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Facial nerve palsy, parotid mass and Epstein–Barr virus
International Journal of Pediatric Otorhinolaryngology Extra 11 (2016) 1–4
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology Extra journal homepage: www.elsevier.com/locate/ijporl
Case report
Facial nerve palsy, parotid mass and Epstein–Barr virus Nancy Grover a, John Leake b, Denise Malicki c, Paritosh Khanna d, Seth Pransky a,* a
Department of Pediatric Otolaryngology, Rady Children’s Hospital, University of San Diego, 3030 Children’s Way, San Diego, CA 92123, United States Department of Infectious Diseases, Rady Children’s Hospital, University of San Diego, 3030 Children’s Way, San Diego CA 92123, United States c Department of Pathology, Rady Children’s Hospital, University of San Diego, 3030 Children’s Way, San Diego, CA 92123, United States d Department of Radiology, Rady Children’s Hospital, University of San Diego, 3030 Children’s Way, San Diego, CA 92123, United States b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 20 August 2015 Received in revised form 7 November 2015 Accepted 13 November 2015 Available online 22 November 2015
We report the case of a seven year old girl with 22q11 deletion mosaicism who presented with a sudden onset rapidly enlarging left parotid mass and ipsilateral facial nerve paresis. MRI and cytology were inconclusive. She underwent partial superficial parotidectomy to obtain definitive histopathology, which was reported as suggestive of acute Epstein Barr infection. A subsequent quantitative Epstein–Barr Virus (EBV) PCR clinched the diagnosis four weeks after her initial presentation. She was stared on oral Valgancyclovir and her facial nerve showed recovery. We discuss the challenges faced in managing this case with delayed conclusive diagnosis of acute Epstein Barr virus infection. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Epstein–Barr virus (EBV) Parotid Facial nerve Valgancyclovir
1. Introduction
2. Case report
Epstein–Barr virus (EBV) is a member of human herpesvirus family. Infection in young children is often subclinical; when symptoms do occur, a variety of manifestations have been observed, including otitis media, diarrhea, hepatitis, abdominal complaints, upper respiratory infection, myocarditis and infectious mononucleosis [1]. Neurologic involvement is uncommon and occurs in 0.37–7.3%, with facial nerve palsy being reported in 0.9% of children with EBV [2]. We report the case of a the case of a seven year old girl with 22q11 deletion mosaicism who presented with a sudden onset rapidly enlarging left parotid mass and ipsilateral facial nerve paresis. We discuss the challenges faced in managing this case due to an atypical presentation and initial negative serology leading to surgical intervention to establish the diagnosis. A definitive diagnosis remained elusive even after the histopathology until confirmed by a positive quantitative EBV PCR and response to Valgancyclovir. Her underlying genetic mutation added to the complexity of her clinical picture, which made treatment decisionmaking challenging and prolonged parental anxiety.
A seven-year-old girl presented to us with a two-week history of left sided facial swelling, inability to completely close her left eye, associated fatigue and subjective fever. She was diagnosed with 22 q11 deletion mosaicism in utero but had a normal appearance and developmental course with no other significant past medical or surgical history. On examination she had a mildly tender, non-mobile 1 cm firm mass in the left pre auricular area. She had grade III House Brackmann (HB) weakness of her left orbital, buccal and marginal mandibular branches of facial nerve. Hematological investigations showed a C reactive protein (CRP) of 0.60, erythrocyte sedimentation rate (ESR) of 11 and white cell count of 4.6—all parameters were normal. MRI of the face without contrast/with contrast (Figs. 1 and 2) was compatible with parotitis, with mild, asymmetric heterogeneous enhancement following contrast administration. Enlarged, reactive intra-parotid lymph nodes were identified; the largest of these was 12 mm 10 mm 11 mm. An additional hypo intense area within the substance of the gland suggested a suppurative versus necrotic node. No additional masses were seen. Fine Needle Aspirate Cytology showed a mixed lymphoid cell population with no features of neoplastic process. She was commenced on Prednisolone 1 mg/kg/day and amoxicillin–clavulanate with the clinical and radiologic diagnosis of an inflammatory process.
* Corresponding author. Tel.: +1 8583955621. E-mail address: [email protected] (S. Pransky). http://dx.doi.org/10.1016/j.pedex.2015.11.001 1871-4048/ß 2015 Elsevier Ireland Ltd. All rights reserved.
