Faculty Bibliography

Involvement of the liver with the same opportunistic organisms and neoplasms affecting other organs has been recognized since the beginning of the AIDS epidemic. In this overview of hepatic histopathologic features in AIDS, we review the range of opportunistic infections and neoplasms accompanying HIV infection. Hepatic disease may result from viral, bacterial, protozoal, or fungal infection, or secondary to drugs and neoplasms. Liver involvement in AIDS usually reflects disseminated rather than primary disease. CMV and mycobacteria are the most common organisms in liver identified in biopsy and autopsy studies. A variety of nonspecific features, including steatosis, granulomas, and sinusoidal abnormalities may also be seen. HIV-1 itself was recently identified in the liver. Speculation regarding the significance of this finding has been discussed in this review. Hepatitis B, C, and D may also complicate the course of disease in patients with AIDS. Hepatitis B behaves differently in the population with AIDS than in immunocompetent patients. We concluded our review with a discussion of the present recommendations regarding the use of liver biopsies in these patients. This topic continues to be widely debated in the literature

Although the histologic manifestation of cytomegalovirus (CMV) is usually characteristic intracellular inclusions and cytomegaly, some investigators, using immunohistochemical or in situ hybridization techniques, have demonstrated the presence of histologically occult infections in certain tissues. A series of lung biopsy specimens from pulmonary transplant recipients were studied using a monoclonal antibody (CCH2) to CMV early viral antigen and the results were compared with routine histologic findings. Occult infection could not be demonstrated in any of these cases. These results may reflect the relative sensitivity of the monoclonal antibody used in this study, although other possible factors are discussed. The results suggest that, in lung allograft biopsy specimens, immunohistochemical analysis using monoclonal antibody CCH2 is not likely to increase significantly the yield of positive cases compared with examination of multiple levels of hematoxylin-and-eosin-stained sections. Additional studies are needed to compare the sensitivity of monoclonal antibodies to CMV antigens using a variety of sampling techniques and clinical settings

We have reviewed 28 esophageal biopsies from 28 patients with the acquired immune deficiency syndrome (AIDS), over a 1-yr period. Indications for esophageal biopsy were dysphagia persisting after antifungal therapy and/or radiologic evidence of esophageal ulcer. We compared the frequency of detecting cytomegalovirus (CMV) infection on hematoxylin and eosin (H&E) stain with immunoperoxidase staining for CMV antigens. Five biopsies were positive for CMV by H&E stain and immunoperoxidase. Infected cells could often be identified in the granulation tissue and, in one severe case, in stromal papillae of the intact mucosa. Squamous cells were never positive. Thirteen biopsies consisted only of squamous epithelium, and all of these were negative by both techniques. Among the remaining 10 cases, no CMV inclusions were identified by H&E. Three of these biopsies displayed staining for viral antigens. In all cases positive by immunoperoxidase, numerous cells positive for viral antigens did not display any of the CMV-specific morphologic diagnostic criteria. Other coexisting diagnoses included candidiasis, Kaposi's sarcoma, and malignant lymphoma. We conclude 1) CMV infection of the esophagus is common in AIDS patients with esophageal ulcer or esophagitis resistant to antifungal therapy; 2) multiple infections or neoplasms may coexist; 3) since CMV apparently does not infect squamous epithelium and only rarely endothelium in stromal papillae, deep biopsies are necessary for diagnosis; and 4) immunoperoxidase staining is required for maximum diagnostic yield

A 17-year-old boy with Gaucher's disease died suddenly 2 days after femoral osteotomy. At autopsy, in addition to extensive infiltrates of Gaucher cells in the cirrhotic liver, lymph nodes, and bone marrow, there were high-grade pulmonary arterial hypertensive changes but virtually no Gaucher cells in the lung. Although previous reports have stressed lung infiltrates with capillary plugging by Gaucher cells as important in the pathogenesis of pulmonary hypertension, the present case raises the question of a different mechanism--possibly a circulating vasoactive substance that bypasses the diseased liver

Acute interstitial nephritis (AIN) is a common pattern of renal injury induced by therapeutic agents. In order to characterize the types of mononuclear leukocytes infiltrating the kidney in drug-induced interstitial nephritis, a panel of monoclonal antibodies (Leu1, Leu3a, OKT8, OKM1, Leu14, OKT17, IL-2) was applied to cryostat sections of 13 renal biopsies (five non-steroidal anti-inflammatory agents (NSAID) (Group I); five beta-lactam antibiotics (Group II), 3 miscellaneous (Group III]. The majority of infiltrating mononuclear leukocytes were Leu1-positive T cells (71.7 +/- 18.7%), followed by monocytes (15.2 +/- 7.7%) and B cells (7.4 +/- 9.1%). Leu3a/OKT8 ratio was 0.954 +/- 0.341. Rare cells reacted with antibody to the interleukin-2 receptor (1.4 +/- 1.2%). No statistically significant differences could be found in the percentages of T lymphocytes, B lymphocytes, monocytes, activated (IL-2+) T cells or Leu3a/OKT8 (helper/suppressor) ratios in the three groups. In Group II, the following pathologic correlations were seen: Leu3a/OKT8 versus interstitial inflammation (R = -0.848), percent Leu3a versus interstitial inflammation (R = -0.818), percent OKT17 versus tubulitis (R = 0.785), percent Leu14 versus tubular atrophy (R = -0.891), and interstitial edema (R = 0.965). Our findings support a role for cellular immune mechanisms in the pathogenesis of AIN related to both NSAIDs and beta-lactam antibiotics