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Aids Pathology

Textbook of AIDS Pathology

Available is the newest (February 2002) version 11 of the electronic Textbook of AIDS Pathology which is approximately 800k (including text, tables, graphics, and references). It is in Acrobat PDF format and can be viewed with the Adobe Acrobat Reader, for which Macintosh, PC, and UNIX compatible versions are available.

The textbook includes a general discussion of the pathophysiology of HIV infection, organ system pathology of AIDS, and descriptions of the opportunistic infections and neoplasms associated with AIDS, and a general discussion of issues, including safety and education, related to the AIDS epidemic.

Go to the Textbook of AIDS Pathology

Human Immunodeficiency Virus

Human immunodeficiency virus (HIV) is the causative agent for AIDS. The most common type is known as HIV-1 and is the infectious agent that has led to the worldwide AIDS epidemic. There is also an HIV-2 that is much less common and less virulent, but eventually produces clinical findings similar to HIV-1. The HIV-1 type itself has a number of subtypes (A through H and O) which have differing geographic distributions but all produce AIDS similarly. HIV is a retrovirus that contains only RNA.

HIV is a sexually transmitted disease. Infection is aided by Langerhans cells in mucosal epithelial surfaces which can become infected. Infection is also aided by the presence of other sexually transmitted diseases that can produce mucosal ulceration and inflammation. The CD4+ T-lymphocytes have surface receptors to which HIV can attach to promote entry into the cell. The infection extends to lymphoid tissues which contain follicular dendritic cells that can become infected and provide a reservoir for continuing infection of CD4+ T-lymphocytes. HIV can also be spread via blood or blood products, most commonly with shared contaminated needles used by persons engaging in intravenous drug use. Mothers who are HIV infected can pass the virus on to their fetuses in utero or to infants via breast milk.

When HIV infects a cell, it must use its reverse transcriptase enzyme to transcribe its RNA to host cell proviral DNA. It is this proviral DNA that directs the cell to produce additional HIV virions which are released.

The genome of HIV contains only three major genes: env, gag, and pol. These genes direct the formation of the basic components of HIV. The env gene directs production of an envelope precursor protein gp160 which undergoes proteolytic cleavage to the outer envelope glycoprotein gp120, which is responsible for tropism to CD4+ receptors, and transmembrane glycoprotein gp41, which catalyzes fusion of HIV to the target cell's membrane. The gag gene directs formation of the proteins of the matrix p17, the "core" capsid p24, and the nucleocapsid p7. The pol gene directs synthesis of important enzymes including reverse transcriptase p51 and p66, integrase p32, and protease p11.

In addition to the CD4 receptor, a coreceptor known as a chemokine is needed for HIV infection. Chemokines are cell surface fusion-mediating molecules. Such coreceptors include CXCR4 and CCR5. Their presence on cells can aid binding of the HIV envelope glycoprotein gp120, promoting infection. Initial binding of HIV to the CD4 receptor is mediated by conformational changes in the gp120 subunit, but such conformational changes are not sufficient of fusion. The chemokine receptors produce a conformational change in the gp41 subunit which allows fusion of HIV. The differences in chemokine coreceptors that are present on a cell also explains how different strains of HIV may infect cells selectively. There are strains of HIV known as T-tropic strains which selectively interact with the CXCR4 chemokine coreceptor to infect lymphocytes. The M-tropic strains of HIV interact with the CCR5 chemokine coreceptor to infect macrophages. Dual tropic HIV stains have been identified. The presence of a CCR5 mutation may explain the phenomenon of resistance to HIV infection in some cases. Over time, mutations in HIV may increase the ability of the virus to infect cells via these routes. Infection with cytomegalovirus may serve to enhance HIV infection via this mechanism, because CMV encodes a chemokine receptor similar to human chemokine receptors.

  1. Human immunodeficiency virus, electron micrograph.
  2. Human immunodeficiency virus, electron micrograph.
  3. Human immunodeficiency virus, electron micrograph.
  4. Human immunodeficiency virus, structural components, diagram.
  5. Human immunodeficiency virus, life cycle, diagram.
  6. Human immunodeficiency virus within lymphoid tissues, diagram.
  7. Human immunodeficiency virus, process of infection, diagram.
  8. Human immunodeficiency virus, schematic diagram of genome.
  9. Human immunodeficiency virus (HIV) subtypes and simian immunodeficiency virus (SIV) phylogeny, diagram.
  10. Life cycle of HIV, with the points of pharmacologic agent effectiveness, diagram.
  11. Schematic diagram of CD4 receptor and chemokine coreceptor.

Acquired Immunodeficiency Syndrome (AIDS)

When the CD4 lymphocyte count drops below 200/microliter, then the stage of clinical AIDS has been reached. This is the point at which the characteristic opportunistic infections and neoplasms of AIDS appear. Listed below are some of the more common complications seen with AIDS with images that illustrate gross and microscopic pathologic findings.

