Introduction
Nasopharyngeal masses in the pediatric population are
rare, the majority of which are benign. The differential diagnosis is diverse
and include inflammatory lesions, vascular lesions, nasopharyngeal cysts,
congenital lesions, benign and malignant tumors, adenoid hypertrophy,
chordomas, and retropharyngeal ganglia tuberculosis [1]. The most common
abnormality in the pediatric population is benign adenoidal hypertrophy [2].
Given the anatomic complexity of the nasopharynx and close proximity to vital
structures (orbit and skull base), a thorough workup with radiographic imaging
is often necessary. In the juvenile male population, one must have a high index
of suspicion for Juvenile Nasopharyngeal Angiofibroma (JNA) when a patient
presents with a vascular posterior nasal mass, since this is the most common
benign nasopharyngeal tumor in this population [3]. The definitive treatment is
usually surgical excision with varying surgical approaches based on the
anatomic pattern of involvement. JNA has characteristic clinical and
radiographic findings, thus biopsy is not usually indicated. In addition, there
is also a risk for significant hemorrhage following endoscopic biopsy.
Case
A 13-year-old male was referred to our Paediatric Otolaryngology department for a suspected right JNA. This was discovered incidentally when he had a magnetic resonance imaging (MRI) (Figure 1) to investigate his persistent right-sided otalgia, headache and neck pain following a basketball injury to his right mandible. He reported intermittent spontaneous right anterior epistaxis that resolves with pressure. He attributed this, as well as nasal congestion and facial fullness to the cold weather.
Figure 1: T2 weighted axial MRI
demonstrating the lesion filling the right choanae, extending anteriorly
suspicious for JNA
His flexible nasendoscopy (FNE) revealed a hypervascular mass suspicious for a right JNA (Figure 2). Surgical excision was recommended. He was referred to the interventional radiologist for pre-operative embolization. This 4.5 x 4.3cm mass was supplied by arterial branches from the sphenopalatine, distal internal maxillary and anterior divisions of ascending pharyngeal arteries. Embolization was performed successfully with Onyx. There was complete devascularisation of the mass on the angiography. He had an endoscopic approach to the tumor resection, combined with Caldwell Luc to remove the portion extending laterally beyond the pterygopalatine fossa.
Figure 2: FNE showing a
hypervascular mass arising from the right lateral nasal wall filling the
posterior choanae.
The initial histopathology was suspicious for sarcoma. However, as the material was too necrotic, he underwent an excisional biopsy of his right jugulodigastric lymph node. This was diagnosed as nasopharyngeal carcinoma (NPC). It was re-staged as a right stage 4a (T4N2M0) EBER positive NPC. He was enrolled in the Children’s Oncology Group protocol ARAR0331 and completed his concurrent chemoradiotherapy (cisplatin and 5-FU chemotherapy; 70.2 gray to the gross disease and 45 gray to bilateral cervical nodes delivered with 7 field 6 MV intensity modulated radiotherapy). This was completed in November 2011. His follow up positron emission tomography (PET) demonstrated no enhancement. His follow up FNE (Figure 3) also did not demonstrate any recurrence.
Figure 3: Follow up FNE in 2012
demonstrating no recurrence.
His follow up PET 17 months later was suspicious for
metastatic lesions to his liver and spleen. This was confirmed on MRI and
biopsy. He was enrolled in the Texas Children’s Phase II Carbo/Docetaxel
followed by EBV CTL protocol (5 cycles of chemotherapy, followed by cytotoxic T
cell infusions), completed in the following 7 months. However, there was
evidence of progression on the follow up imaging, so he underwent salvage
chemotherapy (12 cycles of Gemcitabine and Vinorelbine) in the following 9
months. Unfortunately imaging three months after the salvage chemotherapy was
concerning for persistent disease. He was resumed on chemotherapy with
Vinorelbine and Gemcitabine (6 cycles), which was completed in the following 6
months. He then underwent 2 treatments of TGF beta resistant cytotoxic T
lymphocyters therapy, completed a month later. He continued to have progressive
disease and elected to pursue alternative therapies in addition to the
recommended chemotherapy with Cyclophosphamide and Topotecan in California. He
has since relocated there.
