HIV associated benign lymphoepithelial cysts of parotid glands
Roughly 1-10% of patients with HIV infection have salivary gland enlargement. Parotid gland is commonly involved. Presence of benign lymphoepithelial cysts (BLECs) should be a pointer to HIV diagnosis. Detection of HIV-1 p24 antigen by immunohistochemistry is the commonly used diagnostic tool.
Parotid gland swelling in patients with HIV is often associated with salivary gland disorders like
Benign lymphoepithelial cysts.
Among these disorders BLECs are common. This case was first reported by Hildebrandt in 1895. HIV was not known those days. Only 21 cases of BLECs have been reported since the first case till 1981. BLEC increased in incidence with the emergence of HIV infections. This condition has shown a decline with the development of antiretroviral therapy.
BLEC is a cystic disease involving parotid glands. It should be differentiated from Warthin's tumor and cystic deneration of benign and malignant tumors. HIV associated BLEC is considered to be a local manifestation of persistent generalized lymphadenopathy associated with HIV infection. Eventhough this condition is rather rare it could very well be the first manifestation of HIV.
The exact pathophysiology of the disease still remains unknown. Proliferation of BLEC has been shown to increase with HIV replication. Currently there are two hypothesis that attempt to explain this disorder.
BLECs are solitary / multiple cysts within the lymph nodes trapped during the parotid gland embyrogenesis. HIV associated reactive proliferation occurs in the intraparotid lymph nodes. The parotid glandular epithelium becomes trapped within the normal intraparotid nodes resulting in cystic enlargement.
This hypothesis assumes that HIV infected cells migrate into the parotid glands. This migration triggers lymphoid proliferation and salivary duct dysplasia which leads to ductal obstruction. Cystic lesions are commonly caused due to ductal obstruction. These cysts serve as a reservoir of HIV-1p24 antigen and RNA copies that are about 1000 fold higher than plasma concentrations. HIV has a predilection for lymphoid tissue and elevated concentrations of HIV can be found within these nodes.
BLEC is considered as single or multiple cysts in the parotid lymph nodes. The clinical presentation of BLEC is gradual, painless and comprises bilateral parotid swelling with diffuse cervical adenopathy. Unilateral parotid swelling has also been reported. Most patients who develop BLEC are not aware of potential HIV infection, but they are more concerned about cosmetic implications of the swelling. BLEC is not known to cause facial nerve palsy and xerostomia. If patients with BLEC present with systemic symptoms like fever, weight loss, nocturnal sweating should always be diligently examined for presence of tuberculosis / lymphoma.
BLEC is diagnosed basically based on medical history, physical examination, and biopsy.
Non invasive diagnostic tools involve CT and MRI scanning. Imaging can detect multiple thin walled cysts with diffuse cervical adenopathy.
FNAC / Excision biopsy to confirm the diagnosis as well as to rule out malignancy. Malignancy occurs in 1% of patients with HIV assocaited cystic lesions of parotid gland. Pathological tissue examiantion is the only method to diagnose BLEC on definite terms.
Lymphoepithelial cysts consists of multiple epithelial cysts accompanied by dense lymphoid tissue. The epithelial lining can be squamous / cuboidal / columnar. Some cysts can even be lined by pseudostratified ciliated epithelium. Stratified squamous epithelium is the most common lining encountered. The lymphoid tissue replaces normal parotid parenchyma. The lymphoid follicles are larger and irregularly shaped than unreactive follicles in normal lymph nodes. The germinal centres contain numerous macrophages and some of the germinal centers may have attenuated mantle of small lyphocytes that invaginate into the follicles. The number of cysts could vary but they are not pathognomonic of HIV associated lymphoepithelial cysts as similar features can also be seen in HIV negative lymphoepithelial sialadenitis. HIV -1 p24 antigen immunostaining could be additionally useful as the follicular dendritic cells and interfollicular macrophages are positive for HIV -1 p 24 antigen.
The lesion is asymptomatic but for the cosmetic issues. Management include repeated aspiration, ART, sclerotherapy or surgery. Radiotherapy which was practised for sometime is contraindicated these days for the fear of malignancy. Studies reveal that sclerotherapy with doxycycline / bleomycin can reduce the size of these cysts without any serious complications.
Surgery is a little risky because there is about 5% risk of facial nerve injury, bleeding and seroma formation. Surgery should only be attempted in cases of malignancy or poor patient response to conservative treatment already described.