A 6-year-old boy presented to his pediatrician with clear drainage from his left eye for 1 to 2 days. He denied itchiness, pain, vision changes, nasal congestion, or history of allergies. What's the diagnosis?
A 6-year-old boy presented to his pediatrician with clear drainage from his left eye for 1 to 2 days. Of note, the patient was not immunized due to family preference. He denied itchiness, pain, vision changes, nasal congestion, or history of allergies. He was initially treated with topical and systemic antihistamines due to concern for possible allergies. He was switched to antibiotic eyedrops shortly thereafter due to persistent symptoms. Over the next several days, he developed clear nasal drainage and slight redness of the bulbar conjunctiva in addition to his eye drainage and swelling. He was seen at an eye clinic where he was diagnosed with conjunctivitis and switched to an eyedrop containing antibiotics and dexamethasone.
Two weeks after his initial symptoms, his mother became more concerned and brought him to the emergency department (ED). His physical exam was remarkable for rhinorrhea, left maxillary sinus pain on percussion, and periorbital edema. Physical exam was negative for lymphadenopathy and periorbital erythema, and extraocular movements were intact. Routine chemistry studies, complete blood cell count with differential, and erythrocyte sedimentation rate were unremarkable. A blood culture was sent and eventually showed no growth.
He was diagnosed with preseptal cellulitis of the left eye and acute maxillary sinusitis, admitted for further monitoring, and treated with ampicillin-sulbactam (Unasyn), diphenhydramine (Benadryl), and fluticasone (Flonase). He was discharged home the following day on oral amoxicillin/clavulanate (Augmentin) after some clinical improvement.
A few days later, he presented to the dentist due to tooth pain and was found to have a loose upper molar. The dentist did panoramic x-rays and noted soft tissue swelling in his maxillary sinus. The dentist suspected a cyst and referred the patient to a local university’s dentistry school for further evaluation. The patient’s mother then decided to take him to a different ED. A computed tomography (CT) scan of his head was performed due to the patient’s lack of improvement and abnormal dental x-rays. The scan showed a large heterogeneously enhancing soft tissue abnormality centered in the left maxillary sinus with extension into the adjacent spaces (Figure). The differential diagnosis was primarily oncologic and included rhabdomyosarcoma, non-Hodgkin lymphoma, osteosarcoma, and Ewing sarcoma (ES).
He then underwent biopsy for a definitive diagnosis. During surgery, a highly vascular soft-tissue mass was found filling the maxillary sinus with extension into the nasal cavity. The biopsy was positive for ES. Further staging with lumbar puncture, bone marrow biopsy, and CT chest/abdomen/pelvis and positron emission tomography/CT did not demonstrate any evidence of metastatic disease.
There are several common conditions in children associated with acute unilateral eye swelling (Table). One common condition is conjunctivitis, of which a viral or bacterial cause would be considered rather than an allergic cause, which is usually bilateral. However, the child did not improve with antihistamines or antibiotic eyedrops, so these diagnoses became less likely. Also, his lack of fever or history of allergies pointed away from an infectious or allergic cause of his symptoms. Next to consider was maxillary sinusitis, due to the facial pain and pain at the upper molars. Maxillary sinusitis also can lead to preseptal cellulitis or orbital cellulitis, and all of these conditions were considered and treated for in this patient. However, the child did not improve after his first hospitalization where he was treated for presumed preseptal cellulitis. The patient was even seen by the dentist to rule out a periodontal abscess, which would have been seen with imaging. Typical conditions such as these were considered for this patient’s case. However, with lack of improvement and progression of symptoms, a more unusual diagnosis and further imaging required consideration. After the dentist took x-rays and a mass was seen in the sinus, it was clear a biopsy was required to lead to a final diagnosis.
