B e n i g n ly m ph o e pi t h e l i a l c y s ts o f th e

p a rot i d:
l o n g -t e r m s u r g i c a l resu l t s
Matthew K Steehler,1 Mark W Steehler,2,3,4 and Steven P Davison1,5

dr. Dess yta Sukma N urma ulinda

 Abstract
Benign lymphoepithelial cysts (BLEC) are a widely recognized cause of parotid
gland swelling in patients infected with the human immunodeficiency virus
(HIV).

These cysts are pathognomonic for HIV.

The cysts frequently grow to be exceptionally large, causing physical deformity

and gross asymmetry of facial contour.

Based on this surgical case-control and our review of the literature, it is concluded
that surgical intervention offers the best cosmetic result for these patients.

Keywords: parotid, benign lymphoepithelial cyst, parotidectomy, human immunodeficiency virus, head and
neck surgery, cosmetic surgery
A 32-year-old female with human immunodeficiency virus (HIV) infection presented to our
office six years after we had performed a right superficial parotidectomy for a benign
lymphoepithelial cyst (BLEC). This was cured surgically with excellent cosmetic outcome.
The patient presented at this time with a similarly large lesion on the contralateral side which
was removed in a similar fashion (see Figure 1).
 Literature Review
Benign lymphoepithelial cysts (BLECs) are a widely recognized
cause of parotid gland swelling in HIV-infected patients.

These lesions can be a cosmetically devastating physical deformity,

causing isolation and depression.16

They are easily recognized as a manifestation of HIV in the aware

population.
BLEC has two hypothesized etiologic mechanisms.

The first : obstructive theory

Lymphoid proliferation in the parotid gland
ductal obstruction and salivary dilation = mimics a true cyst.

The second
HIV-related reactive lymphoproliferation occurs in the lymph nodes
of the parotid gland
glandular epithelium becomes trapped in normal intraparotid lymph
nodes = cystic enlargement.
Diagnosis of BLEC is made based on history, physical examination,
and fine-needle aspiration biopsy.

Physical examination will show obvious fluctuant cystic facial

deformity.

Fine-needle aspiration biopsy of BLEC results in clear,

proteinaceous (straw-colored) fluid, with a mixture of epithelial
(squamous) and benign lymphoid cells.7,10
Treatment of this particular pathology has been widely debated in the
literature.

Previous treatments for BLEC have included

Repeated fine-needle aspiration and drainage
Surgery
Radiotherapy
Sclerotherapy
Conservative therapy with institution of highly active antiretroviral
therapy (HAART) medications.26,1022
 HAART
Resource Modality Sample Follow-up Results

Stavidune
Syebele and 90% of patients with
Btow
Lamivudine 10 3 months
significant response
Efavirenz
 Fine-needle aspiration
and drainage
Repeated fine-needle aspiration and drainage is a popular treatment
for BLEC.

The first aspiration typically occurs in the setting of the fine-needle

aspiration biopsy, which rules out the possibility of another
pathologic condition.

Cysts can be drained up to twice per month, but there is a 100%

recurrence rate in spite of this treatment.15,16,20
 Radiation therapy
Resource Modality Sample Follow-up Results

12 9.5 1/12 with adequate cosmetic

Beitler et al 3 810 Gray months
(twelve) control

One 5/8 complete response

Goldstein et al 19 810 Gray 8
month 3/8 partial response
 Sclerotherapy
Resource Modality Sample Follow-up Results

Marcus and Sodium 2.5 6/6 reduction in size

morrhuate 6
Moore 4 months 1/6 complete response
(50 mg/mL to 3 mL)

Berg and Sodium 5/9 additional cyst formation

morrhuate 9
Moore 22 4/9 compete response
(50 mg/mL, 4 mL)

Doxycycline 1217 7/9 reduction in size

Lustig et al 17 9
(1 mg/mL, 2 mL) months 2/9 complete response

Tetracycline 1436
Chavez et al 14
(250 mg/2 mL)
3
months
3/3 resolution
 Surgery
Resource Modality Sample Follow-up Results

Superficial Up to 6
Shaha et al 15 35
years
Complete response
parotidectomy

Ferraro et al 336 1 recurrence

Enucleation 20
months
16
19 complete response
 Discussion
The indication for treatment of BLEC is cosmetic.
The treatment that provides the best cosmetic outcome should be the
treatment of choice.

