Final Diagnosis -- Intracerebral Langerhans cell histiocytosis

DIAGNOSIS

Intracerebral Langerhans cell histiocytosis.

DISCUSSION

Langerhans cell histiocytosis (LCH) is a dendritic cell-related disorder that is characterized by tumor-like masses composed of histiocytes. Cranial lesions are typically accompanied by identical extracranial foci as well (8). Previously, LCH was referred to as histiocytosis X, a group of histiocytic disorders which occurred as a clinical spectrum, ranging from solitary eosinophilic granuloma of the skull, to skull base and hypothalamic involvement with resultant diabetes insipidus (Hand-Schüller-Christian disease), to disseminated disease involving skin, lymph nodes, visceral organs, and rarely, the central nervous system (Abt-Lettterer-Siwe disease) (8). Cranial tumors are typically extra-axial lytic lesions; from an osseous center, such lesions may extend to involve the axial cerebral parenchyma. Discrete CNS intra-axial lesions are rare (2, 3, 4, 7). A case of intracerebral LCH and concurrent Erdheim-Chester disease, a non-Langerhans cell histiocytosis, has also been described (5).

LCH can be readily recognized on, or suggested by H&E examination, where a mixture of inflammatory cells is present; these include macrophages, lymphocytes, plasma cells, and Langerhans cells, characterized by slightly eccentric, ovoid, reniform or convoluted nuclei. Eosinophils may also be evident. The Langerhans cells should demonstrate reactivity for S-100 protein. In order for a definitive diagnosis of LCH to be rendered, there must be either expression of CD1a, or demonstration of Birbeck granules by electron microscopy (8). Although the significance of atypia and mitotic activity is undetermined, a distinct clinical entity of malignant LCH, with cytologically malignant Langerhans cells, atypical organ involvement, and a male predominance; has been characterized (1).

The behavior of LCH is variable. Unifocal cases may spontaneously regress or require minimal intervention, such as surgery (6, 8). Multisystem disease may follow a more aggressive course, and be refractory to chemotherapy (8).

In this patient, following the diagnosis of LCH, additional body imaging revealed multiple pulmonary nodules, all measuring less than 5mm in greatest dimension. No other sizable mass lesions, lymphadenopathy, or effusions were observed. These pulmonary findings, in consideration the intracerebral pathology, are clinically interpreted as also consistent with involvement by LCH, indicating multifocal disease.

REFERENCES

1. Ben-Ezra J, Bailey A, Azumi N, Delsol G. Stroup R, Sheibani K, Rappaport H. Malignant histiocytosis X. A distinct clinicopathologic entity. Cancer 68(5): 1050-1060.
2. Bergmann M, Yuan Y, Bruck W, Palm KV, Rohkamm R. Solitary Langerhans cell histiocytosis lesion of the parieto-occipital lobe: a case report and review of the literature. Clin Neurol Neurosurg 99(1):50-55, 1997.
3. Cagli S, Oktar N, Demirtas E. Langerhans' cell histiocytosis of the temporal lobe and pons. Br J Neurosurg 18(2):174-180, 2004.
4. D'Avella D, Giusa M, Blandino A, Angileri FF, La Rosa G, Tomasello F. Microsurgical excision of a primary isolated hypothalamic eosinophilic granuloma. Case report. J Neurosurg 87(5):768-72, 1997.
5. Granier M, Micheau A, Serre I. A rare cause of cardiac tumour: an Erdheim-Chester disease with cardiac involvement co-existing with an intracerebral Langerhans cell histiocytosis. Eur Hear J. 29(16):1929, 2008.
6. Gunny R, Clifton A, Al-Memar A. Spontaneous regression of supratentorial intracerebral Langerhans' cell histiocytosis. Br J Radiol 77:685-687, 2004.
7. Mathis S, Levillain P, Vandermarcq P, Gil R, Auche V, Ciron J, Neau JP. Solitary intracerebral Langerhans cell histiocytosis: report of one case and literature review. Rev Med Interne 28(9):645-650, 2007.
8. Paulus W, Perry A (2007) Histiocytic tumours. In WHO Classification of Tumours of the Central Nervous System. D.N. Louis, H. Ohgaki, O.D. Wiestler, W.K. Cavenee, Editors. International Agency for Research on Cancer, 193-196.

Contributed by Brian H. Le, MD, Raymond C. Truex, MD