Neoplastic and Infiltrative Diseases

  • Ellen S. Haddock
  • Wynnis L. TomEmail author


Several pediatric neoplasms present as nonspecific pink, red-blue, or purple-colored nodules on the skin. A benign process versus one of malignant potential can be difficult to determine clinically, making index of suspicion and histologic examination important. This chapter highlights four neoplastic conditions that may present in early childhood and uses a case-based approach to discuss the appropriate workup.


Neoplastic Cancer Leukemia cutis Acute lymphoid leukemia Acute myeloid leukemia Blueberry muffin phenotype Neuroblastoma Fibrosarcoma Infantile myofibroma Myofibromatosis 



Acute lymphoid leukemia


Acute myeloid leukemia


B cell lymphoma


Complete blood count


Computed tomography


Fluorescence in situ hybridization


Glucose transporter 1


Homovanillic acid


Lactate dehydrogenase




Mixed lineage leukemia


Magnetic resonance imaging


Neuroblastoma 84


Neurofilament protein


Neuron-specific enolase


Neurotrophic tyrosine kinase receptor type 3


Paired box 5


Polymerase chain reaction


Perineal hemangioma, external genitalia malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, skin tag


Protein gene product 9.5


Paired-like homeobox 2b


Smooth muscle actin


Terminal deoxynucleotidyl transferase


Toxoplasmosis, other, rubella, cytomegalovirus, herpes


Total skin electron beam


Vanillylmandelic acid


  1. 1.
    Handler MZ, Schwartz RA. Neonatal leukaemia cutis. J Eur Acad Dermatol Venereol. 2015;29(10):1884–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Gottesfeld E, Silverman RA, Coccia PF, Jacobs G, Zaim MT. Transient blueberry muffin appearance of a newborn with congenital monoblastic leukemia. J Am Dermatol. 1989;21(2 Pt 2):347–51.CrossRefGoogle Scholar
  3. 3.
    Zhang IH, Zane LT, Braun BS, Maize J, Zoger S. Congenital leukemia cutis with subsequent development of leukemia. J Am Acad Dermatol. 2006;54(2 Suppl):S22–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Resnik KS, Brod BB. Leukemia cutis in congenital leukemia: analysis and review of the world literature with report of an additional case. Arch Dermatol. 1993;129(10):1301–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Choi JH, Lee HB, Park CW, Lee CH. A case of congenital leukemia cutis. Ann Dermatol. 2009;21(1):66–70.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Cho-Vega JH, Medeiros LJ, Prieto VG, Vega F. Leukemia cutis. Am J Clin Pathol. 2008;129(1):130–42.CrossRefPubMedGoogle Scholar
  7. 7.
    Aboutalebi A, Korman JB, Sohani AR, Hasserjian RP, Louissaint Jr A, Le L, et al. Aleukemic cutaneous myeloid sarcoma. J Cutan Pathol. 2013;40(12):996–1005.CrossRefPubMedGoogle Scholar
  8. 8.
    Paller AS, Mancini AJ. Histiocytoses and malignant skin diseases. In: Paller AS, Mancini AJ, editors. Hurwitz clinical pediatric dermatology. 4th ed. Philadelphia: Elsevier Saunders; 2011. p. 228–9.Google Scholar
  9. 9.
    Boggs DR, Wintrobe MM, Cartwright GE. The acute leukemias. Analysis of 322 cases and review of the literature. Medicine (Baltimore). 1962;41:163–225.CrossRefGoogle Scholar
  10. 10.
