Rare presentation of Neurofibromatosis type1 with oral lesion

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Department of Oral Medicine and Radiology, G Pullareddy Dental College, Kurnool, Andhra Pradesh
Copyright ©2017
Case Report
J Res Adv Dent 2016;6:1:18-22.
Rare Presentation of Neurofibromatosis Type I with Oral Lesion
Sairam V1* Gareema Raju P2 Praveen B3 Geethamalika MV4
1Professor and Head, Department of Oral Medicine and Radiology, G Pullareddy Dental College, Kurnool, Andhra Pradesh, India.
2PG Student, Department of Oral Medicine and Radiology, G Pullareddy Dental College, Kurnool, Andhra Pradesh, India.
3Reader, Department of Oral Medicine and Radiology, G Pullareddy Dental College, Kurnool, Andhra Pradesh, India.
4PG Student, Department of Oral Medicine and Radiology, G Pullareddy Dental College, Kurnool, Andhra Pradesh, India.
ABSTRACT
Background: The term neurofibromatoses is applied to a group of autosomal dominant disorders characterized
by neuroectodermal tumors involving several parts of the body. Among the eight types recognized,
Neurofibromatosis Type-1 is common without racial differences. It is chiefly characterized by six or more cafe´-
au-lait macules, two or more neurofibromas, freckling in the axillary or inguinal region and Lisch nodules over
the iris. Oral neurofibromas are extremely variable and rare, posing a diagnostic challenge to oral healthcare
providers. We present a rare case of Neurofibromatosis type- 1 with oral nuerofibromas (two) in the hard palate,
presence of cafe au lait (coffee with milk) pigmentation, discrete multiple nodules over different regions of the
body, two Lisch’s nodules of Iris. Clinical presentation of this patient is in accordance with the diagnostic criteria
given by the National Institutes of Health Criteria for Neurofibromatosis Type 1.
Keywords: Cafe´-Au-Lait Macules, Lisch’s Nodules, Oral Neurofibroma, Neurofibromatosis Type-1.
INTRODUCTION
Neurofibromatosis was described in 1882,
by German pathologist Friedrich Daniel Von
Recklinghausen, when he found a series of patients
with a combination of cutaneous lesions and tumors
of the peripheral and central nervous system. [1]
Neurofibromatosis type-1 is a neuro-cutaneous
autosomal dominant disorder, affecting all 3
germinal layers, having the potential to involve any
organ system.[2] It is caused by a mutation in the
NF1 gene on chromosome 17q11.2, which encodes
for the protein neurofibromin. [ 3] Neurofibroma
appears either as a solitary lesion or in a syndrome
or as von Recklinghausen's disease of the skin. [4]
Benign oral peripheral nerve tumors including
schwannoma, neurofibroma, nerve sheath myxoma,
palisded encapsulated neuroma etc, not only share a
neural origin, but also exhibit notable
heterogenecity in terms of microscopic and
pathogenetic aspects. [5]
Oral neurofibromas usually appear as
painless pedunculated or sessile nodules, with slow
growth pattern. Pain or paraesthesia may occur on
nerve compression. [6] Lisch nodules are pigmented
hamartomas, which appear as translucent brown-
pigmented spots on the iris. Lisch nodules are the
characteristic features of the affected individuals. [7]
In this paper we report a case of Neurofibromatosis
type 1 that received its diagnosis, after observation
of its significant presentation along the oral cavity
and its confirmation by histopathology.
CASE REPORT
A 39-year-old female patient reported to
the Department of Oral Medicine and Radiology
with a chief complaint of swellings along the roof of
the mouth since past 12 months. About 20 years
back the patient noticed a swelling along her lip ,
for which she underwent a surgery. Later she
developed similar swellings all over her body. The
swelling was not associated with any pain or any

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Fig 1 & 2: Dermal Neurofibromas with café – au –
lait spots and pre axillary freckling.
Fig 3: Dermal Neurofibromas with café – au – lait
spots and pre axillary freckling.
Fig 4: Oral Neurofibromas along hard palate 11,21
and 11,12.
other relevant symptoms. Patient was not aware of
any such similar condition in her family. On
comprehensive general physical examination, the
patient was moderately built and nourished, calm,
coherent, able to respond well to the questions with
Fig 5: Gross Tissue Specimen.
Fig 6: H&E sections, showing parakeratinized
stratified squamous epithelium with underlying
connective showing loosely arranged collagen fibers
along with neural component with wavy nuclei.
no visual spatial difficulties. Vital signs were within
the normal range. Extra oral examination revealed
diffuse flat, oval to rounded brownish black
pigmentation with smooth borders measuring 0.5-
1.5cm. Non inflammatory purple nodular masses
(figure 1,2,3) of various sizes were present all over
her body including the chest, back, abdomen region.
On palpation these nodules were discrete, well
circumscribed, soft to firm in consistency,
nontender and compressible in nature. Diffuse
freckling in the axilla was appreciated.
Ophthalmological examination through slit lamp,
revealed the presence of pigmented hamartomatous
nodular aggregate along the iris resembling Lisch
nodules and early onset of cataract, with no signs of
glaucoma. Intraoral examination revealed two oval,
well defined sessile growth (figure 4) along the pre-
maxilla region of the hard palate, one growth in
relation to 11,21 and another in relation to 11,12.
The former and latter swellings measured about
0.25 × 0.25 and 0.5 × 0.5 cm in dimension. The

