Brain histiocytosis with precocious puberty and growth hormone deficiency at early childhood – A case report

Dragan Katanić; Jovanka Kolarović; Danica Grujičić; Milica Skender Gazibara; Marija Knežević Pogančev; Katarina Koprivšek; Jovan Vlaški; Ivana Vorgučin; Jasmina Katanić

doi:10.2298/VSP1702080028K

Dragan Katanić University of Novi Sad, Faculty of Medicine, Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia
Jovanka Kolarović University of Novi Sad, Faculty of Medicine, I ns titute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia
Danica Grujičić Clinical Centre of Serbia, Neurosurgery Clinic, Belgrade, Serbia
Milica Skender Gazibara University of Belgrade, Faculty of Medicine, Institute of Pathology, Belgrade, Serbia
Marija Knežević Pogančev University of Novi Sad, Faculty of Medicine, Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia
Katarina Koprivšek University of Novi Sad, Faculty of Medicine, Institute of Oncology – Sremska Kamenica, Novi Sad, Serbia
Jovan Vlaški University of Novi Sad, Faculty of Medicine, Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia
Ivana Vorgučin University of Novi Sad, Faculty of Medicine, Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia
Jasmina Katanić University of Novi Sad, Faculty of Medicine, Institute for Child and Youth Health Care of Vojvodina, Novi Sad, Serbia

DOI: https://doi.org/10.2298/VSP1702080028K

Keywords: histocytosis, brain, diagnosis, diabetes insipidus, drug therapy, treatment outcome

Abstract

Introduction. Langerhans Cell Histiocytosis (LCH) is a rare chronic granulomatous, usually multisystem disease of elusive etiology, with peak incidence in early childhood and slow progressing course. Isolated brain histiocytosis is a very rare condition and neurological finding does not correlate with the extent of space-occupying anatomical lesions and degenerative changes. Case report. A girl, age 2.5 years was presented with diabetes insipidus and nearly fatal full spectrum isolated brain histiocytosis. Brain magnetic resonance imaging (MRI) showed multiple nodules with perifocal edema, the most prominent in the projection of the hypothalamus/pituitary and the stalk and in the region of the pineal gland. Identical nodules were present in both caudate nucleus and putamen, left insular subcortex, both temporal lobes, tegmental area of the midbrain, central part of pons and medulla, both cerebellar hemispheres and leptomeningeal membranes. The pattern resembled snow balls and flakes. Biopsy showed positivity for vimentin, S-100, CD-68 and CD1a markers. Treatment protocol LCH-III was not successful and a salvage treatment was refused by parents. She appeared again at the age of 7 with growth deceleration and fully developed precocious puberty. The control MRI of the brain revealed similar nodules in certain regression. Due to central precocious puberty, treatment with luteinizing hormone–releasing hormone (LH-RH) analogue was introduced. School performance was mediocre with cocktail-party effect behavior and slower speech. Conclusion. Brain histiocytosis is potentially fatal disease with chronic, variable, slowly progressive course and unpredictable responses to treatment protocols.

References

Foulet-Roge A, Josselin N, Guyetant S, Gardet J, Bescancon A, Saint-Andre J, et al. Incidental langerhans cell histiocytosis of thyroid: case report and review of the literature. Endo Pathol 2002; 13(3): 227–33.

Grois N, Prayer D, Prosch H, Lassmann H. Neuropathology of CNS disease in Langerhans cell histiocytosis. Brain 2005; 128(Pt 4): 829–38.

Prayer D, Grois N, Prosch H, Gadner H, Barkovich AJ. MR imag-ing presentation of intracranial disease associated with Lang-erhans cell histiocytosis. AJNR Am J Neuroradiol 2004; 25(5): 880–91.

Prosch H, Grois N, Wnorowski M, Steiner M, Prayer D. Long-term MR imaging course of Langerhans cell histiocytosis neu-rodegenerative. Am J Neuroradiol 2007; 28(6): 1022–8.

Imashuku S, Shioda Y, Kobayashi R, Hosoi G, Fujino H, Seto S, et al. Neurodegenerative central nervous system disease as late sequelae of Langerhans cell histiocytosis. Report from the Ja-pan LCH Study Group. Haematologica 2008; 93(4): 615–8.

Grois N, Fahrner B, Arceci RJ, Henter J, McClain K, Lassmann H, et al. Central Nervous System Disease in Langerhans Cell His-tiocytosis. J Pediatr 2010; 156(6): 873–81.e1.

Schmidt S, Eich G, Hanquinet S, Tschäppeler H, Waibel P, Gudinchet F. Extra-osseous involvement of Langerhans? cell histiocytosis in children. Pediatr Radiol 2004; 34(4): 313–21.

Badalian-Very G, Vergilio JA, Degar BA, MacConaill LE, Brandner B, Calicchio ML, et al. Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 2010; 116(11): 1919–23.

Imashuku S, Fujita N, Shioda Y, Noma H, Seto S, Minato T, et al. Follow-up of pediatric patients treated by IVIG for Langer-hans cell histiocytosis (LCH)-related neurodegenerative CNS disease. Int J Hematol 2015; 101(2): 191–7.

Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, et al. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mu-tation. Blood 2013; 121(9): 1495–500.

Héritier S, Jehanne M, Leverger G, Emile J, Alvarez J, Haroche J, et al. Vemurafenib Use in an Infant for High-Risk Langerhans Cell Histiocytosis. JAMA Oncol 2015; 1(6): 836–38.

Cugati G, Pande A, Vasudevan M, Singh M, Ramamurthi R. Hand Schuller Christian disease. Indian J Med Paediatr Oncol 2011; 32(3): 183–4.

Minkov M. Multisystem Langerhans cell histiocytosis in chil-dren: current treatment and future directions. Pediatr Drugs 2011; 13(2): 75–86.

Baumann M, Cerny T, Sommacal A, Koeberle D. Langerhans cell histiocytosis with central nervous system involvement-complete response to 2-chlorodeoxyadenosine after failure of tyrosine kinase inhibitor therapies with sorafenib and imatinib. Hematol Oncol 2011; 30(2): 101–4.