HIV infection causes depletion of CD4-positive lymphocytes with consequent immunodeficiency. HIV infection also causes, by direct or indirect mechanisms, both reactive and neoplastic changes in lymphoid tissue. Nasopharyngeal adenoidal hypertrophy is common in patients with HIV infection on pathologic study. In a report by Barzan et al. [7
], 80% of 36 HIV-positive patients had pathologically confirmed nasopharyngeal lymphatic tissue hypertrophy. Most published observations suggested that nasopharyngeal lesions in HIV-infected patients were reactive and represented follicular hyperplasia [8
], but malignant lesions were also reported in nasopharyngeal lesions of patients with HIV infection [10
]. There was a case report about malignant transformation of nasopharyngeal lymphoid hypertrophy [11
]. However, to date there is no publication specifically regarding the nasopharyngeal abnormalities on FDG-PET-CT imaging in patients with HIV infection.
Lymphadenopathy is one of the most common and earliest presentations of HIV infection. The most common conditions affecting the lymph nodes in HIV-positive patients are reactive changes, opportunistic infections, and malignant neoplasms. Persistent generalized lymphadenopathy often precedes the development of lymphoma and is indicative of an increased risk of lymphoma [12
]. The differentiation between reactive/inflammatory lymph nodes and malignant lymphoma is very challenging without histopathological investigation by invasive procedure. A few studies had suggested that FDG PET-CT is contributory to diagnosis of lymphoma and identification of both nodal and extranodal disease in patients with HIV infection. O'Doherty et al. reported that FDG-PET correctly identified 13 non-Hodgkin's lymphomas in patients with HIV infection, in which 7 with only persistent generalized lymphadenopathy, 3 with only extranodal lesions in the oropharynx, esophagus, sinus, and stomach, and 3 with concurrent nodal and extranodal lesions in the breast, joint and lung [13
]. Goshen et al. also found that FDG PET-CT accurately detected lymphoma in patients with HIV infection, but 6 of 7 patients in their series had known non-Hodgkin's lymphoma prior to PET imaging [14
]. In Goshen's case series, only 1 patient was for diagnosis due to lymhadenopathy, and PET finding about the lymph nodes was false positive for lymphoma.
Our study, for the first time, demonstrated the significance and diagnostic value of incidentally noted nasopharyngeal lesions on FDG PET-CT imaging in HIV-infected patients. In this study, 7 of 22 patients with generalized lymphadenopathy had coexistent FDG avid nasopharyngeal masses or lesions, which suggested that although nasopharyngeal lymphoid hypertrophy is commonly seen in HIV infection on pathological studies, most patients with lymphadenopathy have no visible nasopharyngeal masses or lesions or abnormal nasopharyngeal uptake on FDG PET-CT imaging. The nasopharyngeal lymphoid proliferative disease is less common than lymphadenopathy and may only appear late in the spectrum of HIV infection. However, if FDG avid nasopharyngeal lesion is present on PET-CT imaging, it is highly predictive of a malignant lymphoma. In this series, all 7 patients with concurrent FDG avid nasopharyngeal lesions and lymphadenopathy were confirmed to have lymphomas, 6 NHL, and 1 HL. In contrast, only 4 patients had lymphomas among 9 patients with FDG avid lymphadenopathy but no nasopharyngeal lesions. The findings suggested that concurrent conditions of nasopharyngeal lesion and lymphadenopathy have a higher diagnostic value for lymphoma than lymphadenopathy only and are relatively specific for lymphoma rather than a benign/inflammatory process or other neoplasms such as nasopharyngeal carcinoma.
After Kaposi's sarcoma, NHL is the second most common malignancy associated with HIV infection. Consistent with prior reports [15
], histologies in our series were predominantly DLBCL in NHL cases, in all 9 NHL cases. Although it was reported that the most common extranodal locations of NHL in HIV infection are in the central nervous system and bone marrow [16
], the present data suggested that the nasopharynx is a common site of extranodal lymphoma as well.
The location of lymphadenopathy may have diagnostic value for lymphoma. In the series, 9 of 9 patients with FDG avid retroperitoneal lymph nodes had DLBCL. Among other 7 patients with lymphadenopathy only located in the upper torso, 2 had HL and 5 were lymphoma-free. Extended lymphadenopathy with the retroperitoneal or intra-abdominal involvement has a greater probability for malignant lymphoma especially NHL, compared to that only localized in the upper torso such as the mediastinum, neck, and axillae.
Our study has a limitation of small sample size. Obviously, larger studies are needed to substantiate the findings. In addition, there was a referral bias. Almost all patients had significant lymphadenopathy in the series, and those without or only mild lymphadenopathy were not referred for investigation of lymphoma with FDG PET-CT. Therefore, the incidence and significance of FDG avid nasopharyngeal lesion is unknown in patients without or with only mild lymphadenopathy.