Diagnosis: Ewing sarcoma
The ES family of tumors consist of osseous tumors, extraosseous soft tissue tumors, and primitive neuroectodermal tumor.1 Histologically, these tumors classically have the small round blue cells that form Homer-Wright rosettes.1 CD99 detected by immunohistochemistry is the hallmark of diagnosis, although fluorescence in situ hybridization can also be used to detect the classic t(11;22) fusion.2 This collection of tumors is the second most common type of bone sarcomas in children after osteosarcoma, and most commonly occurs in White males in their second decade. The tumors can occur in any skeletal bone but most often occur in the pelvis, axial skeleton, and femur.3 For localized disease, the combination of surgery and/or radiotherapy along with multiagent chemotherapy results in an overall survival of approximately 70%, which is significantly worse in the setting of metastatic disease with 5-year survival rates of 20% to 40%.4 This case of ES of the left maxillary sinus is a rare clinical scenario given the child’s young age, as well as the rare location, with only 20% of ES being extra skeletal and even fewer (6%) located in the head and neck.2,5 ES has been reported in the maxillofacial region in approximately 2% of cases.6
The patient began receiving induction chemotherapy treatment via the AEWS1031 trial (NCT01231906) regimen A. After 3 months of induction chemotherapy, the patient underwent conventionally fractionated proton beam therapy (PBT) for local control. The patient continued concurrent consolidation chemotherapy at the same time he was receiving PBT. Treatment was delivered uneventfully except for a 3-day break when he was admitted after his eighth fraction of PBT for febrile neutropenia without a source of infection, grade 1 mucositis, and reduced oral intake that required a gastrostomy tube. Otherwise, treatment was tolerated well with anticipated erythema and a small area of moist-desquamation.
Twenty-one days after completion of radiation therapy, the mass in the maxillary sinus measured 3.4 cm × 3.3 cm × 2.5 cm on magnetic resonance imaging as compared with the original presentation at 5.0 × 4.8 × 4.5 cm, a 75% reduction in tumor volume. When the patient completed chemotherapy and radiation therapy, scans showed a response to treatment, and to date the patient has shown no evidence of disease. The patient will receive scans every 3 months for the first year following the end of treatment.
The first step in treatment for pediatric ES of the head and neck is recognition and diagnosis. The patient in this case was initially misdiagnosed with conjunctivitis and then preseptal cellulitis. It was not until images of the left maxillary sinus were obtained by the patient’s dentist that a heterogenous mass was seen and further investigated. Although it is unlikely to have altered the course of this patient’s treatment as it was 10 days later that he was diagnosed with ES, it illustrates the point that many physicians may not be aware of the rare occurrence of ES in the head and neck. The hope is to raise awareness about the occurrence of ES and other soft-tissue sarcomas in the head and neck region with this case in order to increase recognition and diagnosis.
1. Thorn D, Mamot C, Krasniqi F, Metternich F, Prestin S. Multimodality treatment in Ewing’s sarcoma family tumors of the maxilla and maxillary sinus: review of the literature. Sarcoma. 2016;2016:1-15. doi:10.1155/2016/3872768
2. Kaliki S, Rathi SG, Palkonda VAR. Primary orbital Ewing sarcoma family of tumors: a study of 12 cases. Eye (Lond). 2018;32(3):615-621. doi:10.1038/eye.2017.278
3. Sbaraglia M, Righi A, Gambarotti M, Dei Tos AP. Ewing sarcoma and Ewing-like tumors. Virchows Arch. 2020;476(1):109-119. doi:10.1007/s00428-019-02720-8
4. Uyeturk U, Helvaci K, Demirci A, et al. Clinical outcomes and prognostic factors of adult’s Ewing sarcoma family of tumors: single center experience. Contemp Oncol. 2016;20(2):141-146. doi:10.5114/wo.2016.58487
5. Hafezi S, Seethala RR, Stelow EB, et al. Ewing’s family of tumors of the sinonasal tract and maxillary bone. Head Neck Pathol. 2011;5(1):8-16. doi:10.1007/s12105-010-0227-x
6. Chi WJ, Hanasono MM, Hofstede TM, Aponte-Wesson RA. Prosthodontic treatment of a patient with Ewing sarcoma of the left maxillary sinus: a clinical report. J Prosthet Dent. 2019;121(4):698-702. doi:10.1016/j.prosdent.2018.06.012