Shear wave elastography of parotid glands in pediatric patients with HIV infection.

OBJECTIVES: Parotid gland (PG) involvement is common among the patients with HIV infection. Shear wave elastography (SWE) is a noninvasive method used to measure the tissue stiffness of several organs including PG. The aim of this study was to evaluate the tissue stiffness values of PGs of HIV-infected children via SWE and compare the results with the counterparts of healthy subjects. MATERIALS AND METHODS: This single-center, prospective study included the PG examinations of 23 pediatric HIV patients and 40 healthy children via grayscale ultrasound and SWE. Independent sample T test and Mann-Whitney U test were used in statistical analysis. RESULTS: Stiffness of both PGs was significantly higher in patients' group when compared with control subjects. In addition, when the patients were separated into two groups according to the appearance of PG on grayscale ultrasound as homogeneous and heterogeneous, stiffness values were increased in the patients with homogeneous parenchymal appearance. No significant difference was achieved in terms of median CD4 and CD8 counts, HIV RNA levels or median duration of illnesses. CONCLUSIONS: PG examination of HIV-infected children via SWE reveals increased tissue stiffness when compared with healthy subjects. SWE can be used as an ultrasound-assisted noninvasive technique in this manner.

Nonsurgical management of human immunodeficiency virus-associated parotid cysts: A systematic review and meta-analysis.

BACKGROUND: The purpose of this clinical review was to analyze the effectiveness of nonsurgical management options for human immunodeficiency virus (HIV)-associated parotid cysts. METHODS: We conducted systematic and meta-analysis reviews. Primary outcomes were complete or partial responses. RESULTS: Systematic review identified 12 relevant studies. The average rates of complete response for antiretroviral therapy (ART), sclerotherapy, and fine-needle aspiration (FNA) were 52.8%, 55.5%, and 33.3%, respectively. Three radiotherapy studies, totaling 104 patients, were included in a meta-analysis. Patients receiving high-dose therapy achieved complete and partial response rates of 65.8% (95% confidence interval [CI] 54.3%-76.2%) and 25.2% (95% CI 16.1%-36.3%), respectively. Patients receiving low-dose therapy achieved complete and partial response rates of 23.2% (95% CI 1.2%-60.9%) and 22.3% (95% CI 5.2%-87.8%), respectively. The rate of complete response was significantly greater for high-dose radiotherapy compared to low-dose (P < .001). CONCLUSION: Among nonsurgical treatment modalities for HIV-associated parotid cysts, radiotherapy has the highest number of reported outcomes in the literature and our analysis suggests that higher dose radiotherapy has higher rates of achieving complete response.

HIV-associated benign lymphoepithelial cysts of the parotid glands confirmed by HIV-1 p24 antigen immunostaining.

Approximately 1%-10% of patients with HIV infection have been reported to have salivary gland enlargement. Parotid swelling in patients with HIV is often associated with salivary gland disease, including benign lymphoepithelial cysts (BLECs). The presence of BLEC can serve as an indicator of HIV infection, and the diagnosis of HIV-associated BLEC is usually based on clinical course, HIV confirmatory blood testing, such as western blot or viral detection, and imaging studies, but not on biopsies or immunostaining. To exclude other diseases such as tuberculosis and malignant lymphoma and to further improve the diagnostic accuracy of BLEC, the detection of the HIV-1 p24 antigen by immunohistochemistry is a useful diagnostic method. We report a case of a 65-year-old Japanese man with swelling of the parotid glands and HIV-associated BLEC confirmed via HIV-1 p24 immunohistochemical staining.

An Adult Case of Fulminant Mumps Keratitis With Positive Viral RNA in Aqueous Humor Detected by RT-PCR.

PURPOSE: To report an adult case of mumps keratitis with mumps virus in aqueous humor and decreased corneal endothelial cell density. METHODS: Case report. RESULTS: A 60-year-old female with a 39°C fever and bilateral parotid swelling diagnosed with mumps and treated for photophobia, pain, redness, and decreased vision in 1 eye, was referred to our hospital when her condition deteriorated despite receiving betamethasone phosphate instillation and antiglaucoma agents for elevated intraocular pressure (52 mm Hg) and iritis. Her right eye was normal, whereas her left eye showed 20/400 visual acuity, 21 mm Hg intraocular pressure, ciliary injection and edema, opacity, and Descemet folds in the entire cornea. Round white keratic precipitates were present on the posterior corneal surface, whereas anterior chamber cells could not be examined in detail because of corneal edema. Mumps virus was detected by reverse transcriptase polymerase chain reaction in an aqueous humor sample taken at the time of admission. Following diagnosis of keratitis, administration of 30 mg oral prednisolone daily and frequent instillation of betamethasone phosphate steadily improved her corneal edema and opacity. In her left eye, visual acuity recovered to 20/16 and keratitis was resolved at 4 weeks; however, corneal endothelial cell density was significantly decreased to less than 400 per square millimeter. CONCLUSIONS: Mumps keratitis may cause severe corneal endothelial cell loss.

