Benign lymphoepithelial cysts are non-neoplastic parotid cysts that form when lymphoid tissue in and around the intraparotid lymph nodes proliferates and obstructs the salivary ducts running through it. When they are multiple and bilateral in an adult, they are HIV-associated salivary gland disease until proven otherwise. The combination of innumerable bilateral parotid cysts, reactive cervical lymphadenopathy and adenotonsillar hypertrophy is close to diagnostic, and in a substantial number of patients the parotid swelling is the first clinical manifestation of HIV infection, which is why a radiology report is sometimes what prompts the test [1][2][17].
The lesion also exists in a sporadic, non-HIV form, which is usually a single unilateral cyst, and in an autoimmune form linked to Sjogren disease. This article covers the entity and the wider question that brings most readers here: how to work through a cystic lesion in the parotid gland on CT, MRI and ultrasound, what normal parotid anatomy you need to report before you characterise the lesion, and which features mean the cyst is not benign.
- Key facts for practice and radiology exams
- Spot diagnosis
- Parotid gland anatomy on CT and MRI: what to report before you characterise the lesion
- What are benign lymphoepithelial cysts?
- Imaging features on CT, MRI and ultrasound
- The spectrum of HIV parotid lymphoid disease
- Cystic lesions of the parotid gland: the differential diagnosis
- When a cystic parotid lesion is not benign
- Sjogren disease, lymphoepithelial sialadenitis and the lymphoma question
- How to work up a cystic parotid mass
- Management of HIV-associated lymphoepithelial cysts
- What to put in the report
- Frequently asked questions
- References
Key facts for practice and radiology exams
- The pattern is the diagnosis. Innumerable bilateral thin-walled parotid cysts plus cervical lymphadenopathy plus adenoid, palatine and lingual tonsillar hypertrophy equals HIV-associated salivary gland disease. None of those three findings alone is specific; together they are [2].
- How common. Benign lymphoepithelial cysts are reported in roughly 3 to 6 percent of people living with HIV, and salivary gland disease of some kind in a larger fraction. They usually precede AIDS and can be the presenting feature [1].
- Why the parotid and not the submandibular gland. The parotid is the only major salivary gland that encapsulates late enough in development to trap lymph nodes inside its capsule. Lymphoid hyperplasia in those intraglandular nodes obstructs the ducts passing through them, which is the accepted mechanism for both these cysts and Warthin tumour.
- Terminology. Benign lymphoepithelial cyst (BLEC), benign lymphoepithelial lesion (BLEL), cystic lymphoid hyperplasia and HIV-associated salivary gland disease all describe points along the same spectrum, from purely solid lymphoid hyperplasia to purely cystic disease [2].
- Where it sits in the WHO classification. In the 5th edition of the WHO classification of head and neck tumours the salivary non-neoplastic epithelial lesions category was cut to two entries, nodular oncocytic hyperplasia and lymphoepithelial sialadenitis, and sclerosing polycystic adenosis was renamed sclerosing polycystic adenoma and reclassified as a benign neoplasm. The lymphoepithelial cyst is listed separately, among cysts and cyst-like lesions, alongside ranula, branchial cleft cyst and thyroglossal duct cyst [6][7].
- Treatment is medical first. Antiretroviral therapy, then sclerotherapy or repeated aspiration for cosmesis. Parotidectomy is a last resort because of the facial nerve [12].
- The trap. A unilateral solitary cystic parotid lesion in an older smoker is a Warthin tumour or a cystic nodal metastasis until proven otherwise, not a lymphoepithelial cyst. A cyst with a thick irregular wall or an enhancing mural nodule needs tissue [4][5].
Spot diagnosis
Benign lymphoepithelial lesions are associated with all of the following except?
- Parotid gland enlargement
- Sialolithiasis
- Cervical lymphadenopathy
- Tonsillar hypertrophy
Click here for the answer
Sialolithiasis. Calculi are far more common in the submandibular gland, and they cause obstructive sialadenitis, not lymphoepithelial cysts. The other three findings are the classic triad of HIV-associated salivary gland disease.
