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J Cytol. 2009 Oct-Dec; 26(4): 146–148.
PMCID: PMC3168000

HIV lymphadenitis of the salivary gland: A case with cytological and histological correlation


Human immunodeficiency virus infection associated lymphadenitis of the salivary glands (HIVLSG) and benign lymphoepithelial cysts are described as early events in HIV patients. The diagnosis is not usually made clinically as it mimics a salivary gland tumor. We present here a patient with two painless nodules in the right parotid and submandibular glands. The cytological diagnosis was florid reactive lymphoid hyperplasia. Histopathology revealed features of HIVLSG with multiple, small, cystic, benign lymphoepithelial lesions.

Keywords: Benign lymphoepithelial cyst, HIV/AIDS lymphadenitis, lymphoid hyperplasia of salivary glands


Lymphoid aggregates or fully structured lymph nodes are present in relation to the parotid and submandibular salivary glands.[1] The parotid gland is the only salivary gland to contain lymphoid tissue within its capsule while the submandibular lymph nodes lie adjacent to, but outside the glandular capsule.[2,3] Occasionally, these lymph nodes become the site of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-associated lymphadenopathy and present with clinical and morphological features that may resemble salivary gland disorders.[17] Unilateral or bilateral parotid gland lymphadenopathy with or without benign lymphoepithelial cysts is recognized as an early or sometimes primary symptom of HIV infection.[1] As only a few cases have been published in literature, we are reporting this case to bring this entity and its cytohistopathological features to the attention of clinicians and pathologists.

Case Report

A 55 year-old woman presented with a nine months’ history of two painless nodules in the right parotid and submandibular gland regions. The swellings were nontender, firm, well circumscribed and measured 3 × 2 cm and 2.5 × 0.5 cm, respectively. No other swellings were felt, either in the involved salivary glands or on the contralateral side. The swellings did not fluctuate in size with the intake of food and the overlying skin was not inflamed. She denied having any dryness of the mouth. The only relevant past history was herpes zoster six years back, the scars of which were seen on the left side of her face. Three months ago, she had undergone fine needle aspiration (FNA) of these nodules in another laboratory. These smears were reviewed and showed high cellularity consisting of a mixed population of lymphoid cells. Seen predominantly were mature small lymphocytes, immunoblasts, plasma cells, occasional multinucleate histiocytic giant cells, and lymphohistiocytic tangles [Figure 1]. There were no epithelioid cells, Langhans type giant cells, caseous necrosis, Warthin-Finkeldey giant cells, salivary ductal, acinar, or squamous epithelial cells. A diagnosis of florid reactive hyperplasia was made.

Figure 1
Lymphohistiocytic tangle and multinucleate giant cell (inset) (Pap, ×400)

Subsequently, as these nodules progressively increased in size, an excision biopsy was done. Grossly the nodules measured 3 × 2 × 1 cm and 2.5 × 1.5 × 1 cm respectively, were encapsulated, grey-white, and firm. The cut surface was predominantly solid, lobulated, and grey-white, except for a few small cysts measuring 0.3 cm in diameter and containing greenish, gelatinous material.

Microscopy showed lymph nodes with intact capsules. The cortex showed large, irregular, confluent follicles with prominent germinal centres [Figure 2] enclosed by mantles of variable thickness with focal disruption and effacement (geographic follicles). Scattered interfollicular aggregates of monocytoid B-cells were seen along with numerous, plump, endothelium-lined blood vessels. Four small cysts [Figure 3] were seen lined by cuboidal to stratified squamous epithelium that was profusely infiltrated by lymphocytes (benign lymphoepithelial cysts). The lumen contained eosinophilic secretions along with aggregates of foamy macrophages and lymphocytes. Epithelial inclusions of ductal origin were seen amidst the lymphoid tissue [Figure 3]; however, there were no acinar structures. Epimyoepithelial lesions consisting of squamous islands infiltrated by lymphocytes were evident [Figure 4] but there were no Warthin-Finkeldey giant cells, granulomas, necrosis, or perinodal salivary gland tissue. The Ziehl-Neelsen and PAS stains were negative for organisms; a diagnosis of HIV-lymphadenitis of the salivary gland (HIVSLG) was made.