All treatments for BLEC show a partial response, but the only
treatment to show a complete response in this pathology
consistently with no recurrence is surgical intervention.
Sclerotherapy ?

Although sclerotherapy injections have shown promising results, the

data are currently limited.

In addition, the majority of BLECs are multiloculated, making

injections into each loculation on multiple occasions challenging,
time-consuming, and often unsuccessful.

The last potential pitfall of sclerotherapy is that these agents aim to

scar the particular area of injection to cause obliteration. If
sclerotherapy is unsuccessful, then surgical intervention for cure
is more difficult in the setting of scarring and sclerosis.
Surgery ?

Reservations regarding parotidectomy in HIV-infected patients include

the following:

1. Immunocompromised patients have a higher rate of postoperative

infections.

2. There is an unnecessary risk of HIV transmission imposed on the

surgeon and the surgical team.

3. There could be facial nerve injury.

Surgery ? (2)

Answer 1 & 2

Recent studies show that the postoperative rate of infection in HIV-

infected patients is similar to that in the normal population,
and is likely due to advances in the treatment of this disease.24

New drug regimens for the medical treatment of HIV patients in the
perioperative period have been developed, and with the advent of
viral load measurement, the risks of HIV transmission during
surgery have been dramatically reduced.25
Surgery ? (3)

Answer 3

Regarding the complications of parotidectomy in the treatment of

BLEC, in the hands of an experienced surgeon :

Parotid gland surgery has been shown to have a permanent paresis

rate of 2.3% (one or more branches of the facial nerve)

While partial superficial parotidectomy has a permanent paresis rate

of 0%
Surgery ? (4)

And also,

There are two other issues that must be addressed regarding surgical
intervention.
Surgery ? (5)

First issue

+ HAART ?

Given the success of surgery in BLEC, the argument for surgical

intervention is further strengthened by the improved health and
longevity of HIV-infected patients.
Surgery ? (6)

Second issue

Some surgeons believe that the surgical defect will cause a

substantial cosmetically deforming indentation.

Parotidectomy defects can be cosmetically reconstructed in a variety

of ways, including use of :
1. Cadaveric dermal matrix (Alloderm)
2. Abdominal fat grafts
3. Sternocleidomastoid muscle flaps
4. De-epithelialized radial forearm free flaps
5. Rectus abdominus free flaps.29
Patient 6 weeks postoperatively after left superficial parotidectomy.
A similar result can be seen as compared to the right side. Facial
contour and symmetry has been restored with excellent cosmetic
outcome. (see Figure 2).
 Conclusion
There are many suboptimal cosmetic therapies used in the treatment
of BLEC.