Discussion
JNA is a highly vascular benign but locally invasive
tumor, which represents about 0.05% of all head and neck tumors [4]. They arise
almost exclusively in adolescent males. Presenting symptoms include unilateral
nasal congestion, epistaxis, hyposmia, rhinorrhea, and facial pain. Less
commonly, the expansile bony changes may result in facial deformity, vision
changes or cranial nerve palsy. These tumors can extend through the
sphenopalatine foramen into the pteryopalatine fossa with subsequent expansion
and displacement of the surrounding anatomic structures [5]. The blood supply
is most commonly from the branches of the internal maxillary artery, but may
also be from the external carotid artery, internal carotid artery, common
carotid artery, or ascending pharyngeal artery [6]. FNE often reveals a
pink/red, lobulated submucosal mass seated in the posterior nasal cavity.
Typical computed tomographic (CT) findings include an enhancing mass emanating
from the posterolateral wall of the nasal cavity, involving the sphenopalatine
foramen and pterygomaxillary fossa. The Holman-Miller sign is a pathognomonic
CT finding which includes anterior bowing of the posterior maxillary wall from
the expansile pressure exerted by the tumor [4].
Preoperative biopsy is usually discouraged due to the
risk of significant, even life-threatening hemorrhage. A probable diagnosis of
JNA is often thought to be sufficient based on the characteristic clinical and
radiographic findings [7-9]. The definitive treatment is embolization followed
by surgery. Other treatment options include radiotherapy, chemotherapy, and or
hormone therapy [6].
NPC is a rare aggressive malignancy often diagnosed in
the setting of advance locoregional disease and distant metastasis. NPC
represents approximately 1% of all childhood cancers in the U.S. and Europe,
and as high as 10-20% in Southeast Asia and Africa [10]. They account for
40-50% of childhood malignancies isolated to the nasopharynx [11]. Similarities
in etiology have been shown between juvenile and adult NPC with its frequent
concomitant infection with EBV, association with consumption of salted fish
containing volatile nitrosamines and male predominance (1.8:1) [12,13]. The
World Health Organization has classified NPC into three subtypes: Type I includes
keratinising squamous cell carcinoma, Type II includes non-keratinizing
epidermoid carcinoma and Type III includes undifferentiated carcinoma. The most
common histologic type of NPC found in the juvenile population is the WHO Type
III form which is classically associated with more advanced locoregional
disease and distant metastasis [13]. The most common presenting symptoms
include a painless neck mass, nasal obstruction, epistaxis, conductive hearing
loss or serous otitis media caused by eustachian tube obstruction. The invasive
nature of these tumors can lead to cranial nerve palsies from skull base
extension.
Diagnosis is obtained by a combination of physical
examination, FNE and radiographic imaging studies. On FNE, it is typically a
submucosal pink, friable lesion emanating most commonly from the fossa of
Rosenmuller. Workup often includes MRI to further detail the characteristics of
the tumor as well as the extent of invasion. On MRI, it has a heterogeneous
intermediate signal intensity on T2-weighted images and moderate contrast
enhancement (less than that of normal mucosa) on T1-weighted images with or
without infiltration outside of the nasopharynx.
The mainstay of treatment for NPC includes concomitant
chemo-radiotherapy [12]. Undifferentiated NPC is particularly radiosensitive.
Salvage neck dissection is limited to the setting of persistent nodal disease
following systemic therapy. Despite apparent local tumor control after
high-dose radiotherapy, treatment commonly fails due to locoregional recurrence
or development of distant metastatic disease. Most recurrences occur within two
years (median 8 months) and over 50% of these patients develop distant
metastatic disease [10,14]. This was the case in our patient. With radiotherapy
alone, 5-year survival rates have been reported as low as 20-60% [10,14]. With
the addition of neoadjuvant or concurrent chemotherapy to standard high dose
radiotherapy regimens, there has been a significantly decreased risk of
developing distant metastasis as well as increased disease-free survival [14-
16]. Wolden et al reported improved metastasis-free survival (16% vs 57%
p=0.01) as well as 10-year disease-free survival (84% vs 35%, p<0.01) with
the addition of chemotherapy versus radiation alone in pediatric patients with
ages ranging from 12-20 years [15]. Targeted therapies addressing the
pathogenic role of EBV have been developed with promising results including
interferon-beta administration as well as EBV-specific cytotoxic T-lymphocytes
[17]. The risks of long-term, treatment-related toxicity can be quite
significant in the juvenile population: growth retardation, dental pathologies,
life-long xerostomia, endocrine derangements, ototoxicity and development of
secondary malignancies (relating to high-dose radiotherapy) [3].