2
N. Grover et al. / International Journal of Pediatric Otorhinolaryngology Extra 11 (2016) 1–4
Fig. 1. Axial (A) and Coronal (B) STIR images demonstrate a 12 10 11 mm nodule/mass (white arrows) in the anterior and superior portion of the superficial right parotid gland. Additional smaller nodules were seen in both parotid glands, especially the left. These are non-specific by imaging and thought most consistent with reactive intraparotid lymph nodes.
Fig. 2. Axial (A) and Coronal (B) T1 post-contrast images demonstrate asymmetric hyper-enhancement of the left parotid gland, suggesting parotitis. The anterior parotid nodule identified on preceding STIR images is relatively hypo enhancing as seen on the axial post-contrast image (black arrow). There is an additional hypo intense area in the mid portion of this parotid gland, posterior to the larger anterior node, which demonstrates mild rim-enhancement, consistent with a suppurative or necrotic node.
There was no improvement in her symptoms with initial medical management. With her underlying 22q11 deletion mosaicism and necrotic appearance of the mass on MRI there was a concern for malignancy and hence she underwent an excisional biopsy of the mass. Histopathology showed benign salivary gland tissue diffusely infiltrated by an atypical lymphoid proliferation (Fig. 3) with scattered EBER (Epstein–Barr virus-encoded small RNAs) – positive cells by in situ hybridization [ISH] (Fig. 4) – most suggestive of acute EBV infection. Immunohistochemistry (IHC) was negative for CD15, CD30, CD3, EBV LMP and diffusely positive for CD45 Subsequently she underwent EBV serology antibody panel testing which was negative for EBV viral capsid antigen (VCA) IgM, VCA IgG and EBV nuclear antigen (EBNA) on day 18 of presentation.
An EBV DNA quantitative plasma PCR analysis was obtained after an infectious disease (ID) consult; this was positive at 1460 copies/ml four weeks after initial presentation hence strongly supporting the histopathologic diagnosis of acute EBV. She was commenced on valgancyclovir—32 mg/kg/day for 2 weeks and she made complete recovery. Her viral load reduced to 857 copies/ml upon repeat testing and she seroconverted to positive EBV VCA Ig G. Considering that she did not mount an immune response against EBV, by day 18, her modest but relatively prolonged virema, her underlying 22 q11 deletion and her atypical clinical presentation, she underwent immunologic testing to measure quantitative immunoglobulin (QUIGs), antibody to streptococcus pneumoniae and tetanus and B and T cell numbers. All of these were normal.
N. Grover et al. / International Journal of Pediatric Otorhinolaryngology Extra 11 (2016) 1–4
Fig. 3. Residual salivary gland ductal epithelium surrounded by a dense infiltrate of polymorphous inflammatory cells including small lymphocytes and large pleomorphic cells with occasionally prominent nucleoli (H&E, 600).
3
temporary facial weakness to 2% for permanent palsy [7] weighed against the need for obtaining adequate tissue for diagnosis. We decided on excision of the mass without a parotidectomy. Although the histopathology was suggestive of acute EBV infection, her negative EBV serologies were unusual and led to further need to verify the etiology of her parotid mass. EBV serologies have a sensitivity and specificity of 97 and 94 percent, respectively [8]. With anti VCA IgM and IgG and EBNA antibodies being non-reactive we faced the ongoing concern for malignancy and consideration of a more invasive operative procedure. Infectious disease was consulted and they recommended quantitative EBV DNA plasma PCR, which has been shown to identify patients with active EBV infection and also provides information on viral load which maybe elevated in patents with EBV-driven malignancy [9]. The detection of a moderate viral load (1460 copies) provided reassuring evidence of the diagnosis and of her immune system’s ability to mount adequate antiviral defences. Her response to valgancyclovir with significantly decreased parotid swelling, improved facial nerve function and a concurrent reduction in viral load was reassuring. Steroids are the mainstay of treatment for viral neuropathies. In a previous case series on the role of anti viral treatment for severe EBV infection, which included two children with facial nerve palsy treated with acyclovir [10] the authors cited a hypothetical advantage of using antivirals by way of avoiding viral lytic reactivation especially after administration of corticosteroids and the ensuing immunosuppression. One can always expect parental anxiety in surgical cases involving the parotid and facial nerve. In this case the routine anxiety was heightened by the extreme difficulty the mother had in conceiving and her inability to conceive again superimposed on the rare underlying genetic mutation that had been identified in utero. Managing the mother’s emotional distress regarding possible malignancy and the need for aggressive and extensive investigation and intervention with surgery and its attendant risks required a great deal of patience, time and counselling. Fortunately the parents were able to overcome their angst and the surgery was successfully accomplished.
