CASE REPORT

Neurofibromatosis 1 vasculopathy manifesting as a peripheralaneurysm in an adolescent

Shannon G. Farmakis & Min Han & Frances White &

Geetika Khanna

Received: 13 December 2013 /Revised: 26 February 2014 /Accepted: 30 March 2014# Springer-Verlag Berlin Heidelberg 2014

Abstract Arterial vasculopathy is a well-recognized but un-common manifestation of neurofibromatosis type 1 (NF-1). Itcan manifest as stenoses, aneurysms or arteriovenousmalformations. NF-1 vasculopathy typically involves the aorta,visceral arteries or carotid-vertebral circulation. Aortic and vis-ceral vasculopathy typically presents as stenotic lesions, whileaneurysms have been reported primarily in the subclavian/vertebral arteries. Aneurysms of the peripheral/extremity arter-ies are an extremely rare complication of NF-1 that may presentas a mass or spontaneous rupture. We present the case of ateenage boy with an arm mass secondary to an aneurysm. Wehope this case will increase recognition of the variable clinicalmanifestations of NF-1 vasculopathy among radiologists.

Keywords Vasculopathy . Aneurysm . Neurofibromatosistype 1 .Magnetic resonance imaging . Adolescent

Introduction

Neurofibromatosis-1 (NF-1) is one of the most common au-tosomal dominant disorders. NF-1 lesions that are commonlyencountered by radiologists include neurofibromas, opticpathway gliomas and skeletal manifestations, such as scolio-sis, long bone dysplasia and dural ectasia. A neurofibroma isthe primary clinical consideration in the presence of a

superficial mass in a patient with NF-1. Rapid growth of aplexiform neurofibroma, or new pain or neurological dysfunc-tion at the site of an existing neurofibroma raises concern for amalignant peripheral nerve sheath tumor. NF-1 vasculopathyis a less common manifestation, the characteristic imagingfindings of which include renal fibromuscular dysplasia, ab-dominal aortic coarctation and moyamoya syndrome. Aneu-rysms of the peripheral vasculature of the extremities are anextremely uncommon clinical manifestation of NF-1, withmost cases reported in the adult literature. We report the caseof a teenage boy with a thrombosed aneurysm of a superficialarm vessel that presented as an elbow mass.

Case report

A 15-year-old boy with known NF-1 presented with a 1-yearhistory of a painless mass on his right elbow. The mass hadrapidly increased in size over the last 3–4 months. On physicalexam, a large mass was seen over the radial aspect of theelbow (Fig. 1). The mass was somewhat compressible, fixedand nonpulsatile. It was felt to be distinct from the course ofthe major neurovascular bundles and there was no associatedbruit. Given the history of rapid growth, the primary clinicalconsideration was a malignant peripheral nerve sheath tumor,and the boy was referred for an MRI which revealed a well-circumscribed mass (5×3×3.5 cm) within the subcutaneoussoft tissues causing some mass effect on the underlyingbrachioradialis muscle. The mass was hyperintense on T1-weighted imaging and heterogeneous on T2-weighted imag-ing with heterogeneous internal signal intensity (Fig. 2). It hada peripheral rim of hypointensity on both T1- and T2-weighted images. No enhancement was seen in the massfollowing contrast administration (Fig. 2). This was thoughtto represent a thrombosed aneurysm onMR imaging; DopplerUS was recommended by the interpreting radiologist.

S. G. Farmakis (*) :G. KhannaMallinckrodt Institute of Radiology,Washington University School of Medicine,510 South Kingshighway Blvd., St. Louis, MO 63110, USAe-mail: farmakiss@mir.wustl.edu

M. Han : F. WhiteDepartment of Pathology & Immunology,Washington University School of Medicine, 509 S. Euclid Ave.,St. Louis, MO 63110, USA

Pediatr RadiolDOI 10.1007/s00247-014-2991-3

However, due to the clinical concern for malignancy, thetreating physician decided against further imaging andproceeded with surgical resection.

Intraoperatively, a small superficial vessel was identifiedfeeding into and exiting themass (Fig. 3). This was ligated andthe aneurysmal sac was excised. Histology showed a dilatedarterial wall with extensive replacement of smooth muscle byfibrous tissue, disruption and loss of elastic fibers, and at-tached organizing thrombus consistent with a thrombosedaneurysm (Fig. 4). The boy did well after surgery, but pre-sented 1.5 years later with a recurrent mass in the forearm thatwas surgically resected. The second mass arose from a super-ficial small vessel just distal to the site of the original mass.Histological findings were similar and confirmed a dilatedblood vessel with fibrosis, loss of smooth muscle and earlyorganizing thrombus.

Discussion

NF-1 is an autosomal dominant disease with extremely vari-able phenotypic expression. It results from a mutation of theNF1 gene located on the long arm of chromosome 17. Com-mon clinical manifestations include café-au-lait spots,intertriginous freckling, dermal and plexiform neurofibromas,skeletal abnormalities and learning disabilities. It is character-ized by the presence of 2 or more of the following manifesta-tions: ≥6 café-au-lait spots (≥1.5 cm after puberty and≤0.5 cmbefore puberty), ≥2 neurofibromas of any type or ≥1 plexi-form neurofibroma, intertriginous freckling (axilla, neck,groin, inframammary), optic pathway glioma, ≥2 Lisch nod-ules (iris hamartomas), skeletal dysplasia (tibial or sphenoidwing dysplasia), or a 1st-degree relative with NF-1 [1].

