CLINICAL PRACTICE
CASE REPORT |
DIFFERENTIATING HIV-1 PAROTID CYSTS
FROM PAPILLARY CYSTADENOMA LYMPHOMATOSUM
LOUIS MANDEL, D.D.S. and
ANITA TOMKORIA, B.S.
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ABSTRACT
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Background. Patients with parotid cystic lesions may first be seen in the dental office. These conditions most often represent either papillary cystadenoma lymphomatosum, or PCL, or lymphoepithelial cysts associated with human immunodeficiency virus, or HIV, disease. The authors present a case report to illustrate the differential diagnosis.
Case Description. PCL represents a benign, usually unilateral, circumscribed parotid tumor with cystic elements. HIV-associated lymphoepithelial cysts of the parotid gland usually are seen bilaterally, create cosmetic concerns and are hallmarked by an associated cervical lymphadenopathy. Therapy for PCL demands surgical excision, while patients with HIV-associated lymphoepithelial cysts may be treated with antiviral therapy and undergo periodic monitoring by a physician.
Clinical Implications. As a member of the health care team, the dentist must be familiar with head and neck swellings. Early clinical recognition of parotid swellings leads to successful treatment.
Dentists see many patients with head and neck swellings that are unrelated to dental disease. An accurate diagnosis depends on the dentist’s thorough knowledge of the diverse local and systemic disease processes that may cause such swellings. Some of these swellings, which often cause no symptoms other than an obvious cosmetic deformity, originate from the parotid salivary gland.
The parotid gland is prone to a variety of swellings that, on cursory examination, have similar clinical features. Consequently, diagnosis becomes difficult. The purpose of this article is to illustrate the clinical steps taken in establishing a differential diagnosis for a clinically asymptomatic cystic parotid gland swelling. A complete understanding of the pathogenesis and symptoms of these cystic conditions is required to make an accurate diagnosis.
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CASE REPORT
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A 60-year-old man, in apparently good health, was seen in the Salivary Gland Center of the New York–Presbyterian Hospital (Columbia campus) because of a persistent painless swelling of the left parotid salivary gland (Figure 1
). The patient reported that the swelling had been present for at least two years and recently had begun to slowly increase in size.
We took a medical history, which indicated that the patient had undergone a left nephrectomy secondary to a stab wound in 1968. He had been treated for alcohol abuse and anemia several years previously.
One of us (L.M.) conducted an extraoral examination, which revealed that the swelling was well-circumscribed, measuring about 5 centimeters in diameter, and located anatomically over the mandibular angle. Palpation indicated that the swelling was soft and similar to that of a cyst. We noted neither abnormalities of the right parotid salivary gland nor cervical lymphadenopathy.
Because a human immunodeficiency virus, or HIV, lymphoepithelial cyst was a possibility, we questioned the patient regarding risk factors. He denied intravenous drug abuse, homosexuality and/or having received blood transfusions within the past 25 years.
Because a slow-growing, painless unilateral cystic lesion appeared to be present in the lower pole of the parotid gland and because the patient denied having any risk factors for HIV, we could not rule out a papillary cystadenoma lymphomatosum, or PCL. Therefore, to further clarify the gland’s status, we obtained a computed tomographic, or CT, scan, which revealed multiple cystic foci in the left parotid gland. Although we did not expect this finding, the scan also clearly imaged lucent lesions in the asymptomatic right parotid gland (Figure 2). In addition, we observed cervical lymphadenopathies (Figure 3).
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Figure 2. Lymphoepithelial cyst (C) in the left parotid gland. Note the lucencies in the right parotid gland (arrow).
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Figure 3. Enlarged submandibular lymph nodes (arrows) at the level of the hyoid bone. The lymphoepithelial cyst (C) is at the level of the hyoid bone.