    Agis H, Weltermann A, Fonatsch C, Haas O, Mitterbauer G, Müllauer L, et al. A comparative study on demographic, hematological, and cytogenetic findings and prognosis in acute myeloid leukemia with and without leukemia cutis. Ann Hematol. 2002;81(2):90–5.CrossRefPubMedGoogle Scholar
  11. 11.
    Reinhardt D, Creutzig U. Isolated myelosarcoma in children—update and review. Leuk Lymphoma. 2002;43(3):565–74.CrossRefPubMedGoogle Scholar
  12. 12.
    Su W, Buechner SA, Li CY. Clinicopathologic correlations in leukemia cutis. J Am Acad Dermatol. 1984;11(1):121–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Sisack MJ, Dunsmore K, Sidhu-Malik N. Granulocytic sarcoma in the absence of myeloid leukemia. J Am Acad Dermatol. 1997;37(2 Pt 2):308–11.CrossRefPubMedGoogle Scholar
  14. 14.
    Straus DJ, Mertelsmann R, Koziner B, McKenzie S, de Harven E, Arlin ZA, et al. The acute monocytic leukemias: multidisciplinary studies in 45 patients. Medicine (Baltimore). 1980;59(6):409–25.CrossRefGoogle Scholar
  15. 15.
    Bresters D, Reus ACW, Veerman AJP, van Wering ER, van der Does-van den Berg A, Kaspers GJL. Congenital leukaemia: the Dutch experience and review of the literature. Br J Haematol. 2002;117(3):513–24.CrossRefPubMedGoogle Scholar
  16. 16.
    Paydas S, Zorludemir S. Leukaemia cutis and leukaemic vasculitis. Br J Dermatol. 2001;143(4):773–9.CrossRefGoogle Scholar
  17. 17.
    Kaddu S, Zenahlik P, Beham-Schmid C, Kerl H, Cerroni L. Specific cutaneous infiltrates in patients with myelogenous leukemia: a clinicopathologic study of 26 patients with assessment of diagnostic criteria. J Am Dermatol. 1999;40(6):966–78.CrossRefGoogle Scholar
  18. 18.
    Grundy RG, Martinez A, Kempski H, Malone M, Atherton D. Spontaneous remission of congenital leukemia: a case for conservative treatment. J Pediatr Hematol Oncol. 2000;22(3):252–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Cronin DMP, George TI, Sundram UN. An updated approach to the diagnosis of myeloid leukemia cutis. Am J Clin Pathol. 2009;132(1):101–10.CrossRefPubMedGoogle Scholar
  20. 20.
    Buechner SA, Li C-Y, Daniel Su WP, Hunter JAA, Holubar K. Leukemia cutis. A histopathologic study of 42 cases. Am J Dermatopathol. 1985;7(2):109–20.CrossRefPubMedGoogle Scholar
  21. 21.
    Dabbs DJ. Diagnostic immunohistochemistry. 4th ed. Philadelphia: Elsevier Sciences; 2013. p 488.Google Scholar
  22. 22.
    Fender AB, Gust A, Wang N, Scott GA, Mercurio MG. Congenital leukemia cutis. Pediatr Dermatol. 2008;25(1):34–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Dinulos JG, Hawkins DS, Clark BS, Francis JS. Spontaneous remission of congenital leukemia. J Pediatr. 1997;131(2):300–3.CrossRefPubMedGoogle Scholar
  24. 24.
    van der Linden MH, Creemers S, Pieters R. Diagnosis and management of neonatal leukaemia. Semin Fetal Neonatal Med. 2012;17(4):192–5.CrossRefPubMedGoogle Scholar
  25. 25.
    Balgobind BV, Raimondi SC, Harbott J, Zimmermann M, Alonzo TA, Auvrignon A, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood. 2009;114(12):2489–96.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Yilmaz Karapinar D, Kamer SA, Karadaş N, Anacak Y, Delcastello BE, Balkan C, et al. Successful treatment with total skin electron beam therapy in a child with isolated cutaneous relapsed AML. J Pediatr Hematol Oncol. 2015;37(6):e372–4.CrossRefGoogle Scholar