Fig. 4. EBER staining – the brown staining nuclei are EBER positive – arrow.
4. Conclusion 3. Discussion Neurologic involvement with EBV infection is uncommon and occurs in 0.37–7.3% percent of patients, with facial nerve palsy being reported in 0.9% of children with EBV [2]. Two cases similar to ours have been reported previously, however the diagnosis in these patients was made by the presence of clinical and radiologic signs, haematology and a positive monospot test [2,3]. Our case was unusual in many aspects and challenging to manage. Patients with 22 q11 deletion have a reportedly higher risk of lymphoma [4]. Initial investigations were unrevealing and she failed to show a clinical response to steroids and antibiotics. Though the MRI was suggestive of parotitis, with its sensitivity being quoted as 80% in a recent publication, there was still concern for malignancy in the clinical context [5]. And although FNAC has a known diagnostic accuracy of 85–90% in the pediatric population [6] and our specimen was strongly suggestive of an inflammatory process, the combination of a parotid mass facial palsy and lack of response to medication led us to open surgical excision. Potential operative approaches included excisional biopsy vs superficial parotidectomy or total parotidectomy. Considerations included the risk of injury to facial nerve, with complication rates of 19% for
EBV infection can have a variable clinical course. In this child with 22 q11 deletion the EBV infection presentation was markedly atypical and proved to be a challenging diagnostic dilemma. A multidisciplinary approach was required to extensively investigate and treat an ultimately benign condition to avoid morbidity from a more extensive surgery for presumed malignancy and to achieve full resolution of the process. Tissue diagnosis with ISH and IHC and a full panel of EBV serologies and plasma PCR analysis may increase diagnostic sensitivity for such patients. References [1] C. Grose, The many phases of infectious mononucleosis; the spectrum of Epstein– Barr virus infection in children, Pediatr. Rev. 7 (1985) 35. [2] C.M. Long, J.E. Kerschner, Parotid mass: Epstein–Barr virus and facial paralysis, Int. J. Pediatr. Otorhinolaryngol. 59 (2001) 143–146. [3] P.A. Johnson, C. Avery, Infectious Mononucleosis presenting as a parotid mass and associated facial palsy, Int. J. Oral Maxillofac. Surg. 20 (4) (1991) 193–195. [4] S. Itoh, T. Ohno, S. Kakizaki, R. Ichinohasama, Epstein-Barr virus-positive T-cell lymphoma cells having chromosome 22q11.2 deletion: an autopsy report of DiGeorge syndrome, Hum. Pathol. 42 (12) (2011) 2037–2041. [5] H. Yerli, E. Aydin, N. Haberal, A. Harman, T. Kaskati, S. Alibek, Diagnosing common parotid tumours with magnetic resonance imaging including diffusion-weighted imaging vs fine-needle aspiration cytology: a comparative study, Dentomaxillofacial Radiol. 39 (Sep (6)) (2010) 349–355.
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N. Grover et al. / International Journal of Pediatric Otorhinolaryngology Extra 11 (2016) 1–4
[6] D.H. Lee, T.M. Yoon, J.K. Lee, S.C. Lim, Clinical utility of fine needle aspiration cytology in pediatric parotid tumors, Int. J. Pediatr. Otorhinolaryngol. 77 (8) (2013) 1272–1275. [7] L.J. Orvidas, J.L. Kasperbauer, J.E. Lewis, K.D. Olsen, T.G. Lesnick, Pediatric parotid masses, Arch. Otolaryngol. Head Neck Surg. 126 (2) (2000) 177–184. [8] A.L. Bruu, R. Hjetland, E. Holter, L. Mortensen, O. Nata˚s, W. Petterson, A.G. Skar, T. Skarpaas, T. Tjade, B. Asjø, Evaluation of 12 commercial tests for detection of Epstein–Barr virusspecific and heterophile antibodies, Clin. Diagn. Lab. Immunol. 7 (3) (2000) 451.
