Keywords
plexiform neurofibroma - larynx - neck
Introduction
Laryngeal neurofibromas are extremely rare, accounting for only 0.03 to 0.1% of benign
tumors of the larynx.[1] We report a case of massive neck plexiform neurofibroma (PN) with intralaryngeal
extension in a 5-year-old boy with neurofibromatosis type 1 (NF-I). The PN was surgically
removed.
Review of Literature with Differential Diagnosis
Review of Literature with Differential Diagnosis
Histologic subtypes of neurofibromas include the cutaneous, subcutaneous, nodular,
and diffuse plexiform variants. PN is a nonmetastatic and locally invasive tumor that
can occur on the skin or along the peripheral nerves.[2]
Sarcomatous degeneration occurs in 5% of neurofibromas,[3] and the risk for malignant degeneration of PN into the peripheral nerve sheath tumor
is 20%. Furthermore, these spindle cell sarcomas tend to be poorly responsive to therapy,
are frequently metastatic at the time of diagnosis, and are associated with a 28%
5-year survival.
NF-I, also known as von Recklinghausen disease, is an autosomal dominant disease with
an incidence of 1 in 2,600 to 3,000 individuals.[4]
The differential diagnosis of neck mass in children includes cystic hygromas, branchial
cleft cysts, thyroglossal duct cysts, dermoid and teratoid cysts, and cystic vascular
abnormalities.[5] Neck PN should be considered in this differential diagnosis and in stridor in children.
Case Report
A 5-year-old boy presented with exertional inspiratory stridor and vague throat discomfort
on swallowing with no change of voice, hemoptysis, pain, cough, or snoring. The patient
had no known systemic or congenital abnormalities, and the developmental milestones
were within the normal ranges.
General examination showed a moderately built and nourished child with steady gait
and satisfactory vital signs. There were no signs of icterus, clubbing, or anemia.
No neurologic or ophthalmologic symptoms were evident. The abdomen had many brown
café au lait patches (>6) ranging from 3 to 4 mm in diameter with smooth borders ([Fig. 1]). No axillary or inguinal freckling, superficial neurofibromas, or Lisch nodules
were evident, as might be expected in NF-I. Audiological evaluation was normal for
both ears.
Fig. 1 Postoperative images of the patient. (A) Early while tracheostomy in place. (B) After
decannulation. (C) Well-healed neck scar at 2 years postoperatively, with no recurrent
neck masses and one café au lait patch (blue arrow). (D) Abdomen showing many brown
café au lait patches (>6).
Neck examination revealed large, diffuse, and soft swelling in the right neck with
ill-defined edges with no redness, hotness, tenderness, superficial vessels, pigmentation,
or ulceration. There were no palpable cervical lymph nodes.
Endoscopy of the larynx revealed a large submucosal pinkish mass covered by apparently
normal mucosa located in the right aryepiglottic fold, bulging into the supraglottic
area and obstructing the view of the ipsilateral true vocal cord. The right arytenoid
appeared to be pushed anteriorly ([Fig. 2]). His hypopharynx, left supraglottic area, and valleculae were normal.
Fig. 2 Endoscopic evaluation of larynx. (A) Preoperative endoscopy shows large supraglottic
mass located in the right aryepiglottic fold and covered by apparently normal mucosa,
obstructing the view of the vocal cord. The right arytenoid appeared to be pushed
anteriorly (yellow arrow). (B and C) Postoperative endoscopy showed no recurrence.
Routine laboratory tests, including complete blood count, erythrocyte sedimentation
rate, and bleeding profile were normal. There was no clinical evidence (by history,
examination, and laboratory tests) of inflammatory and autoimmune disease.
Computed tomography revealed a large, noninfiltrative heterogeneous neck mass. Magnetic
resonance examination of the neck revealed a large right mass extending from the lower
neck to the level of the hyoid bone, associated with supraglottic extension involving
the right aryepiglottic fold. It encroached on the retrotracheal and prevertebral
areas. It was isointense with muscle on T1-weighted imaging, hyperintense on T2-weighted
imaging, and enhanced after gadolinium contrast injection ([Fig. 3]).
