Pediatric and Developmental Pathology

, Volume 7, Issue 5, pp 538–545 | Cite as

Primary Subcutaneous Primitive Neuroectodermal Tumor with Aggressive Behavior and an Unusual Karyotype: Case Report

  • Gino R. Somers
  • Mary Shago
  • Maria Zielenska
  • Helen S.L. Chan
  • Bo Y. Ngan


Primitive neuroectodermal tumor/Ewing sarcoma (PNET/ES) rarely occurs in the skin and subcutaneous tissues. We present a case of a 16-year-old girl with primary cutaneous and subcutaneous PNET/ES of the abdominal wall. Despite wide local excision and chemotherapy, she rapidly developed cranial bone and brain metastases, followed by lung and skeletal metastases, and died shortly thereafter. The recurrent tumor exhibited light microscopic features of a small, round, blue cell tumor with intracytoplasmic glycogen. Immunohistochemical analysis showed positivity for CD99, CD56, S100, and glial fibrillary acid protein, and ultrastructural features included cytoplasmic glycogen and focal complex interdigitating synaptic junction-like cytoplasmic folds. Cytogenetic analysis of the relapsed tumor showed a complex karyotype: 47,XX,i(1)(q10), der(4)t(4;19) (q33∼q35;q13.1), + 8,t(15;17)(q24;p11.2∼p12),der(19)t (19;20)(q13.1;p11.2),der(22)t(20;22)(q13;q13). Cytogenetic, interphase fluorescence in situ hybridization, and molecular genetic analyses failed to show t(11:22) (q24;q12) or abnormalities of chromosome region 22q12. The clinical behavior and atypical and complex cytogenetic abnormalities exhibited by the tumor in this patient are unusual and represent the most aggressive end of the clinical spectrum of cutaneous and subcutaneous PNET/ES.


subcutaneous primitive neuroectodermal tumor electron microscopy immunohistochemistry karyotype metastases reverse transcriptase polymerase chain reaction 


  1. 1.
    Ushigome, S, Machinami, R, Sorensen, PH 2002

    Ewing sarcoma/primitive neuroectodermal tumor (PNET)

    Fletcher, CDMUnni, KKMertens, F eds. World Health Organisation Classification of Tumors: Tumors of Soft Tissue and BoneIARC PressLyon298300
    Google Scholar
  2. 2.
    Coffin, CM, Dehner, LP 1997