[9] R.D. Pitetti, S. Laus, R.M. Wadowsky, Clinical evaluation of a quantitative real time polymerase chain reaction assay for diagnosis of primary Epstein–Barr virus infection in children, Pediatr. Infect. Dis. J. 22 (8) (2003) 736. [10] Petros I. Rafailidis, Michael N. Mavros, Anastasios Kapaskelis, Matthew E. Falagas, Antiviral treatment for severe EBV infections in apparently immunocompetent patients, Mol. Cytogenet. 1 (2008) 18.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology Extra journal homepage: www.elsevier.com/locate/ijporl
Case report
Facial nerve palsy, parotid mass and Epstein–Barr virus Nancy Grover a, John Leake b, Denise Malicki c, Paritosh Khanna d, Seth Pransky a,* a
Department of Pediatric Otolaryngology, Rady Children’s Hospital, University of San Diego, 3030 Children’s Way, San Diego, CA 92123, United States Department of Infectious Diseases, Rady Children’s Hospital, University of San Diego, 3030 Children’s Way, San Diego CA 92123, United States c Department of Pathology, Rady Children’s Hospital, University of San Diego, 3030 Children’s Way, San Diego, CA 92123, United States d Department of Radiology, Rady Children’s Hospital, University of San Diego, 3030 Children’s Way, San Diego, CA 92123, United States b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 20 August 2015 Received in revised form 7 November 2015 Accepted 13 November 2015 Available online 22 November 2015
We report the case of a seven year old girl with 22q11 deletion mosaicism who presented with a sudden onset rapidly enlarging left parotid mass and ipsilateral facial nerve paresis. MRI and cytology were inconclusive. She underwent partial superficial parotidectomy to obtain definitive histopathology, which was reported as suggestive of acute Epstein Barr infection. A subsequent quantitative Epstein–Barr Virus (EBV) PCR clinched the diagnosis four weeks after her initial presentation. She was stared on oral Valgancyclovir and her facial nerve showed recovery. We discuss the challenges faced in managing this case with delayed conclusive diagnosis of acute Epstein Barr virus infection. ß 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords: Epstein–Barr virus (EBV) Parotid Facial nerve Valgancyclovir
1. Introduction
2. Case report
Epstein–Barr virus (EBV) is a member of human herpesvirus family. Infection in young children is often subclinical; when symptoms do occur, a variety of manifestations have been observed, including otitis media, diarrhea, hepatitis, abdominal complaints, upper respiratory infection, myocarditis and infectious mononucleosis [1]. Neurologic involvement is uncommon and occurs in 0.37–7.3%, with facial nerve palsy being reported in 0.9% of children with EBV [2]. We report the case of a the case of a seven year old girl with 22q11 deletion mosaicism who presented with a sudden onset rapidly enlarging left parotid mass and ipsilateral facial nerve paresis. We discuss the challenges faced in managing this case due to an atypical presentation and initial negative serology leading to surgical intervention to establish the diagnosis. A definitive diagnosis remained elusive even after the histopathology until confirmed by a positive quantitative EBV PCR and response to Valgancyclovir. Her underlying genetic mutation added to the complexity of her clinical picture, which made treatment decisionmaking challenging and prolonged parental anxiety.
A seven-year-old girl presented to us with a two-week history of left sided facial swelling, inability to completely close her left eye, associated fatigue and subjective fever. She was diagnosed with 22 q11 deletion mosaicism in utero but had a normal appearance and developmental course with no other significant past medical or surgical history. On examination she had a mildly tender, non-mobile 1 cm firm mass in the left pre auricular area. She had grade III House Brackmann (HB) weakness of her left orbital, buccal and marginal mandibular branches of facial nerve. Hematological investigations showed a C reactive protein (CRP) of 0.60, erythrocyte sedimentation rate (ESR) of 11 and white cell count of 4.6—all parameters were normal. MRI of the face without contrast/with contrast (Figs. 1 and 2) was compatible with parotitis, with mild, asymmetric heterogeneous enhancement following contrast administration. Enlarged, reactive intra-parotid lymph nodes were identified; the largest of these was 12 mm 10 mm 11 mm. An additional hypo intense area within the substance of the gland suggested a suppurative versus necrotic node. No additional masses were seen. Fine Needle Aspirate Cytology showed a mixed lymphoid cell population with no features of neoplastic process. She was commenced on Prednisolone 1 mg/kg/day and amoxicillin–clavulanate with the clinical and radiologic diagnosis of an inflammatory process.
* Corresponding author. Tel.: +1 8583955621. E-mail address: [email protected] (S. Pransky). http://dx.doi.org/10.1016/j.pedex.2015.11.001 1871-4048/ß 2015 Elsevier Ireland Ltd. All rights reserved.
