Advertisement

Virchows Archiv

, Volume 474, Issue 1, pp 111–115 | Cite as

Novel KHDRBS1-NTRK3 rearrangement in a congenital pediatric CD34-positive skin tumor: a case report

  • Matthias Tallegas
  • Sylvie Fraitag
  • Aurélien Binet
  • Daniel Orbach
  • Anne Jourdain
  • Stéphanie Reynaud
  • Gaëlle Pierron
  • Marie-Christine Machet
  • Annabel MaruaniEmail author
Brief Report
  • 160 Downloads

Abstract

Cutaneous spindle-cell neoplasms in adults as well as children represent a frequent dilemma for pathologists. Along this neoplasm spectrum, the differential diagnosis with CD34-positive proliferations can be challenging, particularly concerning neoplasms of fibrohistiocytic and fibroblastic lineages. In children, cutaneous and superficial soft-tissue neoplasms with CD34-positive spindle cells are associated with benign to intermediate malignancy potential and include lipofibromatosis, plaque-like CD34-positive dermal fibroma, fibroblastic connective tissue nevus, and congenital dermatofibrosarcoma protuberans. Molecular biology has been valuable in showing dermatofibrosarcoma protuberans and infantile fibrosarcoma that are characterized by COL1A1-PDGFB and ETV6-NTRK3 rearrangements respectively. We report a case of congenital CD34-positive dermohypodermal spindle-cell neoplasm occurring in a female infant and harboring a novel KHDRBS1-NTRK3 fusion. This tumor could belong to a new subgroup of pediatric cutaneous spindle-cell neoplasms, be an atypical presentation of a plaque-like CD34-positive dermal fibroma, of a fibroblastic connective tissue nevus, or represent a dermatofibrosarcoma protuberans with an alternative gene rearrangement.

Keywords

Cutaneous Neoplasms Spindle-cell 

Notes

Contributions

The first author and last author (M. Tallegas and A. Maruani) have written the first draft of the manuscript. A. Binet performed the skin samples which were analyzed by MC. Machet and S. Fraitag (histological findings). Molecular findings were performed by G. Pierron and S. Reynaud. Management of the child was organized by A. Jourdain and D. Orbach.

Compliance with ethical standards

The study followed the ethical declaration of Helsinki.

Conflict of interest

The authors declare that they have no conflict of interest.

Disclaimer

Each author listed on the manuscript has seen and approved the submission of this version of the manuscript and takes full responsibility for the manuscript.

References

  1. 1.
    Kutzner H, Mentzel T, Palmedo G et al (2010) Plaque-like CD34-positive dermal fibroma (“medallion-like dermal dendrocyte hamartoma”): clinicopathologic, immunohistochemical, and molecular analysis of 5 cases emphasizing its distinction from superficial, plaque-like dermatofibrosarcoma protuberans. Am J Surg Pathol 34:190–201CrossRefGoogle Scholar
  2. 2.
    Fletcher CDM (2013) WHO classification of tumours of soft tissue and bone. IARC PressGoogle Scholar
  3. 3.
    Requena L (2014) Cutaneous soft tissue tumors, 1 edition. LWW, PhiladelphiaGoogle Scholar
  4. 4.
    de Feraudy S, Fletcher CDM (2012) Fibroblastic connective tissue nevus: a rare cutaneous lesion analyzed in a series of 25 cases. Am J Surg Pathol 36:1509–1515CrossRefGoogle Scholar
  5. 5.
    Agaram NP, Zhang L, Sung Y-S et al (2016) Recurrent NTRK1 gene fusions define a novel subset of locally aggressive lipofibromatosis-like neural tumors. Am J Surg Pathol 40:1407–1416CrossRefGoogle Scholar
  6. 6.
    Weinstein JM, Drolet BA, Esterly NB et al (2003) Congenital dermatofibrosarcoma protuberans: variability in presentation. Arch Dermatol 139:207–211CrossRefGoogle Scholar
  7. 7.
    Orbach D, Brennan B, De Paoli A, et al (2016) Conservative strategy in infantile fibrosarcoma is possible: the European paediatric soft tissue sarcoma study group experience. Eur J Cancer Oxf Engl 1990 57:1–9Google Scholar
  8. 8.
    Frisone P, Pradella D, Di Matteo A et al (2015) SAM68: signal transduction and RNA metabolism in human cancer. Biomed Res Int 2015:528954CrossRefGoogle Scholar
  9. 9.
    Davis JL, Lockwood CM, Albert CM et al (2018) Infantile NTRK-associated mesenchymal tumors. Pediatr Dev Pathol Off J Soc Pediatr Pathol Paediatr Pathol Soc 21:68–78CrossRefGoogle Scholar
  10. 10.
    Khotskaya YB, Holla VR, Farago AF et al (2017) Targeting TRK family proteins in cancer. Pharmacol Ther 173:58–66CrossRefGoogle Scholar
  11. 11.
    Church AJ, Calicchio ML, Nardi V et al (2018) Recurrent EML4–NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy. Mod Pathol 31:463–473CrossRefGoogle Scholar
  12. 12.
    Anderson J, Gibson S, Sebire NJ (2006) Expression of ETV6-NTRK in classical, cellular and mixed subtypes of congenital mesoblastic nephroma. Histopathology 48:748–753CrossRefGoogle Scholar
  13. 13.
    Vokuhl C, Nourkami-Tutdibi N, Furtwängler R et al (2018) ETV6-NTRK3 in congenital mesoblastic nephroma: a report of the SIOP/GPOH nephroblastoma study. Pediatr Blood Cancer 65.  https://doi.org/10.1002/pbc.26925
  14. 14.
    Nagasubramanian R, Wei J, Gordon P et al (2016) Infantile fibrosarcoma with NTRK3-ETV6 fusion successfully treated with the tropomyosin-related kinase inhibitor LOXO-101. Pediatr Blood Cancer 63:1468–1470CrossRefGoogle Scholar
  15. 15.
    Drilon A, Siena S, S-HI O et al (2017) Safety and antitumor activity of the multitargeted Pan-TRK, ROS1, and ALK inhibitor Entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov 7:400–409CrossRefGoogle Scholar
  16. 16.
    Hechtman JF, Benayed R, Hyman DM et al (2017) Pan-Trk immunohistochemistry is an efficient and reliable screen for the detection of NTRK fusions. Am J Surg Pathol 41:1547–1551CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Matthias Tallegas
    • 1
  • Sylvie Fraitag
    • 2
  • Aurélien Binet
    • 3
  • Daniel Orbach
    • 4
  • Anne Jourdain
    • 5
  • Stéphanie Reynaud
    • 6
  • Gaëlle Pierron
    • 6
  • Marie-Christine Machet
    • 1
    • 8
  • Annabel Maruani
    • 7
    • 8
    • 9
    Email author
  1. 1.Department of PathologyTrousseau Hospital – CHRU ToursToursFrance
  2. 2.Department of PathologyNecker-Enfants Malades HospitalParisFrance
  3. 3.Department of Visceral and Plastic Pediatric SurgeryClocheville Hospital - CHRU ToursToursFrance
  4. 4.SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with cancer), Institute CuriePSL UniversityParisFrance
  5. 5.Department of Pediatric Oncology and HematologyCHU ToursToursFrance
  6. 6.Department of GeneticInstitute CurieParisFrance
  7. 7.Department of DermatologyUnit of Pediatric Dermatology - CHRU ToursToursFrance
  8. 8.Faculty of MedicineUniversity of ToursToursFrance
  9. 9.Department of DermatologyTrousseau Hospital - CHRU ToursTours Cedex 9France

Personalised recommendations