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Parotid lymphoepithelial cysts in human immunodeficiency virus: a review

Published online by Cambridge University Press:  29 October 2013

D Sujatha ,
K Babitha ,
R S Prasad  and
A Pai
D Sujatha
Affiliation:
Department of Oral Medicine and Radiology, The Oxford Dental College, Bommanahalli, Bangalore, Karnataka, India
K Babitha*
Affiliation:
Department of Oral Medicine and Radiology, The Oxford Dental College, Bommanahalli, Bangalore, Karnataka, India
R S Prasad
Affiliation:
Department of Oral Medicine and Radiology, The Oxford Dental College, Bommanahalli, Bangalore, Karnataka, India
A Pai
Affiliation:
Department of Oral Medicine and Radiology, The Oxford Dental College, Bommanahalli, Bangalore, Karnataka, India
*
Address for correspondence: Dr K Babitha, Department of Oral Medicine and Radiology, The Oxford Dental College, Bommanahalli, Hosur Road, Bangalore 560068, Karnataka, India E-mail: dr.babitha.k@gmail.com
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Abstract

Background:

Many patients with human immunodeficiency virus present with atypical features. Early indicators of human immunodeficiency virus are scarce and hence most affected patients are diagnosed in the later stages of the disease, which is associated with poor prognosis. Salivary gland disease usually develops before acquired immunodeficiency syndrome, and is sometimes the first manifestation of human immunodeficiency virus infection. Salivary gland lesions include benign lymphoepithelial cysts of the parotid gland, which are seen in 3–6 per cent of patients. Many of the reported lesions are diagnosed on routine examination.

Objective:

This review aimed to highlight the association between parotid gland benign lymphoepithelial cyst and human immunodeficiency virus infection, in order to aid early diagnosis and management of the disease.

Conclusion:

Human immunodeficiency virus testing is recommended for patients with benign lymphoepithelial cysts, as this can often be the first indication of human immunodeficiency virus infection. Benign lymphoepithelial cysts are important diagnostic and prognostic indicators in human immunodeficiency virus infection.

Keywords

Parotid GlandCystHIVDiagnosis
Type
Review Articles
Information
The Journal of Laryngology & Otology , Volume 127 , Issue 11 , November 2013 , pp. 1046 - 1049
Copyright
Copyright © JLO (1984) Limited 2013 

Introduction

Benign lymphoepithelial cyst of the parotid gland is the most common salivary gland pathology in human immunodeficiency virus (HIV) patients.Reference Maremonti, Colmenero Ruiz, Patron, Zupi, Longo and Califano1 The cysts are early indicators of HIV infection, with an incidence rate of 3–6 per cent in affected adultsReference Kothari, Madiwale and Deshpande2 and 30 per cent in the paediatric population.Reference Kabenge, Ng, Muyinda and Ameda3

Hildebrandt (1895) was the first to report benign lymphoepithelial cyst of the parotid gland. Its association with HIV infection was first described by Ryan and colleagues in 1985.Reference Kumar and Sharma4

Lymphoid hyperplasia of the salivary gland is an important diagnostic and prognostic indicator in HIV infection, which may reflect a localised manifestation of persistent, generalised lymphadenopathy.Reference Kumar and Sharma4

Other parotid gland pathologies seen in HIV infection include: sicca syndrome, diffuse infiltrative lymphocytosis syndrome, parotitis secondary to infection, intraparotid lymphadenopathy, cryptococcus infection, benign lymphoepithelial lesions, and salivary gland neoplasms such as adenoid cystic carcinoma, Kaposi sarcoma and lymphoma.Reference Kumar and Sharma4

Aetiopathogenesis

Human immunodeficiency virus infection is associated with hyperplasia of the intraparotid lymph nodes with interstitial lymphoid infiltrate. Parotid benign lymphoepithelial cysts occur secondary to this hyperplasia.Reference Kothari, Madiwale and Deshpande2