  27. 27.
    Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood [Internet]. 2011;118(14):3785–93. Scholar
  28. 28.
    Dhir S, Wheeler K. Neonatal neuroblastoma. Early Hum Dev. 2010;86(10):601–5.CrossRefPubMedGoogle Scholar
  29. 29.
    Paller AS, Mancini AJ, editors. Hurwitz clinical pediatric dermatology. Histiocytosis and malignant skin diseases. 4th ed. Philadelphia: WB Saunders; 2011. p. 232–3.Google Scholar
  30. 30.
    Schneider KM, Becker JM, Krasna IH. Neonatal neuroblastoma. Pediatrics. 1965;36(3P1):359–66.Google Scholar
  31. 31.
    Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 2003;3(3):203–16.CrossRefPubMedGoogle Scholar
  32. 32.
    Isaacs Jr H. Cutaneous metastases in neonates: a review. Pediatr Dermatol. 2011;28(2):85–93.CrossRefPubMedGoogle Scholar
  33. 33.
    Lukens JN. Neuroblastoma in the neonate. Semin Perinatol. 1999;23(4):263–73.CrossRefPubMedGoogle Scholar
  34. 34.
    Gale GB, D’Angio GJ, Uri A, Chatten J, Koop CE. Cancer in neonates: the experience at the Children’s Hospital of Philadelphia. Pediatrics. 1982;70(3):409–13.PubMedGoogle Scholar
  35. 35.
    Campbell AN, Chan HS, O’Brien A, Smith CR, Becker LE. Malignant tumours in the neonate. Arch Dis Child. 1987;62(1):19–23.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Lucky AW, McGuire J, Komp DM. Infantile neuroblastoma presenting with cutaneous blanching nodules. J Am Dermatol. 1982;6(3):389–91.CrossRefGoogle Scholar
  37. 37.
    Hawthorne HC, Nelson JS, Giangiacomo J, Witzleben CL. Blanching subcutaneous nodules in neonatal neuroblastoma. J Pediatr. 1970;77(2):297–300.CrossRefPubMedGoogle Scholar
  38. 38.
    Nguyen AV, Argenyi ZB. Cutaneous neuroblastoma. Am J Dermatopathol. 1993;15(1):7–14.CrossRefPubMedGoogle Scholar
  39. 39.
    van Erp I. Cutaneous metastases in neuroblastoma. Dermatologica. 1968;136(4):265–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Hicks MJ, Mackay B. Comparison of ultrastructural features among neuroblastic tumors: maturation from neuroblastoma to ganglioneuroma. Ultrastruct Pathol. 1995;19(4):311–22.CrossRefPubMedGoogle Scholar
  41. 41.
    Cohn SL. Diagnosis and classification of the small round-cell tumors of childhood. Am J Pathol. 1999;155(1):11–5.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Wick MR. Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumors. Ann Diagn Pathol. 2008;12(1):72–84.CrossRefPubMedGoogle Scholar
  43. 43.
    Dabbs DJ. Diagnostic immunohistochemistry. 4th ed. Philadelphia: Elsevier; 2013. p 349–351.Google Scholar
  44. 44.
    Hero B, Simon T, Spitz R, Ernestus K, Gnekow AK, Scheel-Walter HG, et al. Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. J Clin Oncol. 2008;26(9):1504–10.CrossRefPubMedGoogle Scholar
  45. 45.
