Lymphoepithelial cyst - A sign of unappreciated HIV infection.

Sir,

Infection with the human immunodeficiency virus (HIV) presents itself with a myriad of symptoms.[1] Approximately 40% of HIV-positive patients present for the first time with head and neck-related symptoms and some of which involve the salivary glands.[2] Six percent of those patients examined by Schiodtet al. specifically experienced parotid gland swelling.[1] Recently, cystic parotid enlargements have been reported in the medical literature as a new manifestation of HIV.[3] A comprehensive physical examination reveals that a subset of these patients also develop an increase in CD8 T-cells and a diffuse infiltrative lymphocytic syndrome (DILS).[1]

The parotid swelling results from a lymphoproliferation originating from the intraparotidlymphnodes or from a lymphoid infiltration whose origin is extraglandular.[2] Lymphoepithelial cyst (LEC) was first identified in 1985 and they commonly develop later in the course of the disease.[1] In the last few years, such cysts have been found in increasing number in acquired immunodeficiency syndrome (AIDS) patients as well as in the patients belonging to the AIDS risk group.[4]

The LEC has equal distribution in male and female, can be single or multiple and often become very large. They are painless, soft and involve the superficial lobes of the parotid glands, often bilaterally. They gradually increase in size, can cause gross cosmetic deformities and may involve the facial nerve.[2] We report a case of LEC in a 48-year-old female which was the first sign of an otherwise unappreciated HIV infection and which served as a well-described marker for the HIV status.

A 48-year-old female presented with a painless swelling below the left ear lobe since 5 months. After 2 months of appearance of the swelling, the patient developed deviation of the angle of the mouth to the right side. On examination there was a solitary globular swelling in the left infra-aural region measuring 5×4 cm, it was non-tender and soft in consistency. There was no associated regional lymphadenopathy. Left facial nerve examination revealed a lower motor nerve facial palsy of grade II. With these features a clinical diagnosis of a neoplastic lesion of superficial lobe of left parotid was done. Confirming that the routine hematological and biochemical parameters were within the normal limits a superficial parotidectomy was done and the specimen was sent for histopathological examination (HPE).

Macroscopically, the specimen consisted of a single grey pink tissue mass measuring 3×2×1 cm and the cut section showed a cyst filled with hemorrhage. Microscopically, the sections revealed a cystic lesion lined by multilayered squamous epithelium, with lymphocytic infiltration [Figure 1]. There was a dense lymphocytic infiltration with prominent germinal centers in the subepithelium [Figure 2]. These features were diagnostic of LEC. As LECs are commonly found in increasing numbers in AIDS patients, the HIV status of the patient was checked and the patient was found to be HIV-positive.

Figure 1

H and E, ×10, cyst lined by multilayered squamous epithelium with lymphocytic infiltration

Figure 2

H and E, ×20, dense lymphocytic infiltration in the subepithelium

DILS, a subset of HIV disease, occurs in certain immunogenetically distinct adults and children. It is characterized by a persistent CD8 lymphocytosis, a diffuse visceral CD8 lymphocytic infiltration, bilateral parotid swelling and cervical lymphadenopathy.[5] The parotid swelling results from a lymphoproliferation.[2] Although Mikculicz is credited with the first description of salivary gland lymphoepithelial lesion (LEL) in 1885, Ryan etal. first identified this condition in HIV-positive patients in 1985. The emergence of the HIV pandemic has been associated with a steady increase in the frequency of parotid LELs. Furthermore, these lesions have become a well-described marker for HIV infection, occurring in about 5% of HIV-positive patients, indeed the presentation of this lesion may be the first sign of an otherwise unappreciated HIV infection, as was in the present case.[6]

The exact etiology of these lesions is unknown and remains speculative. Bernier and Bhaskar have defined benign LECs as solitary or multiple cysts within lymph nodes trapped during the parotid gland embryogenesis; these represent cystic degeneration of salivary gland inclusions within the intraparotidlymphnodes. The intraparotid gland lymph nodes are largely located along the tail of the gland, thereby predisposing this part of the gland as seen in the present case to early enlargement.[6]

HIV has a predilection for lymphoid tissue and high concentrations of the virus can be found within these nodes.[6] As the virus replicates bilateral parotid LECs develop.[4] But development of cyst has little impact on the progress of HIV.[2]

The investigations including ultrasound scanning, aspiration and magnetic resonance imaging are important in diagnosis and treatment planning of these lesions, as the clinical examination may not always confirm the cystic nature of the lesion. The preoperative diagnosis of LEC remains uncertain as the nature and clinical symptoms resemble the other cystic lesions of the parotid such as retention cysts, extravasation cysts or cystic degenerative salivary gland tumor. The definitive diagnosis depends solely on HPE.[4]

Histologically the cysts were observed in a lymph node, adjacent to or embedded in a major salivary gland (Elliot and Oertel 1990). LEC was characterized by multiple parenchymal cysts of varying size and shape. The cysts were lined with either multiple layers of flattened epithelia or stratified squamous epithelial lining. As seen in the present case the epithelium was intimately associated with reactive lymphoid follicles containing germinal centers of varying size and shape. Single and aggregates of lymphocytes were noted in the cyst epithelium. The lumen contains a pale homogenous material with foamy macrophages and lymphocytes.[26]

Historically LELs have been indications for surgical intervention on the parotid gland accounting for <1% of parotidectomies undertaken. But in the HIV era the profile of indications of parotidectomy has changed, with LEL becoming a common indication for parotidectomy. Post-parotidectomy, the HIV-positive patients as in the present case was referred for antiviral therapy.[6]

A lymphoma can result from activation of existing B-cells in conjunction with dysfunction of the patient's immune system. Sudden increase in gland size heralds a lymphomatous transformation. Hence a close follow-up of these patients is indicated.[2]