Parotid gland anatomy on CT and MRI: what to report before you characterise the lesion
Half of the value of a parotid study is anatomical rather than diagnostic. The surgeon needs to know which lobe the lesion is in, whether the duct is involved and whether there is more than one lesion, and those answers change the operation more often than a confident histological guess does.
| Structure | How to find it on CT or MRI | Why it matters |
|---|---|---|
| Superficial and deep lobe | The facial nerve is not reliably seen on routine imaging. Use the retromandibular vein and external carotid artery at the level of the mandibular ramus as a surrogate plane: lateral to the vein is superficial, medial is deep. | Decides superficial versus total parotidectomy. In a meta-analysis of 21 studies and 2225 patients, the anatomical lines together gave a pooled sensitivity of 0.67 and specificity of 0.92, area under the summary ROC curve 0.879 [9]. |
| Intraparotid facial nerve | Directly traceable on high-resolution 3D heavily T2-weighted MRI with a surface coil, running just lateral to the retromandibular vein. | Direct tracing and the minimum distance from the parotid fascia to the tumour outperformed the vein line alone in the same meta-analysis [9]. |
| Stensen duct | Runs forward over the masseter, turns medially at its anterior border and pierces buccinator opposite the second upper molar. Normally not visible unless dilated. | A dilated duct points to obstruction (calculus, stricture, tumour) rather than a primary cystic lesion, and a cyst communicating with the duct is a salivary duct cyst or sialocele. |
| Intraparotid lymph nodes | Small ovoid structures with a fatty hilum, mostly in the superficial lobe. | The parotid is the only major salivary gland with nodes inside its capsule. That is why lymphoepithelial cysts, Warthin tumour and cystic nodal metastases from scalp or ear skin cancers all happen here. |
| Accessory parotid gland | Separate islet of salivary tissue sitting on the masseter along the course of Stensen duct, present in a minority of people. | Do not report it as a mass, and remember it can host the same tumours as the main gland. |
| Stylomandibular tunnel and parapharyngeal fat | The gap between the mandibular ramus and the styloid process, with the fat pad medial to it. | A deep-lobe lesion that squeezes through this tunnel takes the dumbbell shape and displaces the parapharyngeal fat medially. |
| Gland attenuation and signal | The normal adult parotid is fattier than the submandibular gland, so it is relatively low in attenuation on CT and relatively high on T1. | That fatty background makes a T1-hypointense cyst conspicuous, and a diffusely dense, non-fatty gland is itself abnormal (infiltration, sialadenitis or lymphoid disease). |
What are benign lymphoepithelial cysts?
Lymphoid tissue within and around the intraparotid lymph nodes proliferates, and the salivary ducts that pass through that lymphoid tissue become obstructed and dilate cystically. The result is a lesion with two components, a lymphoid one and an epithelial one, which is where the name comes from: the cyst is lined by squamous, cuboidal or columnar epithelium and its wall is packed with reactive lymphoid follicles [2].
In HIV the process is florid. Germinal centres are large and irregular, lymphoepithelial islands form, and interfollicular lymphocytes are predominantly CD8-positive, mirroring the systemic CD8 expansion. Immunostaining for HIV-1 p24 antigen can confirm the association directly in equivocal cases [19]. The important practical point is that the lesion is a reactive process, not a tumour, and it behaves like one: it regresses when the viral load falls [20].
The same histology without HIV occurs in two settings. A sporadic lymphoepithelial cyst is usually solitary and unilateral and may arise from branchial remnants or from ducts within an intraparotid node. In Sjogren disease the counterpart is lymphoepithelial sialadenitis, in which B cells infiltrate ductal epithelium and produce the same lymphoepithelial islands, often with cystic change. Because a solitary lymphoepithelial cyst can be the first sign of undiagnosed HIV, the pathology literature explicitly warns against reporting one without asking about serostatus [17].
