title: Paediatric and adult soft tissue sarcomas with NTRK1 gene fusions: a subset of spindle cell sarcomas unified by a prominent myopericytic/haemangiopericytic pattern.
abstract: Neoplasms with a myopericytomatous pattern represent a morphological spectrum of lesions encompassing myopericytoma of the skin and soft tissue, angioleiomyoma, myofibromatosis/infantile haemangiopericytoma and putative neoplasms reported as malignant myopericytoma. Lack of reproducible phenotypic and genetic features of malignant myopericytic neoplasms have prevented the establishment of myopericytic sarcoma as an acceptable diagnostic category. Following detection of a LMNA-NTRK1 gene fusion in an index case of paediatric haemangiopericytoma-like sarcoma by combined whole-genome and RNA sequencing, we identified three additional sarcomas harbouring NTRK1 gene fusions, termed 'spindle cell sarcoma, NOS with myo/haemangiopericytic growth pattern'. The patients were two children aged 11 months and 2 years and two adults aged 51 and 80 years. While the tumours of the adults were strikingly myopericytoma-like, but with clear-cut atypical features, the paediatric cases were more akin to infantile myofibromatosis/haemangiopericytoma. All cases contained numerous thick-walled dysplastic-like vessels with segmental or diffuse nodular myxohyaline myo-intimal proliferations of smooth muscle actin-positive cells, occasionally associated with thrombosis. Immunohistochemistry showed variable expression of smooth muscle actin and CD34, but other mesenchymal markers, including STAT6, were negative. This study showed a novel variant of myo/haemangiopericytic sarcoma with recurrent NTRK1 gene fusions. Given the recent introduction of a novel therapeutic approach targeting NTRK fusion-positive neoplasms, recognition of this rare but likely under-reported sarcoma variant is strongly encouraged.
authors: Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Florian
authors: F
authors: Haller
authors: Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Jasmin
authors: J
authors: Knopf
authors: Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Anne
authors: A
authors: Ackermann
authors: Division of Theoretical Bioinformatics (B080), German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors: Matthias
authors: M
authors: Bieg
authors: Division of Theoretical Bioinformatics (B080), German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors: Kortine
authors: K
authors: Kleinheinz
authors: Division of Theoretical Bioinformatics (B080), German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors: Matthias
authors: M
authors: Schlesner
authors: Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Evgeny A
authors: EA
authors: Moskalev
authors: Genomics and Proteomics Core Facility, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors: Rainer
authors: R
authors: Will
authors: HistoCentre, Khartoum, Sudan.
authors: Ali Abdel
authors: AA
authors: Satir
authors: National Public Health Laboratory, Khartoum, Sudan.
authors: Ibtihalat E
authors: IE
authors: Abdelmagid
authors: Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Johannes
authors: J
authors: Giedl
authors: Department of Paediatric Surgery, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Roman
authors: R
authors: Carbon
authors: Department of Radiology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Oliver
authors: O
authors: Rompel
authors: Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Arndt
authors: A
authors: Hartmann
authors: Genomics and Proteomics Core Facility, German Cancer Research Centre (DKFZ), Heidelberg, Germany.|Division Molecular Genome Analysis, German Cancer Research Centre (DKFZ), Heidelberg.
authors: Stefan
authors: S
authors: Wiemann
authors: Department of Paediatrics, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Markus
authors: M
authors: Metzler
authors: Institute of Pathology, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors: Abbas
authors: A
authors: Agaimy
mesh_terms: D000367:Age Factors; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002675:Child, Preschool; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D050939:Gene Fusion; D020022:Genetic Predisposition to Disease; D006393:Hemangiopericytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D034904:Lamin Type A / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020286:Pericytes / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D020917:Receptor, trkA / Q000235:genetics* / Q000378:metabolism; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017422:Sequence Analysis, DNA; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014335:Tropomyosin / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; C494847:LMNA protein, human; D034904:Lamin Type A; C498783:TPM3 protein, human; D014335:Tropomyosin; D020917:Receptor, trkA
keywords: NTRK1; haemangiopericytoma; infantile fibrosarcoma; myopericytic sarcoma; sarcoma