Teaching Case

34 years male presenting with swelling over left upper eyelid and forehead with left eye ptosis from 1 year. On examination, café u lait spots seen on back and few small swellings on both the forearms appeared as dermal neurofibromas. The patient gave history of similar cutaneous findings in sibling.

On non-contrast CT (Fig. 1), an ill-defined soft tissue lesion is seen in left superior palpebral region. Contrast-enhanced T1 fat-saturated axial and coronal MR images (Fig. 3a, 3b) show enhancing soft tissue lesion in left superior palpebral region and its intraconal extension. These findings are suggestive of plexiform neurofibroma. Coronal bone window CT (Fig. 2a) reveals hypoplastic left greater sphenoid wing. 3D VRT reconstructed image (Fig. 2b) highlights the same and shows persistent metopic suture. Features suggestive of dysplastic left greater wing of sphenoid (Bare orbit sign). CISS axial MR sequence (Fig. 4a) depicts tortuous left intraorbital optic nerve with prominent CSF sleeve. T2 oblique sequence (Fig. 4b) confirms the same.  These suggest dural ectasia of left optic nerve CSF sleeve leading to its tortuosity. T2 FLAIR axial and T1 fat-saturated MR sequences (Fig. 5a, 5b) show ill-defined symmetric hyperintense areas in bilateral lentiform nuclei and adjacent white matter, features in favour of Focal Areas of Signal Intensity (FASI).

Background

Neurofibromatosis type 1 (NF 1) is also known as Von Recklinghausen disease. It is a multisystem neurocutaneous autosomal dominant disorder. The most common phakomatosis and a RASopathy. It has breast, CNS, cutaneous, musculoskeletal, pulmonary and orbital manifestations. NF1 gene is located on chromosome 17q11.2, and the gene product neurofibromin is a tumour suppressor of Ras/MAPK pathway. Hence, its inactivation results in tumour development [1].

Clinical Perspective

Clinically, it is diagnosed with two or more of the following findings: [1]

1. >6 cafe au lait spots evident during one year (prepubertal >0.5 cm, postpubertal >1.5 cm in size)
2. two or more neurofibromas or one plexiform neurofibroma
3. optic nerve glioma
4. distinctive osseous lesion (such as sphenoid wing dysplasia or thinning of long bone cortex with or without pseudoarthrosis)
5. two or more iris hamartomas (Lisch nodules)  
6. axillary or inguinal freckling
7. a primary relative with NF1 with above criteria

The role of imaging is to demonstrate the location and relations of a plexiform neurofibroma to aid in its surgical excision. The hidden bony findings are revealed on imaging. Major role comes in diagnosing and ruling out associated tumours, i.e. Gliomas [2], pheochromocytoma, Wilm’s tumour, rhabdomyoscarcoma, renal angiomyolipoma, carcinoid tumour and leiomyomas.

Imaging Perspective

FASI (focal areas of signal intensity) are seen in deep white matter and basal ganglia or corpus callosum, they are T2/FLAIR hyperintense with no enhancement [3]. An enlarged optic foramen should give a clue to look for optic nerve glioma. Sphenoid wing dysplasia [4, 5] is usually progressive and forms the classical Bare orbit sign-on coronal CT and AP skull radiograph.  A radiographic skeletal survey and MR spine screening should be carried out to look for ribbon rib deformity, rib notching, tibial pseudoarthrosis, non-ossifying fibromas and enlarged neural foramina indicating presence of neurofibromas. An important differentiating imaging feature of neurofibroma from schwannoma is that the neurofibroma encases the nerve root and the later displaces it. The final diagnosis is based on plethora of imaging and clinical findings which are reinforced with a positive family history.

Outcome

Based on the tumours and anomalies present a supportive and/or surgical approach is planned in disease management. Imaging mainly aids the surgeons for excising the tumours and neurofibromas.

Take-Home Message

Think of a syndrome in case of multiple positive imaging findings. Advice further imaging to look into other systems, correlate with cutaneous findings and family history in diagnosing phakomatosis.

Written informed patient consent for publication has been obtained.