Imaging features on CT, MRI and ultrasound
| Modality | Findings | Pitfalls and pearls |
|---|---|---|
| Ultrasound | Enlarged, heterogeneous gland containing multiple anechoic or hypoechoic lesions with posterior acoustic enhancement. Thin internal septa, a vascular pedicle or a small mural nodule may be present. Reactive intraparotid and cervical nodes with preserved fatty hila. | First-line and the modality that guides fine-needle aspiration. Deep-lobe lesions are poorly seen because the mandibular ramus blocks the beam [10]. Doppler was used in the original description to show the internal vascular stalk of the solid components [3]. |
| Contrast-enhanced CT | Bilaterally enlarged, diffusely dense parotid glands containing multiple well-defined, thin rim-enhancing cystic lesions. Solid components enhance heterogeneously. Reactive cervical lymphadenopathy and adenoid, palatine and lingual tonsillar hypertrophy complete the picture. | Scan from the skull base to the clavicles so that the nodes and Waldeyer ring are included. Look specifically for a thick or irregular wall or an enhancing mural nodule, which takes the lesion out of this diagnosis. |
| MRI | Cystic components follow fluid: low on T1, markedly high on T2 and STIR, with thin rim enhancement. Solid components are intermediate on T1 and T2 and enhance. Cervical nodes and Waldeyer ring are hyperintense on fluid-sensitive sequences. | The most sensitive modality for the number of lesions and for deep-lobe extent. Proteinaceous or haemorrhagic cyst content can raise T1 signal and mimic a solid lesion, so read the post-contrast subtraction or the T2 before calling enhancement. |
| Diffusion-weighted imaging | Simple cyst contents show facilitated diffusion with high apparent diffusion coefficient values. | A low ADC in a nominally cystic parotid lesion should prompt a rethink. In a systematic review of parotid MRI, ADC thresholds separating benign from malignant tumours fell between 1.267 and 1.60 x 10 to the minus 3 mm squared per second, with Warthin tumour sitting low because of its lymphoid stroma [8]. |
| Dynamic contrast-enhanced MRI | Cystic lesions show minimal enhancement of the contents with rim enhancement only. | Perfusion curve shape separates pleomorphic adenoma (slow progressive enhancement), Warthin tumour (early peak, rapid washout), malignancy and cystic lesions better than any single morphological sign [8]. |
| Technetium-99m pertechnetate | No uptake in lymphoepithelial cysts. | Warthin tumour and oncocytoma concentrate pertechnetate, which is a cheap way to settle that specific differential when it is available. |
Annotated case
Slide to see the annotated image.
The spectrum of HIV parotid lymphoid disease
The parotid findings in HIV sit on a continuum, and the three-tier description below is a way of naming where on that continuum a given gland is rather than three separate diseases. All three regress on effective antiretroviral therapy.
| Tier | Imaging appearance | Notes |
|---|---|---|
| Persistent generalised lymphadenopathy of the parotid | Multiple solid intraparotid nodules, no cysts. Gland mildly enlarged. | Reactive intraparotid nodes. Usually accompanied by generalised lymphadenopathy elsewhere. |
| Benign lymphoepithelial lesion (BLEL) | Mixed solid and cystic lesions within an enlarged gland. | The commonest appearance, and the reason the terminology is inconsistent in the literature. |
| Benign lymphoepithelial cyst (BLEC) | Purely cystic, innumerable, bilateral, thin-walled. | The end of the spectrum most likely to be disfiguring and the one most often treated with sclerotherapy. |
One further HIV entity belongs here and is often missed. Diffuse infiltrative lymphocytosis syndrome (DILS) is a CD8-positive T-cell infiltration of multiple organs that presents as a Sjogren-like illness: sicca symptoms with bilateral parotitis, lymphadenopathy, and extraglandular disease including lymphocytic interstitial pneumonia, facial nerve palsy, aseptic meningitis, polyneuropathy, interstitial nephritis and hepatic infiltration. It is diagnosed on labial salivary gland biopsy with a focus score of 1 or more, and it too responds to antiretroviral therapy [13]. If a patient with bilateral parotid enlargement has an unexplained neuropathy or interstitial lung disease, DILS is the link.