Surgery is the gold standard treatment for BLEC, as evidenced

by this literature review and case example.
1. Shanti RM, Aziz SR. HIV-associated salivary gland disease. Oral Maxillofac Surg Clin North Am. 2009;21:339343. [PubMed]
2. Syebele K, Btow KW. Comparative study of the effect of antiretroviral therapy on benign lymphoepithelial cyst of parotid glands and ranulas in HIV-positive
patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:205210. [PubMed]
3. Beitler JJ, Vikram B, Silver CE, et al. Low dose radiotherapy for multicystic benign lymphoepithelial lesions of the parotid gland in HIV-positive patients: Long-term
results. Head Neck. 1995;17:3135. [PubMed]
4. Marcus A, Moore CE. Sodium morrhuate sclerotherapy for treatment of benign lymphoepithelial cysts of parotid gland in an HIV patient. Laryngoscope.
2005;4:746749. [PubMed]
5. Michelow P, Dezube BJ, Pantanowitz L. Fine needle aspiration of salivary gland masses in HIV-infected patients. Diagn Cytopathol. 2011 Jan 6; [Epub ahead of
print.] [PubMed]
6. Monama GM, Tshifularo MI. Intralesional bleomycin injections in the treatment of benign lymphoepithelial cysts of the parotid gland in HIV-positive patients: case
reports. Laryngoscope. 2010;120:243246. [PubMed]
7. Wu L, Cheng J, Maruyama S, et al. Lymphoepithelial cyst of the parotid gland: its possible histopathogenesis based on clinicopathologic analysis of 64 cases.
Hum Pathol. 2009;40:683692. [PubMed]
8. Malorano E, Favia G, Viale G. Lymphoepithelial cysts of salivary glands: an immunohistochemical study of HIV-related and HIV-unrelated lesions. Hum Pathol.
1998;29:260265. [PubMed]
9. Mandel L, Surattanont F. Regression of HIV parotid swellings after antiviral therapy: case reports with computed tomographic scan evidence. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod. 2002;94:454459. [PubMed]
10. Witt RL. Salivary Gland Diseases: Surgical and Medical Management. New York, NY: Thieme Publishing; 2005.
11. Syebele K. Regression of both oral mucocele and parotid swellings, following antiretroviral therapy. Int J Pediatr Otorhinolaryngol. 2010;74:8992. [PubMed]
12. Meyer E, Lubbe DE, Fagan JJ. Alcohol sclerotherapy of human immunodeficiency virus related parotid lymphoepithelial cysts. J Laryngol Otol. 2009;123:422
425. [PubMed]
13. Suskind DL, Tavill MA, Handler SD. Doxycycline sclerotherapy of benign lymphoepithelial cysts of the parotid: a minimally invasive treatment. Int J Pediatr
Otorhinolaryngol. 2000;52:157161. [PubMed]
14. Echavez MI, Lee KC, Sooy CD. Tetracycline sclerosis for treatment of benign lymphoepithelial cysts of the parotid gland in patients infected with human
immunodeficiency virus. Laryngoscope. 1994;104:14991502. [PubMed]
15. Shaha AR, DiMaio T, Webber C, Thelmo W, Jaffe BM. Benign lymphoepithelial lesions of the parotid. Am J Surg. 1993;166:403406. [PubMed]