The organ involvement of infections with AIDS represents the typical appearance of opportunistic infections in the immunocompromised host--that of an overwhelming infection--that makes treatment more difficult. The strategies employed in AIDS patients to meet this challenge consist of (1) preserving immune function as long as possible with antiretroviral therapies, (2) using prophylactic pharmacologic therapies to prevent infections (such as Pneumocystis carinii pneumonia), and (3) diagnosing and treating acute infections as soon as possible.

Pneumocystis carinii

Pneumocystis carinii is the most frequent opportunistic infection seen with AIDS. It produces a pulmonary infection, called Pneumocystis carinii pneumonia (PCP), but rarely disseminates outside of lung. The most common clinical findings in patients with PCP are acute onset of fever, non-productive cough, and dyspnea. Chest radiograph may show perihilar infiltrates. Diagnosis is made histologically by finding the organisms in cytologic (bronchoalveolar lavage) or biopsy (transbronchial biopsy) material from lung, typically via bronchoscopy. The cysts of P carinii stain brown to black with the Gomori methenamine silver stain. With Giemsa or Dif-Quik stain on cytologic smears, the dot-like intracystic bodies are seen.

  1. Pneumocystis carinii, appearance of organisms, diagram.
  2. Pneumocystis carinii pneumonia, gross.
  3. Pneumocystis carinii pneumonia with cavitary change, gross.
  4. Pneumocystis carinii pneumonia, low power microscopic.
  5. Pneumocystis carinii pneumonia, medium power microscopic, GMS stain.
  6. Pneumocystis carinii pneumonia, high power microscopic, GMS stain.
  7. Pneumocystis carinii pneumonia, microscopic, bronchoalveolar lavage, cytologic smear, Giemsa stain.
  8. Pneumocystis carinii pneumonia, microscopic, bronchoalveolar lavage, cytologic smear, Giemsa stain.
  9. Pneumocystis carinii pneumonia, microscopic, bronchoalveolar lavage, cytologic smear, Pap stain.
  10. Pneumocystis carinii pneumonia, lung, microscopic, immunoperoxidase stain.
  11. Pneumocystis carinii, disseminated, gross.
  12. Pneumocystis carinii, disseminated, spleen, CT scan.
  13. Pneumocystis carinii, exudate with calcification, medium power microscopic.
  14. Pneumocystis carinii pneumonia, interstitial fibrosis, medium power microscopic.

Cytomegalovirus

Cytomegalovirus (CMV) is the most frequent disseminated opportunistic infection seen with AIDS. It causes the most serious disease as a pneumonia in the lung, but it can also cause serious disease in the brain and gastrointestinal tract. It is also a common cause for retinitis and blindness in persons with AIDS. CMV is identified by the presence of very large cytomegalic cells with enlarged nuclei that contain a violaceous intranuclear inclusion surrounded by a clear halo. Sometimes, basophilic stippling is present in the cytoplasm.

  1. Cytomegalovirus, appearance of organisms, diagram.
  2. Cytomegalovirus, ulcers in cecum, gross.
  3. Cytomegalovirus pneumonia, microscopic.
  4. Cytomegalovirus pneumonia, microscopic.
  5. Cytomegalovirus pneumonia, microscopic.
  6. Cytomegalovirus adrenalitis, microscopic.
  7. Cytomegalovirus, liver, microscopic.
  8. Cytomegalovirus pneumonitis, immunoperoxidase stain, medium and high power microscopic.

Mycobacteria

Mycobacterial infections are frequently seen with AIDS. Mycobacterium tuberculosis has been increasing in frequency since the start of the AIDS epidemic. The appearance of M tuberculosis with AIDS is similar to that of non-AIDS patients, with granulomatous pulmonary disease, though the infection may be more extensive or may be disseminated to other organs. Mycobacterium avium complex (MAC) infection is more unique to AIDS and is characterized by involvement mostly of the organs of the mononuclear phagocyte system (lymph node, spleen, liver, marrow). MAC infections are less likely to produce visible granulomas, and the lesions often consist of clusters of macrophages filled with numerous mycobacteria. Definitive diagnosis of mycobacterial disease is made by culture.

  1. Mycobacterium tuberculosis, lung, gross.
  2. Mycobacterium tuberculosis, lung, AFB stain, microscopic.
  3. Mycobacterium avium complex (MAC), spleen with miliary granulomas, gross.
  4. Mycobacterium avium complex (MAC), mesenteric lymph nodes, gross.
  5. Mycobacterium avium complex (MAC), diagram.
  6. Mycobacterium avium complex (MAC), macrophages filled with mycobacteria, spleen, AFB stain, microscopic.

Fungal Infections

There are many types of fungi that can complicate the course of AIDS. One of the most frequent (though uncommonly life-threatening) is Candida. Oral candidiasis is often seen with HIV infection and may presage the progression to AIDS. Candida can occasionally produce invasive infections in esophagus, upper respiratory tract, and lung.

Infections with the dimorphic fungi Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis are more serious infections that are often widely disseminated. C neoformans often produces pneumonia and meningitis.