Management algorithm for HIV-associated parotid lymphoepithelial cysts.

We report an evidence-based management algorithm for benign lymphoepithelial cysts (BLEC) of the parotid glands in HIV patients based on long-term outcomes after radiation therapy. From 1987 to 2013, 72 HIV-positive patients with BLEC of the parotid glands treated at our institutions were identified and their medical records were reviewed and analyzed. The primary endpoint of our study was to determine a dose response in HIV patients with BLEC. In group A (≤18 Gy), which received a median dose of 10 Gy (8-18), overall response (OvR), complete response (CR), partial response (PR), and local failure (LF) was experienced by 7, 7, 0, and 93 %, respectively. In group B (≥22.5 Gy), which received a median dose of 24 Gy (22.5-30), OvR, CR, PR, and LF was experienced by 88, 65, 23, and 12 %. Logistic regression revealed that higher dose (≥22.5 Gy) predicted for cosmetic control (p = 0.0003). Multiple regression analysis revealed higher dose predicted for cosmetic control (p = 0.0001) after adjusting for confounding variables (age, gender, race, HAART use, BLEC duration, and fractionation size). No patients in either group experienced RTOG grade ≥3 toxicities. A radiation dose of 24 Gy delivered in 12-16 fractions of 1.5-2 Gy per fraction provides long-term cosmetic control in HIV-positive patients with BLEC of the parotid glands.

Parotid lymphoepithelial cysts in human immunodeficiency virus: a review.

BACKGROUND: Many patients with human immunodeficiency virus present with atypical features. Early indicators of human immunodeficiency virus are scarce and hence most affected patients are diagnosed in the later stages of the disease, which is associated with poor prognosis. Salivary gland disease usually develops before acquired immunodeficiency syndrome, and is sometimes the first manifestation of human immunodeficiency virus infection. Salivary gland lesions include benign lymphoepithelial cysts of the parotid gland, which are seen in 3-6 per cent of patients. Many of the reported lesions are diagnosed on routine examination. OBJECTIVE: This review aimed to highlight the association between parotid gland benign lymphoepithelial cyst and human immunodeficiency virus infection, in order to aid early diagnosis and management of the disease. CONCLUSION: Human immunodeficiency virus testing is recommended for patients with benign lymphoepithelial cysts, as this can often be the first indication of human immunodeficiency virus infection. Benign lymphoepithelial cysts are important diagnostic and prognostic indicators in human immunodeficiency virus infection.

Viruses and salivary gland disease (SGD): lessons from HIV SGD.

Viral infections are often associated with salivary gland pathology. Here we review the pathogenesis of HIV-associated salivary gland disease (HIV-SGD), a hallmark of diffuse infiltrative lymphocytosis syndrome. We investigate the presence and contributions of viral diseases to the pathogenesis of salivary gland diseases, particularly HIV-SGD. We have detected BK viral shedding in the saliva of HIV-SGD patients consistent with viral infection and replication, suggesting a role for oral transmission. For further investigation of BKV pathogenesis in salivary glands, an in vitro model of BKV infection is described. Submandibular (HSG) and parotid (HSY) gland salivary cell lines were capable of permissive BKV infection, as determined by BKV gene expression and replication. Analysis of these data collectively suggests the potential for a BKV oral route of transmission and salivary gland pathogenesis within HIV-SGD.

Comparative study of the effect of antiretroviral therapy on benign lymphoepithelial cyst of parotid glands and ranulas in HIV-positive patients.

OBJECTIVE: This study's aim was to assess the effect of highly active antiretroviral drugs (HAART) on benign lymphoepithelial cysts (BLEC) of the parotid and ranulas. STUDY DESIGN: The records of 10 HIV-positive patients who presented with BLEC were reviewed, and 14 HIV-positive patients who presented with ranulas were prospectively enrolled. Patients in both groups received the same combination of HAART and were clinically evaluated for the first 3 months. Patients with ranulas were followed for an additional 3 months. A clinical reduction in the size of the lesions was considered to be a positive outcome. RESULTS: All parotid glands with BLEC resolved within 3 months. No positive results were observed in ranulas during the first 3 months. However, some of the ranulas displayed a positive result after the initial 3 months of HAART. CONCLUSIONS: In contrast to BLEC, ranulas in HIV-positive patients seem to present a mixed and delayed response to HAART.

Parotid localized Castleman's disease and HHV-8 infection: a case report.

