcinoma, classical Hodgkin's lymphoma (CHL), anaplastic large cell lymphoma (ALCL) and hemangiopericytoma. These morphologic variants were potential diagnostic pitfalls and warranted attention. Immunohistochemistry showed that more than two markers of follicular dendritic cells (such as CD21, CD23, CD35, etc.) were expressed in cases showing typical morphology and the special variants. All 25 cases were all negative for EBER by in situ hybridization. Conclusions: Classical FDCS is rare, besides the typical morphologic features, there are many special variants. In particular, these may be confused with lymphoepithelioma-like carcinoma in the nasopharynx, CHL or ALCL in the mediastinum/lymph node. Awareness of these variants is essential for accurate diagnosis.

Follicular Dendritic Cell Sarcoma of the Tonsil: A Multimodality Approach

Follicular dendritic cell sarcoma (FDCS) accounts for < 0.4% of soft tissue sarcomas. Only 35 cases of tonsillar FDCS have been reported, and majority had localized presentation. We present a case of FDCS of the tonsil, wherein a well-coordinated trimodality approach provided good disease control in advanced disease. A 53-year-old man presented with a painless and enlarging neck mass of 11-month duration, with no other symptoms. Close examination revealed a 10 × 5 cm mass at the left carotid triangle, and a 3.2 × 2.2 cm mass at the left tonsillar fossa. Imaging revealed the tumor to be unresectable due to its attachment to the great vessels. There were no distant metastases. Biopsy and immunohistochemistry were initially deemed consistent with an undifferentiated sarcoma. Palliative chemotherapy was given using single agent doxorubicin and subsequent dacarbazine, resulting in partial response and stable disease, respectively. Pathological re-evaluation was pursued because of the uncharacteristic slow progression of the tumor, revealing diffuse positivity for CD21 and negative for CD1A and CD34, consistent with FDCS. The patient underwent three cycles of gemcitabine plus docetaxel resulting in 50% regression. This allowed dissection of level IB-V lymph nodes and subsequent radiotherapy for the neck and tonsillar mass, with weekly gemcitabine as a radiosensitizer. Evaluation 8 months post-treatment showed no signs of disease progression. Treatment-related complications included radiation dermatitis and swallowing dysfunction, which both resolved on follow-up. This case highlights the multidisciplinary management of a rare type of sarcoma in an uncommon anatomic location. Precise pathologic diagnosis is important in soft tissue sarcoma because of its therapeutic implications. For FDCS, effective response may still be achieved in the third-line setting.

Comprehensive Genomic Profiling of 104 Rare Histiocytic and Dendritic Cell Neoplasms Reveals Shared and Distinct Targetable Genomic Alterations

