A 40-year-old man who had been generally healthy came to our hospital in June 1996, with chief complaints of fever with chills and malaise for 2 months. He also had a weight loss of 8 kg within 1 month. Physical examination showed right cervical lymphadenopathy and a posterior pharyngeal tumor. The cervical lymph node proved to be tuberculosis on biopsy and acid-fast stain and the posterior pharyngeal tumor showed KS on histology. An abdomen to pelvic computed tomography (CT) scan did not show any abnormal lesion in the liver, spleen, and bilateral kidneys. Both HIV enzyme-linked immunosorbent assay and western blot were positive for HIV-1. The serologic test for syphilis was positive. He was treated with a combination of three antituberculosis drugs (ethanbuthol, pyrazinamide, isoniazid), acyclovir for herpes simplex virus infection, ceftriaxone, amikacin, and trimethoprim-sulfamethoxazole. He began receiving zidovudine in October in 1996. This was replaced by didanosine (ddI) 1 month later because of refractory bone marrow suppression.
At his second admission to our hospital in December 1996, multiple skin lesions were found over his chin and anterior neck. Excisional biopsies of those lesions revealed cutaneous KS. The CD4+ T-cell absolute count was only 18 cells/muL. Tuberculosis, syphilis, candidiasis, and cytomegalovirus retinitis were diagnosed and treated. The antiretroviral drug ddI was discontinued in January 1997. Bilateral pulmonary infiltrations were observed in chest radiographs. Pneumocystic pneumonia was impressed and treated with trimethoprim-sulfamethoxazole. The symptoms had improved at the time of hospital discharge.
The patient was admitted again 1 month later for dyspnea and cough with sputum production for 2 weeks. More immunosuppression was noted with a CD4+ T-cell absolute count of 10 cells/muL. HAART was initiated in April 1997 with zalcitabine, lamivudine, and saquinavir. The pre-HAART serum HIV RNA level was 313.1 x 103 copies/mL.
The HIV viral load decreased to 20.93 copies/mL (4 log10 drop) at 32 days after initiation of HAART. Meanwhile, the CD4+ T-cell count increased to 41 cells/muL (4-fold rise). However, the patient's skin lesions progressed to involve the trunk, all extremities, the perianal region, and foreskin of the penis. He received amputation of the right big toe because of KS following a biopsy.
After 5 months, the patient developed fever with dyspnea. Bilateral diffuse pulmonary infiltrations were observed again in plain chest radiographs. Despite treatment with antituberculosis drugs, HAART, trimethoprim-sulfamethoxazole, cephapirin, and gentamycin, he died approximately 6 months after starting HAART.
At autopsy, multiple KS lesions were seen over the chin, neck, left flank, four extremities, perianal area, and prepuce of the penis, mostly presenting as nodular or ulcerative lesions. Two tumor masses were seen between the tonsils and between the tongue base and oropharynx. No pleural effusion was seen in the thoracic cavity. The right and left lungs weighed 750 and 780 g, respectively, and had thickened pleurae and foci of adhesions. Some hemorrhagic nodules were seen on the pleural surfaces. On cutting, hemorrhagic, yellowish nodules involving all segments of all lobes were found [Figure 1a]. The hilar nodes and paratracheal nodes were also involved by tumors. Serous ascitic fluid 300 mL was obtained from the abdominal cavity. Some foci of KS lesions were observed in the liver appearing as small nodules [Figure 1b]. The kidneys weighed 120 g each and were also involved by KS, especially in the cortical areas [Figure 1c]. In the gastrointestinal (GI) tract, many KS nodules were observed in the mucosa of the stomach (especially at the lesser curvature), duodenum, jejunum, ileum, colon, and anal canal. Those tumors presented with polypoid, nodular, and/or ulcerative patterns [Figure 1d-g].
Microscopically, all representative tumor nodules were composed of spindle cells in fascicles or bundles or storiform, vascular channels filled with erythrocytes lined by flat endothelial cells and extravasated erythrocytes [Figure 2a], with HHV-8 antigen positivity [Figure 2b], diagnostic of KS. Multiple disseminated KS nodules involving the lungs surrounded the bronchioles and vessels (bronchocentric and angiocentric patterns), which were the cause of death in this patient [Figure 2c].
The patient had no lesions in the liver, kidneys, or GI tract in the abdomen to pelvic CT scans taken in June 1996. Multiple disseminated KS was observed in several visceral organs at autopsy. Skin KS progression was noted 1 month after HAART in spite of a rise in the CD4+ T-cell count and a significant reduction in the viral load. Thus, his rapid progression before death could be explained as a consequence of IRIS.