Epithelioid fibrous histiocytoma: three diagnostically challenging cases with novel ALK gene fusions, unusual storiform growth pattern, and a prominent spindled morphology

Novel, clinically relevant genomic patterns identified by comprehensive genomic profiling in ATRX-deficient IDH-wildtype adult high-grade gliomas

“…This rearrangement increases the peculiarity of this case, considering the rarity of fusions involving the NTRK2 gene in adult high-grade gliomas 36 and the previously unreported partner gene. An LRRFIP2::ALK fusion was recently described in a case of epithelioid fibrous histiocytoma 37 , but the exact mechanism by which LRRFIP2 activates its partner genes remains to be elucidated. Among the detected NTRK2 -fusions, the most likely to carry biological relevance is LRRFIP2::NTRK2 involving the 3’ end of NTRK2 with the protein kinase domain.…”

A Novel Fusion Partner, SP100, Drives Nuclear Dot Localization of ALK in Epithelioid Fibrous Histiocytoma

“…DNA was analyzed using a targeted massively parallel sequencing platform which incorporates 447 cancer-related genes and which can detect structural rearrangements in 60 genes (including ALK), as previously described. 14,15 The 447 genes targeted were as follows: ABCB11,ABL1,ACVR1,AKT1,AKT2,AKT3,ALK,APC,AR,AR-AF,ARHGAP35,ARHGEF12,ARIDA,ARID1B, ARID2,ASXL1,ATM,ATR,ATRX,AURKA,AURKB,AXIN2,AX-L,B2M,BABAM1,BAP1,BARD1,BCL11B, BCL2,BCL2L1,BCL2L12,BCL6,BCOR,BCORL1,BLM,BMP-R1A,BRAF,BRCA1,BRCA2,BRCC3,BRD3, BRD4,BRE,BRIP1,BUB1B,C17ORF70,C19ORF40,C10OR-F86,CALR,CARD11,CASP8,CBFA2T3,CBFB, CBL,CBLB,CCND1,CCND2,CCND3,CCNE1,CD274,CD79-B,CDC73,CDH1,CDH4,CDK12,CDK4,CDK6, CDK8,CDKN1A,CDKN1B,CDKN1C,CDKN2A,CDKN2B,C-DKN2C,CEBPA,CHEK1,CHEK2,CIC,CIITA, COL7A1,CREBBP,CRKL,CRLF2,CRTC1,CSF3R,CTCF,CT-LA4,CTNNA1,CTNNB1,CUX1,CXCR4,CYLD, DAXX,DCLRE1C,DDB1,DDB2,DDR2,DICER1,DIS3,DIS3-L2,DKC1,DMC1,DNMT3A,DOCK8,EGFR, EGLN1,ELANE,EME1,ENG,EP300,EPCAM,ERBB2,ERB-B3,ERBB4,ERCC1,ERCC2,ERCC3,ERCC4, ERCC5,ERCC6,ERG,ESR1,ETV1,ETV4,ETV5,ETV6,EWS-R1,EXO1,EXT1,EXT2,EZH2,FAH,FAM175A, FAM46C,FAN1,FANCA,FANCB,FANCC,FANCD2,FANCE,-FANCF,FANCG,FANCI,FANCL,FANCM,FAS, FAT1,FBXW7,FGFR1,FGFR2,FGFR3,FGFR4,FH,FLCN,F-LT1,FLT3,FLT4,FOXA1,FOXL2,FUS, GALNT12,GATA2,GATA3,GATA4,GATA6,GBA,GEN1,GL-I1,GLI2,GNA11,GNAQ,GNAS,GPC3,GREM1, H19,H3F3A,H3F3B,HABP2,HELQ,HFE,HIST1H3B,HIST1-H3C,HMBS,HNF1A,HOXB13,HRAS,ID3,ID4, IDH1,IDH2,IGF1R,IGF2,IKZF1,IL7R,ITK,JAK1,JAK2,JA-K3,JAZF1,KAT6A,KAT6B,KCNQ1,KDM5A,KDM5 C,KDM6A,KDR,KEAP1,KIF1B,KIT,KLF2,KLF4,KLLN,KM-T2A,KMT2D,KRAS,LIG4, LMO1,LMO2,MAF,MAFB,MAP2K1,MAP2K2,MAP2K4,MA-P3K1,MAPK1,MAX,MBD4,MCL1,MCM8, MDM2,MDM4,MECOM,MED12,MEF2B,MEN1,MET,MG-A,MITF,MLH1,MLH3,MPL,MRE11A,MSH2,MSH6,MTA1,-MTAP,MTOR,MUS81,MUTYH,MYB,MYBL1,MYC,MYCL1,-MYCN,MYD88,NBN,NEIL1, NEIL2,NEIL3,NF1,NF2, NFE2L2,NFKBIA,NFKBIE,NFKBIZ,NKX2-1,NKX3-1,NOTCH1,NOTCH2, NOTCH3,NPM1,NR0B1,NRAS,NRG1,NSD1,NT5C2,NTH-L1,NTRK1,NTRK2,NTRK3,OGG1,PALB2,PARK2,PAX5,PA-XIP1,PBRM1,PDCD1LG2,PDGFRA,PDGFRB,PHF6,PHO-X2B,PIK3C2B,PIK3CA,PIK3R1,PIM1,PML,PMS1,PMS2,P- Perinuclear dot-like PRKAR2A::ALK Kazlouskaya et al 5 3/3 (100) Cytoplasmic DCTN1::ALK Dawson et al 12 1/1 (100) Perinuclear dot-like PRKAR2A::ALK Mansour et al 6 3/3 (100) Cytoplasmic AP3D1::ALK COL1A::ALK LRRFIP2::ALK Secco et al 8 1/1 (100) Cytoplasmic CARS::ALK…”

“…2 In recent years, new morphologic variants have been described, including those which show a spindled and chondroblastoma-like morphology. 3–8…”

“…2 In recent years, new morphologic variants have been described, including those which show a spindled and chondroblastoma-like morphology. [3][4][5][6][7][8] The defining molecular feature of EFH is the presence of anaplastic lymphoma kinase (ALK) gene fusions 9,10 which lead to hyperactive ALK signaling. At least 14 different ALK fusion partners have been described to date (summarized in Table 1).…”

An Unusual Case of an ALK‐Negative Epithelioid Fibrous Histiocytoma in the External Auditory Canal

“…1,5 Arguments in favor of their separate classification point to the absence of ALK rearrangements in BFH, although a subset of EFH is ALK negative. 1,4 EFH is most frequently observed in the lower extremities of young to middle-aged adults. 1,2 The lesion often appears as a solitary exophytic nodule, with histopathology demonstrating an epidermal collarette and pronounced vascularity.…”