Plexiform Neurofibroma

Features:

• Describe the findings of the Observation

  • On inspection, there is an S-shaped deformity of the left upper eyelid, due to a mass present on the lateral half of the eyelid, about 6x12 mm in size. The surface is smooth and the lesion merges into the surrounding tissue. There is no erythema or discharge present.  The mass is causing drooping of the upper eyelid obscuring the pupil.

• Describe the findings of Palpation –

  • The mass is non-tender to touch

  • the lesion has bag of worm feeling

  • the temperature of the lesion is comparable to the surrounding skin,

  •  it is adherent to the overlying skin and no posterior extent can be found.

  • There are CSF pulsations being transmitted,  

  • The draining lymph nodes are non-palpable.

• Look for other ocular manifestations.

  • Prominent corneal nerves

  • IOP for congenital glaucoma and optic disc cupping

  • Lisch nodules and ectropion uvae

  • Retinal Tumors

  • Choroidal hamartomas

  • Optic nerve Gliomas – Check VA and pupillary reactions

  • Optic disc for Glaucoma and pallor / atrophy (gliomas)

• Check Visual acuity and refractive status to rule out amblyopia due to Sensory deprivation or anisometropia / astigmatism.

• CT scan for orbital involvement, and Absence of greater wing of Sphenoid.

• Look for cutaneous Signs of NF1

  • Café au lait spots on the back

  • Axillary freckles

  • RAPD and proptosis for Optic nerve Glioma

Narration:

Questions:

How is type 1 neurofibromatosis transmitted?

Autosomal dominant in which the abnormal gene is located in chromosome 17 q11.2.

Irregularities in the neurofibromin gene within the pericentromeric region of chromosome 17 are linked to type I neurofibromatosis. Microarray analysis has revealed alterations in the expression levels of various genes, both increasing and decreasing, which are involved in the development of tumors.

What physical signs in type 1 neurofibromatosis is most strongly associated with glaucoma?

Plexiform neuroma and ectopia uvea.

What is the differential diagnosis of S-shaped deformity of upper eyelid?

Plexiform Neurofibroma

Acute dacryoadenitis

Large Chalazion / pre-septal Cellulitis

What is the criterion for diagnosis of NF1?

The diagnostic criteria for neurofibromatosis type 1 are based on the features, remembered with the “CRABBING” mnemonic:

C – Café-au-lait spots (more than 15mm diameter is significant in adults)

R – Relative with NF1

A – Axillary or inguinal freckling

BB – Bony dysplasia, such as Bowing of a long bone or sphenoid wing dysplasia

I – Iris hamartomas (Lisch nodules), which are yellow-brown spots on the iris 

N – Neurofibromas

G – Glioma of the optic pathway

What is the most common cause of hamartomas?

What is the most serious ophthalmic manifestation of NF1?

The most serious ophthalmic manifestation of NF1 is the visual loss secondary to optic nerve glioma.

What do you know about Lisch Nodules?

Most common type of ocular involvement in NF1, that appear as yellow to brown, well defined, dome shaped elevations projecting from the surface of iris.

Following are the characteristics of Lisch Nodules:

Melanocytic Hamartomas

Specific for NF1

Smooth, Usually bilateral, elevated nodules.

Usually appear in the first decade. Almost all patients with NF-1 have Lisch nodules by age 20 years (1)

What do you about Optic nerve Gliomas and NF1? 

ONG have close association with NF1, it has been estimated that about 15-40% of children with NF-1 have optic enrve glioma or visual pathwahy gliomas involving the optic nerve, chiasm or optic tract. (2)

Gliomas appear fusiform on neuroimaging.

Optic nerve gliomas are locally invasive and slow growing with low malignant potential. However, chiasmatic gliomas may invade the hypothalamus and third ventricle, causing obstructive hydrocephalus. (3)

What is the difference between Lisch Nodules and Iris Naevi?

Lisch Nodules are benign hamartomas, histologically identical to iris nevi. However, morphologically Lisch nodules are clear yellow to brown, well defined, dome shaped elevations of the surface of iris whereas naevi are flat or minimally elevated, densely pigmented lesions with blurry margins.

What do you know about plexiform neurofibromas (PNF) and NF1?

Although PNF are less common than gliomas still they are one of the sight threatening associations of NF1. Defective vision is due to amblyopia secondary to ptosis and anisometropia.

They present as S shaped deformity of the upper eyelid, having increased thickness of upper eyelid and bag of worms sensation. Ipsilateral congenital Glaucoma may be seen.

What are the characteristics of choroid hamartomas in NF1?

Hamartomas of the choroid have the following characteristics:

Usually in the posterior pole

Flat, ill-defined lesions

Contain neuronal and melanocytic components

What retinal tumors are seen in association with NF1?

The following are characteristics of retinal tumors:

Astrocytic hamartomas (white tumors involving the optic nerve)

Combined hamartomas of the retina and retinal pigment epithelium

Retinal capillary hemangiomas

Possible increase in the incidence of choroidal melanomas

What are the cutaneous associations of NF1?

Café au lait spots

The majority of individuals with neurofibromatosis exhibit 6 or more café au lait spots, each measuring 1.5 cm or more in diameter. In young children, the presence of 5 or more café au lait macules exceeding 0.5 cm in diameter suggests neurofibromatosis, warranting additional diagnostic investigation. While less than 1% of healthy children typically have 3 or more such spots, it's common for 1 or 2 café au lait macules to be present in individuals without any underlying health issues.

Axillary freckles

The Crowe sign, characterized by freckling in the axillary and perineal regions, serves as a valuable diagnostic indicator in neurofibromatosis, as depicted in the accompanying image. Axillary and inguinal freckling commonly emerges during puberty. While the appearance of freckles often trails the development of café au lait macules, it precedes the onset of neurofibromas. Approximately 80% of individuals with type 1 neurofibromatosis exhibit freckling in the axillary area. In some cases, regions with freckles and areas of excessive hair growth (hypertrichosis) may coincide with plexiform neurofibromas.

Neurofibromas

Neurofibromas, the most prevalent benign tumors associated with type 1 neurofibromatosis, consist of Schwann cells, fibroblasts, mast cells, and vascular components. They can emerge at any location along a nerve. Neurofibromas come in three subtypes: cutaneous, subcutaneous, and plexiform. Both cutaneous and subcutaneous lesions are well-defined, lacking specificity for type 1 neurofibromatosis. These nodules may exhibit various colors such as brown, pink, or skin-colored. They can have varying textures, being either soft or firm, and often demonstrate the characteristic buttonhole invagination when pressed with a finger.

References:

1.        (Savar A, Cestari DM. Neurofibromatosis type I: genetics and clinical manifestations. Semin Ophthalmol. 2008 Jan-Feb. 23(1):45-51)

2.        (Listernick R, Charrow J, Greenwald MJ, Esterly NB. Optic gliomas in children with neurofibromatosis type 1. J Pediatr. 1989 May. 114(5):788-92)

3.        Glaser JS, Hoyt WF, Corbett J. Visual morbidity with chiasmal glioma. Long-term studies of visual fields in untreated and irradiated cases. Arch Ophthalmol. 1971 Jan. 85(1):3-12.