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PAPILLARY CYSTADENOMA LYMPHOMATOSUM (WARTHIN’S TUMOR)
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The PCL, also referred to as Warthin’s tumor, is a relatively common benign tumor of the parotid gland. The PCL represents approximately 61 to 13.5 percent2 of all benign parotid tumors. Most occur in the sixth decade of life,3–6 predominantly in men. The reported ratio of male-to-female patients ranges from 10:17 to 1.6:1.8 An increase in the number of female cases has been linked to the increased incidence of smoking among women.6,9
Clinical findings.
The patient with PCL has a smooth, encapsulated, spheroidal parotid mass measuring 2 to 3.6 cm in diameter.4,7 Because it is painless and grows slowly, the PCL usually has been present for years before diagnosis. Palpation indicates that the parotid swelling is usually soft and cystlike and involves the tail of the gland’s superficial lobe just anterior to the earlobe. Five to 12 percent of cases have been reported to occur bilaterally, either synchronously or metachronously.4,5,10,11 Furthermore, in 4 to 8 percent of cases, the tumor can appear as if it has multicentric foci, in one or both parotid glands.4,7,10,12
Salivary gland epithelium.
The PCL is thought to originate from salivary gland epithelium that becomes included in a developing lymph node during embryogenesis.5,12 Because the parotid capsule develops late, the lymph nodes in the parotid area, with their included epithelium, become separated anatomically into intraparotid and paraparotid nodes. Proliferation of the trapped epithelium in more than one node is the most likely explanation for the tendency of the tumor to be bilateral and multicentric.
A histologic analysis demonstrates that solid and cystic elements are present in varying amounts. The epithelial component of the tumor is formed by a double layer of eosinophilic columnar or cuboidal cells projecting in a papillary fashion into cystic areas. The stroma consists of variable amounts of lymphoid tissue, which represents the neoplasm’s lymph node origin.
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HIV DIFFUSE INFILTRATIVE CD8 LYMPHOCYTOSIS SYNDROME
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Approximately 40 percent of HIV-1–positive patients have head- and neck-related symptoms.13 Parotid enlargement has been reported to occur in 5 percent of this seropositive population.14
Diffuse infiltrative lymphocytosis syndrome, or DILS, represents a subset of HIV disease that occurs in immunogenetically distinct adults.15,16 Characteristic findings include a persistent CD8 lymphocytosis, bilateral parotid swelling, cervical lymphadenopathy and a diffuse visceral CD8 lymphocytic infiltration.17–23 It is surprising that patients with the DILS subset of HIV seem to have a better prognosis than patients with HIV alone.15
The parotid swellings represent a lymphoproliferation originating from the intraparotid lymph nodes or from an extraglandular lymphoidal infiltration. Parotid lymphoepithelial cysts, first identified in 1985,24 commonly develop. These cysts are painless and soft, involve the superficial lobe of the parotid, can be multicentric and can become extremely large. Most often, they are observed bilaterally, either during the clinical examination or after an imaging procedure. On occasion, unilateral involvement only is present.
As with PCL, the lymphoepithelial cysts in DILS may have originated from glandular epithelium trapped during development within intraparotid lymph nodes.25,26 Conversely, some authors believe that the glandular lymphoproliferation causes ductal obstruction, with ductal dilatation and the development of a cystlike structure.27–29
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DIAGNOSIS
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Because CT imaging in this case depicted a bilateral cervical lymphadenopathy combined with bilateral parotid lucencies, we made a tentative diagnosis of HIV. Again, we questioned the patient regarding risk factors for HIV and again he denied any exposure. Despite this, we referred the patient for serologic testing. The results proved that the patient was HIV-positive and had the DILS subset.
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DISCUSSION
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Cystic swellings involving the parotid gland can develop in several conditions. Unilateral parotid ductal cysts secondary to ductal obstruction have been observed.30 In addition, a unilateral solitary lymphoepithelial cyst in the parotid gland, unrelated to HIV, occasionally is seen in adults.30 Another entity, poly-cystic parotid disease, is congenital and manifests itself bilaterally in girls and women.30,31 Furthermore, malignant neoplasms of the parotid gland often have cystic components resulting from cellular activity or may demonstrate areas of cystic degeneration.
PCL and DILS.