16. Ferraro FJ, Jr, Rush BF, Jr, Ruark D, Oleske J. Enucleation of parotid lymphoepithelial cyst in patients who are human immunodeficiency virus positive. Surg
Gynecol Obstet. 1993;177:524526. [PubMed]
17. Lustig LR, Lee KC, Murr A, et al. Doxycycline sclerosis of benign lymphoepithelial cysts in patients infected with HIV. Laryngoscope. 1998;108:11991205. [
PubMed]
18. Beitler JJ, Smith RV, Brook A, et al. Benign parotid hypertrophy in HIV+ patients: limited late failures after external radiation. Int J Radiat Oncol Biol Phys.
1999;45:451455. [PubMed]
19. Goldstein J, Rubin J, Silver C, et al. Radiation therapy as a treatment for benign lymphoepithelial parotid cysts in patients infected with human
immunodeficiency virus-1. Int J Radiat Oncol Biol Phys. 1992;23:10451050. [PubMed]
20. Terry JH, Loree TR, Thomas MD, et al. Major salivary gland lymphoepithelial lesions and the acquired immunodeficiency syndrome. Am J Surg. 1991;162:324
329. [PubMed]
21. Heran MKS, Legiehn GM. OK-432 sclerotherapy of parotid lymphoepithelial cysts in an HIV patient. Poster presented at the Cardiovascular and Interventional
Radiological Society of Europe meeting; September 1923, 2009; Lisbon, Portugal.
22. Berg EE, Moore CE. Office-based sclerotherapy for benign parotid lymphoepithelial cysts in the HIV-positive patient. Laryngoscope. 2009;119:868870. [
PubMed]
23. Smith MC, Zimmerman MB, Burke DK, et al. Efficacy and safety of OK-432 immunotherapy of lymphatic malformations. Laryngoscope. 2009;119:107115. [
PubMed]
24. Cavasin H, Dola T, Uribe O, et al. Postoperative infectious morbidities of cesarean delivery in human immunodeficiency virus-infected women. Infect Dis Obstet
Gynecol. 2009 May 25; [Epub ahead of print.] [PMC free article] [PubMed]
25. Papendorp SG, van den Berk GE. Preoperative use of raltegravir-containing regimen as induction therapy: very rapid decline of HIV-1 viral load. AIDS.
2010;24:16031608. [PubMed]
26. Koch M, Zenk J, Iro H. Long-term results of morbidity after parotid gland surgery in benign disease. Laryngoscope. 2010;120:724730. [PubMed]
27. Guntinas-Lichius O, Klussmann JP, Wittekindt C, Stennert E. Parotidectomy for benign parotid disease at a university teaching hospital: outcome of 963
operations. Laryngoscope. 2006;116(4):534540. [PubMed]
28. Lisette O, Mansi S, Rovini H. HIV combination products. Nat Rev Drug Discov. 2007;6:951952.
Thanks.
 Artery Transverse facial artery
Vein External jugular vein
Nerve Glossopharyngeal nerve otic ganglion
Lymph Preauricular deep parotid lymph nodes
 Structure
The parotid glands are a pair of mainly serous salivary glands located below and in
front of each ear canal, draining their secretions into the vestibule of the mouth
through the parotid duct.[1]