A review of the English literature was conducted to
identify other cases similar to our patient. There were a total of 5 reports,
which are summarised in (Table 1). We included a description of the
pre-operative finding as the images were unavailable.
Table 1: Case report summary of
nasal masses presenting as JNA.
|
Case |
Pre-Op
Image |
Pre-Op
Radiology |
Tumor
Location |
Pathology |
Follow Up |
|
Mani et al
[18] |
Anterior
2/3 of NP filled with a bilobular reddish-grey, firm mass |
X-ray: Nasopharyngeal
(NP) mass & Homan miller sign Angio:
Arterial supply from ascending pharyngeal and maxillary arteries |
Left
spheno-ethmoidal recess, anterior bowing of posterior maxillary sinus wall on
exam/imaging. Actual from Left posterior septum at time of surgery |
Embryonal
rhabdomyosarcoma |
Recurrence
at 1 yr follow up requiring subtotal palatectomy; 3mo later recurrence at R
anterior torus palatine requiring cryosurgery and XRT |
|
Harrison DF
[19] |
No description available |
X-ray: NP mass with erosion
of lateral pterygoid plate CT: Erosion of sphenopalatine foramen with
extension into the pterygopalatine fossa MRI: Extension through
infratemporal fossa |
Musculature of the right
lateral pterygoid |
Embryonal rhabdomyosarcoma |
Information unavailable |
|
Shaffer et
al [20] |
Tan
lobulated mass in the nasopharynx |
Xray: NP
mass with erosion of sphenoid sinus & Homan Miller sign Angio:
Arterial supply by internal maxillary artery |
Nasopharynx
with extension into the pterogomaxillary space and infratemporal fossa |
Lymphoepithelioma |
Information
unavailable |
|
Burkey et
al [16] |
Deep red submucosal NP mass |
CT: NP mass with widening of
pterygopalatine fossa, erosion of posterior maxillary wall and base of
pterygoid bone, fills masticator space, extends into nasopharynx & middle
cranial fossa Angio: Arterial supply from
ascending pharyngeal & internal maxillary arteries MRI: Extension through
foramen ovale, L inferior orbital fissure and orbital apex as well as
cavernous sinus |
Per pre-op radiology |
Embryonal rhabdomyosarcoma |
Information unavvailable |
Mani et al published the first case report of a
malignant nasopharyngeal mass misdiagnosed as a JNA. Final surgical
histopathology revealed embryonal rhabdomyosarcoma [18]. Harrison reported his
personal experience of 44 patients treated surgically for presumed JNA, one of
which was an embryonal rhabdomyosarcoma on final histopathologic review [19].
Shaffer et al. reported cases suspicious for JNA on angiography, which were
later found to be lymphoepithelioma and fibrous dysplasia following surgical
excisions [20]. Burkey et al from our own institution presented a case in 1990
with clinical and radiographic findings consistent with JNA. However, their
team had concern for malignancy given the extent of disease and young age of
the patient thus endoscopic biopsy was performed under a general anesthetic
following pre-operative embolization. Histopathology revealed embryonal
rhabdomyosarcoma [16].
There may be a role for performing endoscopic biopsy
under a general anesthetic in lesions probable for JNA, but with atypical
presenting signs and symptoms. The risk of post-operative hemorrhage is
significantly reduced with the advent of pre-operative embolization. While this
does lead to the patient undergoing an additional general anesthetic, we feel
that in a healthy patient population these risks are acceptable as the
definitive histopathologic diagnosis may have the potential to change the
management. Alternatively, a frozen section can be obtained to confirm the pathology
prior to proceeding with the definitive surgery.
Conclusion
Our present case and the review of cases in the
literature suggest that there may be a role for performing endoscopic biopsy
under a general anesthetic in lesions probable for JNA, but with atypical
presenting signs and symptoms. The ultimate goal is to prevent inappropriate
surgical intervention in patients with malignant and potentially metastatic
disease.
