FINAL DIAGNOSIS: Langerhans' cell histiocytosis.
The histologic examination of this case shows typical features of Langerhans' cell histiocytosis. There is an atypical population of Langerhans' cells admixed with acute and chronic inflammatory cells. These large atypical cells often have deep grooved nuclei and are frequently nicknamed "coffee bean" nuclei. These atypical cells also share typical immunohistochemical features with Langerhans' cells and express CD1a and S100. The multinucleated giant cells, however, express features of macrophages and are positive for CD68 but negative for CD1a. The amount of eosinophils is not overwhelming but Langerhans' histiocytosis without eosinophils have been reported (1). The demonstration of Birbeck granules supported the presence of Langerhans' cells in this lesion. The minor trauma sustained by the patient probably produced a pathologic fracture of the lesion and this also explained the unusually high amount of osteoclast-like giant cells in this case.
Langerhans' cell histiocytosis (histiocytosis X) is a clonal proliferative disorder (2) of the antigen presenting Langerhans' cell (3). Local proliferation at the lesion sites has been shown by immunostaining for Ki-67 (4). Typically, the Langerhans' cells are admixed with a mixed population of acute and chronic inflammatory cells. The Langerhans' cells express CD1a and S100 (4,5,6). Demonstration of Birbeck granules that are characteristically 34 nm wide rod-shaped pentalaminar tubular structures with characteristic periodicity, a zipper-like central core, and a dilated end bulb, provides solid strong morphologic evidence on their Langerhans' cell origin (6). Birbeck granules, interestingly, are not real granules, but cytoplasmic invaginations of the cell surface membrane within the cytosol that are not associated with other organelles or the nuclear envelope (7).
Langerhans' histiocytosis is an all-encompassing term that covers the formerly known clinicopathologic entities of histiocytosis X that includes Lettere-Siwe disease, Hand-Schüller-Christan, disease, and eosinophilic granulomas. Based on the clonal proliferative properties of Langerhans' cell histiocytosis, it should be classified as a neoplastic disease. Langerhans' cell histiocytosis typically affects young patients and almost half of the cases occur under ten years of age. The skull and femur are most commonly involved. When the skull is involved, the orbit and the cranial base are frequently involved and produce the classic triad of bony defects, exophthalmos and diabetes insipidus. The cranial base involvement may extend into the brain and involve the hypothalamus. Involvement of other parts of the brain has also been reported.
Contributed by Kar-Ming Fung, MD, PhD, Jason M Schwalb, MD, Howard A Riina, MD, Jasvir S Kurana, MD, Justina M Mindaxy, MS, M. Sean Grady, MD, Ehud Lavi, MD