1
ATYPICAL PRESENTATION OF NEUROFIBROMATOSIS
TYPE 1 IN A 10-MONTH-OLD GIRL: A CASE REPORT
Marui Asad1*, Fatima Al-Zahra2, Gaurishankar Pandit2, Rafi Raza Ahmad2,
Muhammad Awais2, Prof. Dr. Nadeem Akhtar2
1
Department of General Surgery, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
2
Department of Paediatric Surgery, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
*Correspondence:
Dr. Fatima Al-Zahra
E-mail:
Abstract:
Neurofibromatosis type 1 (NF1) is a neurocutaneous genetic disorder of heterogenic symptoms
majorly affecting the nervous system, eye, skin, and bone. This study is about a 10-month-old
female child who developed a lump/mass on the left side of neck 3 months ago that rapidly
increased in size along with ulceration and bleeding for one month with no associated symptoms.
MRI of neck showed large heterogeneous and enhancing lesion with thick lobulated folds noted
posteriorly, located in the left posterior cervical space deep to the sternocleidomastoid muscle.
On histopathological examination nerve sheath tumor favoring neurofibromatosis type 1 was
confirmed. Child underwent debulking/excision of the mass.
Keywords: NF1; Peripheral Nerve Sheath Tumor; Neurofibroma; Neurofibromatosis 1;
Neurofibromin; Optic Pathway Glioma; Lisch Nodules; Acoustic Neuroma.
Introduction: NF1: six or more café au lait macules (0.5 cm
in children or >1.5 cm in adults), two or more
NF1 is the most common hereditary multi- cutaneous/subcutaneous neurofibromas or
tumor syndrome with an incidence at birth of one plexiform neurofibroma, axillary or
approximately 1:3000 and it is caused by groin freckling, optic pathway glioma, two or
mutations in the NF1 gene. NF1 is localized more Lisch nodules (iris hamartomas seen on
on chromosome band 17q11.2 and it acts as a slit lamp examination) and bony dysplasia
tumor suppressor gene. The diagnosis of NF1 (sphenoid wing dysplasia, bowing of long
is based upon the presence of characteristic bone ± pseudoarthrosis), first degree relative
clinical features. According to NIH criteria, with NF1. Genetic testing is not required, but
at least two of the following clinical features can it be a useful tool in confirming the
must be present to make the diagnosis of diagnoses of children who do not meet
2
diagnostic criteria or only exhibit café-au-lait The mass was causing distortion of the left
macules and axillary freckling.1 It has ear lobule. It was firm in consistency, fixed
multimodal therapeutic approach.2 to the overlying skin and the underlying
structures (immobile), with no active
bleeding from the ulcerated surface. The
Case Report: inferior limit was palpable hence, there was
The patient, a 10-month-old child, presented no retrosternal extension. There were no
through the OPD with complaints of mass on café-au-lait spots on the body. Slit Lamp
the left side of the neck for 3 months. This examination was conclusive of Lisch nodules.
left-sided neck mass rapidly increased in size MRI of neck showed a large heterogeneous
with associated ulceration and bleeding from and enhancing lesion with thick lobulated
the surface of the mass for one month. There folds noted posteriorly, located in the left
was no history of fever, weight loss, pain, posterior cervical space deep to the
dysphagia, dyspnea, syncopal episodes sternocleidomastoid muscle splaying the
associated with the mass. On general carotid vessel, however, the fat planes
examination an ulcerated mass (12 x 14 cm) remained intact (Figures 3 and 4).
was evident on the left side of neck (Figures
1 and 2) that did not move on deglutition, and
there were no matted lymph nodes along the
length of the sternocleidomastoid.
Figures 3 & 4: Figures 3 and 4: MRI of the Neck
with splaying of the carotid sheath, however,
deep to the sternocleidomastoid.
Differential diagnoses were cervical teratoma
and lymphomatous node. Histopathological
Figures 1 & 2: Ulcerated and fungating left- examination following the Tru-cut biopsy
sided neck mass
3
showed nerve sheath tumor favoring
neurofibromatosis type-I (Figure 6). A tumor
composed of proliferating nerve fibers
comprising Schwann cells, fibroblasts and
perineural cells with elongated nuclei having
wavy, serpentine configuration in extra
myxoid background of thin collagenous
stroma. No verocay bodies or palisading of
nuclei was observed. No evidence of
granuloma or malignancy was obtained.
