Brain Pathology Case of the Month - August 2007



The disparate group of diseases now collectively referred to as Langerhans cell histiocytosis (LCH) include diseases previously designated histiocytosis X, eosinophilic granuloma, Letterer-Siwe disease and Hand-Sch¨šller-Christian syndrome, Hashimoto-Pritzker syndrome, self-healing histiocytosis, pure cutaneous histiocytosis, Langerhans cell granulomatosis, Type II histiocytosis, and the generic term nonlipid reticuloendotheliosis [1]. LCH is a disease of unclear etiology characterized by neoplastic proliferation of Langerhans cells [6, 7]. LCH usually affects children and frequently involves bone structures including bones of the cranium and the skull base [6]. However, manifestation of LCH within the clivus is extremely rare. To our knowledge this is the second report of an adult patient with unifocal LCH of the clivus [5]. Neuroradiologically, the lesion mimicked a chordoma, chondroma or chondrosarcoma, all lesions that usually occur in adults and - except from chondroma - are more commonly located in the clivus than LCH [3, 4].

The present case differs clinically from the case previously reported by Sampson and colleagues [5] regarding pain type (frontal in our case vs. retro-orbital), cranial nerve involvement (inconspicuous vs. unilateral palsy of abducent nerve) and gadolinium enhancement (heterogeneous vs. homogeneous).

So far no standardized therapeutic strategy for LCH exists. Prognosis and treatment options depend essentially on the number of affected sites (unifocal or multifocal disease) and on the number of affected systems (single system or multiple systems disease). Unifocal single system disease (formerly referred as eosinophilic granuloma) has a relatively favorable prognosis with overall survival rates of more than 95% and spontaneous remission being not uncommon, although progression to multifocal disease occurs in about 10% of cases [2, 6]. In our case there was no evidence for additional osseous or extra-osseous manifestation of LCH, corresponding to unifocal osseous LCH of the clivus.

While chordomas and chondrosarcomas are usually radically resected, neurological morbidity following aggressive surgical treatment for LCH is not warranted. The optimal treatment for chordomas and chondrosarcomas of the cranial base is gross total removal associated with radiotherapy, preferentially proton beam therapy or carbon ion radiotherapy. Conservative lesion removal rather than total resection has priority in the management of LCH lesions. Therefore, pre- and intraoperative diagnosis suspicion based on radiological images and intraoperative frozen section exam have a fundamental impact on the proper management of such disease. The present case shows us that LCH of the clivus may mimic chordomas and chondrosarcomas of the skull base and should be included in the differential diagnosis of clival lesions.


To Professor Marx (National reference center for lymph node pathology, Institute of Pathology, University of Wurzburg, Germany) for confirmation of our diagnosis.


  1. Chu T, D'Angio GJ, Favara BE, Ladisch S, Nesbit M, Pritchard J (1987) Histiocytosis syndromes in children. Lancet 2: 41-42
  2. Howarth DM, Gilchrist GS, Mullan BP, Wiseman GA, Edmonson JH, Schomberg PJ (1999) Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome. Cancer 85: 2278-2290
  3. Korten AG, ter Berg HJ, Spincemaille GH, van der Laan RT, Van de Wel AM (1998) Intracranial chondrosarcoma: review of the literature and report of 15 cases. J.Neurol.Neurosurg.Psychiatry 65: 88-92
  4. Rosenberg AE, Nielsen GP, Keel SB, Renard LG, Fitzek MM, Munzenrider JE, Liebsch NJ (1999) Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma. Am.J.Surg.Pathol. 23: 1370-1378
  5. Sampson JH, Rossitch EJ, Young JN, Lane KL, Friedman AH (1992) Solitary eosinophilic granuloma invading the clivus of an adult: case report. Neurosurgery 31: 755-757
  6. Weiss LM, Grogan TM, M¨šller-Hermelink H-K, Stein H (2001) Langerhans cell histiocytosis. In: Pathology and genetics of tumours of the hematopoietic and lymphoid tissue. Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) p 280-283, IARCPress: Lyon,
  7. Willman CL (1994) Detection of clonal histiocytes in Langerhans cell histiocytosis: biology and clinical significance. Br.J.Cancer Suppl 23: S29-S33

Contributed by Rudi Beschorner, Andrei Koerbel, Jens Schittenhelm, Jan Kaminsky, Hubert Loewenheim, Eva Bueltmann, Marcos Tatagiba, Richard Meyermann, Manfred Wehrmann

International Society of Neuropathology