  1. Candida albicans, lung, gross.
  2. Candida albicans, diagram.
  3. Candida albicans, invasive in bronchus, H&E stain, microscopic.
  4. Candida albicans, invasive in esophagus, PAS stain, microscopic.
  5. Candida albicans, invasive in esophagus, GMS stain, microscopic.
  6. Cryptococcus neoformans, diagram.
  7. Cryptococcus neoformans (with capsules), H&E stain, microscopic.
  8. Cryptococcus neoformans (without capsules), meninges, GMS stain, microscopic.
  9. Cryptococcus neoformans, India ink preparation of cerebrospinal fluid, microscopic.
  10. Histoplasma capsulatum, diagram.
  11. Histoplasma capsulatum, granulomas in liver, gross.
  12. Histoplasma capsulatum, liver, H and E stain, microscopic.
  13. Histoplasma capsulatum, liver, PAS stain, microscopic.
  14. Coccidioides immitis, diagram.
  15. Coccidioides immitis, lung, H&E stain, microscopic.
  16. Coccidioides immitis, liver, H&E stain, microscopic.

Toxoplasmosis

Toxoplasma gondii is a protozoan parasite that most often leads to infection of the brain with AIDS. The lesions are usually multiple and have the appearance of abscesses. Less commonly, T gondii infection is disseminated to other organs.

  1. Toxoplasma gondii, organizing cerebral abscess, gross.
  2. Toxoplasma gondii, diagram.
  3. Toxoplasma gondii, pseudocysts, microglial nodule, microscopic.
  4. Toxoplasma gondii, myocardium, microscopic.
  5. Toxoplasma gondii, lung, immunoperoxidase stain, microscopic.

Herpes simplex

Herpes simplex virus infection with AIDS is most likely to involve the gastrointestinal tract, mainly the esophagus and the perianal region. Herpes zoster infection of the skin can also occur prior to the onset of clinical AIDS. Herpes infections are rarely life-threatening.

  1. Herpes simplex virus, diagram.
  2. Herpes simplex virus, esophagus, microscopic.
  3. Herpes simplex virus, esophagus, microscopic.

Gastrointestinal Protozoal Infections

Cryptosporidium, Microsporidium, and Isospora are all capable of producing a voluminous watery diarrhea in patients with AIDS. Diagnosis can be made by examination of stool specimens and/or intestinal biopsy.

  1. Gastrointestinal protozoa, diagram.
  2. Cryptosporidiosis, small intestine, H and E stain, microscopic.
  3. Cryptosporidiosis, stool specimen, AFB stain,microscopic.
  4. Cryptosporidia, electron micrograph.
  5. Isospora belli, stool specimen, AFB stain, microscopic.

Malignant Neoplasms

Kaposi's sarcoma (KS) produces reddish purple patches, plaques, or nodules over the skin and can be diagnosed with skin biopsy. Visceral organ involvement eventually occurs in 3/4 of patients with KS.

Malignant lymphomas seen with AIDS are typically of a high grade and extranodal, often in the brain. They are very aggressive and respond poorly to therapy.

  1. Kaposi's sarcoma, skin, gross.
  2. Kaposi's sarcoma, skin, patch stage, microscopic.
  3. Kaposi's sarcoma, skin, nodule, microscopic.
  4. Kaposi's sarcoma, skin, extravasation of RBC's, microscopic.
  5. Kaposi's sarcoma, skin, hemosiderin and hyaline globules, microscopic.
  6. Kaposi's sarcoma, skin, hyaline globules, PAS stain, microscopic.
  7. Kaposi's sarcoma, oral cavity, immunoperoxidase with antibody to CD34, microscopic.
  8. Kaposi's sarcoma, stomach, gross.
  9. Kaposi's sarcoma, liver, gross.
  10. Malignant lymphoma, lymph node, gross.
  11. Malignant lymphoma, small intestine, gross.
  12. Malignant lymphoma, liver, gross.
  13. Malignant lymphoma, small intestine, high power microscopic.
  14. Malignant lymphoma, brain, low power microscopic.
  15. Malignant lymphoma, brain, high power microscopic.

Miscellaneous

Lymphoid interstitial pneumonitis (LIP) is a condition involving the lung that can be seen in AIDS in children. By chest radiograph, bilateral reticulonodular interstitial pulmonary infiltrates are seen. The earliest pathologic finding is a hyperplasia of bronchial associated lymphoid tissue with aggregates of lymphocytes and plasma cells in a bronchovascular distribution. Later lesions demonstrate diffuse lung round cell infiltrates, and lymphoid aggregates can be present.

  1. Lymphoid interstitial pneumonitis (LIP) of lung, low power microscopic.
  2. Lymphoid interstitial pneumonitis (LIP) of lung, low power microscopic.
  3. Lymphoid interstitial pneumonitis (LIP) of lung, medium power microscopic.
  4. Lymphoid interstitial pneumonitis (LIP) of lung, high power microscopic.
  5. Progressive multifocal leukoencephalopathy (PML), gross.
  6. Progressive multifocal leukoencephalopathy (PML), Luxol fast blue stain, low power microscopic.
  7. Progressive multifocal leukoencephalopathy (PML), high power microscopic.
  8. Progressive multifocal leukoencephalopathy (PML) JC viral particles in nucleus, electron micrograph.
  9. HIV lymphadenopathy, early phase with follicular hyperplasia, medium power microscopic.

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