There are two main hypotheses concerning the development of benign lymphoepithelial cyst. The ‘obstructive theory’ states that lymphoid proliferation in the parotid gland leads to ductal obstruction and salivary dilatation that mimics a true cyst.Reference Steehler, Steehler and Davison5 The other hypothesis states that HIV-related reactive lymphoid proliferation occurs in the lymph nodes of the parotid gland; the parotid glandular epithelium becomes trapped in normal intraparotid lymph nodes, resulting in cystic enlargement (Figure 1).Reference Steehler, Steehler and Davison5

Fig. 1 Schematic representation of aetiopathogenesis of benign lymphoepithelial cyst in human immunodeficiency virus.6–10 HIV = human immunodeficiency virus; LEC = lymphoepithelial cyst

Clinical features

Benign lymphoepithelial cyst affects males and females equally, and occurs in both adults and children.Reference Kabenge, Ng, Muyinda and Ameda3, Reference Meyer, Lubbe and Fagan11 The cysts are painless, slow-growing,Reference Meyer, Lubbe and Fagan11 frequently bilateral,Reference Kumar and Sharma4, Reference Meyer, Lubbe and Fagan11 soft in consistency and involve the superficial lobe of the parotid gland,Reference Kumar and Sharma4 with multiple cysts being more common than single.Reference Ellis12 Their size varies from 0.5 cm to 5 cm in diameter. Cervical lymphadenopathyReference Ellis12 is evident in 50 per cent of patients.Reference Kothari, Madiwale and Deshpande2, Reference Kumar and Sharma4 Parotid benign lymphoepithelial cyst rarely involves the facial nerve, and can cause gross facial deformities.

Non-HIV patients presenting with benign lymphoepithelial cyst can be differentiated from HIV-infected counterparts (Table I).

Table I Benign lymphoepithelial cyst in HIV and Non-HIV patientsReference Kothari, Madiwale and Deshpande2, Reference Kabenge, Ng, Muyinda and Ameda3, Reference Alves, Ribeiro Júnior, Borba, Souza and Naclério-Homem13, Reference Naidoo, Singh, Ramdial, Moodley, Allopi and Lester14

HIV = human immunodeficiency virus; CT = computed tomography; MRI = magnetic resonance imaging; Bcl = B-cell lymphoma

Numerous benign lymphoepithelial cysts are associated with a condition called diffuse infiltrative lymphocytosis syndrome, which is considered to be a subset of HIV that affects 1 to 2 per cent of patients.Reference Tripathi, Gupta, Ahmad, Bhandari and Kalra15 Prior to the association between diffuse infiltrative lymphocytosis syndrome and HIV, diffuse infiltrative lymphocytosis syndrome was thought to be associated with Sjögren's syndrome (Table II).Reference Krishnamurthy, Gowdanakatte and Gubanna7, Reference Tripathi, Gupta, Ahmad, Bhandari and Kalra15

Table II Diffuse infiltrative lymphocytosis syndrome and sjögren's syndrome comparisonReference Tiwari, Kini, Pai and Rau6, Reference Tripathi, Gupta, Ahmad, Bhandari and Kalra15

Investigations

Those diagnosed with parotid benign lymphoepithelial cysts, with or without systemic manifestations, should undergo tests for HIV infection. Other investigations might include fine needle aspiration cytology, imaging (e.g. ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI)), histopathology, immunoperoxidase studies and immunohistochemistry.

Fine needle aspiration cytology is considered to be the basic diagnostic tool for differentiating lymphoproliferative lesions (Table III).Reference Kothari, Madiwale and Deshpande2, Reference Steehler, Steehler and Davison5, Reference Tiwari, Kini, Pai and Rau6, Reference Chhieng, Cangiarella and Cohen16

Table III FNAC findings in various lymphoproliferative lesionsReference Kothari, Madiwale and Deshpande2, Reference Steehler, Steehler and Davison5, Reference Tiwari, Kini, Pai and Rau6, Reference Chhieng, Cangiarella and Cohen16

FNAC = fine needle aspiration cytology

Imaging modalities

Ultrasonography

Benign lymphoepithelial lesions in the parotid gland can manifest in HIV-positive patients with a wide spectrum of heterogeneous appearances sonographically, ranging from simple cysts to mixed masses.Reference Martinoli, Pretolesi, Del Bono, Derchi, Mecca and Chiaramondia17