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former being regular and the latter irregular in
shape, with mucosa over the growth appearing pink
in color. On palpation the swellings were sessile
with variable consistency, non-tender.
The patient was subjected to intraoral
periapical radiographic investigation of the anterior
teeth region, which showed no visible bony
involvement. Based on clinical presentation of
cutaneous pigmentation, generalized multiple
nodules, Lisch nodules in the eyes and intraoral
well-circumscribed tumor growth, a provisional
diagnosis of Oral Neurofibroma with
Neurofibromatosis type I was made. With the
patients consent, an excisional biopsy procedure
was performed under L.A (figure 5).The biopsy
specimen, stained with H&E, showed
parakeratinized stratified squamous epithelium
with underlying connective tissue along with focal
area of sub-epithelial hyalinization. The connective
tissue showed loosely arranged collagen fibers
along with neural component with wavy nuclei
dispersed all over the connective tissue with
moderate vascularity along with inflammatory cells
(figure 6), confirming the diagnosis of
Neurofibromatosis Type I.
Hence the based on the clinical as well as
histopathological features, a final diagnosis of
Neurofibromatosis Type I was given. Further review
could not be done, as patient did not turn up for
consecutive follow ups.
DISCUSSION
In 1882 German pathologist, Friedrich
Daniel von Recklinghausen, accurately described
the diverse findings of Neurofibromatosis as a
single entity. Since then, the condition is often
referred to as von Recklinghausen’s disease.
According to the most widely accepted
classification, there are four recognized forms of
neurofibromatosis:
1. von Recklinghausen’s neurofibromatosis (or
neurofibromatosis type 1 [NF-1] or peripheral
neurofibromatosis)
2. Bilateral acoustic neurofibromatosis (or
neurofibromatosis type 2 [NF-2] or central
neurofibromatosis)
3. Segmental neurofibromatosis
4. Cutaneous neurofibromatosis
Further the presence of three additional
forms: type 3 (mixed), type 4 (variant) and type 5
(late-onset), were suggested by Riccardi.[8]
Neurofibromatoses type1 disorder, presents with
signs and symptoms, which may begin at birth and
evolve over a life time, they may include both tumor
and non-tumor manifestations.[9] The following are
the diagnostic criteria laid down by National
Institute of Health Consensus Development
Conference, [ 10] which states at least four cardinal
features should be present to confirm the diagnoses
as Neurofibromatosis Type-1:
1. 6 or more café-au-lait macules larger than
5mm before puberty or 15mm after puberty
2. Freckling in the axillary or inguinal region
3. 2 or more neurofibromas or 1 plexiform
neurofibroma
4. 2 or more Lisch nodules
5. Optic Glioma
6. A distinctive osseous lesion such as sphenoid
dysplasia
7. Affected first-degree relative
This patient was evaluated initially by experts
in Oral Medicine at Dental Hospital with referral
consultations made to (Dermatologist,
Ophthalmologist, Neurologist, Obstetrician) for
comprehensive general evaluation. Our case was
found to fulfill the diagnostic criteria.
Neurofibroma’s are rare slow-growing benign
tumors, that are derived from the neural sheaths of
peripheral nerves. They comprise of Schwann cells,
fibroblast-like cells and intermediate cells.[11] In this
patient, multiple dermal neurofibromas involved
several regions of the body (figure 1).
Café au lait spots are hyperpigmented
maculae, with either smooth or irregular borders.
These maculae vary in their color and size, and
appear anywhere on the skin, with rare occurrence
on the face. [12] In Neurofibromatosis type I, inguinal
and axillary freckles (Crowe's sign) are seen
occuring, diffusely over the trunk, extremities,
upper eyelids, and base of the neck.[13] This patient
presented with both, the pigmentation and the
preaxillary freckling (figure 1, 2).
Lisch nodules are well defined, avascular,
smooth, regular, dome-shaped melanocytic

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hamartomas, which are variable in color (yellow to
brown), size and number. They are located on the
surface of the iris, with their prevalence increasing
with age. [14]. In the head and neck region,
neurofibromas are frequently seen affecting scalp,
cheek, neck and oral cavity. In the oral cavity they
commonly occur on the tongue, lip, palate, gingiva,
major salivary glands, and maxillary bones. [14]
Prompt diagnosis of NF1 is essential, to prevent the
risk of development of complications such as
neurofibrosarcoma, pheochromocytoma, leukemia,
rhabdomyosarcoma, Wilms’ tumor, CNS tumors and
optic gliomas. [15]
CONFLICT OF INTEREST
No potential conflict of interest relevant to this
article was reported.
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