2
N. Grover et al. / International Journal of Pediatric Otorhinolaryngology Extra 11 (2016) 1–4
Fig. 1. Axial (A) and Coronal (B) STIR images demonstrate a 12 10 11 mm nodule/mass (white arrows) in the anterior and superior portion of the superficial right parotid gland. Additional smaller nodules were seen in both parotid glands, especially the left. These are non-specific by imaging and thought most consistent with reactive intraparotid lymph nodes.
Fig. 2. Axial (A) and Coronal (B) T1 post-contrast images demonstrate asymmetric hyper-enhancement of the left parotid gland, suggesting parotitis. The anterior parotid nodule identified on preceding STIR images is relatively hypo enhancing as seen on the axial post-contrast image (black arrow). There is an additional hypo intense area in the mid portion of this parotid gland, posterior to the larger anterior node, which demonstrates mild rim-enhancement, consistent with a suppurative or necrotic node.
There was no improvement in her symptoms with initial medical management. With her underlying 22q11 deletion mosaicism and necrotic appearance of the mass on MRI there was a concern for malignancy and hence she underwent an excisional biopsy of the mass. Histopathology showed benign salivary gland tissue diffusely infiltrated by an atypical lymphoid proliferation (Fig. 3) with scattered EBER (Epstein–Barr virus-encoded small RNAs) – positive cells by in situ hybridization [ISH] (Fig. 4) – most suggestive of acute EBV infection. Immunohistochemistry (IHC) was negative for CD15, CD30, CD3, EBV LMP and diffusely positive for CD45 Subsequently she underwent EBV serology antibody panel testing which was negative for EBV viral capsid antigen (VCA) IgM, VCA IgG and EBV nuclear antigen (EBNA) on day 18 of presentation.
An EBV DNA quantitative plasma PCR analysis was obtained after an infectious disease (ID) consult; this was positive at 1460 copies/ml four weeks after initial presentation hence strongly supporting the histopathologic diagnosis of acute EBV. She was commenced on valgancyclovir—32 mg/kg/day for 2 weeks and she made complete recovery. Her viral load reduced to 857 copies/ml upon repeat testing and she seroconverted to positive EBV VCA Ig G. Considering that she did not mount an immune response against EBV, by day 18, her modest but relatively prolonged virema, her underlying 22 q11 deletion and her atypical clinical presentation, she underwent immunologic testing to measure quantitative immunoglobulin (QUIGs), antibody to streptococcus pneumoniae and tetanus and B and T cell numbers. All of these were normal.
N. Grover et al. / International Journal of Pediatric Otorhinolaryngology Extra 11 (2016) 1–4
Fig. 3. Residual salivary gland ductal epithelium surrounded by a dense infiltrate of polymorphous inflammatory cells including small lymphocytes and large pleomorphic cells with occasionally prominent nucleoli (H&E, 600).
3
temporary facial weakness to 2% for permanent palsy [7] weighed against the need for obtaining adequate tissue for diagnosis. We decided on excision of the mass without a parotidectomy. Although the histopathology was suggestive of acute EBV infection, her negative EBV serologies were unusual and led to further need to verify the etiology of her parotid mass. EBV serologies have a sensitivity and specificity of 97 and 94 percent, respectively [8]. With anti VCA IgM and IgG and EBNA antibodies being non-reactive we faced the ongoing concern for malignancy and consideration of a more invasive operative procedure. Infectious disease was consulted and they recommended quantitative EBV DNA plasma PCR, which has been shown to identify patients with active EBV infection and also provides information on viral load which maybe elevated in patents with EBV-driven malignancy [9]. The detection of a moderate viral load (1460 copies) provided reassuring evidence of the diagnosis and of her immune system’s ability to mount adequate antiviral defences. Her response to valgancyclovir with significantly decreased parotid swelling, improved facial nerve function and a concurrent reduction in viral load was reassuring. Steroids are the mainstay of treatment for viral neuropathies. In a previous case series on the role of anti viral treatment for severe EBV infection, which included two children with facial nerve palsy treated with acyclovir [10] the authors cited a hypothetical advantage of using antivirals by way of avoiding viral lytic reactivation especially after administration of corticosteroids and the ensuing immunosuppression. One can always expect parental anxiety in surgical cases involving the parotid and facial nerve. In this case the routine anxiety was heightened by the extreme difficulty the mother had in conceiving and her inability to conceive again superimposed on the rare underlying genetic mutation that had been identified in utero. Managing the mother’s emotional distress regarding possible malignancy and the need for aggressive and extensive investigation and intervention with surgery and its attendant risks required a great deal of patience, time and counselling. Fortunately the parents were able to overcome their angst and the surgery was successfully accomplished.