    Neurogenic tumors of soft tissue

    Coffin, CMDehner, LPO’Shea, PA eds. Pediatric Soft Tissue Tumors: A Clinical, Pathological and Therapeutic ApproachWilliams & WilkinsBaltimore80132
    Google Scholar
  3. 3.
    Coffin, CM, Dehner, LP 1989Peripheral neurogenic tumors of the soft tissues in children and adolescents: a clinicopathologic study of 139 casesPediatr Pathol9387407CrossRefPubMedGoogle Scholar
  4. 4.
    Hashimoto, H, Enjoji, M, Nakajima, T,  et al. 1983Malignant neuroepithelioma (peripheral neuroblastoma): a clinicopathologic study of 15 casesAm J Surg Pathol7309318CrossRefPubMedGoogle Scholar
  5. 5.
    Schmidt, D, Harms, D, Burdach, S 1985Malignant peripheral neuroectodermal tumors of childhood and adolescenceVirchows Arch406351365CrossRefGoogle Scholar
  6. 6.
    Peters, MS, Reiman, HM, Muller, SA 1985Cutaneous extraskeletal Ewing’s sarcomaJ. Cutan Pathol12476485CrossRefPubMedGoogle Scholar
  7. 7.
    Patterson, JW, Maygarden, SJ 1986Extraskeletal Ewing’s sarcoma with cutaneous involvementJ. Cutan Pathol134658CrossRefPubMedGoogle Scholar
  8. 8.
    Hasegawa, SL, Davidson, JM, Rutten, A, Fletcher, JA, Fletcher, CD 1998Primary cutaneous Ewing’s sarcoma: immunophenotypic and molecular cytogenetic evaluation of five casesAm J Surg Pathol22310318CrossRefPubMedGoogle Scholar
  9. 9.
    Banerjee, SS, Agbamu, DA, Eyden, BP, Harris, M 1997Clinicopathological characteristics of peripheral primitive neuroectoderm tumor of skin and subcutaneous tissueHistopathology31355366CrossRefPubMedGoogle Scholar
  10. 10.
    Smith, LM, Adams, RH, Brothman, AR, Vanderhooft Coffin, SL CM 1998Peripheral primitive neuroectoderm tumor presenting with diffuse cutaneous involvement and 7;22 translocationMed Pediatr Oncol30357363CrossRefPubMedGoogle Scholar
  11. 11.
    Chow, E, Merchant, TE, Pappo, A, Jenkins, JJ, Shah, AB, Kun, LE 2000Cutaneous and subcutaneous Ewing’s sarcoma: an indolent diseaseInt J Radiat Oncol Biol Phys46433438CrossRefPubMedGoogle Scholar
  12. 12.
    Taylor, GB, Chan, YF 2000Subcutaneous primitive neuroectoderm tumor in the abdominal wall of a child: long-term survival after local excisionPathology32294298CrossRefPubMedGoogle Scholar
  13. 13.
    Izqueierdo, MJ, Pastor, MA, Carrasco, L,  et al. 2002Cutaneous metastasis from Ewing’s sarcoma: report of two casesClin Exp Dermatol27123128CrossRefGoogle Scholar
  14. 14.
    Zielenska, M, Zhang, ZM, Ng, K,  et al. 2001Acquisition of secondary structural chromosomal changes in pediatric Ewing sarcoma is a probable prognostic factor for tumor response and clinical outcomeCancer9121562164CrossRefPubMedGoogle Scholar
  15. 15.
    Mitelman F, Johansson B, Mertens F, eds. Mitelman Database of Chromosome Aberrations in Cancer [database online]. Bethesda (MD): National Cancer Institute Cancer Genome Anatomy Project; 2003 [updated August 2003]. Available from: Accessed October 14, 2003Google Scholar
  16. 16.
    Thorner, PS, Squire, JA, Plavsic, N, Jong, R, Greenberg, M, Zielenska, M 1999Expression of WT1 in pediatric small cell tumors: Report of two cases with a possible mesothelial originPediatr Dev Pathol23341CrossRefPubMedGoogle Scholar
  17. 17.
    Delattre, O, Zucman, J, Melot, T,  et al. 1994The Ewing family of tumors—a subgroup of small-round-cell tumors defined by specific chimeric transcriptsN Engl J Med331294299CrossRefPubMedGoogle Scholar
  18. 18.
    Fritsch, MK, Bridge, JA, Schuster, AE, Perlman, EJ, Argani, P 2002Performance characteristics of a reverse transcriptase-polymerase chain reaction assay for the detection of tumor-specific fusion transcripts from archival tissuePediatr Dev Pathol64353CrossRefPubMedGoogle Scholar
  19. 19.
    Ladanyi, M, Gerald, W 1994Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumorCancer Res5428372840PubMedGoogle Scholar
  20. 20.
    Galili, N, Davis, RJ, Fredericks, WJ,  et al. 1993Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcomaNat Genet5230235CrossRefPubMedGoogle Scholar
  21. 21.
    la Luz Orozco-Covarrubias, M, Tamayo-Sanchez, L, Duran-McKinster, C, Ridaura, C, Ruiz-Maldonato, R 1994Malignant cutaneous tumors in children. Twenty years of experience at a large pediatric hospitalJ Acad Dermatol30243249CrossRefGoogle Scholar
  22. 22.
    Wesche, WA, Khare, VK, Chesney, TM, Jenkins, JJ 2000Non-hematopietic cutaneous metastases in children and adolescents: thirty years experience at St. Jude Children’s Research HospitalJ Cutan Pathol27485492CrossRefPubMedGoogle Scholar
