Thymic 18F-fluorodeoxyglucose uptake on positron emission tomography scanning after doxorubicin, bleomycin, vincristin and dacarbazine chemotherapy and highly-active antiretroviral therapy in HIV-associated Hodgkin's disease in an adult

Abstract

Positron emission tomography (PET) scanning is being increasing used to stage disease and monitor response to therapy in lymphoma patients [1]. More recently, it has been used as a prognostic tool to predict disease recurrence after chemotherapy [2,3]. PET-positive residual mass with standardized uptake value (SUV) > 3 after chemotherapy is associated with recurrence rate of 60–80% [4,5] PET imaging has a high sensitivity and specificity of 86% and 96%, respectively, and, in many centres, treatment recommendations were made solely on the basis of PET results for diagnosis of recurrence without confirmatory tissue diagnosis. This is the first report of a patient in whom anterior mediastinal PET positivity was due to thymic reconstitution after successful chemotherapy for HIV-related Hodgkin's disease and highly-active antiretroviral therapy (HAART) rather than disease relapse. A 26-year-old HIV-infected man presented with a 3-month history of night sweats, fevers and generalised lymphadenopathy. He had been diagnosed with HIV infection 2 years previously. His CD4 count was 330 cells/μl and his HIV RNA load was 12 000 copies/ml. A computed tomography (CT) scan showed a large anterior mediastinal mass measuring 10 × 6 cm with further enlarged nodes seen in the right para-tracheal, sub-carinal, right hilar, retroperitoneal and inguinal regions. Biopsy of the mediastinal mass was performed and the histological examination showed large cells with Reed–Sternberg morphology and expressing both CD30 and CD15, establishing the diagnosis of classical Hodgkin's lymphoma, nodular sclerosis subtype. Bone marrow aspirate and trephine showed no evidence of bone marrow involvement. The patient was staged as stage IIIb. Treatment with doxorubicin, bleomycin, vincristin, and dacarbazine (ABVD) was started. He was also treated with HAART using efavirenz 600 mg daily, emtricitabine 200 mg daily, and tenofovir 245 mg daily in an attempt to maintain and/or improve his immune status while undergoing chemotherapy treatment. His HIV RNA became undetectable (<50 copies/ml) and the CD4 cell counts remained reasonably stable during the chemotherapy treatments. A CT scan after six cycles of chemotherapy showed a residual anterior mediastinal mass measuring 7 × 4 cm but this was shown not to take up fluorodeoxyglucose (FDG) on PET scanning (Fig. 1a).Fig. 1: Positron emission tomography (PET)–computed tomography (CT) scan performed 1 month after the completion of chemotherapy showed residual anterior mediastinal mass which was, however, not fluorodeoxyglucose (FDG)-avid (a). Another CT–PET scan was performed 16 months after the completion of chemotherapy and it showed increased FDG uptake with an SUV of 3.2 (arrow) in the anterior mediastinum, consistent with disease relapse (b). Biopsy of the mediastinal mass that was positive on FDG–PET 16 months after the completion of chemotherapy was performed but the histological examination showed regenerated thymus with a lobular architecture and containing morphologically normal cortex, medulla, and Hassall's corpuscles (c); original magnification × 45).The patient continued to receive HAART and maintained good virological control. Sixteen months later, he presented with enlarged 1.0 cm axillary lymph node and a CT–PET scan was requested to exclude disease recurrence. His CD4 count was 600 cells/μl and HIV RNA remained undetectable. On this CT–PET scan, there was now an increased uptake detected in the anterior mediastinum with an SUV of 3.2, suggesting disease relapse (Fig. 1b; arrow). Mediastinoscopic biopsy was requested to confirm disease progression with the view of high-dose chemotherapy and peripheral blood stem cell transplantation. To our surprise, the histology revealed normal regenerating thymic tissue with no evidence of lymphoma (Fig. 1c). In our patient, the PET positivity in the mediastinum after chemotherapy in a HAART patient with HIV-associated Hodgkin's lymphoma is the result of T-cell immune reconstitution in a functional thymus gland. Initiation of HAART in HIV-infected patients is associated with immune reconstitution of T cells and this is correlated with thymus volume increase and generally occurs in patients with initial low CD4 counts and/or rising CD4 counts [6–8]. The thymic reconstitution is also associated with increased thymic metabolism, which is reflected by increased FDG uptake detected by PET [9]. Interestingly, in our patient, the number of CD4 cell was high prior to treatment. It is possible that HAART in combination with transient lymphopenia induced by chemotherapy could have triggered the thymic reconstitution. In conclusion, this is the first case to report on the occurrence of FDG-avid uptake in functional thymic tissue in a HAART patient with HIV-associated Hodgkin's lymphoma previously treated with chemotherapy. Our case illustrates the importance of verification of PET findings by a biopsy. It is also important to consider this differential diagnosis in HIV-infected patients treated with HAART and chemotherapy if a post-treatment PET scan shows increased mediastinal uptake.