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Contents 1 Disease 2 Disease Entity 2.1 Pathophysiology 2.2 Etiology 2.3 Incidence  3 Diagnosis 3.1 History 3.2 Differential diagnosis 4 Management and Treatment 4.1 Prognosis 5 Additional Resources 6 References

Disease

Langerhans Cell Histiocytosis (LCH) involving the orbit.^[1]

Disease Entity

Langerhans Cell Histiocytosis (LCH), formerly known as “histiocytosis X,” historically includes three subgroups: eosinophilic granuloma, Hand-Schuller-Christian disease, and Letterer-Siwe disease, representing a spectrum from unifocal to multifocal/multisystem involvement. The lesions of LCH may involve the bones, skin, hypothalamus-pituitary region, as well as other organs.^[2]

Pathophysiology

While the characteristic granuloma-like lesions of LCH consists of Langerhans cells, macrophages, eosinophils, T lymphocytes and plasma cells, it is thought that clonal expansion of defective immature Langerhans cells is the key pathogenetic element.^[3]

Etiology

Langerhans cell histiocytosis remains an enigmatic disease and the dispute over its neoplastic versus reactive nature is unsettled. The current understanding of histiocyte development is based on in vitro studies and suggests an immune/inflammatory reaction leads susceptible langerhans cells to undergo a clonal expansion resulting in LCH.^[4]

Incidence 

LCH is predominantly a disease of childhood with a peak incidence between 1 and 4 years.  Children less than one year tend to have more aggressive disease with a worse prognosis.  The estimated annual incidence is 2-5 in one million children and represents 1% to 3% of pediatric orbital tumors.^[5][6] In a retrospective chart review of 24 consecutive patients with LCH treated at a tertiary referral center, the orbit was involved in 9 (37.5%) of patients. The most common site of involvement was the frontal bone (n = 6) followed by zygomatic (n = 3), sphenoid (n = 3), and maxillary (n = 2).^[7] 

Diagnosis

The histological diagnosis of LCH lesions is based on staining for S-100 protein and CD1a antigen or finding Birbeck granules (shaped like tennis racquets) on electron microscopy.^[8][9]

History

Epidermal langerhans cells were first described by the German physician Paul Langerhans in 1868. Because the branched cells demonstrated an affinity for gold chloride (a stain for nervous tissue) the cells were thought to be of neural origin. The hematopoietic origin and antigen presenting function of the dendritic cells would remain unknown for more than a century.^[10]

Differential diagnosis

Orbital cellulitis is the most common cause of proptosis in children. Orbital psuedotumor represents the second most common inflammatory disorder of the orbit in childhood and may present with unilateral or bilateral proptosis of explosive onset with restriction of ocular motility. Less common orbital inflammatory process that should be considered include Wegener’s granulomatosis, sarcoidosis, and Langerhans cell histiocytosis, with the latter occurring in childhood more frequently.  If imaging reveals a bony defect and/or the presentation is of rapid onset, the tumors histopathologically described as the “small round blue-cell tumors of childhood” should be considered and include rhabdomyosarcoma, leukemia, and metastatic neuroblastoma.^[11]

Management and Treatment

All patients with unifocal orbital disease require a biopsy to establish and confirm the diagnosis and rule out other malignant disease. Patients should be referred to a pediatric oncologist for a comprehensive systemic evaluation and ongoing follow-up in order to monitor for recurrence or progression. Single-system disease confined to a single site (e.g., small orbital lesions withoutintracranial extension) usually only requires local therapy (e.g., curettage, steroid injection or radiation therapy) or observation. On the other hand, multifocal disease usually requires systemic therapy with prednisone with or without chemotherapeutic agents (vinblastine and/or etoposide) depending on the extent of the disease.^[12]

Prognosis

LCH represents a spectrum from the benign unifocal bone lesion to aggressive multisystem disease. In a large cohort study of 314 Mayo Clinic patients with histologically proven LCH, 97% (114 of 314) of patients with isolated bone LCH lesions achieved disease free survival after treatment. The proportion of patients achieving disease free survival was significantly less in patients with multisystem disease versus single system disease (74% vs. 91%; P <0.003; 95% CI, 0.26 and 0.08).^[13] While isolated LCH of the orbit is thought to be a relatively benign condition responsive to limited local treatment, it should be noted that in a recent retrospective study by Vosoghi, et al. 7 of 9 patients with unifocal bone disease progressed to multifocal bone disease during follow-up, including 2 patients with unifocal orbital disease. Even though these results may be inflated due to a strong referral bias, the study highlights the possible progression of unifocal bone disease and the importance of a comprehensive workup and follow-up.^[14]

Additional Resources

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References

1. ↑ Hester CC, Silkiss RZ. The Cellulitis That Wouldn’t Go Away. Morning Rounds. EyeNet. Morning Rounds. EyeNet. October 2010.
2. ↑ Savasan, S. Int J Dermatol 2006;45:182–188.
3. ↑ Savasan, S. Int J Dermatol 2006;45:182–188.
4. ↑ Savasan S. An enigmatic disease: childhood Langerhans cell histiocytosis in 2005. Int J Dermatol 2006;45:182-8.
5. ↑ Vosoghi, H. et al. Ophthal Plast Reconstr Surg 2009;25:430–433.
6. ↑ Savasan, S. Int J Dermatol 2006;45:182–188.
7. ↑ Castillo, B. V. and L. Kaufman. Pediatr Clin North Am 2003;50:149–172.
8. ↑ Savasan, S. Int J Dermatol 2006;45:182–188.
9. ↑ Harris, G. J. Am J Ophthalmol 2006;141:374–378.
10. ↑ Namazi, M. R. Arch Dermatol 2008;144:1109.
11. ↑ Hurwitz CA, et al. N Engl J Med 2002;346:513-20.
12. ↑ Vosoghi, H. et al. Ophthal Plast Reconstr Surg 2009;25:430–433.
13. ↑ Howarth, D. M. et al. Cancer 1999;85: 2278–2290.
14. ↑ Vosoghi, H. et al. Ophthal Plast Reconstr Surg 2009;25:430–433.