Fig. 4. EBER staining – the brown staining nuclei are EBER positive – arrow.
4. Conclusion 3. Discussion Neurologic involvement with EBV infection is uncommon and occurs in 0.37–7.3% percent of patients, with facial nerve palsy being reported in 0.9% of children with EBV [2]. Two cases similar to ours have been reported previously, however the diagnosis in these patients was made by the presence of clinical and radiologic signs, haematology and a positive monospot test [2,3]. Our case was unusual in many aspects and challenging to manage. Patients with 22 q11 deletion have a reportedly higher risk of lymphoma [4]. Initial investigations were unrevealing and she failed to show a clinical response to steroids and antibiotics. Though the MRI was suggestive of parotitis, with its sensitivity being quoted as 80% in a recent publication, there was still concern for malignancy in the clinical context [5]. And although FNAC has a known diagnostic accuracy of 85–90% in the pediatric population [6] and our specimen was strongly suggestive of an inflammatory process, the combination of a parotid mass facial palsy and lack of response to medication led us to open surgical excision. Potential operative approaches included excisional biopsy vs superficial parotidectomy or total parotidectomy. Considerations included the risk of injury to facial nerve, with complication rates of 19% for
EBV infection can have a variable clinical course. In this child with 22 q11 deletion the EBV infection presentation was markedly atypical and proved to be a challenging diagnostic dilemma. A multidisciplinary approach was required to extensively investigate and treat an ultimately benign condition to avoid morbidity from a more extensive surgery for presumed malignancy and to achieve full resolution of the process. Tissue diagnosis with ISH and IHC and a full panel of EBV serologies and plasma PCR analysis may increase diagnostic sensitivity for such patients. References [1] C. Grose, The many phases of infectious mononucleosis; the spectrum of Epstein– Barr virus infection in children, Pediatr. Rev. 7 (1985) 35. [2] C.M. Long, J.E. Kerschner, Parotid mass: Epstein–Barr virus and facial paralysis, Int. J. Pediatr. Otorhinolaryngol. 59 (2001) 143–146. [3] P.A. Johnson, C. Avery, Infectious Mononucleosis presenting as a parotid mass and associated facial palsy, Int. J. Oral Maxillofac. Surg. 20 (4) (1991) 193–195. [4] S. Itoh, T. Ohno, S. Kakizaki, R. Ichinohasama, Epstein-Barr virus-positive T-cell lymphoma cells having chromosome 22q11.2 deletion: an autopsy report of DiGeorge syndrome, Hum. Pathol. 42 (12) (2011) 2037–2041. [5] H. Yerli, E. Aydin, N. Haberal, A. Harman, T. Kaskati, S. Alibek, Diagnosing common parotid tumours with magnetic resonance imaging including diffusion-weighted imaging vs fine-needle aspiration cytology: a comparative study, Dentomaxillofacial Radiol. 39 (Sep (6)) (2010) 349–355.
4
N. Grover et al. / International Journal of Pediatric Otorhinolaryngology Extra 11 (2016) 1–4
[6] D.H. Lee, T.M. Yoon, J.K. Lee, S.C. Lim, Clinical utility of fine needle aspiration cytology in pediatric parotid tumors, Int. J. Pediatr. Otorhinolaryngol. 77 (8) (2013) 1272–1275. [7] L.J. Orvidas, J.L. Kasperbauer, J.E. Lewis, K.D. Olsen, T.G. Lesnick, Pediatric parotid masses, Arch. Otolaryngol. Head Neck Surg. 126 (2) (2000) 177–184. [8] A.L. Bruu, R. Hjetland, E. Holter, L. Mortensen, O. Nata˚s, W. Petterson, A.G. Skar, T. Skarpaas, T. Tjade, B. Asjø, Evaluation of 12 commercial tests for detection of Epstein–Barr virusspecific and heterophile antibodies, Clin. Diagn. Lab. Immunol. 7 (3) (2000) 451.
[9] R.D. Pitetti, S. Laus, R.M. Wadowsky, Clinical evaluation of a quantitative real time polymerase chain reaction assay for diagnosis of primary Epstein–Barr virus infection in children, Pediatr. Infect. Dis. J. 22 (8) (2003) 736. [10] Petros I. Rafailidis, Michael N. Mavros, Anastasios Kapaskelis, Matthew E. Falagas, Antiviral treatment for severe EBV infections in apparently immunocompetent patients, Mol. Cytogenet. 1 (2008) 18.