Introduction: Histiocytic and dendritic neoplasms are a diverse group of uncommon hematologic tumors arising from monocytic or dendritic cell lineage. While genomic profiles for the more common entities Langerhans cell histiocytosis and Erdheim-Chester disease are established, less common neoplasms in this broad category are poorly characterized. In the current study, we assessed the genomic landscape of these often aggressive histiocytic and dendritic cell neoplasms to identify distinct mutational signatures for each subtype in the current WHO classification system. Methods: 104 histiocytic and dendritic cell neoplasmswere tested during routine clinical care by hybridization capture of 406 cancer-related genes to detect base substitutions, small indels, amplifications (amp), deletions, and rearrangements. Tumor mutational burden (TMB, mutations/Mb) was determined on ~1.1 Mbp of sequenced DNA. Review of pathology reports, histopathology, and patient clinical data was performed. Cases included 48 follicular dendritic cell sarcoma (FDCS), 37 histiocytic sarcoma (HS), 8 interdigitating dendritic cell sarcoma (IDCS), 5 Langerhans cell sarcoma (LCS), 4 indeterminate cell histiocytosis (ICH), 1 fibroblastic reticular cell tumor (FRCT), and 1 inflammatory pseudotumor-like follicular/fibroblastic dendritic cell sarcoma (FDC/FRCS). Results: Pathogenic or likely-pathogenic genomic alterations (GAs) in the four most common sarcoma subgroups are summarized in the Table. CDKN2A and TP53 pathogenic mutations were the most frequent GAs observed in the cohort, present in 27% and 20% of the cases, respectively. Compared to the rest of the cohort, FDCS showed significantly more cases harboring a pathogenic GA in genes involved with NFkB pathway regulation (58% vs. 18%, p&lt;0.0001). Other relevant alterations in FDCS included NTRK1 (2 cases; 1 NTRK1-PDIA3 fusion and 1 amp), NTRK3 (1 case), FGFR3 (1 amp), STAT3 (3 cases) and PTEN (3 cases). Compared to the rest of the cohort, HS showed significantly more cases with pathogenic GAs in the MAPK pathway (59% vs. 19%, p&lt;0.0001), including 3 cases with BRAF fusions. Other relevant alterations in HS included PTEN (3 cases), PDGFRA (2 amp), MET (2 amp), 2 IGH-BCL2 fusions, and 1 IGH-BCL6 fusion. IDCS cases showed pathogenic MAPK GAs in 88% (7/8), and TET2 mutations were identified in 50% (4/8). A single NTRK1-TPR fusion was identified. LCS cases demonstrated GAs in both MAPK and NFkB pathways (4/5 and 3/5 cases, respectively). 2/4 cases of ICH demonstrated NCOA2-ETV3 fusions; TET2 mutations were present in the remaining two cases. The FRCT case contained an NRAS GA, and the FDC/FRCS cases had EBV (HHV-4) sequence reads. Conclusions: Our findings provide a comprehensive view of the shared and distinct genomic features among these rare histiocytic and dendritic cell neoplasms. The frequent inactivation of CDKN2A, which normally encodes an endogenous CDK inhibitor, suggests possible effectiveness of pharmacologic CDK4/6 inhibitors in treatment of this subset of cases. There are significant differences in the molecular profiles of different diseases: 58% of FDCS cases contain at least one pathogenic alteration in the NFkB pathway, while 59% and 88% of HS and IDCS cases contain potentially-actionable MAPK pathway mutations, respectively. LCS cases show frequent mutations in both pathways. Potentially-actionable molecular alterations are identified in 63/104 (61%) histiocytic and dendritic tumors in our cohort. These results illustrate the importance of performing comprehensive genomic profiling to define treatment strategies, including clinical trial "molecular eligibility" and more fully inform personalized therapeutic options. Disclosures Hasserjian: Jazz Pharmaceuticals: Consultancy; Promedior, Inc.: Consultancy. Montesion:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Sokol:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Pavlick:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Shah:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Danziger:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Killian:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Severson:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Duncan:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Elvin:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Miller:F. Hoffman La Roche, Ltd.: Equity Ownership; Foundation Medicine, Inc.: Employment. Ross:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Vergilio:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership. Williams:Foundation Medicine, Inc.: Employment; F. Hoffman La Roche, Ltd.: Equity Ownership.

Clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma

Objective: To investigate the clinical pathologic characteristics of extranodal follicular dendritic cell sarcoma (FDCS). Methods: We collected 7 cases of extranodal FDCS, HE staining, immunohistochemical study were performed. The V600E mutation of BRAF in 7 cases were detected by real-time PCR and EBER in situ hybridization was performed on 4 cases. Results: Among the 7 cases of FDCS, 5 cases were male and 2 cases were female, the median age was 55 years old, including 4 cases of low-grade FDCS and 3 cases of high-grade FDCS. The tumor location of 2 cases was in mediastinum, the tumor locations of others were in nasopharynx, kidney, lung, rectum and liver, respectively. The results of immunohistochemistry showed that, the tumor cells were diffusely or focally positive for CD21, CD23, CD35, D2-40, EGFR and CXCL13, but negative for S-100, CD68, HMB45, SMA, Desmin, CD117, Dog-1, CD34, CD30, EMA and CK.Five cases were positive for PD-L1 and the its expression in high-grade FDCS were higher than that in low-grade FDCS.Two cases of low-grade FDCS were positive for BRAF V600E, but the BRAF V600E mutation weren't detected in all of 7 cases. The result of EBER in-situ hybridization showed that only the nasopharynx FDCS was positive.The follow-up information of 5 patients were available (7~43 months), 4 patients died and 1 still alive with rectum metastasis. Conclusions: FDCS is a rare malignant disease with relapse and metastatic tendency. The combined applications of the first-line antibodies including CD21, CD23, CD35 and second-line antibodies including D2-40, CXCL13, EGFR are helpful for its diagnosis and differential diagnosis. The high expression of PD-L1 implicates the potential benefit of FDCS patients acquired from immunotherapy.