  23. 23.
    Lee, CS, Southey, MC, Slater, H, Auldist, AW, Chow, CW, Venter, DJ 1995Primary cutaneous Ewing’s sarcoma/peripheral primitive neuroectodermal tumors in childhood. A molecular, cytogenetic, and immunohistologic studyDiagn Mol Pathol4174181CrossRefPubMedGoogle Scholar
  24. 24.
    Sexton, CW, White, WL 1996Primary cutaneous Ewing’s family sarcoma. Report of a case with immunostaining for glycoprotein p30/32 mic2Am J Dermatopathol18601605CrossRefPubMedGoogle Scholar
  25. 25.
    Perlman, EJ, Lumadue, JA, Hawkins, AL, Cohen, K, Colombani, P, Griffin, CA 1995Primary cutaneous neuroendocrine tumors. Diagnostic use of cytogenetic and MIC analysisCancer Genet Cytogenet823034CrossRefPubMedGoogle Scholar
  26. 26.
    Smolle-Juettner, FM, Smolle, J, Richtig, E,  et al. 1992Primitive neuroectodermal tumor arising from the skin. Differentiation from neuroendocrine carcinoma of the skinDermatology185272275CrossRefPubMedGoogle Scholar
  27. 27.
    Yu, L, Craver, R, Baliga, M,  et al. 1990Isolated CNS involvement in Ewing’s sarcomaMed Pediatr Oncol18354358CrossRefPubMedGoogle Scholar
  28. 28.
    Taets ven Amerongen, AH, Kaiser, MC, Waal, FC 1987Metastatic Ewing’s sarcoma to the skull: CNS involvement excluded by MRIPediatr Radiol17242243CrossRefPubMedGoogle Scholar
  29. 29.
    Sarno, JB, Wiener, L, Waxman, M, Kwee, J 1985Sarcoma metastatic to the central nervous system parenchyma: a review of the literatureMed Pediatr Oncol13280292CrossRefPubMedGoogle Scholar
  30. 30.
    Marciani, MG, Stefani, N, Peroni, L,  et al. 1990Intracerebral metastasis in Ewing’s sarcomaActa Neurol Belg90149156PubMedGoogle Scholar
  31. 31.
    Arvand, A, Denny, CT 2001Biology of EWS/ETS fusions in Ewing’s family tumorsOncogene2057475754CrossRefPubMedGoogle Scholar
  32. 32.
    Udayakumar, AM, Sundareshan, TS, Goud, TM,  et al. 2001Cytogenetic characterisation of Ewing tumors using fine needle aspiration samples. A 10-year experience and review of the literatureCancer Genet Cytogenet1274248CrossRefPubMedGoogle Scholar
  33. 33.
    Sandberg, AA, Bridge, JA 2000Updates on cytogenetics and molecular genetics of bone and soft tissue tumors: Ewing sarcoma and peripheral primitive neuroectodermal tumorsCancer Genet Cytogenet123126CrossRefPubMedGoogle Scholar
  34. 34.
    Fletcher, JA, Kozakewich, HP, Hoffer, FA,  et al. 1991Diagnostic relevance of clonal cytogenetic aberrations in malignant soft-tissue tumorsN Engl J Med324436443CrossRefPubMedGoogle Scholar
  35. 35.
    Dressler, LG, Duncan, MH, Varsa, EE, McConnell, TS 1993DNA content measurement can be obtained using archival material for DNA flow cytometryCancer7220332041CrossRefPubMedGoogle Scholar
  36. 36.
    Dagher, R, Pham, TA, Sorbara, L,  et al. 2001Molecular confirmation of Ewing sarcomaJ Pediatr Hematol Oncol23221224CrossRefPubMedGoogle Scholar
  37. 37.
    Batanian, JR, Bridge, JA, Wickert, R, Vogler, C, Gadre, B, Huang, Y 2002EWS/FLI-1 fusion signal inserted into chromosome 11 in one patient with morphologic features of Ewing sarcoma, but lacking t(11;22)Cancer Genet Cytogenet1337275CrossRefPubMedGoogle Scholar
  38. 38.
    Barr, FG, Qualman, SJ, Macris, MH,  et al. 2002Genetic heterogeneity in the alveolar rhabdomyosarcoma subset without typical gene fusionsCancer Res6247044710PubMedGoogle Scholar
  39. 39.
    Shing, DC, Morley-Jacob, CA, Roberts, I, Nacheva, E, Coleman, N 2002Ewing’s tumor: novel recurrent chromosomal abnormalities demonstrated by molecular cytogenetic analysis of seven cell lines and one primary cultureCytogenet Genome Res972027CrossRefPubMedGoogle Scholar
  40. 40.
    Online Mendelian Inheritance in Man, OMIM (TM). Baltimore (MD): McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University, and National Center for Biotechnology Information, National Library of Medicine; 2000. Available from: Accessed April 28, 2004Google Scholar

Copyright information

© Society of Pediatric Pathology 2004

Authors and Affiliations

  • Gino R. Somers
    • 1
  • Mary Shago
    • 2
  • Maria Zielenska
    • 2
  • Helen S.L. Chan
    • 3
  • Bo Y. Ngan
    • 1
  1. 1.Division of Pathology, Department of Paediatric Laboratory MedicineHospital for Sick ChildrenTorontoCanada
  2. 2.Division of Molecular Genetics, Department of Paediatric Laboratory MedicineHospital for Sick ChildrenTorontoCanada
  3. 3.Division of Haematology/Oncology, Department of PaediatricsHospital for Sick ChildrenTorontoCanada

Personalised recommendations