Supplemental Tables S1-S4 and S6-S13. Supplemental Table S1: Summary of Patient Characteristics. Supplemental Table S2: Patient Characteristics and Key Mutations. Supplemental Table S3: Tumor purity and ploidy calculations. Supplemental Table S4: Sequencing Coverages. Supplemental Table S6: Allele fraction analysis. Supplemental Table S7: MutSig analysis. Supplemental Table S8: IntOGen mutational significance analysis. Supplemental Table S9: Chi-square mutational significance analysis. Supplemental Table S10: Multinomial mutational significance analysis. Supplemental Table S11: Kappa analysis for gene-gene associations. Supplemental Table S12: ABSOLUTE copy number analysis segmentation data. Supplemental Table S13: Clinical and mutation associations.

Supplemental Table S5: mutation annotation file.

Follicular dendritic cell sarcoma (FDCS) can be divided into the conventional type, and the inflammatory pseudotumor (IPT)-like variant type. Epstein-Barr virus (EBV) infection is considered to be closely associated with the pathogenesis of IPT-like variant of FDCS. Hepatic FDCS has an exceedingly low incidence of only 29 cases reported, with most of these tumors being classified as the IPT-like type. We report a case of an IPT-like variant of FDCS of the liver in a 61-year old man who presented with no marked symptoms. The patient underwent laparoscopic surgery for the mass and was well during a 13-month follow-up periods. The postoperative pathological examination found a proliferation of spindle cells and a diffuse infiltration of inflammatory cells within the tumor. Immunohistochemistry revealed that neoplastic cells were positive for CD23, clusterin, fascin, and PD-L1, and weakly positive for CD35, SMA, and D2-40. The infiltrating lymphocytes were strongly positive for PD1, and IgG4-positive plasma cells were less than 10 cells/high-power field. In situ hybridization for Epstein-Barr virus encoded RNA (EBER) was negative. To our knowledge, the present case is the second case of hepatic IPT-like variant of FDCS without EBV involvement, indicating that EBV infection is not an absolute prerequisite for a diagnosis of the IPT-like variant of FDCS.

Dendritic cell sarcomas are rare tumours of antigen presenting cells. Data regarding their biology, management and outcomes are sparse. We analysed 66 patients with follicular dendritic cell sarcoma (FDCS). Six patients also had Castleman disease, 9 had another malignancy and 13 had an autoimmune disease. Fifty-four per cent of patients presented with localized disease and 46% with systemic involvement. The median progression-free (PFS) and overall survival (OS) following frontline therapy was 21 and 50 months, respectively. Survival outcomes were significantly inferior in patients with extranodal, bulky or intra-abdominal disease at presentation. Stage was not associated with survival. Management approaches were heterogeneous. Patients who underwent an upfront gross total resection (GTR) experienced better PFS and OS (both P < 0·0001). In patients who underwent a GTR, consolidative radiotherapy was associated with improved local control (P = 0·03), PFS (P = 0·04) and OS (P = 0·05). In patients with measureable disease, gemcitabine with a taxane yielded an overall response rate of 80%. The pattern of relapse was predominantly locoregional. Salvage rates after recurrence were poor. Studies are underway at our institution to define the genomic profile in FDCS and identify potential novel therapeutic targets.

Abstract Purpose: Aggressive cutaneous squamous cell carcinoma (cSCC) is often a disfiguring and lethal disease. Very little is currently known about the mutations that drive aggressive cSCC. Experimental Design: Whole-exome sequencing was performed on 39 cases of aggressive cSCC to identify driver genes and novel therapeutic targets. Significantly, mutated genes were identified with MutSig or complementary methods developed to specifically identify candidate tumor suppressors based upon their inactivating mutation bias. Results: Despite the very high-mutational background caused by UV exposure, 23 candidate drivers were identified, including the well-known cancer-associated genes TP53, CDKN2A, NOTCH1, AJUBA, HRAS, CASP8, FAT1, and KMT2C (MLL3). Three novel candidate tumor suppressors with putative links to cancer or differentiation, NOTCH2, PARD3, and RASA1, were also identified as possible drivers in cSCC. KMT2C mutations were associated with poor outcome and increased bone invasion. Conclusions: The mutational spectrum of cSCC is similar to that of head and neck squamous cell carcinoma and dominated by tumor-suppressor genes. These results improve the foundation for understanding this disease and should aid in identifying and treating aggressive cSCC. Clin Cancer Res; 20(24); 6582–92. ©2014 AACR.