Cystic lesions of the parotid gland: the differential diagnosis
The cleanest way to think about a cystic parotid lesion is the three-group scheme used in the radiologic-pathologic literature: non-neoplastic cysts, benign tumours with cystic change, and malignant tumours with cystic change [5]. The single most useful discriminators at the scanner are laterality, number, and whether there is a mural nodule.
| Lesion | Typical appearance | What gives it away |
|---|---|---|
| HIV-associated lymphoepithelial cysts | Innumerable, bilateral, thin-walled cysts in expanded glands, often with solid components. | Cervical lymphadenopathy plus adenotonsillar hypertrophy. Ask about HIV status [1][2]. |
| Sporadic lymphoepithelial cyst | Solitary, unilateral, thin-walled, well-circumscribed. | Identical histology without HIV, but it can be the first sign of undiagnosed HIV, so it is not a reason to stop asking [17]. |
| Lymphoepithelial sialadenitis in Sjogren disease | Bilateral heterogeneous glands with a micronodular or honeycomb pattern, small cysts, later fatty atrophy. Submandibular glands involved too. | Dry eyes and mouth, anti-Ro and anti-La antibodies, and the salivary gland ultrasound pattern. Carries lymphoma risk [14][16]. |
| Warthin tumour | Solid-cystic mass, usually in the parotid tail, bilateral or multifocal in a minority. Enhancing mural nodule, low ADC, early enhancement with washout. | Older smoker. Takes up technetium-99m pertechnetate. Discrete masses, not innumerable cysts [8]. |
| First branchial cleft cyst | Unilateral cyst in or adjacent to the parotid, often near the external auditory canal or angle of the mandible, sometimes with a tract. | Younger patient, recurrent infection, a sinus opening in the neck or ear canal [4]. |
| Salivary duct cyst or sialocele | Unilocular cyst that communicates with a dilated Stensen duct. | Trace the duct. History of trauma, surgery or obstruction [4]. |
| Plunging ranula | Unilocular, thin-walled cyst that starts in the sublingual space and tails through mylohyoid into the submandibular space. | Location, not the parotid, but a common confusion on a neck study. The tail sign is diagnostic [4]. |
| Abscess | Thick irregular enhancing wall, restricted diffusion of the contents, surrounding fat stranding, clinically hot and painful. | The one cystic lesion where restricted diffusion is expected. |
| Lymphatic malformation | Multiloculated, transspatial, fluid-fluid levels after bleeding, no solid enhancing component. | Crosses fascial planes, which epithelial cysts do not. |
| Low-grade mucoepidermoid carcinoma | Can be predominantly cystic with an enhancing mural nodule and internal septa. | The commonest malignancy to masquerade as a benign parotid cyst. Any mural nodule mandates tissue [5]. |
| Cystic nodal metastasis | Unilateral cystic intraparotid or level II node with a thick wall, in an adult. | HPV-related oropharyngeal squamous cell carcinoma or cutaneous cancer of the scalp, ear or face. Examine the skin and the tonsil, not just the gland. |
| Parotid lymphoma | Homogeneous solid intraparotid masses, sometimes with cystic change, often bilateral. | In Sjogren disease and in HIV. A new solid mass in a gland known to carry lymphoepithelial lesions is the scenario that must not be dismissed [16]. |
When a cystic parotid lesion is not benign
These are the findings that should stop you writing a reassuring report. None of them is specific on its own, and all of them are a reason to recommend tissue rather than follow-up imaging.
| Red flag | Why it matters |
|---|---|
| An enhancing mural nodule or thick irregular wall | The commonest imaging appearance of cystic low-grade mucoepidermoid carcinoma and of cystic nodal metastasis. |
| Solitary and unilateral in an adult over 50 | Shifts the differential from reactive disease to Warthin tumour, cystic malignancy or a cystic node. |
| Low ADC in the solid component | Lymphoid and high-cellularity tumours restrict diffusion. Reported benign-malignant ADC thresholds sit between 1.267 and 1.60 x 10 to the minus 3 mm squared per second [8]. |
| T2-hypointense solid component | Most benign parotid tumours are T2-bright. T2 hypointensity is one of the features proposed as suspicious in the ACR review of parotid imaging [10]. |
| Ill-defined margins or infiltration beyond the gland | Extraglandular extension into masseter, the parapharyngeal space or the mandible. |
| Perineural enhancement along the facial nerve or the mandibular division of the trigeminal nerve | Perineural spread. MRI is the only modality that shows it, which is why it is preferred when malignancy is a concern [10]. |
| Facial nerve weakness on examination | The single most robust clinical predictor of a malignant parotid mass, and it outranks anything on the images. |
| Growth or a new solid component on antiretroviral therapy | Lymphoepithelial disease should shrink on treatment. A lesion that does the opposite is a different disease, and lymphoma is the one to exclude [20]. |
| New or enlarging cervical nodes with loss of the fatty hilum | Reactive adenopathy is part of the picture in HIV, but necrotic or round nodes without a hilum are not. |
Sjogren disease, lymphoepithelial sialadenitis and the lymphoma question
Sjogren disease produces the same histological lesion in the parotid without HIV, and it is the differential the referring physician most often wants excluded. The imaging pattern is different in a way that is usually obvious: Sjogren disease gives a bilaterally heterogeneous, micronodular or honeycomb gland with small cysts and, in late disease, fatty atrophy, and it involves the submandibular glands too. HIV-associated disease gives discrete, larger, more uniformly cystic lesions in glands that are enlarged rather than atrophic.