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.

Next-generation sequencing of idiopathic multicentric and unicentric Castleman disease and follicular dendritic cell sarcomas

AbstractCastleman disease (CD) is a rare lymphoproliferative disorder subclassified as unicentric CD (UCD) or multicentric CD (MCD) based on clinical features and the distribution of enlarged lymph nodes with characteristic histopathology. MCD can be further subtyped based on human herpes virus 8 (HHV8) infection into HHV8-associated MCD, HHV8−/idiopathic MCD (iMCD), and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin change (POEMS)–associated MCD. In a subset of cases of UCD, an associated follicular dendritic cell sarcoma (FDCS) may be seen. Although numerous reports of the clinical and histologic features of UCD, MCD, and FDCS exist, an understanding of the genetic and epigenetic landscape of these rare diseases is lacking. Given this paucity of knowledge, we analyzed 15 cases of UCD and 3 cases of iMCD by targeted next-generation sequencing (NGS; 405 genes) and 3 cases of FDCS associated with UCD hyaline vascular variant (UCD-HVV) by whole-exome sequencing. Common amplifications of ETS1, PTPN6, and TGFBR2 were seen in 1 iMCD and 1 UCD case; the iMCD case also had a somatic DNMT3A L295Q mutation. This iMCD patient also showed clinicopathologic features consistent with a specific subtype known as Castleman-Kojima disease (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly [TAFRO] clinical subtype). Additionally, 1 case of UCD-HVV showed amplification of the cluster of histone genes on chromosome 6p. FDCS associated with UCD-HVV showed mutations and copy number changes in known oncogenes, tumor suppressors, and chromatin structural-remodeling proteins.

Intraabdominal follicular dendritic cell sarcoma: a report of three cases and review of the literature.

Follicular dendritic cell sarcoma (FDCS) is a rare neoplasm that originates from follicular dendritic cells in lymphoid follicles. FDCS has been increasingly reported in recent years. However, data on FDCS are mostly based on single case reports or case series and its natural history and standard treatment are not clear. To increase the understanding of this rare disease, we report our experience of three cases of FDCS with an analysis of the morphological and immunophenotypic characteristics, clinical course, treatment options and response to treatment. In addition, we reviewed the literature on FDCS.

Primary follicular dendritic cell sarcoma of the urinary bladder: the first case report and potential diagnostic pitfalls

BackgroundExtranodal follicular dendritic cell sarcoma (FDCS) is a very rare malignancy with a variable clinical course. It is often not considered and has the potential to result in a misdiagnosis of other common sarcomas or sarcomatoid carcinomas. This is particularly true with the preoperative biopsy specimen, in which the tissue sample is often small.Case presentationA case of FDCS in a 63-year-old woman, arising in the urinary bladder, a previously unreported site, is described. The patient presented with the typical clinical symptoms of a bladder cancer, and the morphology of the tumor was similar to a lymphoepithelioma-like carcinoma, ultimately resulting in it being misdiagnosed. The patient received radical cystectomy, without further radiotherapy or chemotherapy. Two years after operation, a metastatic tumor to the lung was found. The mass of the right main bronchus lumen was frozen and resected through bronchoscopy, and radiotherapy was performed. The patient has lived with the tumor since then.ConclusionsThis paper presents the first FDCS occurring in the urinary bladder with metastasis to the lung and emphasizes potential diagnostic pitfalls.