Langerhans cell histiocytosis

Definition : Langerhans cell histiocytosis (histiocytosis X) is a disorder of unknown etiology characterized by solitary (eosinophilic granuloma) or multiple bone and visceral masses.

Cytologically, the smears are hypercellular with numerous Langerhans cell histiocytes, which are large, polygonal cells with eosinophilic cytoplasm and oval nuclei with longitudinal grooves (‘coffee bean nuclei’).

Scattered eosinophils, mixed inflammatory cells, osteoclast-like giant cells, and necrosis are identified in the background.

The histiocytes stain with CD1a, S100, vimentin, and CD68 (variable), and are negative for HAM56, CD21, and CD35.

Tennis racket-shaped, electron-dense cross striations (Birbeck granules) are identified on electron microscopy.

While the presence of eosinophils may be a clue to the diagnosis, the distinctive immunohistochemical pattern of the histiocytes differentiates Langerhans cell histiocytosis from XG disease.

Digital cases

 HPC:245 : Orbital Langerhans cell histiocytosis
 JRC:1610 : Pulmonary localized Langerhans cell histiocytosis.
 JRC:6344 : Pulmonary localized Langerhans cell histiocytosis.

Images

 https://twitter.com/CArnold_GI/status/726767164242419712

Epidemiology

 congenital Langerhans cell histiocytosis (rare)

Ultrastructure

 Birbeck granules

Localization

 skin
 digestive system
 lymph node
 liver
 female genital tract (12801274)

Variants

 malignant Langerhans cell tumor (11437944, 12963924)

Immunochemistry

 CD1a+
 Langherin +
 S100+
 CD68-
 fascine+

CGH

 losses of DNA sequences on chromosomes 1p, 5, 6, 7, 9, 16, 17, and 22q (12094383)

 gain of DNA copy number was seen on chromosomes 2q, 4q, and 12 (12094383)

LOH (17378622)

 1p LOH (12094383)
 5q23 LOH (17378622)
 Chr.7 LOH (12094383)
 Chr.9 LOH (12094383)
 22q LOH (12094383)

Molecular biology

 Detection of clonal lymphoid receptor gene rearrangements in langerhans cell histiocytosis. (20551822)

Case records

 Case 11335: Femoral Langerhans histiocytosis
 Case 12691: Faciocranial Langerhans cell histiocytosis

References

 Detection of clonal lymphoid receptor gene rearrangements in langerhans cell histiocytosis. Chen W, Wang J, Wang E, Lu Y, Lau SK, Weiss LM, Huang Q. Am J Surg Pathol. 2010 Jul;34(7):1049-57. PMID: 20551822

 Chikwava KR, Hunt JL, Mantha GS, Murphy JE, Jaffe R. Analysis of loss of heterozygosity in single-system and multisystem langerhans’ cell histiocytosis. Pediatr Dev Pathol. 2007 Jan-Feb;10(1):18-24. PMID: 17378622

 Murakami I, Gogusev J, Fournet JC, Glorion C, Jaubert F. Detection of molecular cytogenetic aberrations in langerhans cell histiocytosis of bone. Hum Pathol. 2002 May;33(5):555-60. PMID: 12094383