Fig. 3 Preoperative imaging. (A) Axial MRI shows large diffuse noninfiltrative neck mass.
(B) Axial MRI shows the mass encroaching on laryngeal inlet. (C) Axial MRI shows enhancement
of the mass. (D) Sagittal MRI shows large mass extending to lower neck. (E) Axial
computed tomography (CT) shows large heterogeneous density noninfiltrative neck mass.
(F) Axial CT shows encroachment on laryngeal inlet and supraglottic region.
Radiologic size was massive (65 × 28 × 20 mm). It did not affect the cartilaginous
framework of the larynx and vocal cords, and no vertebral lytic lesions were detected.
The vascular structures of the neck were normal ([Fig. 3]).
Based on these findings, a tentative diagnosis of benign neck and laryngeal tumor
was made. Clinical and imaging features favored a massive neurofibroma. A punch biopsy
was not performed, but an excisional biopsy was selected.
The case was then submitted to a physician and pediatrician, who ruled out other features
of NF-I and who also excluded the possibility of any systemic involvement.
Under general hypotensive anesthesia, the surgical site was prepared with povidone
iodine solution and the patient was draped. A collar neck incision of two finger breadths
above the suprasternal notch was performed. The incision was deepened to the subplatysmal
plane and the skin flap was raised. Tracheotomy was done first. The mass was identified,
dissected, and removed with its laryngeal part resected after cutting the attachment
of superior constrictor muscle to the thyroid cartilage, dissecting the mass from
the mucosa without injury of the mucosa and without jeopardizing the great vessels
of the neck and laryngeal cartilage framework. We were unable to totally remove the
tumor, so near-total removal was done; a residual part at the right lower neck near
the apex of the pleura could not be excised and was left. Recovery from general anesthesia
was uneventful. Endoscopic examination of the larynx reported immobile right vocal
cord ([Fig. 2]). The child was extubated (of tracheotomy) after 7 days ([Fig. 1]) and was discharged from the hospital with no further complaint. The patient experienced
a complete relief of symptoms.
The histopathologic sections showed a lesion composed of bundles of nerve fibers arranged
in a concentric manner with areas of myxoid changes. Schwann cells and fibroblasts
were also seen. A histopathologic diagnosis of PN was established ([Fig. 4]). The immunohistochemical staining for S-100 protein was positive and confirmed
the diagnosis of a neurofibroma. Because the child had PN and >6 café au lait patches,
he was diagnosed with NF-I.[6]
Fig. 4 Postoperative axial magnetic resonance imaging (MRI) showing (A) normal laryngeal
inlet and (B) removal of mass from the neck. Postoperative histopathology of the plexiform
neurofibroma showing (C) neurofibromas unencapsulated and showing zonation with a
more cellular central region containing residual nerve twigs and more myxoid areas
at the periphery (×100). (B) Typically, the Schwann cells predominate and are spindled
to ovoid and slender with characteristic wavy nuclei (×200). (F) Neurofibromas are
composed of several elements, including Schwann cells, perineurial cells, intraneural
fibroblasts, bundles of collagen arrayed in a characteristic “shredded carrot” pattern,
and scattered enlarged cells with hyperchromatic nuclei representing degenerative
change (×400).
The patient was followed for 24 months with no recurrence or further complaints. Moreover,
endoscopic examination of the larynx at 1 and 2 year after excision showed apparently
normal laryngeal mucosa without recurrent masses with immobile right vocal cord ([Fig. 1]). Apart from the residual piece, postoperative magnetic resonance imaging showed
apparently normal larynx and neck ([Fig. 4]).
Discussion
To date, fewer than 30 cases of endolaryngeal neurofibromas have been reported in
the English literature since its first description by Hollinger in 1950.[7] Most of these lesions have been reported in the pediatric population and in association
with NF-1.[1] Our patient differs from this conventional profile as he was young (only 5 years
old) and had no personal or family history of von Recklinghausen disease. Moreover,
the neurofibroma reported here was plexiform type, involving deep neck spaces with
intralaryngeal extension. It was removed surgically by an external neck approach without
thyrotomy.