Vasculopathy is a well-recognized but relatively rare fea-ture of NF-1 with a reported prevalence of 0.4% to 6.4% [2].

Fig. 1 Large oval mass over the radial aspect of the elbow. Notice thecafé-au-lait spots over the medial elbow (arrow). “Yes” identifies thecorrect surgical site as marked by the surgeon (Photograph courtesy ofBrad Warner, M.D.)

Fig. 2 MRI of the right elbow. Sagittal T1- (a) and fat-saturated (b) T2-weighted images show a well-circumscribed mass within the subcutane-ous tissues overlying the brachioradialis muscle. The mass is hyperin-tense to skeletal muscle on all sequences with heterogeneous internal

signal (arrowhead). It lies along the course of a superficial small vessel(arrows). c Post-contrast sagittal T1 with fat saturation shows no signif-icant change in signal intensity of the mass to suggest enhancement

Fig. 3 Intraoperative photograph shows the in situ large aneurysmal sacwith a single exiting vessel (suture looped around vessel). The feedingvessel is not visible in this photograph

Pediatr Radiol

NF-1 vasculopathy is often asymptomatic, though it has po-tential for significant morbidity and mortality. It is the secondmost common cause of death, after soft tissue malignancies, inpatients with NF-1 [2]. The most common clinical manifesta-tion of NF-1 vasculopathy in children is hypertension. NF-1vasculopathy can affect vessels of any size and may producestenosis, occlusion, aneurysm, pseudoaneurysm, rupture orfistula formation. It typically involves the systemic arterialcirculation, though involvement of veins or pulmonary vesselshas also been reported. The most common site of vasculopa-thy is the renal artery, accounting for approximately 41% ofcases of NF-1 vasculopathy [2]. Abdominal aortic coarctationmay be seen in association with or without renal artery steno-sis. The secondmost common site of NF-1 vasculopathy is thecerebrovascular circuit. This can manifest as moyamoya syn-drome secondary to stenosis or occlusion of the internalcarotid, middle cerebral or anterior cerebral artery. The thirdmost common reported site of disease is the subclavian/vertebral vasculature where aneurysms and fistulae have beenreported that can result in catastrophic hemorrhage [3].

Vasculopathy of extremity vessels has been reported but isrelatively rare. There are case reports of aneurysms in thefemoral, popliteal, anterior tibial, radial and ulnar arteriesprimarily in the adult population [1]. These include a 33-year-old woman with a ruptured popliteal artery aneurysm, a35-year-old woman with 2 brachial artery aneurysms whounderwent surgical resection but died several days later, a48-year-old woman with multiple radial artery aneurysmspresenting with rupture, and a 61-year-old woman with aruptured ulnar artery aneurysm [4–7]. To the best of ourknowledge, the only reported pediatric patient with aneurys-mal disease in the extremities in the English literature is an 11-year-old girl with aneurysms of the common femoral andpopliteal arteries [8]. Our case is unique because the largeaneurysm formed in a small superficial peripheral artery in ateenager. The occurrence of a second aneurysm in our patientconforms to the fact that NF-1 vasculopathy often involvesmultiple vessels, though the disease can be patchy indistribution.

Several different etiologies have been proposed for NF-1vasculopathy including neural/Schwann cell hyperplasia andfibromuscular hyperplasia in the vessel wall. NF-1 vasculop-athy is classified into 4 subtypes based on the vessel size,histology and morphology [1]. The pure intimal type demon-strates circumferential intimal proliferation resulting in lumi-nal stenosis. The aneurysmal intimal type demonstrates hya-line intimal thickening with disruption of the elastic fibers andmembrane. Aneurysms form since the media is lost, but theadventitia is normal. This is the type that was seen in ourpatient. The nodular periarterial type demonstrates formationof nodules between the media and adventitia. The nodulescause luminal narrowing by protruding into the lumen. Thefinal type is epitheliod, which demonstrates diffuse prolifera-tion of the fusiform cells ultimately resulting in luminalstenosis.

In summary, NF-1 vasculopathy can result in a peripheralarterial aneurysm that can present as a palpable mass. Thoughthe primary considerations for a palpable mass and a growingmass in the setting of NF-1 are neurofibroma and malignantperipheral nerve sheath tumors, respectively, radiologistsshould be aware of the varied clinical manifestations of NF-1 vasculopathy.

Conflicts of interest None.

References

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Fig. 4 Hematoxylin and eosin stained section of vessel wall (a, 400×)shows organized thrombus (arrow) and replacement of subintima andsmooth muscle by hyalinized fibrous tissue (arrowheads). Elastic stained

sections (b, 200×; c, 400×) show disruption of elastic fibers (arrows) andresidual atrophic smooth muscle (asterisks) surrounded by hyalinizedfibrous tissue (arrowheads)

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