    Monclair T, Brodeur GM, Ambros PF, Brisse HJ, Cecchetto G, Holmes K, et al. The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force Report. J Clin Oncol. 2009;27(2):298–303.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Nickerson HJ, Matthay KK, Seeger RC, Brodeur GM, Shimada H, Perez C, et al. Favorable biology and outcome of stage IV-S neuroblastoma with supportive care or minimal therapy: a Children’s Cancer Group study. J Clin Oncol. 2000;18(3):477–86.PubMedGoogle Scholar
  47. 47.
    Pinto NR, Applebaum MA, Volchenboum SL, Matthay KK, London WB, Ambros PF, et al. Advances in risk classification and treatment strategies for neuroblastoma. J Clin Oncol. 2015;33(27):3008–17.CrossRefPubMedGoogle Scholar
  48. 48.
    Frieden IJ, Rogers M, Garzon MC. Conditions masquerading as infantile haemangioma: part 1. Australas J Dermatol. 2009;50(2):77–97; quiz 98.CrossRefPubMedGoogle Scholar
  49. 49.
    Loh ML, Ahn P, Perez-Atayde AR, Gebhardt MC, Shamberger RC, Grier HE. Treatment of infantile fibrosarcoma with chemotherapy and surgery: results from the Dana-Farber Cancer Institute and Children’s Hospital, Boston. J Pediatr Hematol Oncol. 2002;24(9):722–6.CrossRefPubMedGoogle Scholar
  50. 50.
    Ries L, Smith MA, Gurney JG, Linet M, editors. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. National Cancer Institute, SEER Program. NIH Pub. No. 99-4649, Bethesda; 1999.Google Scholar
  51. 51.
    Ferguson WS. Advances in the adjuvant treatment of infantile fibrosarcoma. Expert Rev Anticancer Ther. 2003;3(2):185–91.CrossRefPubMedGoogle Scholar
  52. 52.
    Miller RW, Young JL, Novakovic B. Childhood cancer. Cancer. 1995;75(1):395–405.CrossRefPubMedGoogle Scholar
  53. 53.
    Dabbs DJ. Diagnostic immunohistochemistry. 4th ed. Philadelphia: Elsevier; 2013. p 107.Google Scholar
  54. 54.
    Okcu MF, Pappo AS, Hicks J. The nonrhabdomyosarcoma soft tissue sarcomas. In: Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2011. p. 976–7.Google Scholar
  55. 55.
    Khoury JD, Coffin CM, Spunt SL, Anderson JR, Meyer WH, Parham DM. Grading of nonrhabdomyosarcoma soft tissue sarcoma in children and adolescents. Cancer. 2010;116(9):2266–74.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Coffin CM, Jaszcz W, O’Shea PA, Dehner LP. So-called congenital-infantile fibrosarcoma: does it exist and what is it? Pediatr Pathol. 1994;14(1):133–50.CrossRefPubMedGoogle Scholar
  57. 57.
    Chung EB, Enzinger FM. Infantile fibrosarcoma. Cancer. 1976;38(2):729–39.CrossRefPubMedGoogle Scholar
  58. 58.
    Ainsworth KE, Chavhan GB, Gupta AA, Hopyan S, Taylor G. Congenital infantile fibrosarcoma: review of imaging features. Pediatr Radiol. 2014;44(9):1124–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Balsaver AM, Butler JJ, Martin RG. Congenital fibrosarcoma. Cancer. 1967;20(10):1607–16.CrossRefPubMedGoogle Scholar
  60. 60.
    Teo HEL, Peh WCG. A 7-week-old female infant with a left thigh swelling. Am J Orthop. 2003;32(10):513–5.PubMedGoogle Scholar
  61. 61.
    Hu Z, Chou PM, Jennings LJ, Arva NC. Infantile fibrosarcoma—a clinical and histologic mimicker of vascular malformations: case report and review of the literature. Pediatr Dev Pathol. 2013;16(5):357–63.CrossRefPubMedGoogle Scholar
  62. 62.
    Bourgeois JM, Knezevich SR, Mathers JA, Sorensen PH. Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors. Am J Surg Pathol. 2000;24(7):937–46.CrossRefPubMedGoogle Scholar
