CLINICAL ISSUES IN PEDIATRIC OTOLARYNGOLOGY
From Clinical Frontiers in Otolaryngology presented by the Research Study Club of Los Angeles
Nina Shaprio, MD, Associate Professor, Pediatric Otolaryngology, Division of Head and Neck Surgery, David
Geffen School of Medicine at the University of California, Los Angeles
| PEDIATRIC HEAD AND NECK CANCER
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| Background: cancer second leading cause of death (after trauma) in children 1 to 14 yr of age; only 5% of malignancies
in children but 50% of those in infants occur in head or neck; lymphoma and rhabdomyosarcoma most common; thyroid
and salivary glands common sites of glandular malignancies; few deaths, but vigilance still required (especially in teenagers,
who have higher rate of mortality)
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| Evaluation: although most children who present with asymptomatic neck masses have benign lesions, imaging important
to rule out malignancy; options include computed tomography (CT), magnetic resonance imaging (MRI; children may
need sedation), radionuclide bone scan, and positron emission tomography (PET); fine needle aspiration (FNA) biopsies
performed in office or under brief sedation, if necessary; treatment—based on histopathologic diagnosis and stage of tumor
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Rhabdomyosarcoma
| General: represents 3% to 4% of childhood malignancies and 50% to 70% of childhood sarcomas; generally occurs in
children <10 yr of age; location—35% of malignancies localized to head and neck; subtypes—embryonal (most common);
alveolar; botryoid; undifferentiated
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| Intergroup rhabdomyosarcoma staging (IRS) system: group 1—localized disease with no nodal involvement;
group 2—localized disease with microscopic residual disease; group 3—gross residual disease; group 4—metastatic
disease
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| Survival: before IRS system established, patients with rhabdomyosarcoma of head and neck had 5-yr survival rate of 8%
to 20%; after IRS system in place, 3-yr survival rate with no evidence of disease (NED) increased to 50% to 90%
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| Treatment: surgical resection recommended if low risk for surgical morbidity; resection generally inappropriate for children
with orbital tumors due to potential for functional disability; resection of parameningeal tumors controversial for
similar reason; standard of care includes postoperative irradiation and chemotherapy; preoperative chemotherapy appropriate
for large tumors; neck dissection sometimes necessary; patients with distant metastases undergo chemotherapy
with multiple agents
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Posttransplantation Lymphoproliferative Disorders (PTLD)
| General: spectrum of diseases, ranging from mild lymphoid hyperplasia to widespread B-cell lymphoma, often seen in
young children after solid-organ transplantation; younger age increases risk, because patient more likely naïve to Epstein-
Barr virus (EBV), whereas most organ donors EBV-positive; low-grade infection may cause PTLD; EBV status monitored
using polymerase chain reaction (PCR) technique
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| Presentation and treatment: symptoms similar to typical adenotonsillar hypertrophy; treatment requires removal of
tonsils and adenoids and may require reduction or cessation of immunosuppression (may endanger transplanted organ);
adjuvant chemotherapy considered; fulminant PTLD—rare; patient presents with severe mononucleosis-like illness
(acute adenotonsillar hypertrophy; high fever; airway obstruction; lethargy; change in mental status)
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Thyroid Carcinoma
| General: no established guidelines for treatment; malignancy 6 times as common in girls; subtypes—papillary (most
common); follicular; medullary
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| Registry data: review of 566 pediatric cases (papillary and follicular) compiled in Surveillance, Epidemiology, and End-
Results (SEER) database looked at mean age at diagnosis (16 yr), mean tumor size (2.5 cm), prevalence of nodal disease
(37%), and progression (≈75% isolated to thyroid; 12% had minor local extension; ≈2.5% had major local extension;
≈2.5% had extravisceral extension); survival variables—age, nodal disease, extent of surgery (total thyroidectomy,
subtotal thyroidectomy, or simple lobectomy), and use of radioactive iodine did not affect survival; sex (poorer prognosis
in boys), extent of primary disease at presentation, and tumor histology (better survival with papillary tumors) had significant
impact on survival; limitations of data—no information about comorbidities or recurrence
