A 31-year-old Japanese man who had sex with men complained of lasting fever over 38 C, severe general fatigue, and an 8.5% reduction of body weight over the preceding four months, for which he had visited a nearby hospital in March 2008. A HIV screening test was positive and he was transferred to Kyushu University Hospital after 10 days at the original hospital. On admission, physical examination revealed a fever of 39.8 C, blood pressure 110/69 mmHg, pulse rate 110 beats per min, body weight 54 kg, height 168 cm, and body mass index 19.1 kg/m2. Examination of the oral cavity showed small mucosal nodules, suggesting oral Candidiasis and mild hepatosplenomegaly without any other lymphadenopathy.
Table 1 shows the patient's biochemical laboratory data on admission. The CD4 cell count and HIV viral load were 26/muL and 100,000 copies/mL, respectively. Epstein-barr virus and Cytomegalovirus infection were ruled out in his sera. Plasma beta-D glucan and other antigens for fungal infections, such as Cryptococcus neoformans and Toxoplasma gondii, were negative, and cultures taken several times from blood, urine, and sputum were all negative.
Imaging tests such as chest and abdominal X-ray; cervical, thoracic and abdominal computed tomography (CT) scans; head, trunk, and total spinal magnetic resonance imaging (MRI); and gallium scintigraphy were done. Thoracic CT showed some small masses (<5 mm) in the bilateral lower lobes of the lung. The first MRI and gallium scintigraphy showed high signals in the spine and sacroiliac joint, but indicated no other specific findings. Bone marrow aspiration showed normo to hypercellular marrow tissue. A lower gastrointestinal endoscopy showed no other abnormalities, such as malignant diseases.
Although there was no evidence of Mycobacterium avium complex (MAC) infection, we suspected MAC infection and at day 2 after admission and began an oral, multi-drug regimen that included rifampicin 600 mg/day, clarithromycin 800 mg/day, and ethambutol 750 mg/day. Because these treatments were not effective, we considered the possibility of HIV-associated fever, and started ART with raltegravir, tenofovir/emtricitabine, and lopinavir/ritonavir at hospital day 13 after admission. After induction of ART therapy, body temperature once decreased to under 37 C, but again increased to over 39 C after a few days. At 12 days after induction of ART, his CD4 cell count increased from 26/muL to 72/muL and HIV viral load decreased from 100,000 copies/mL to 59 copies/mL. Considering the possibility of drug induced fever, we stopped all drugs for the MAC and Candida infections, but fever over 39 C continued.
A second thoracic CT showed another lesion in the left lung, and on that occasion his blood was positive by Quanti FERON-TB Gold In Tube assay, which is used for the screening of latent tuberculosis. To rule out pulmonary tuberculosis, bronchoscopy was done, but the bronchoalveolar lavage indicated no pulmonary diseases. Repeated cultures of sputum, gastric fluid, and bone marrow tissue were negative for Mycobacterium tuberculosis and MAC. The second trunk MRI at hospital day 31 showed high signals in the spine and sacroiliac joint. At hospital day 38, the second gallium scintigraphy showed high up-take of systematic bone marrow and in the right sacroiliac joint (Figure 1A and 1B).
At hospital day 56, fluoro-2-deoxy-D-glucose positron emission tomography revealed abnormal uptake in some ribs, the spine, sacroiliac joint, mediastinal lymph nodes, and bilateral hilum of the lung (Figure 1C and 1D). We strongly suspected malignant lymphoma, although there was little up-take in the inguinal lymph node. Because of newly palpable swelling in the right inguinal lymph node, biopsy was done. The tissue section showed a variable proportion of large hallmark cells with eccentric horseshoe or kidney-shaped nuclei with an eosinophilic region near the nucleus and many scattered, atypical large lymphoid cells together with small lymphocytes (Figure 2A). Atypical lymphoid cells showed large, atypical lymphoid cells with bizarre nuclei (Figure 2B). Immunohistochemically, these cells were positive for T-cell markers (CD3, CD45RO), CD30 and CD4, but negative for B-cell markers (CD20, CD79a) and anaplastic lymphoma kinase (ALK) (Figure 2C and 2D). Other types of T-cell lymphoma, such as ATL, were ruled out. These features confirmed T-cell lymphoma of the ALK-negative ALCL type. At the same time, flow cytometry indicated the likely pattern of ALCL. The second bone marrow aspiration showed normal to hypercellular marrow tissue. The final diagnosis was HIV-associated ALK-negative ALCL (stage IV) in May 2008. His performance status was 0 and age adjusted International Prognostic Index was 3. Immediately, chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone; CHOP) was administered in eight courses done at an interval of three weeks. There was a little reduction of the white blood cell count due to chemotherapy and no other toxicity related to the therapy was shown, thus no dose reduction was necessary at any time during the therapy. After induction of an eight-cycle course of CHOP, systemic lymph node swelling was markedly decreased and clinical symptoms and laboratory data showed complete remission. After completion of CHOP therapy, ART was continued and led to a favorable increase of CD4 cells. The patient has had no recurrence of ALCL until August 2013, suggesting the overall survival period of the patients after diagnose is 63 months.