  63. 63.
    Cessna MH, Zhou H, Perkins SL, Tripp SR, Layfield L, Daines C, et al. Are myogenin and myoD1 expression specific for rhabdomyosarcoma? A study of 150 cases, with emphasis on spindle cell mimics. Am J Surg Pathol. 2001;25(9):1150–7.CrossRefPubMedGoogle Scholar
  64. 64.
    Yan AC, Chamlin SL, Liang MG, Hoffman B, Attiyeh EF, Chang B, et al. Congenital infantile fibrosarcoma: a masquerader of ulcerated hemangioma. Pediatr Dermatol. 2006;23(4):330–4.CrossRefPubMedGoogle Scholar
  65. 65.
    Orbach D, Rey A, Cecchetto G, Oberlin O, Casanova M, Thebaud E, et al. Infantile fibrosarcoma: management based on the European experience. J Clin Oncol. 2010;28(2):318–23.CrossRefPubMedGoogle Scholar
  66. 66.
    McCahon E, Sorensen PHB, Davis JH, Rogers PCJ, Schultz KR. Non-resectable congenital tumors with the ETV6-NTRK3 gene fusion are highly responsive to chemotherapy. Med Pediatr Oncol. 2003;40(5):288–92.CrossRefPubMedGoogle Scholar
  67. 67.
    Punnett HH, Tomczak EZ, Pawel BR, de Chadarevian JP, Sorensen PH. ETV6-NTRK3 gene fusion in metastasizing congenital fibrosarcoma. Med Pediatr Oncol. 2000;35(2):137–9.CrossRefPubMedGoogle Scholar
  68. 68.
    Shah NN, Price MR, Loeb DM. Cardiac metastasis and hypertrophic osteoarthropathy in recurrent infantile fibrosarcoma. Pediatr Blood Cancer. 2011;59(1):179–81.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Blocker S, Koenig J, Ternberg J. Congenital fibrosarcoma. J Pediatr Surg. 1987;22(7):665–70.CrossRefPubMedGoogle Scholar
  70. 70.
    Soule EH, Pritchard DJ. Fibrosarcoma in infants and children: a review of 110 cases. Cancer. 1977;40(4):1711–21.CrossRefPubMedGoogle Scholar
  71. 71.
    Ferrari A, Orbach D, Sultan I, Casanova M, Bisogno G. Neonatal soft tissue sarcomas. Semin Fetal Neonatal Med. 2012;17(4):231–8.CrossRefPubMedGoogle Scholar
  72. 72.
    Iwafuchi H, Tsuzuki T, Ito R, Miyake H, Okita H, Hamazaki M. Generalized infantile myofibromatosis with a monophasic primitive pattern. Pathol Int. 2015;65(8):432–7.CrossRefPubMedGoogle Scholar
  73. 73.
    Wiswell TE, Davis J, Cunningham BE, Solenberger R, Thomas PJ. Infantile myofibromatosis: the most common fibrous tumor of infancy. J Pediatr Surg. 1988;23(4):314–8.CrossRefGoogle Scholar
  74. 74.
    Mashiah J, Hadj-Rabia S, Dompmartin A, Harroche A, Laloum-Grynberg E, Wolter M, et al. Infantile myofibromatosis: a series of 28 cases. J Am Acad Dermatol. 2014;71(2):264–70.CrossRefPubMedGoogle Scholar
  75. 75.
    Coffin CM, Alaggio R. Fibroblastic and myofibroblastic tumors in children and adolescents. Pediatr Dev Pathol. 2012;15 Suppl 1:127–80. Scholar
  76. 76.
    Goldberg NS, Bauer BS, Kraus H, Crussi FG, Esterly NB. Infantile myofibromatosis: a review of clinicopathology with perspectives on new treatment choices. Pediatr Dermatol. 1988;5(1):37–46.CrossRefPubMedGoogle Scholar
  77. 77.
    Brill PW, Yandow DR, Langer LO, Breed AL, Laxova R, Gilbert EF. Congenital generalized fibromatosis. Case report and literature review. Pediatr Radiol. 1982;12(6):269–78.CrossRefPubMedGoogle Scholar
  78. 78.