Ultrasound of abdomen and pelvis showed
multiple sub-centimetric mesenteric lymph
Figure 6: Spindle Cells with Hyperchromatic
nodes. Based on these findings, diagnosis of
Nuclei with “Shredded Carrot Collagen”.
nerve sheath tumor (Neurofibromatosis type
1) was established. The patient underwent
surgical debulking/excision of mass (benign
tumor). Discussion:
Per-operative findings were those of a large, The Neurofibromatoses are a group of
highly vascular, and firm fungating mass on heterogeneous disorders that include
the left side of the neck (Figure 5) having the Neurofibromatosis type 1 (NF1),
following features: Neurofibromatosis type 2 (NF2), and
Schwannomatosis. NF1, formerly known as
1. Presence of the mass in the anterior von Recklinghausen disease3, is the most
triangle of the neck extending to the common of these three conditions and
posterior triangle and attached to the represents one of the most frequently
mastoid process and the occipital diagnosed cancer predisposition disorders
bone. involving the nervous system. While NF1
2. The mass was external to the carotid primarily affects the central and peripheral
sheath and had a necrotic center. nervous system, multisystem involvement is
the rule, with dermatologic, cardiovascular,
gastrointestinal, and orthopedic affectation
often reported. Importantly, NF1 is a disorder
of heterogeneity, such that affected
individuals can be variably affected, even
within the same family.4 Individuals with
NF1 have a predisposition to benign and
malignant tumor formation and the hallmark
lesion is the neurofibroma, a benign
peripheral nerve sheath tumor. The gene for
NF1 was cloned on chromosome 17q11.2 and
neurofibromin, the NF1 protein, controls cell
Figure 5: Post-resection tumor
growth and proliferation by regulating the
proto-oncogene Ras and cyclic adenosine
4
monophosphate (AMP).5 Neurofibromin is 1 are becoming available. Although no single
necessary for embryonic development and treatment exists, current clinical management
involved mainly in the differentiation of strategies include early detection of disease
neural crest derived cells, mesenchymal cells, phenotypes (risk assessment) and
neural cells, melanocytes and bone cells. biologically targeted therapies. Similarly,
Over 1485 different mutations have been new medical and behavioral interventions are
identified in the NF1 gene so far, most of emerging to improve the quality of life of
which led to a synthesis of truncated, non- patients.7
functional protein. It is estimated that the
point mutations are responsible for
approximately 90% of cases of NF1. The Conclusion:
remaining 5-7% of NF1 cases are associated
with the presence of a single exon or whole The prevalence of neurofibromatosis type 1
NF1 gene deletion (17q11.2 microdeletion (NF1) is about 1:3000. There are no known
syndrome).6 Nearly all individuals with ethnic groups in which NF1 does not occur or
neurofibromatosis type 1 develop pigmentary is unusually common. The prevalence is
lesions (café-au-lait macules, skinfold higher in children than in adults, a difference
freckling and Lisch nodules) and dermal that results at least in part from the early
neurofibromas. Some individuals develop death of some NF1 patients.8 The classic
skeletal abnormalities (scoliosis, tibial manifestations of NF1 include café-au-lait
pseudarthrosis and orbital dysplasia), brain macules, skinfold freckling, neurofibromas,
tumors (optic pathway gliomas and brain tumors, iris hamartomas, and
glioblastoma), peripheral nerve tumors characteristic bony lesions. In addition,
(spinal neurofibromas, plexiform patients with NF1 are at increased risk for
neurofibromas and malignant peripheral learning and intellectual
nerve sheath tumors), learning disabilities, disabilities, aqueduct stenosis,
attention deficits, and social and behavioral pheochromocytoma, vascular dysplasia,
problems, which can negatively affect quality scoliosis, and cancer.9 High-intensity signals
of life. In 50% of NF1 patients, the clinical on brain magnetic resonance imaging are a
symptoms become apparent below 1st year frequent finding without known clinical
and in 97%, before the age of 8 years. 6 All significance. Most brain tumors are benign
these manifestations (except the malignant and asymptomatic, but malignant brain
peripheral nerve sheath tumors) are stable or tumors occur. The major cause of death is
slowly progressive. Treatment is malignancy, including brain tumors and
symptomatic in all cases except for the malignant peripheral nerve sheath tumors.
patient with malignant peripheral nerve Management includes genetic counseling,
sheath tumors, who need extensive surgery regular eye examinations, and careful
and radiotherapy. With the identification physical exams.10
of NF1 and the generation of accurate
preclinical mouse strains that model some of
these clinical features, therapies that target References:
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