Neurofibromatosis Type I : Spinal Neoplasia Without

Symptoms
Sheffali Gulati, Surbhi Leekha, Arun K. Gupta 1 and Veena Kalra

Departments of Pediatrics and 1Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India.

Abstract. Neurofibromatosisl (NF-1) or von Recklinghausen disease is the most common of the neur0cutaneous syndromes.
It is characterized by presence of hamartomas in multiple organs. Inheritance is autosomal dominant but spontaneous mutations
are seen in half the cases. The authors are reporting a classical case of this syndrome with spinal neoplasia which was
interestingly asymptomatic. Authorities seem to agree that because the risk of developing intradural disease is significant in
patients with NF-1, a routine MRI of the entire spine should be obtained. [Indian J Pediatr 2004; 71 (9) : 853-855]
E- mail: sheffalig @yahoo.corn

Key words : Neurofibromatosis 1; von Recklinghausen disease; Hamartomas

Neurofibromatosisl (NF-1) or yon Recklinghausen
disease is the most common of the neurocutaneous
syndromes - a group of disorders characterized by
presence of hamartomas in multiple organs. Caused by a
mutation on the long arm of chromosome 17, NF-1 affects
about I in 3000 people worldwide. Although inheritance
is autosomal dominant, about half the cases arise through
spontaneous mutations. 1The authors are reporting a
classical case of this syndrome with spinal neoplasia
which was interestingly asymptomatic.
CASE REPORT
A six-year-old boy born out of a non-consanguineous
marriage presented with nodular thickening and hairy
hyper pigmentation of the right arm since birth. There
was no history of seizures, visual disturbance, hearing or
speech impairment. The mother and maternal grand-
father both had similar nodular swellings.
Examination of the child revealed a massive light-
brown pigmented nevus involving almost the entire chest,
upper two-thirds of the back, and extending from the
shoulder to the wrist of the right arm. The right arm also
had multiple subcutaneous nodules, the growth of which
had resulted in hemihypertrophy of the arm-elephantiasis
neuromatosa (Fig. 1A, B). There were numerous caf6-au-
lait spots on the abdomen, lower back and right arm.
There was no facial dysmorphism or obvious skeletal
deformity. Development was normal for age, and
neurological and ophthalmic examinations did not reveal
any abnormality.
An ultrasound abdomen to look for visceral lesions
Correspondenceand Reprintrequests : Dr. SheffaliGulati,Assistant
Professor, Departmentof Pediatrics,All India Institute of Medical
Sciences,New Delhi- 110029,India. Fax : 91-011-26588663
was normal. The cranial magnetic resonance imaging
(MRI) was normal with no mass lesion in the orbit or
intra-cranial location. MRI spine revealed (Fig. 2A, 2B):
multiple lobulated soft tissue masses in the prevertebral
sof~ttissues of the entire cervical region extending into the
dorsal region as bilateral paravertebral masses (right >
left) causing displacement of trachea and vascular
structures to the left. Intraspinal extension was seen on the
right side through C7-D1/2 neural foramina. The resulting
extradural mass appeared to surround and displace the
cord from the right postero-lateral aspect. A similar
lobulated soft tissue mass was seen at the level of the
carina. Masses of similar intensity were also seen in the
soft tissues of the right axilla. The masses had slightly
greater signal intensity than skeletal muscle on T1-
weighted sequences and showed heterogeneously
increased intensity on T2-weighted sequences. On post
contrast imaging- the smaller lesions enhanced uniformly
while the larger ones showed heterogenous enhancement
that could be due to necrosis. The findings were
suggestive of plexiform neurofibromas in the neck,
posterior mediastinum, right axilla and right lateral chest
wall. A diagnosis of neurofibromatosis-1 was made. In
this patient the inheritance was autosomal dominant. The
MRI spine of mother and maternal grandfather, who were
asymptomatic for a spinal lesion, was not possible due to
financial constraints.
DISCUSSION
Neurofibromatosisl (NF-1) is the most common
neurocutaneous syndrome. There is a wide spectrum of
clinical and imaging findings and the diagnosis is based
on the criteria established by the NIH Consensus
Development Conference in 1987.2Common dermato-

Indian Journal of Pediatrics, Volume 71--September, 2004 853

 Gulati Sheffali et al

Fig. 1A, B. Photograph of the boy showing a massive light-brown pigmented nevus involving almost the entire chest (A), upper two-thirds
of the back (B), and extending from the shoulder to the wrist of the right arm and elephantiasis neuromatosa of right arm.

Fig. 2A, B. MRI cervicodorsal spine, post-GAD T1W coronal (A) and sagittal (B) views: Note numerous enhancing soft tissue masses,
predominantly on the right side in the lower cervical-upper dorsal pre and paraspinal location, and in the right axilla. Masses are
extending intraspinally, displacing and engulfing the cord from the right posterolateral aspect.

logical manifestations include p i g m e n t e d macules (caf6-
au-lait spots, freckles) and b e n i g n nerve sheath t u m o r s
( n e u r o f i b r o m a s ) . E n l a r g e m e n t of c u t a n e o u s a n d
subcutaneous tumors over m a n y years can cause massive
h e m i h y p e r t r o p h y of t h e e x t r e m i t i e s or t h e f a c e -
e l e p h a n t i a s i s n e u r o m a t o s a . A n i n c r e a s e d n u m b e r of
cutaneous nevi occur, either in association with caf6-au-
lait spots or as isolated findings. Giant pigmented nevi, or
bathing trunk nevi are also occasionally seen. 3
N e u r o f i b r o m a s and h a m a r t o m a s can involve various
parts of the eye but the c o m m o n e s t are Lisch nodules that
are hamartomas of iris pigment epithelium. Diplopia and