    Matthews MR, Cockerell CJ. An historic perspective of infantile myofibromatosis. Adv Dermatol. 2006;22:279–305.CrossRefPubMedGoogle Scholar
  79. 79.
    Oudijk L, den Bakker MA, Hop WCJ, Cohen M, Charles AK, Alaggio R, et al. Solitary, multifocal and generalized myofibromas: clinicopathological and immunohistochemical features of 114 cases. Histopathology. 2012;60(6B):E1–11.CrossRefPubMedGoogle Scholar
  80. 80.
    Chung EB, Enzinger FM. Infantile myofibromatosis. Cancer. 1981;48(8):1807–18.CrossRefPubMedGoogle Scholar
  81. 81.
    Hogan SF, Salassa JR. Recurrent adult myofibromatosis. A case report. Am J Clin Pathol. 1992;97(6):810–4.CrossRefPubMedGoogle Scholar
  82. 82.
    Wu SY, McCavit TL, Cederberg K, Galindo RL, Leavey PJ. Chemotherapy for generalized infantile myofibromatosis with visceral involvement. J Pediatr Hematol Oncol. 2015;37(5):402–5.CrossRefPubMedGoogle Scholar
  83. 83.
    Kauffman SL, Stout AP. Congenital mesenchymal tumors. Cancer. 1965;18:460–76.CrossRefPubMedGoogle Scholar
  84. 84.
    Smith A, Orchard D. Infantile myofibromatosis: two families supporting autosomal dominant inheritance. Australas J Dermatol. 2011;52(3):214–7.CrossRefPubMedGoogle Scholar
  85. 85.
    Mentzel T, Kutzner H, Rütten A, Hügel H. Benign fibrous histiocytoma (dermatofibroma) of the face: clinicopathologic and immunohistochemical study of 34 cases associated with an aggressive clinical course. Am J Dermatopathol. 2001;23(5):419–26.CrossRefPubMedGoogle Scholar
  86. 86.
    Schrodt BJ, Callen JP. A case of congenital multiple myofibromatosis developing in an infant. Pediatrics. 1999;104(1 Pt 1):113–5.CrossRefPubMedGoogle Scholar
  87. 87.
    Wiswell TE, Sakas EL, Stephenson SR, Lesica JJ, Reddoch SR. Infantile myofibromatosis. Pediatrics. 1985;76(6):981–4.PubMedGoogle Scholar
  88. 88.
    Benjamin SP, Mercer RD, Hawk WA. Myofibroblastic contraction in spontaneous regression of multiple congenital mesenchymal hamartomas. Cancer. 1977;40(5):2343–52.CrossRefPubMedGoogle Scholar
  89. 89.
    Hatzidaki E, Korakaki E, Voloudaki A, Daskaloyannaki M, Manoura A, Giannakopoulou C. Infantile myofibromatosis with visceral involvement and complete spontaneous regression. J Dermatol. 2001;28(7):379–82.CrossRefPubMedGoogle Scholar
  90. 90.
    Baer JW, Radkowski MA. Congenital multiple fibromatosis. A case report with review of the world literature. Am J Roentgenol Radium Ther Nucl Med. 1973;118(1):200–5.CrossRefPubMedGoogle Scholar
  91. 91.
    Levine E, Fréneaux P, Schleiermacher G, Brisse H, Pannier S, Teissier N, et al. Risk-adapted therapy for infantile myofibromatosis in children. Pediatr Blood Cancer. 2011;59(1):115–20.CrossRefPubMedGoogle Scholar
  92. 92.
    Counsell SJ, DeVile C, Mercuri E, Allsop JM, Birch R, Muntoni F. Magnetic resonance imaging assessment of infantile myofibromatosis. Clin Radiol. 2002;57(1):67–70.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.School of MedicineUniversity of California, San Diego and Pediatric & Adolescent Dermatology, Rady Children’s HospitalSan DiegoUSA
  2. 2.Departments of Dermatology and PediatricsUniversity of California, San Diego and Rady Children’s HospitalSan DiegoUSA

Personalised recommendations