References
- Alves FR,
Granato L, Maia MS, Lambert E. Surgical approaches to juvenile nasopharyngeal
angiofibroma - case report and literature review. Int Arch Otorhinolaryngol.
2006; 10:162-166.
- Stambuk HE,
Patel SG, Mosier KM, Wolden SL, Holodny AI. Nasopharyngeal carcinoma:
recognizing the radiographic features in children. Am J Neuroradiol. 2005; 26:
1575-1579.
- Waldman SR,
Levine HL, Astor F, Wood BG, Weinstein M, Tucker HM. Surgical experience with
nasopharyngeal angiofibroma. Arch Otolaryngology. 1981; 107: 677-682.
- Bakshi SS,
Bhattacharjee S. Juvenile nasopharyngeal angiofibroma. J Pediatric Hematol
Oncol. 2016; 38: 491-492.
- Neel III HB,
Whicker JH, Devine KD, Weiland LH. Juvenile angiofibroma: review of 120 cases.
Am J Surg. 1973; 126: 547-556.
- Wu AW, Mowry
SE, Vinuela F, Abemayor E, Wang MB. Bilateral vascular supply in juvenile
nasopharyngeal angiofibromas. Laryngoscope. 2011; 121: 639-643.
- Doyle PJ,
Riding K, Kahn K. Management of nasopharyngeal angiofibroma. J Otolaryngol.
1977; 6: 224-232.
- Gullane
PJ, Havas TE. Nasopharyngeal Angiofibroma. Current therapy in
Otolaryngology-Head and Neck Surgery, B.C. Decker, Toronto. 1987; 178-181.
- Spector JG.
Management of Juvenile Angiofibroma. Laryngoscope. 1988; 98: 1016-1026.
- R
Mertens R, B Granzen B, L Lassay L, Gademann G, Hess CF, Heimann G.
Nasopharyngeal carcinoma in childhood and adolescence. Cancer. 1997; 80:
951-959.
- Afqir S,
Ismaili N, Alaoui K, Ahid S, Lotz JP, Horn E, et al. Nasopharyngeal carcinoma
in adolescents: a retrospective review of 42 patients. Eur Arch
Otorhinolaryngology. 2009; 266: 1767-1773.
- Downing NL,
Wolden S, Wong P, Petrik DW, Hara W, Le QT. Comparison of treatment results
between adult and juvenile nasopharyngeal carcinoma. Int J Radiat Oncol Biol
Phys. 2009; 75: 1064-1070.
- Ayan I, Altun
M. Nasopharyngeal carcinoma in children: retrospective review of 50 patients.
Int J Radiat Oncol Biol Phys. 1996; 35: 485-492.
- Serin
M, Erkal HS, Elhan AH, Cakmak A. Nasopharyngeal carcinoma in childhood and
adolescence. Med Pediatric Oncol. 1998; 31: 498-505.
- Wolden SL,
Steinherz PG, Kraus DH, Zelefsky MJ, Pfister DG, Wollner N. Improved long-term
survival with combined modality therapy for pediatric nasopharynx cancer. Int J
Radiat Oncol Biol Phys. 2000; 46: 859-864.
- Burkey B,
Koopmann CF, Brunberg J. The use of biopsy in the evaluation of pediatric
nasopharyngeal masses. Int J Pediatric Otorhinolaryngol. 1990; 20: 169-179.
- Gioacchini
FM, Tulli M, Kaleci S, Magliulo G, Re M. Prognostic aspects in the treatment of
juvenile nasopharyngeal carcinoma: a systematic review. Euro Arch
Oto-Rhino-Laryngol. 2016; 274: 1205-1214.
- Mani
RL, Smith MF. Rhabdomyosarcoma simulating nasopharygeal angiofibroma. Oncology.
1968; 22: 74-80.
- Harrison
DFN. The natural history, pathogenesis, and treatment of juvenile angiofibroma.
Arch. Otolaryngol. Head Neck Surg. 1987; 113: 936-942.
- Shaffer K, Haughton V, Farley G, Freidman J. Pitfalls in the radiographic diagnosis of angiofibroma. Radiology. 1978; 127: 425-428.