Unilateral Lisch nodules

KEYWORDS:

• Hamartoma
• Lisch nodules
• mosaicism
• naevi
• Neurofibromatosis

Introduction

Lisch nodules are melanocytic hamartomas on the iris surface.¹ They are the most common ophthalmic manifestation of Neurofibromatosis type 1 (NF1), a genetic neurocutaneous disease.² Occasionally, the nodules are also present in other conditions such as Cushing’s syndrome.³

The nodules tend to form inferiorly on the iris.⁴ In lighter irides they appear copper with blurry margins. In darker eyes they are cream and well demarcated.¹ Histologically, the nodules are like naevi which occur more posteriorly within the iris.⁵ Optical coherence tomography (OCT) localises Lisch nodules to the iris anterior border.⁶ Bilateral presentation is typical, however unilateral cases can occur in both children and adults.⁷

Case report

Examination of an asymptomatic 50-year-old male revealed a cluster of brown circular nodules on the right peripheral iris surface between 4 and 6 o’clock (Figure 1). The nodules had a smooth domed morphology with faded borders consistent with Lisch nodules. The patient did not have a family history of NF1.

Figure 1. OD Lisch nodules. A: Without annotation. B: With circular annotation.

There were no prominent corneal nerves, iris heterochromia, gonioscopic angle vessels or keratic precipitates. The patient had healthy optic nerves, normal pupil reflexes and no choroidal abnormalities. Visual field testing and posterior OCT were unremarkable. There was no evidence of plexiform neurofibroma affecting the eyelid, orbit, periorbita or face. Ophthalmoplegia and proptosis were not present.

Upon discussion, the patient elected to consult their general practitioner who would facilitate magnetic resonance imaging and dermatological evaluation. Future correspondence of these results was requested with the general practitioner. Additionally, annual eye examinations and screening of first-degree relatives was recommended.

Discussion

Lisch nodules may become more numerous over time.² They should be differentiated from naevi and variants including melanocytoma. These are typically larger, penetrate iris stroma and have potential for malignancy.^5,8 Tapioca naevi may appear similar, although they have a more transparent glistening quality.⁹ The domed morphology of Lisch nodules differs from flat iris freckles and they are larger than iris mammillations.^6,10 A lack of inflammatory findings will rule out the possibility of uveitic Busacca nodules, a feature of Sarcoidosis.¹¹

Patients with Lisch nodules require screening for cutaneous signs of NF1, which include Café au lait macules. These are flat light brown patches of melanocytes.¹² Other NF1 findings include, distinctive freckling of the groin or armpit region, tumours on the skin (neurofibromas) and bone deformities.¹²

Ocular complications in NF1 patients can occur in the form of optic pathway glioma, orbital neurofibromas, orbital bone dysplasia and congenital glaucoma.¹³ Potentially fatal complications such as melanoma and central nervous system tumours occur in up to 25% of all Neurofibromatosis patients.¹³

Unilateral Lisch nodules in patients over 16 years can be indicative of a segmental form of NF1 caused by somatic mosaicism.^12,13 Here, post zygotic mutation of the NF1 gene leads to a mosaic of normal and affected cells within a region of the body.¹⁴ Segmental NF1 is 10–15 times less prevalent, is typically not transmitted to progeny and has a lower incidence of systemic complications.^14,15 Nevertheless there remains an increased risk of malignancies such as peripheral nerve sheath tumour.¹⁵ These patients require annual eye examinations targeted at detecting visual pathway glioma. Workup including visual fields, OCT and fundoscopy are thus indicated.¹⁶

Disclosure statement

No potential conflict of interest was reported by the author(s).