Each gland lies behind the mandibular ramus and in front of the mastoid process of
the temporal bone. The gland can be felt on either side, by feeling in front of each
ear, along the cheek, and below the angle of the mandible.[2] The gland is roughly
wedge-shaped when seen from the surface.

The parotid duct, a long excretory duct, emerges from the front of each gland,
superficial to the masseter muscle. The duct pierces the buccinator muscle, then
opens into the mouth on the inner surface of the cheek, usually opposite the maxillary
second molar. The parotid papilla is a small elevation of tissue that marks the opening
of the parotid duct on the inner surface of the cheek.[3]
 The gland has four surfaces superficial or lateral, superior, anteromedial, and
posteromedial. The gland has three borders anterior, medial, and posterior. The
parotid gland has two ends superior end in the form of small superior surface and an
inferior end (apex).

A number of different structures pass through the gland. From lateral to medial, these
are:
Facial nerve
Retromandibular vein
External carotid artery
Superficial temporal artery
Branches of the great auricular nerve
Maxillary artery
 Location
Superficial or lateral relations: The gland is situated deep to the skin, superficial fascia,
superficial lamina of investing layer of deep cervical fascia and great auricular nerve
(anterior ramus of C2 and C3).
Anteromedial relations: The gland is situated posterolaterally to the mandibular ramus,
masseter and medial pterygoid muscles. A part of the gland may extend between the
ramus and medial pterygoid, as the pterygoid process. Branches of facial nerve and
parotid duct emerge through this surface.
Posteromedial relations: The gland is situated anterolaterally to mastoid process of
temporal bone with its attached sternocleidomastoid and digastric muscles, styloid
process of temporal bone with its three attached muscles (stylohyoid, stylopharyngeus,
and styloglossus) and carotid sheath with its contained neurovasculature (internal
carotid artery, internal jugular vein, and 9th, 10th, 11th, and 12th cranial nerves).
Medial relations: The parotid gland comes into contact with the superior pharyngyeal
constrictor muscle at the medial border, where the anteromedial and posteromedial
surfaces meet. Hence, a need exists to examine the fauces in parotitis.
 Blood Supply
The external carotid artery and its terminal branches within the gland, namely, the
superficial temporal and the posterior auricular arteries, supply the parotid gland.
Venous return is to the retromandibular vein.
 Nerve Supply
The parotid gland receives both sensory and autonomic innervation. Sensory
innervation is supplied by the auriculotemporal nerve, a branch of the
mandibular nerve.
The autonomic innervation controls the rate of saliva production and is supplied
by the glossopharyngeal nerve.[4] Postganglionic sympathetic fibers from
superior cervical sympathetic ganglion reach the gland as periarterial nerve
plexuses around the external carotid artery, and their function is mainly
vasoconstriction. The cell bodies of the preganglionic sympathetics usually lie in
the lateral horns of upper thoracic spinal segments. Preganglionic
parasympathetic fibers leave the brain stem from inferior salivatory nucleus in the
glossopharyngeal nerve and then through its tympanic and then the lesser petrosal
branch pass into the otic ganglion. There, they synapse with postganglionic fibers
which reach the gland by hitch-hiking via the auriculotemporal nerve, a branch of
the mandibular nerve.[5][6]
 Microanatomy
The gland has a capsule of its own of dense connective tissue, but is also provided with a false
capsule by investing layer of deep cervical fascia. The fascia at the imaginary line between the
angle of mandible and mastoid process splits into the superficial lamina and a deep lamina to
enclose the gland. The risorius is a small muscle embedded with this capsule substance.
The gland has short, striated ducts and long, intercalated ducts. [7] The intercalated ducts are also
numerous and lined with cuboidal epithelial cells, and have lumina larger than those of the acini.
The striated ducts are also numerous and consist of simple columnar epithelium, having
striations that represent the infolded basal cell membranes and mitochondria. [8]
Though the parotid gland is the largest, it provides only 25% of the total salivary volume. The
serous cell predominates in the parotid, making the gland secrete a mainly serous secretory
product.[7]
The parotid gland also secretes salivary alpha-amylase (sAA), which is the first step in the
decomposition of starches during mastication. It is the main exocrine gland to secrete this. It
breaks down amylose (straight chain starch) and amylopectin (branched starch) by hydrolyzing
alpha 1,4 bonds. Additionally, the alpha amylase has been suggested to prevent bacterial
attachment to oral surfaces and to enable bacterial clearance from the mouth. [9]
 Development
The parotid salivary glands appear early in the sixth week of prenatal
development and are the first major salivary glands formed. The epithelial buds of
these glands are located on the inner part of the cheek, near the labial
commissures of the primitive mouth (from ectodermal lining near angles of the
stomodeum in the 1st/2nd pharyngeal arches; the stomodeum itself is created
from the rupturing of the oropharyngeal membrane at about 26 days.[10]) These
buds grow posteriorly toward the otic placodes of the ears and branch to form
solid cords with rounded terminal ends near the developing facial nerve. Later, at
around 10 weeks of prenatal development, these cords are canalized and form
ducts, with the largest becoming the parotid duct for the parotid gland. The
rounded terminal ends of the cords form the acini of the glands. Secretion by the
parotid glands via the parotid duct begins at about 18 weeks of gestation. Again,
the supporting connective tissue of the gland develops from the surrounding
mesenchyme.[7]
 Surgery
Surgical treatment of parotid gland tumors is sometimes difficult because of the
anatomical relations of the facial nerve parotid lodge, as well as the increased
potential for postoperative relapse. Thus, detection of early stages of a parotid
tumor is extremely important in terms of postoperative prognosis. [11] Operative
technique is laborious, because of relapses and incomplete previous treatment
made in other border specialties.[11]
After surgical removal of the parotid gland (Parotidectomy), the auriculotemporal
nerve is liable to damage and upon recovery it fuses with sweat glands. This can
cause sweating on the cheek on the side of the face of the affected gland. This
condition is known as Frey's syndrome.[14]