854 Indian Journal of Pediatrics, Volume 71--September, 2004

 Neurofibromatosis Type I : Spinal Neoplasia Without Symptoms
loss of vision frequently do not appear till late childhood
or early adult life. Central nervous system lesions include
o p t i c / n o n - o p t i c gliomas, neurofibromas, architectural
abnormalities and aqueductal stenosis. MRI reveals "
u n i d e n t i f i e d b r i g h t objects (UBOs)" or NF-1 related
d y s p l a s i a s as h i g h i n t e n s i t y signals o n T 2 - w e i g h t e d
images. 4
Spinal neoplasia m a y involve the nerve sheath, glia or
the meninges. Studies have shown that most nerve sheath
tumors in neurofibromatosis-1 are neurofibromas. 5 MRI
of neurofibromas shows slightly greater signal intensity
than skeletal muscle on TI-weighted sequences and high
intensity periphery with variable intensity center on T2-
weighted sequences. 5,6 Paraspinal plexiform neurofibro-
mas m a y be unilateral or bilateral and can v a r y in both
size and location along the spine. As they grow, they can
extend through the neural foramina as dumbbell shaped
t u m o r s and cause widening of the neural foramina b y
pressure erosion. Intraspinal extension can lead to spinal
cord displacement or compression (especially if bilateral).
4~,6 The lifetime risk of a patient with NF-1 to develop a
malignant neoptasia is 5%.
In familial spinal neurofibromatosis there is presence
of m u l t i p l e spinal cord t u m o r s , occurring in several
m e m b e r s of the s a m e f a m i l y a n d s e g r e g a t i n g in an
autosomal dominant fashion. It has been described as an
entity that is distinct from NF-1 and in which the main
clinical characteristic is symptomatic spinal cord tumors,
which are present in only 5% of NF-1 cases. 7 Recently it
has been suggested that spinal neurofibromas associated
with NF-1 occur more often than initially thought, since
they were f o u n d , b y spinal MRI, in 36% of NF-1 patients
but were associated with clinical symptoms in only 7% of
the patients, s A l t h o u g h a s y m p t o m a t i c spinal neurofi-
b r o m a s are p r o b a b l y m o r e c o m m o n t h a n p r e v i o u s l y
thought, the occurrence of multiple spinal neurofibromas
in all the a f f e c t e d m e m b e r s of the s a m e f a m i l y is
exceptional. 7
Indian Journal of Pediatrics, Volume 71--September, 2004
Interestingly our patient was still asymptomatic for the
spinal n e o p l a s i a d e s p i t e the fact t h a t the m a s s w a s
d i s p l a c i n g the cord. A u t h o r i t i e s s e e m to a g r e e that
b e c a u s e the risk of d e v e l o p i n g i n t r a d u r a l disease is
significant in patients with NF-1, a routine MRI of the
entire spine should be obtained. There are no guidelines
as to h o w frequently to follow up with an MRI spine in
such cases. It is advisable to follow them up clinically and
in case of occurrence of any new s y m p t o m s to repeat an
MRI spine. To conclude n e u r o f i b r o m a t o s i s l can h a v e
hemihypertrophy of the arm- elephantiasis neuromatosa
a n d a s s o c i a t e d d u m b b e l l t u m o r can be c o m p l e t e l y
asymptomatic.
REFERENCES
1. Jorde LB, Carey JC, White RL. Medical Genetics. St. Louis:
Mosby, 1995; 71-72.
2. Neurofibromatosis Conference Statement. National Institutes
of Health Consensus Development Conference. Arch Neurol,
1988; 45 : 575-578.
3. Shields JA, Shields CL. Systemic Hamartomatoses
(Phakomatoses). In Mannis MJ, Maesni MS, Huntley AC, eds.
Eye and Skin Disease. Pl~iladelphia: Lipincott-RavenPublishers,
1996; 367-380.
4. Mulvihill JJ, Parry DM, Sherman JL, Pikus A, Kaiser-Kupfer
MI, Eldridge R. NIH Conference. Neurofibromatosis 1
(Recklinghausen disease) and neurofibromatosis 2 (bilateral
acoustic neurofibromatosis): an update. Ann Intern Med 1990;
113 : 39-52.
5. Halliday AL, Sobel RA, Martuza RL. Benign spinal nerve
sheath tumors: their occurrence sporadically and in
neurofibromatosis types I and 2. JNeurosurg 1991; 74 : 248-253.
6. Burk DL Jr, Brunberg JA, Kanal E, Latchaw RE, Wolf GL.
Spinal and Paraspinal Neurofibromatosis: Surface Coil MR
Imaging at 1.5 T1.Radiology 1987;162 : 797-801.
7. Ars E, Kruyer H, Gaona A, Casquero P, Rosen J, Volpini Vet
al. A clinical variant of Neurofibromatosis Type 1: Familial
spinal neurofibromatosis with a frame shift mutation in the
NF-1 gene. Am J Hum Genet 1998; 62 : 834-841.
8. Poyhonen M, Leisti EL, Kytola S, Leisti J. Hereditary spinal
neurofibromatosis: a rare form of NF-I? J Med Genet 1997; 34 :
184-187.
855