Ultrasound has become the working tool here. The OMERACT ultrasound working group agreed consensual definitions and a four-grade (0 to 3) scoring system for parotid and submandibular gland involvement, scored on homogeneity and the presence of anechoic or hypoechoic areas, and showed acceptable reliability on video clips and then in patients [14][15]. A score of 2 or 3 in either gland is the threshold most studies use as a positive scan. It is cheap, repeatable and does not need contrast, and it is now widely used alongside the serology and the labial gland biopsy.
The reason it matters to a radiologist is lymphoma. Lymphoepithelial sialadenitis is the substrate for parotid extranodal marginal zone (MALT) lymphoma. In a prospective Spanish cohort of 314 patients followed for a median of 9.5 years, 11 (3.5 percent) developed non-Hodgkin lymphoma, a standardised incidence ratio of 15.36 against the general population, with cryoglobulinaemia the strongest independent predictor (hazard ratio 11.07) [16]. Current EULAR recommendations manage the glandular disease symptomatically and reserve systemic immunosuppression for extraglandular manifestations [18], so the imaging follow-up question is almost always about lymphoma rather than about the sicca symptoms. A new dominant solid mass in a gland that previously showed only diffuse lymphoepithelial change is the finding to flag.
How to work up a cystic parotid mass
The ACR Appropriateness Criteria topic that covers this is Neck Mass/Adenopathy, and its parotid region mass variant rates ultrasound of the neck, contrast-enhanced CT of the neck and MRI of the neck without and with intravenous contrast as equivalent, usually appropriate options for initial imaging. Catheter angiography, CT and MR angiography and FDG PET are all rated usually not appropriate as an initial study [10].
- Ultrasound first in most practices, because the gland is superficial, the study is quick and unguided fine-needle aspiration can be converted to a guided one in the same appointment.
- MRI without and with contrast when the lesion involves or approaches the deep lobe, when perineural spread or skull base extension is a concern, or when the ultrasound is indeterminate. Include diffusion-weighted imaging, and dynamic contrast-enhanced imaging if the protocol allows it [8].
- Contrast-enhanced CT from the skull base to the clavicles when the question is extent of glandular involvement and nodal disease, as in suspected HIV-associated disease, or when MRI is not available or tolerated.
- Fine-needle aspiration, preferably ultrasound-guided, for any lesion that is not a confident simple cyst. Report it using the Milan System.
- HIV testing in any adult with multiple bilateral parotid cysts, and in a solitary lymphoepithelial cyst where serostatus is unknown [1][17].