Figure 2
Intraparotid lymph node with geographic follicles (H and E, ×400)
Figure 3
Lymphoepithelial cyst (right), salivary gland inclusions, and giant cells (H and E, ×100)
Figure 4
Epimyoepithelial islands infiltrated by lymphocytes (H and E, ×400)

The HIV testing done subsequently was positive but the patient has remained free of any AIDS-defining illness in the six months’ follow-up period.


Exclusive involvement of salivary gland lymph nodes in HIV infection was first reported in 1985.[6] These patients present with unilateral or bilateral tumor-like masses, especially in the parotid gland, without any other symptoms.[3] The swellings are frequently excised with the erroneous diagnosis of a salivary gland tumor.

In HIVLSG, the cytological features are similar to those of florid reactive hyperplasia of lymph nodes, except for the presence of foamy histiocytes and squamous cells in cases with associated cystic benign lymphoepithelial lesion. These cysts can vary from a few millimetres to centimetres in size. The differential diagnoses include reactive hyperplasia of the intraparotid lymph nodes, chronic sialadenitis, Sjögren/Mikulicz syndrome, Warthin tumor, and Hodgkin's and non-Hodgkin's lymphomas.[5]

Ulirsch and Jaffe initially considered HIVLSG to be a Sjögren syndrome-like illness and believed that they resulted from autoimmune phenomena.[4] However, demonstration of extensive lysis, HIV antigens, viral particles, and the clinical absence of xerophthalmia, keratoconjunctivitis, and autoantibodies help to distinguish these two entities, which may be cytologically identical.[4] Furthermore, benign lympho-epithelial lesion (BLEL) and cystic BLEL seen in this condition occur within the gland parenchyma whereas the benign lymphoepithelial cysts seen in HIV infection arise within intraparotid lymph nodes. They may or may not be associated with extensive local lymphadenopathy. It has been postulated that progressive intranodal lymphoid hyperplasia leads to entrapment, obstruction, and cystic dilatation of ductular inclusions, leading to swellings mimicking salivary gland tumors.[7]

Chronic sialadenitis and sialolithiasis are characterized by pain, especially on the intake of food. The inflammation is within the salivary gland proper and reactive germinal centres are not usually a part of the process.[3] Aspirates are usually scanty with few lymphocytes, plasma cells, neutrophils, and macrophages in a background of mucus. Fragments of stroma may be present in sialadenitis and calcified debris in sialolithiasis. The atrophy of the epithelial component is reflected in epithelial scarcity in smears.[8]

Warthin tumors are painless, small, 2 to 4 cm nodules, commonly arising from the parotid gland. On FNA, these tumors yield brown, murky to mucoid fluid. Oncocytic cells in cohesive monolayered sheets amidst lymphoid cells usually clinch the diagnosis. This neoplasm is most commonly mistaken for inflammation as the oncocytes are often difficult to recover from cystic lesions.[5,7]

Various neoplasms have been described in HIV cases in relation to these nodes, including Hodgkin's lymphoma, non-Hodgkin's lymphoma, and Kaposi sarcoma.[5] AIDS-associated lymphomas may be preceded by HIV lymphadenitis.[1]

Cytologically, a confident diagnosis of Hodgkin's lymphoma can be made only in the presence of typical Reed-Sternberg cells or atypical mononuclear Hodgkin cells in a background of lymphocytes, eosinophils, plasma cells, and histiocytes.[9]

Non-Hodgkin's lymphomas in AIDS patients are usually high-grade, large cell lymphomas characterised on FNA by a monotonous population of large, atypical lymphoid cells with noncleaved nuclei, multiple nucleoli, and scanty basophilic cytoplasm.[9]

Immunohistochemistry or in situ hybridization has shown the presence of HIV proteins or RNA on the dendritic cells of the salivary gland lymphoid follicles, indicating their active replication.[2]

In conclusion, an awareness of HIVLSG may prevent unnecessary surgeries in these patients, a biopsy being necessary only in those cases suspected of harbouring a malignancy.


Source of Support: Nil

Conflict of Interest: None declared.


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