Regardless of these other possibilities, cystic involvement of the parotid gland more likely represents PCL or HIV parotid disease. Similarities between these two pathologic lesions exist. Clinically, both are slow-growing, soft, cystlike, painless masses involving the superficial lobe. The PCL is usually unilateral but can be bilateral, while the DILS parotid swelling is usually bilateral but can be unilateral. Multicentricity can be seen in both entities, but it is more prevalent in the HIV-infected parotid gland.
The absence or presence of cervical lymphadenopathy is a key factor in differentiating PCL, a benign neoplasm, from HIV parotid disease. Enlarged nodes are not associated with a benign neoplasm. In HIV disease, lymphoidal tissue is a viral target and lymphadenopathy becomes an obvious symptom. Palpation of the cervical areas in our patient did not reveal enlarged cervical nodes. This failure reflects the inadequacy of our palpation.
CT scan.
The next step in diagnosis was to obtain a CT scan. Imaging demonstrates the presence and extent of unilateral or bilateral disease, unicentric or multicentric foci, and the existence of cervical lymphadenopathy. The CT scan in this case showed a large multicentric lucent mass in the left parotid gland and small lucent lesions in the right parotid gland. All lucencies were well-delineated. Such findings can be seen in both HIV parotid disease and PCL. A search for lymphadenopathy, as visualized on the CT scan, was indicated. We observed readily discernible enlarged cervical nodes on the scan. The positive nodes in association with the parotid lucencies left little room for a diagnosis other than HIV disease.
The results of serologic testing were positive, which confirmed the diagnosis. In addition, blood studies revealed a CD4 cell count of 286/cubic millimeters (normal range, 390 to 1,770/mm3). An elevated CD8 cell count of 1,580/mm3 (normal range, 240 to 1,200/mm3), which is consistent with DILS, was also found.
Because the patient denied the more obvious risk factors, we hypothesized that he contracted the disease through heterosexual intercourse. Once the seropositive results were obtained, we confirmed that the patient’s illness was part of the DILS subset of HIV disease. The parotid cystic lesions, the cervical lymphadenopathy and the CD8 lymphocytosis are classic signs of DILS, the combination of which is not seen in PCL.
A histologic specimen would have confirmed the diagnosis because microscopic differences between PCL and HIV parotid disease are readily apparent. Having made a reasonably certain clinical diagnosis, however, we felt there was no need for a surgical specimen and referred the patient to the HIV unit of the hospital where antiviral therapy was initiated. However, clinicians must always consider the possibility of a malignant transformation to a lymphoma. Recall examinations by physicians every six months are indicated. A fine-needle aspiration biopsy is needed to investigate any changes in growth pattern.
Both PCL and DILS enlargements of the parotid gland usually follow a benign course. Surgical intervention—that is, removal of the superficial parotid lobe—is indicated for a neoplasm such as the benign, slow-growing PCL. Provided that cosmetic concerns are not paramount and there are no clinical or cytologic signs of malignancy, observation and reassurance by clinicians combined with antiviral therapy are a reasonable approach to treating the enlarged parotid gland in patients with DILS. These patients must be monitored because there is always the possibility of the enlarged gland undergoing transformation to a lymphoma.
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SUMMARY
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Parotid cystic lesions develop in a variety of disease processes, with the neoplastic PCL and the lymphoepithelial cysts associated with HIV being the most common. Because similarities exist in the clinical manifestations of these two lesions, we have reviewed their symptoms and presented a case report to illustrate the differential diagnosis.
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FOOTNOTES
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Dr. Mandel is director, Salivary Gland Center, clinical professor, Division of Oral and Maxillo-facial Surgery, and assistant dean, Columbia University School of Dental and Oral Surgery, New York–Presbyterian Hospital (Columbia campus), 630 W. 168th St., New York, N.Y. 10032. Address reprint requests to Dr. Mandel.
Ms. Tomkoria is a fourth-year dental student, Columbia University School of Dental and Oral Surgery, New York.
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ABSTRACT
CASE REPORT