Castleman's disease (CD) is an unusual massive proliferation of lymphoid tissue distinct in two clinical forms, localized and multicentric. The multicentric form has been related to human herpesvirus 8 (HHV-8), especially in HIV-infected patients, whereas the localized form of CD is still unrelated to viral pathogens. We report a case of a HIV-negative 16-year-old male referred to our hospital with a 12-month history of a painless swelling in his right parotid region. A parotidectomy was performed, and histological analysis evidenced a localized CD. The search for HHV-8 revealed an active virus infection. The patient was commenced on corticosteroid therapy and a follow-up was performed every 6 months. The patient was commenced on corticosteroid therapy and there has been no recurrence after 24 months. The authors report a case of localized parotid CD in a patient with evidence of an active HHV-8 infection. The results of this study does for the first time suggest an association between HHV-8 and localized CD in HIV-negative subjects.

Benign lymphoepithelial parotid lesions in vertically HIV-infected patients.

Benign lymphoepithelial parotid lesions (BLL) are frequently reported in HIV-infected patients, although their clinical and prognostic significance in HIV infection has not been clearly defined. Ultrasonography (USG) has been shown to be a reliable method in monitoring the progression of such lesions. The purpose of this study was to describe the spectrum of sonographic and Doppler findings and to monitor any clinically evident physical change of parotid glands in a cohort of congenitally HIV-infected patients taking antiretroviral therapy. USG findings-based on their severity-have been grouped in three different patterns (0, 1, 2). Our cohort consisted of 51 patients with HIV in various Centers for Disease Control (CDC) stages and being given different antiretroviral protocols. The median USG follow-up was 36 months. The most frequent USG pattern was aspecific parotid gland enlargement (type 0, 45,1%). Patients with either lower CD4+ % (p < 0.20) and higher absolute and percent CD8+ cell count (p < 0.001 and p < 0.003) presented more frequently a type 2 USG pattern. None of them had any symptoms ascribed to "sicca syndrome" and only one patient developed non-Hodgkin's lymphoma during the follow-up, although his USG pattern at baseline was type 0. In summary, the spectrum of USG findings of BLL in vertically HIV-infected patients is broad. Because of the reported, although rare, possible malignant transformation of BLL in HIV-infected children, it is advisable to perform-even in asymptomatic patients-USG at least once per year or in concomitance with any physical modification of the parotid lesions.

Changing spectrum of the diffuse infiltrative lymphocytosis syndrome.

OBJECTIVE: To describe the changing clinical spectrum of patients with diffuse infiltrative lymphocytosis syndrome (DILS) after the introduction of highly active antiretroviral treatment (HAART), and to carry out HLA class II oligotyping in these patients. METHODS: A retrospective chart review of patients with DILS who were referred to an outpatient facility for human immunodeficiency virus (HIV)-positive individuals between 1994 and 2003 was performed. DILS was diagnosed as suggested by previous criteria. Demographic features and relevant clinical, laboratory, and radiologic data were recorded and results analyzed. RESULTS: A total of 129 patients with DILS were identified. Of them, 56 (43%) were African American, 41 (32%) were white, and 32 (25%) were Hispanic. Parotid gland swelling appeared to be the sine qua non of DILS. Twenty-seven percent of patients had opportunistic infections. The status of 103 patients was available as of December 2003: 26 (25%) had died, of which only 6 (6%) succumbed to opportunistic infections. The prevalence of DILS had significantly decreased in the post-HAART era (1998 onwards) compared with that of the pre-HAART period (P < 0.000001). The prevalence of lymphocytic interstitial pneumonitis had also dropped significantly following introduction of HAART therapy (P = 0.015). A higher frequency of certain HLA class II alleles (DRB1) was found in African Americans with DILS compared with those with HIV without DILS (P = 0.006). CONCLUSION: The epidemiology, clinical presentation, and certain extraglandular manifestations of DILS have changed, concomitant with the introduction of HAART, further suggesting that DILS is an antigen (viral)-driven response and the primary treatment for it is anti-HIV therapy.

[Lymphoepithelial cysts of the parotid gland: a pathology linked to HIV infection]. / Les kystes lymphoépithéliaux de la glande parotide: une pathologie liée à l'infection VIH.

We review the various lesions encountered in the parotid gland associated with HIV infection and propose guidelines for the management of a chronic parotid swelling in this setting. Lymphoepithelial cysts is the main diagnosis of parotid masses presented by HIV positive patients. This benign condition is diagnosed on cytology and the treatment is usually conservative. Patients with a diagnosis of lymphoepithelial cysts should be tested for HIV.

Role of cytomegalovirus, Epstein-Barr virus, and human herpes virus-8 in benign lymphoepithelial cysts of the parotid gland.