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Salivary Gland Carcinoma
| General: rare, especially in children; most commonly occurs in parotid gland; information from SEER database—113
pediatric cases (103 parotid; 10 submandibular); mean age 13 yr (slightly more common in girls); mean tumor size 2.5
cm; extraglandular extension in 20% of cases; nodal disease in 8% of cases (all parotid); primary histology included mucoepidermoid
(most common), acinic cell, rhabdomyosarcoma, and adenocarcinoma
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| Treatment: parotid disease—superficial or total parotidectomy; submandibular disease—resection of submandibular
gland; nodal disease—neck dissection; adjuvant therapy—31 patients in cohort received radiation therapy
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| Survival: 153 mo (increased to 161 mo when patients with rhabdomyosarcoma excluded); 4 of 6 deaths occurred in patients
with rhabdomyosarcoma; overall survival at 13 yr, ≈93%; impact of adjuvant radiation therapy in children unknown; adult
studies suggest benefit of surgery combined with radiation therapy
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| Rhabdomyosarcoma: patients treated with surgery, chemotherapy, and radiation therapy; relatively poor prognosis
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| CONTROVERSIES IN AIRWAY MANAGEMENT
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Recurrent Respiratory Papillomatosis (RRP)
| Background: most common benign noncongenital laryngeal neoplasm in children; human papillomavirus ([HPV]; primarily
HPV-6 and HPV-11), transmitted vertically from infected mother to first-born child (rarely seen in subsequent
births); 1500 to 2500 new cases each year in United States; high rate of recurrence; potential for malignant degeneration;
negative impact on quality of life
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| Treatment: surgery—former treatment of choice; debulking with microlaryngoscopy forceps, CO2 laser, or microdebrider;
placement of tracheotomy tube; adjuvant therapies—current focus of therapy; interferon fell out of favor due to
association with irreversible spastic diplegia; other options include indole-3-carbinol (I3C), mumps vaccine, ribavirin, cidofovir,
and heat-shock protein (Hsp) E7
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| Case 1: boy, 3 yr of age, with acute dysphonia and stridor, previously diagnosed with asthma, but resistant to treatment;
supraglottic and glottic papillomas found during surgery to investigate acute obstruction; recurrent obstructions treated
with laser every 1 to 2 wk; off-label use of cidofovir—dramatic response after 1 intralesional injection; no recurrent
stridor; at 11 yr of age, patient continues to develop papillomas (nonobstructive), but responds to cidofovir
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| Airway management: speaker prefers Parson’s laryngoscope with open side port (for passing instruments) and insufflation
port; 6.0 endotracheal tube connects to anesthesia circuit for minimal anesthesia and O2 (patients breathe spontaneously);
anesthetizing trachea topically avoids intubation; alternative procedure provides only O2 through insufflation
port; sedation induced with mask anesthesia, then maintained with total intravenous anesthesia (TIVA) using fentanyl
and propofol
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| Case 2: boy, 10 yr of age, with history of laryngeal papillomas; subglottic and tracheal papillomas discovered during follow-up
endoscopy; patient asymptomatic; no findings on chest radiograph or computed tomography; prior laser procedures
have left some scarring, but voice not affected; treatment—mechanical debulking and cidofovir injections every 3
mo when lesions recur; other options—pulsed-dye laser (less thermal injury than CO2 laser)
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| Cidofovir: adjuvant therapy not approved by Food and Drug Administration (FDA); cytosine nucleotide analogue that
blocks synthesis of viral DNA; intralesional injections performed in office on adults; patients have partial to complete regression,
improvement in voice quality and airway status, and decreased need for surgery; protocol (experimental)—
injections given every 2 wk at 0, 2, 4, and 6 wk; if lesions have not recurred, 1 wk added to each subsequent interval (eg,
weeks 9, 13, 18, etc); laser ablation performed, if needed; results—all 5 patients had significant improvement after first
treatment; 4 of 5 patients remain disease-free (stage 0); variability among protocols—dose varies from 2 to 57 mg
(speaker’s group uses 1 mg/kg body weight, diluted to 5 mg/mL in saline); higher concentration may cause atrophy, inflammation,
and scarring); dosing intervals from 2 to 8 wk; follow-up from 4 mo to 4 yr; risks associated with
