Download PDF
AJP Rep 2013; 03(02): 063-066
DOI: 10.1055/s-0033-1338168
Case Report
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

BRAF V600E-Positive Multisite Langerhans Cell Histiocytosis in a Preterm Neonate

Sara V. Bates
1   Division of Neonatology and Newborn Medicine, Department of Pediatrics, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts
*   These authors contributed equally as primary authors (co–first authors).
,
Ashwini Lakshmanan
2   Division of Newborn and Infant Critical Care, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, Los Angeles, California
*   These authors contributed equally as primary authors (co–first authors).
,
Adam L. Green
3   Division of Hematology-Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
4   Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
,
Jefferson Terry
5   Department of Pathology, McMaster Children's Hospital, Hamilton, Ontario, Canada
,
Gayane Badalian-Very
6   Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
,
Barrett J. Rollins
6   Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
7   Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Patricia Fleck
8   Department of Pediatrics, Division of Newborn Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
,
Muhammad Aslam
1   Division of Neonatology and Newborn Medicine, Department of Pediatrics, Massachusetts General Hospital for Children, Harvard Medical School, Boston, Massachusetts
†   These authors contributed equally as senior authors (co–senior authors).
,
Barbara A. Degar
3   Division of Hematology-Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
4   Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
†   These authors contributed equally as senior authors (co–senior authors).
› Author Affiliations
Further Information

Publication History

13 December 2012

24 January 2013

Publication Date:
18 March 2013 (online)

   Permissions and Reprints

Abstract

Hemorrhagic pustules with a “blueberry muffin” appearance accompanied by respiratory failure in a neonate present a challenging differential diagnosis that includes infections and neoplasms. We present a case of multiorgan, multisite Langerhans cell histiocytosis (LCH), positive for the oncogenic BRAF V600E mutation, in a preterm neonate. Infants with LCH pose a diagnostic challenge due to their heterogeneous presentations. This case is unusual in that the newborn presented with severe multiorgan involvement. Due to the rare incidence, wide spectrum of clinical manifestations, and high mortality rate, clinicians must maintain a high index of suspicion for LCH.

Keywords

Langerhans cell histiocytosis - BRAF V600E - preterm neonate - multiorgan - multisite - hemorrhagic pustules
 

  • References

  • 1 Syridou G, Spanakis N, Konstantinidou A , et al. Detection of cytomegalovirus, parvovirus B19 and herpes simplex viruses in cases of intrauterine fetal death: association with pathological findings. J Med Virol 2008; 80: 1776-1782
    CrossrefPubMedGoogle Scholar
  • 2 Abdalla KF, el Fakahany AF, Arafa MA, Salama MM, Morsy TA. Congenital toxoplasmosis among premature infants with different clinical pictures in Saudi Arabia. J Egypt Soc Parasitol 1994; 24: 643-648
    PubMedGoogle Scholar
  • 3 Isaacs Jr H. Cutaneous metastases in neonates: a review. Pediatr Dermatol 2011; 28: 85-93
    CrossrefPubMedGoogle Scholar
  • 4 Bechan GI, Egeler RM, Arceci RJ. Biology of Langerhans cells and Langerhans cell histiocytosis. Int Rev Cytol 2006; 254: 1-43
    PubMedGoogle Scholar
  • 5 Nezelof C, Basset F, Rousseau MF. Histiocytosis X histogenetic arguments for a Langerhans cell origin. Biomedicine 1973; 18: 365-371
    PubMedGoogle Scholar
  • 6 Basset F, Turiaf MJ. [Identification by electron microscope of particles of probable viral nature in the granulomatous connections of a pulmonary histiocytosis “X”]. C R Acad Sci Hebd Seances Acad Sci D 1965; 261: 3701-3
    PubMedGoogle Scholar
  • 7 Cancilla PA, Lahey ME, Carnes WH. Cutaneous lesions of Letterer-Siwe disease. Electron microscopic study. Cancer 1967; 20: 1986-91
    CrossrefPubMedGoogle Scholar
  • 8 Rousseau-Merck MF, Barbey S, Jaubert F, Bach MA, Chatenoud L, Nezelof C. Reactivity of histiocytosis X cells with monoclonal antibodies. Pathol Res Pract 1983; 177: 8-12
    CrossrefPubMedGoogle Scholar
  • 9 Geissmann F, Lepelletier Y, Fraitag S , et al. Differentiation of Langerhans cells in Langerhans cell histiocytosis. Blood 2001; 97: 1241-1248
    CrossrefPubMedGoogle Scholar
  • 10 Nezelof C, Frileux-Herbet F, Cronier-Sachot J. Disseminated histiocytosis X: analysis of prognostic factors based on a retrospective study of 50 cases. Cancer 1979; 44: 1824-1838
    CrossrefPubMedGoogle Scholar
  • 11 Guyot-Goubin A, Donadieu J, Barkaoui M, Bellec S, Thomas C, Clavel J. Descriptive epidemiology of childhood Langerhans cell histiocytosis in France, 2000–2004. Pediatr Blood Cancer 2008; 51: 71-75
    CrossrefPubMedGoogle Scholar
  • 12 Stein SL, Paller AS, Haut PR, Mancini AJ. Langerhans cell histiocytosis presenting in the neonatal period: a retrospective case series. Arch Pediatr Adolesc Med 2001; 155: 778-783
    CrossrefPubMedGoogle Scholar
  • 13 Newman B, Hu W, Nigro K, Gilliam AC. Aggressive histiocytic disorders that can involve the skin. J Am Acad Dermatol 2007; 56: 302-316
    CrossrefPubMedGoogle Scholar
  • 14 Minkov M, Prosch H, Steiner M , et al. Langerhans cell histiocytosis in neonates. Pediatr Blood Cancer 2005; 45: 802-807
    CrossrefPubMedGoogle Scholar
  • 15 Allen CE, Li L, Peters TL , et al. Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol 2010; 184: 4557-4567
    CrossrefPubMedGoogle Scholar
  • 16 Degar BA, Rollins BJ. Langerhans cell histiocytosis: malignancy or inflammatory disorder doing a great job of imitating one?. Dis Model Mech 2009; 2: 436-439
    CrossrefPubMedGoogle Scholar
  • 17 Querings K, Starz H, Balda BR. Clinical spectrum of cutaneous Langerhans' cell histiocytosis mimicking various diseases. Acta Derm Venereol 2006; 86: 39-43
    PubMedGoogle Scholar
  • 18 Badalian-Very G, Vergilio JA, Degar BA , et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 2010; 116: 1919-1923
    CrossrefPubMedGoogle Scholar
  • 19 Michaloglou C, Vredeveld LC, Mooi WJ, Peeper DS. BRAF(E600) in benign and malignant human tumours. Oncogene 2008; 27: 877-895
    CrossrefPubMedGoogle Scholar
  • 20 Gadner H, Grois N, Pötschger U , et al; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood 2008; 111: 2556-2562
    CrossrefPubMedGoogle Scholar
  • 21 Chapman PB, Hauschild A, Robert C , et al; BRIM-3 Study Group. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507-2516
    CrossrefPubMedGoogle Scholar
  • 22 Hauschild A, Grob JJ, Demidov LV , et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2012; 380: 358-365
    CrossrefPubMedGoogle Scholar
  • 23 Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, Cluzel P, Drier A, Hervier B, Benameur N, Besnard S, Donadieu J, Amoura Z. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood , February 28, 2013; 121 (9); 1495-500
    CrossrefPubMedGoogle Scholar