Benign lymphoepithelial cysts typically appear as prominent round hypoechoic areas, ranging from 0.5 cm to 5 cm in diameter, with well circumscribed margins, internal septations and posterior acoustic enhancement.Reference Kabenge, Ng, Muyinda and Ameda3

Computed tomography and magnetic resonance imaging

Multiple small cysts with enlarged parotid glands are usually observable on CT and MRI scans. Computed tomography can demonstrate cervical lymphadenopathy in 100 per cent of cases.Reference Krishnamurthy, Gowdanakatte and Gubanna7 However, these features are non-specific and are not diagnostic of benign lymphoepithelial cyst, and hence are used only as diagnostic adjuncts for surgery.Reference Meyer, Lubbe and Fagan11

Histopathology

Histopathology of benign lymphoepithelial cyst reveals a cystic wall formed of multi-layered squamous epithelium comprising germinal centres and dense lymphoid infiltrate. Pale homogeneous material with foamy macrophages and lymphocytes are seen in the lumen. The salivary glandular parenchyma adjacent to these cysts appears normal.Reference Krishnamurthy, Gowdanakatte and Gubanna7, Reference Tripathi, Gupta, Ahmad, Bhandari and Kalra15

Immunoperoxidase studies

Positivity for cytokeratin reveals the epithelial origin of benign lymphoepithelial cyst. Positive staining for cluster of differentiation antigens 45, 20, 79a and 3 indicates a lymphoid component to the cysts.Reference Maiorano and Favia18

Immunohistochemistry

Immunohistochemistry highlights the reactive nature of benign lymphoepithelial cysts.Reference Kothari, Madiwale and Deshpande2 Active replication is indicated by the presence of HIV proteins or RNA on the cells of the salivary gland lymphoid follicles (Table IV).Reference Tiwari, Kini, Pai and Rau6

Management

Treatment for benign lymphoepithelial cyst is sought mainly for cosmetic reasons, as most patients are asymptomatic. Fine needle aspiration cytology or biopsy with adjunctive imaging can indicate malignant transformation, which has to be managed accordingly.Reference Kumar and Sharma4

The combination of azathioprine with newer protease inhibitors is successful in treating benign lymphoepithelial cyst, especially when it coincides with diffuse infiltrative lymphocytosis syndrome. This treatment, which may be used in combination with corticosteroids, seems to be the most effective means of treating the parotid swellings of patients with diffuse infiltrative lymphocytosis syndrome. Patients who do not qualify for anti-retroviral therapy can undergo alcohol sclerotherapy, which is considered to be an effective, safe and simple treatment of diffuse infiltrative lymphocytosis syndrome. Doxycycline sclerotherapy has been used in younger patients to avoid surgery.Reference Kumar and Sharma4 Superficial parotidectomy is favoured over enucleation in the treatment of benign lymphoepithelial cyst owing to the latter's high recurrence rate.Reference Kumar and Sharma4

Conclusion

Benign lymphoepithelial cyst can be an early indicator of HIV infection. The cysts are also rarely seen in non-HIV positive patients; HIV testing is mandatory for all patients presenting with these cysts. It is imperative that oral physicians are aware of this entity, which may mimic other parotid pathologies owing to its atypical features.

References

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Figure 0

Fig. 1 Schematic representation of aetiopathogenesis of benign lymphoepithelial cyst in human immunodeficiency virus.6–10 HIV = human immunodeficiency virus; LEC = lymphoepithelial cyst

Figure 1

Table I Benign lymphoepithelial cyst in HIV and Non-HIV patients2,3,13,14

Figure 2

Table II Diffuse infiltrative lymphocytosis syndrome and sjögren's syndrome comparison6,15

Figure 3

Table III FNAC findings in various lymphoproliferative lesions2,5,6,16

Figure 4

Table IV Conditions mimicking benign lymphoepithelial cyst6,12,15,16,19