OBJECTIVE: To provide background and evaluate the role of herpesviruses in benign lymphoepithelial cysts (BLC) of the parotid gland. STUDY DESIGN: Case series derived from review of pathology specimens. METHODS: Radiolabeled polymerase chain reaction (PCR) analysis was used to detect for the presence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpes virus 8 (HHV-8) DNA sequences in 14 paraffin embedded specimens and 1 freshly aspirated BLC specimen. Thirteen normal parotid tissue specimens obtained from paraffin embedded blocks were used as a control group. RESULTS: CMV was detected with nearly equal frequency between the two groups (23% of normal vs. 20% in BLC). HHV-8 was found in 13% of the BLC group and in none of the normal group (P =.4841). There was significant difference in EBV detection between the normal (0%) and the BLC (33%) groups (P =.0437). CONCLUSION: CMV and HHV-8 does not appear to be associated with BLCs. Although EBV is found more frequently in BLC than in normal parotid controls, further studies are needed to elucidate the role of this virus in BLC pathogenesis.

HIV disease presenting as parotid lymphoepithelial cysts: a presumptive diagnosis of diffuse infiltrative lymphocytic syndrome (DILS).

Diffuse infiltrative lymphocytic syndrome (DILS), is a rare manifestation of human immunodeficiency virus (HIV) disease which is characterized by a diffuse visceral CD8 lymphocytic infiltration, a persistent CD8 lymphocytosis, bilateral parotid swelling and cervical lymphadenopathy. We describe a case of a HIV positive female, who had bilateral parotid swelling and CD8 lymphocytosis, to illustrate this rare clinical entity.

Histopathological analysis and demonstration of EBV and HIV p-24 antigen but not CMV expression in labial minor salivary glands of HIV patients affected by diffuse infiltrative lymphocytosis syndrome.

BACKGROUND: The diffuse infiltrative lymphocytosis syndrome (DILS) in HIV patients is characterized by the persistence of CD8-circulating lymphocytes and lymphocytic infiltration, predominantly in salivary glands. METHODS: We examined seven HIV-positive patients with bilateral parotid enlargement and sicca symptoms. Minor labial salivary gland biopsies were performed in all patients and submitted for histopathological analysis and immunohistochemistry for CD4, CD8, cytomegalovirus (CMV), LMP-EBV protein, and HIV p-24 protein. RESULTS: In all cases, lymphocytic infiltration of the minor salivary glands, mainly periductal, was found. Acinar atrophy, ductal ectasia, and mild to moderate fibrosis were also observed. We noticed strong immunohistochemical reaction for LMP-EBV and p-24 proteins in ductal cells in all cases, while staining for CMV was consistently negative. The lymphocytes were positive for CD8, but consistently negative for CD4. CONCLUSIONS: A role of Epstein-Barr virus (EBV) and HIV, but not CMV, in the pathogenesis of DILS, is suggested by our immunohistochemical findings.

Parotid gland involvement in advanced AIDS.

OBJECTIVE: This study describes the involvement and the histological alterations found in the parotid glands of 100 patients who died with AIDS. MATERIALS AND METHODS: Sex, age, CD4 cell count and clinical history were obtained from the files of 100 patients who died with AIDS. Histological analysis of the parotid glands was performed using H&E, Gomori-Grocott, Ziehl-Neelsen and Mucicarmine. Histological findings were grouped in reactive, infectious, cystic, neoplastic and concomitant lesions. RESULTS: None of the patients presented complaints or symptoms related to salivary gland alterations prior to death. The mean age of the patients and CD4 cell count were 36.4 years and 76.07 cells microliter-1, respectively. Histological alterations of the parotid glands were found in 51% of the patients. The most common alteration was non-specific chronic sialadenitis (29 cases), followed by infectious conditions (22 cases). Mycobacteriosis was the most common infectious disease (10 cases), followed by cytomegalovirus (nine cases), cryptococcosis (three cases) and histoplasmosis (two cases). Lymphoepithelial cysts occurred in six cases, Warthin's tumor and non-Hodgkin Lymphoma in one case each. CONCLUSIONS: These results indicate that infection and other lesions in the parotid glands are more frequent than hitherto described in the specialized literature in AIDS patients. Clinicians should consider parotid gland involvement, when evaluating disease extension in advanced AIDS patients.

Simultaneous occurrence of lymphoepithelial cysts, cytomegalovirus and mycobacterial infections in the intraparotid lymph nodes of a patient with AIDS.

We report the unusual simultaneous occurrence of lymphoepithelial cysts, cytomegalovirus (CMV) and mycobacterial infections in the intraparotid lymph nodes of a 52-year-old AIDS patient who died of disseminated mycobacteriosis. Although cytomegalovirosis is a common finding in the salivary glands of HIV patients, the association of CMV inclusions with lymphoepithelial cyst (LC) has not been previously reported. Parotid mycobacterial infection is an uncommon finding, despite its usual disseminated presentation in HIV patients. These data emphasize that in immunosuppressed patients, simultaneous diseases of the parotid gland may occur and should be considered for diagnosis and treatment.