treatment—nephrotoxicity; neutropenia; liver dysfunction; infertility; malignant degeneration; note—although malignant
changes have occurred during treatment, RRP has inherent risk for malignant degeneration (ie, transformation not
necessarily effect of treatment)
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| Treatment with HSP E-7: recombinant fusion protein (E-7 from HPV-16); open-label trial showed significant improvement
with monthly subcutaneous injections; intersurgical interval and disease progression improved, especially in
women; phase 3 trial in progress
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Subglottic Hemangioma
| Background: common congenital neoplasm in infants; presents most commonly at 6 to 8 wk of age (predominantly in girls);
croup-like presentation (inspiratory or biphasic stridor) may lead to misdiagnosis; infants treated with nebulized corticosteroids
(treatment for croup) initially respond, but symptoms recur when steroids tapered; cutaneous lesions often present (check
under hair); evaluation—endoscopy; MRI, especially if patient has external signs on neck (suggesting large hemangiomas)
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| Treatment: corticosteroids—short-term benefit seen with high-dose prednisone (3-4 mg/kg daily); intralesional injections
also available; long-term treatment required to reduce risk for recurrence; tracheotomy—lesion spontaneously involutes
≈18 mo after procedure; good option for isolated lesions; procedure avoids instrumentation of airway and
subglottic stenosis; laser ablation—procedure performed endoscopically or by open resection with laryngofissure; scarring
minimized by extubating patient at end of procedure; note—endoscope may compress lesions; thorough evaluation
necessary (to ensure identification of “tip of the iceberg” lesions)
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 | Speaker’s protocol: laser treatment (CO2 , potassium titanyl phosphate [KTP], or neodymium:yttrium-aluminum-garnet
[Nd:YAG]), leaving small rim of tumor intact (decreases risk for subglottic stenosis); observation in intensive care unit
(ICU) for 1 to 2 days; steroid taper; endoscopic evaluation at ≈6 wk (unless symptoms recur sooner); residual tissue (if
present) removed with forceps; outpatient follow-up
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| Case 3: boy, 3 mo of age, with large hemangiomas on neck and face; stridor absent, but problems with intermittent dysphagia
and choking; hemangioma involved supraglottis, hypopharynx, palate, and esophagus, but did not obstruct airway;
treatment—low-dose systemic corticosteroids and intermittent intralesional injections; clear endoscopic examination at
9 mo; involution of facial lesions may require reconstruction
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| Treatment issues: benign lesion has known course of spontaneous involution, but treatments have some risk; risks—
laser surgery may cause scarring, stenosis, recurrence, or laser fire; morbidities of tracheotomy include plugging, persistent
dysphagia, and dysphonia; open resection leaves external scar and some stenosis at surgical site; benefits of laser—
improved quality of life and decreased parental anxiety (compared to tracheotomy); improved development (eg, speech,
swallowing); benefits of tracheotomy—bypasses lesion, allowing for spontaneous involution without disruption of subglottic
mucosa; minimizes scarring
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| Review of treatment outcomes: 372 patients; average age at presentation 2.7 mo; stridor and respiratory distress
common; treatment with CO2 laser associated with highest success rate; adding second therapeutic modality to tracheotomy
reduced time to decannulation from 21 mo (tracheotomy alone) to 12 mo; complications of tracheotomy include
plugging, cutaneous fistulae, and death (1 case, caused by plugged tube); intralesional steroids associated with 86% success
rate when combined with second modality (complications rare); open resection associated with good rate of success,
but somewhat higher rate of complications (compared to CO2 laser)
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Bilateral Congenital Vocal Cord Paralysis
| Presentation: inspiratory stridor (high-pitched, musical) noticeable at birth, but newborn has clear-sounding cry; variable
degree of respiratory distress; variable oral intake
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| Work-up: airway endoscopy; MRI of brain, including brainstem (to rule out Arnold-Chiari malformation)
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| Case 4: boy, 5 wk of age, exhibits inspiratory stridor since birth; no cyanosis; child has poor oral intake and respiratory
distress; family history—father had congenital vocal cord paralysis, successfully treated with tracheotomy in childhood;