The second edition of the Milan System for Reporting Salivary Gland Cytopathology, published in July 2023, kept the six categories and revised the risks of malignancy on the basis of systematic reviews. It also added a chapter on salivary gland imaging, which makes it a useful shared vocabulary between the radiologist and the cytopathologist [11].
| Milan category | Revised risk of malignancy (2nd edition) | Usual management |
|---|---|---|
| I. Non-diagnostic | 15 percent | Repeat aspiration, preferably image-guided, with correlation |
| II. Non-neoplastic | 11 percent | Clinical and radiological follow-up |
| III. Atypia of undetermined significance | 30 percent | Repeat aspiration, core biopsy or excision; individualised |
| IVA. Neoplasm: benign | under 3 percent | Surgery or surveillance depending on the tumour and the patient |
| IVB. Neoplasm of uncertain malignant potential (SUMP) | 35 percent | Surgery, usually with intraoperative frozen section |
| V. Suspicious for malignancy | 83 percent | Surgery |
| VI. Malignant | over 98 percent | Surgery with appropriate oncological planning |
Management of HIV-associated lymphoepithelial cysts
- Antiretroviral therapy is first-line. The glands commonly shrink once the viral load is controlled, and the lesion is best understood as a marker of uncontrolled infection [2][20].
- Repeated aspiration and sclerotherapy for cysts that stay disfiguring. A systematic review of 474 sclerotherapy procedures for benign head and neck cystic lesions (OK-432, ethanol, doxycycline, tetracycline and bleomycin) reported complete response in 60.5 percent, partial response in 27.9 percent and no response in 11.6 percent. OK-432 achieved complete response more often than ethanol, 62.0 versus 39.4 percent. Only 11.2 percent needed subsequent surgery, and the only serious complication reported was a single case of laryngeal oedema managed without an operation [12].
- Radiotherapy is historical. It was used before effective antiretroviral therapy and is rarely appropriate now, given the radiation dose to the gland and the long life expectancy of treated patients.
- Parotidectomy is a last resort, reserved for diagnostic uncertainty or failure of conservative management, because of the risk to the facial nerve and the tendency of the disease to recur in remaining gland tissue.
What to put in the report
- Laterality and number of lesions, and whether the glands themselves are enlarged, normal or atrophic.
- For each dominant lesion: size, lobe (superficial or deep, referenced to the retromandibular vein), wall thickness, the presence or absence of a mural nodule or enhancing solid component, and the ADC if diffusion was acquired.
- Relationship to Stensen duct, and whether the duct is dilated.
- Extraglandular extension, masticator or parapharyngeal space involvement, and any perineural enhancement.
- Cervical nodes by level, with size, shape and whether the fatty hilum is preserved.
- Waldeyer ring: adenoid, palatine and lingual tonsillar hypertrophy, which supports the HIV diagnosis.
- An explicit recommendation: HIV testing where the pattern fits and status is unknown, or ultrasound-guided fine-needle aspiration where there is a solid or mural component.
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Frequently asked questions
References
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- Talmor G, Nguyen B, Mir G, Badash I, Kaye R, Caloway C. Sclerotherapy for benign cystic lesions of the head and neck: systematic review of 474 cases. Otolaryngol Head Neck Surg. 2021;165(6):775-783. PMID 33755513
- Ghrenassia E, Martis N, Boyer J, Burel-Vandenbos F, Mekinian A, Coppo P. The diffuse infiltrative lymphocytosis syndrome (DILS). A comprehensive review. J Autoimmun. 2015;59:19-25. PMID 25660200
- Jousse-Joulin S, DAgostino MA, Nicolas C, Naredo E, Ohrndorf S, Backhaus M, et al. Video clip assessment of a salivary gland ultrasound scoring system in Sjogren syndrome using consensual definitions: an OMERACT ultrasound working group reliability exercise. Ann Rheum Dis. 2019;78(7):967-973. PMID 31036626
- Hocevar A, Bruyn GA, Terslev L, De Agustin JJ, Hocevar Y, Iagnocco A, et al. Development of a new ultrasound scoring system to evaluate glandular inflammation in Sjogren syndrome: an OMERACT reliability exercise. Rheumatology (Oxford). 2022;61(8):3341-3350. PMID 34849616
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- Zanelli M, Sanguedolce F, Zizzo M, Ricci S, Bisagni A, Ascani S. Benign lymphoepithelial cyst of the parotid gland: mind the underlying cause. Int J Surg Pathol. 2021;29(1):78-79. PMID 32188312
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Further reading: the head and neck volume of the Diagnostic Imaging series remains the best single desk reference for this material. See our list of recommended radiology books.
Co-Authors: Dr. Mansi Sarmalkar. Illustration by Dr. Disha Lokhandwala.
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