To the best of our knowledge, this is the first reported case of massive neck PN with
intralaryngeal extension as part of NF-1 in a 5-year-old boy with no personal or family
history of similar condition. Moussali et al reported a case of PN of the larynx in
a 4-year-old child, but it was limited to the larynx with no neck extension.[8]
PN is rare and seen in only 5 to 15% of cases with NF-I; 50% of the cases of NF-I
are inherited as autosomal dominant traits. The area most frequently affected by laryngeal
neurofibroma is the supraglottic region, with the majority involving the arytenoids
and the aryepiglottic fold, followed by the false vocal cords, because these areas
are rich in terminal nerve plexuses.[9] These laryngeal sites were encroached in our case.
Although characteristically benign, PN can cause pain, disfigurement, and functional
changes and more importantly may turn malignant. Unlike the other variants, PN carries
an increase risk of malignant peripheral sheath tumors.[3]
As punch biopsy is difficult to perform, a preoperative histologic diagnosis is often
been difficult.[10] We did not do a punch biopsy but decided to perform excisional histopathology for
our patient.
In light of the poor results from medication trials, primary therapy continues to
be complete surgical excision of the neurofibroma.[11] No specific treatment for PN currently exists, aside for surgical resection.[12]
[13]
Younger age, the tumor's location in the head and neck region, and incomplete surgical
resection are predictive factors for a higher risk of the tumor progressing and recurring.[12] Our case fell into these categories. Thus, recurrence was expected, particularly
as we were unable to totally remove the tumor. In such cases, lifelong follow-up is
often warranted.
Neurofibromas have been reported in the literature to be surgically difficult to separate
from normal tissue because they lack a well-defined capsule and are instead made up
of a mesh of interwoven spindle cells, axons, and collagen fibers.[1] Extensive tumors may be associated with massive bleeding.[12] Therefore, it is wise not to delay surgery.[12]
[13] Surgical excision was decided for our case. Early surgical intervention of PN of
the head and neck with a goal of near total resection avoids the loss of function
associated with these tumors, such as tracheostomy dependence, swallowing difficulty,
and speech problems, and prevents the inexorable progression of substantial cosmetic
deformity.[13]
Removal of PN is a challenging procedure as the lesion may involve multiple nerve
fascicles, with serpiginous growth and significant vascularity. Even with surgical
excision, PN has a recurrence rate of 20%.[12]
[14]
Lateral or median thyrotomy and pharyngotomy have been presented by most authors as
the treatments of choice for the surgical excision of these tumors[15]
[16]; we preferred cutting the attachment of superior constrictor muscle to the thyroid
cartilage, dissecting the mass from the mucosa to preserve the laryngopharyngeal function.
No malignant changes were found in our case. No malignant changes have been noted
to occur among isolated neurofibromas to date. The progression from a solitary neurofibroma
to multiple neurofibromatosis and then transformation into malignancy is theoretically
possible but exceedingly rare.[10]
No recurrence had been detected to date (2 years of follow-up), similar to the studies
of Ransom et al,[13] who did near total removal, and Patil et al,[9] who did total removal with follow-up of 4 years. However, recurrence was detected
after debulking of a massive facial neurofibroma by Asha'ari et al,[12] but they did not report recurrence after debulking of a parotid neurofibroma.
It is believed that the laryngeal neurofibroma arises from the superior laryngeal
branch of the glossopharyngeal nerve.[10] But in our reported case, the PN was massive, extending to the lower neck, and its
resection was complicated by recurrent laryngeal nerve injury. These suggest the recurrent
laryngeal nerve to be the origin of the tumor and ensured that these tumors are unencapsulated
and tended to infiltrate and separate the normal nerve fascicles, as was documented
before.[17]
Final Comments
A case of massive neck PN with supraglottic part in a 5-year-old boy with NF-I was
reported; it should be included in differential diagnosis of stridor and neck mass
in children. Massive neck PN can be surgically removed without recurrence if diagnosed
and removed in early childhood, eliminating the respiratory symptoms. This study highlights
the significant of early diagnosis and excision of massive neck PN and its complications.