treatment—tracheotomy; result—partial spontaneous function of vocal cords at ≈22 mo of age; tube removed at 2 yr of
age
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| Vocal cord paralysis: second most common cause of neonatal stridor (after laryngomalacia); 10% of congenital laryngeal
lesions; initial intervention consists of tracheotomy in \>50% of cases; 50% to 60% of patients experience spontaneous
recovery; patients advised to wait ≥12 mo after placement of tracheotomy tube to allow for resolution before
pursuing additional interventions
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| Other interventions: external arytenoidopexy or arytenoidectomy and endoscopic CO2 arytenoidectomy have similar
rates of decannulation (25%-30%); posterior cartilage graft widens posterior glottis, improving static airway and allowing
compensation; partial arytenoidectomy (cut posterior to vocal process) combined with suture technique to lateralize
vocal cord has highest rate of decannulation, minimum morbidity, and excellent voice result
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| Final comments: spontaneous ventilation during procedures minimizes intubation and instrumentation of airway (which
increases risk for seeding of papillomatosis into airway); preoperative case planning with anesthesiologist important for
discussing airway techniques and other issues
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Educational Objectives
| The goal of this program is to educate the listener about current treatment practices and controversies in managing pediatric
patients with malignant and benign lesions of the head and neck. After hearing and assimilating this program,
the clinician will be better able to:
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| 1. Identify surgical candidates for resection of rhabdomyosarcoma.
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| 2. Discuss intervention strategies for pediatric patients with glandular carcinoma of the head and neck.
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| 3. Identify factors that affect prognosis and survival in patients with specified otolaryngologic malignancies.
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| 4. Compare treatment options for patients with recurrent respiratory papillomatosis and subglottic hemangiomas.
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| 5. Recognize infants with bilateral vocal cord paralysis
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Discussed on This Program
Cidofovir [Forvade (investigational), Vistide]
Fentanyl citrate [Sublimaze]
Prednisone [Deltasone, Liquid Pred, Meticorten, Orasone, Panasol-S, Prednicen-M, Prednisone Intensol Concentrate,
Strerapred DS]
Propofol [Diprivan]
Suggested Reading
Buwalda J, et al: AMORE protocol in pediatric head and neck rhabdomyosarcoma: descriptive analysis of failure patterns.
Head Neck 27:390, 2005; Derkay CS, et al: HspE7 treatment of pediatric recurrent respiratory papillomatosis:
final results of an open-label trial. Ann Otol Rhinol Laryngol 114:730, 2005; Green M, et al: CMV-IVIG for prevention
of Epstein-Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients.
Am J Transplant 6:1906, 2006; Meazza C, et al: Rhabdomyosarcoma of the head and neck region: experience at
the pediatric unit of the Istituto Nazionale Tumori, Milan. J Otolaryngol 35:53, 2006; Nicolai T, et al: Subglottic hemangioma:
a comparison of CO2 laser, Neodym-YAG laser, and tracheostomy. Pediatr Pulmonol 39:233, 2005;
Niedziela M: Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer 13:427,
2006; Rahbar R, et al: Mucoepidermoid carcinoma of the parotid gland in children: a 10-year experience. Arch Otolaryngol
Head Neck Surg 132:375, 2006; Setz AC, et al: Anesthetic management in a child with Arnold-Chiari malformation
and bilateral vocal cord paralysis. Paediatr Anaesth 15:1105, 2005; Shapiro NL, Bhattacharyya N: Clinical
characteristics and survival for major salivary gland malignancies in children. Otolaryngol Head Neck Surg 134:631,
2006; Sheahan P, et al: Is intralesional cidofovir worthwhile in juvenile recurrent respiratory papillomatosis? J
Laryngol Otol 120:561, 2006; Vijayasekaran S, et al: Open excision of subglottic hemangiomas to avoid tracheostomy.
Arch Otolaryngol Head Neck Surg 132:159, 2006.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the following has been disclosed: Dr. Shapiro receives support and is on the Speakers’ Bureau for ArthroCare ENT.
Dr. Shapiro was recorded at Clinical Frontiers in Otolaryngology, sponsored by the Research Study Club of Los Angeles,
and held January 13-14, 2006 in Los Angeles, CA. The Audio-Digest Foundation thanks Dr. Shapiro and the
Research Study Club of Los Angeles for their cooperation in the production of this program.
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