editorial aids-relatedpathologydownloads.hindawi.com/archive/2011/437431.pdf · science articles...

SAGE-Hindawi Access to ResearchPathology Research InternationalVolume 2011, Article ID 437431, 3 pagesdoi:10.4061/2011/437431

Editorial

AIDS-Related Pathology

Liron Pantanowitz,1 Antonino Carbone,2 and Justin Stebbing3

1 Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA2 Division of Pathology, Centro di Riferimento Oncologico Aviano, Istituto Nazionale Tumori, Aviano, Italy3 Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK

Correspondence should be addressed to Liron Pantanowitz, [email protected]

Received 27 April 2011; Accepted 27 April 2011

Copyright © 2011 Liron Pantanowitz et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Since the first announcement of acquired immune deficiencysyndrome (AIDS) in 1981, around 33 million people world-wide are now infected with human immunodeficiency virus(HIV) [1]. This pandemic is associated with 6 million newannual HIV infections, resulting in 1.8 million deaths eachyear due to AIDS. During these past 30 years, an immenseamount of knowledge regarding the pathology of HIV/AIDShas accrued. These valiant efforts have provided greaterunderstanding about HIV/AIDS and its associated diseasesand have undoubtedly improved the clinical management ofafflicted persons. Despite this noteworthy effort, however, atangible cure still seems remote as HIV infected individualscontinue to succumb to many AIDS-defining and non-AIDS-defining conditions. In this special issue on AIDS-relatedpathology, we have assembled diverse papers that showcasethis fascinating disease and underscore some of the manyunanswered questions.

We are fortunate to have some truly superb papers withaccompanying striking images. They teach us that the obser-vation of subtle defects can immediately lead to diagnoseswith enormous implications for the patient. Such conditionsare often seldom observed outside of HIV. Occam’s razor, theprinciple named after the 14th century philosopher Williamof Occam, does not apply in this setting. This generalizationstates that if there are a number of explanations for observedphenomena, the simplest explanation is preferred—calledalso scientific parsimony. Rare manifestations of commondiseases and common presentations of rare conditions maybe seen together; only HIV and its subsequent immunosup-pression link these phenomena. Fortunately, with the adventof HAART in established market economies, the spectrumhas changed with a notable shift from infection to cancer

and “standard” diseases that non-HIV-infected people areroutinely affected by, but often their manifestations havesubtle differences.

A variety of diseases may be encountered related directlyand/or indirectly to HIV infection. This is well illustratedin the paper reporting the spectrum of pathological man-ifestations of AIDS in a series of 236 autopsied casesin Mumbai, India. This article points out that the vastmajority of underlying pathologies discovered by necropsywere either preventable or treatable conditions. The paperdealing with HIV-associated gastrointestinal (GI) diseasediagnosed with endoscopic biopsy nicely portrays the varietyof inflammatory, infectious and neoplastic diseases that maybe seen in the upper and lower GI tract. Given the increasedfrequency of coinfections and broad diversity of diseaseslikely to be seen, it is not surprising that pathology specimensprocured from HIV-infected are diagnostically challengingfor anatomic pathologists. This is demonstrated in thebeautifully illustrated article about multiple pathologies seenin skin biopsies from patients with HIV/AIDS, as well as thecomprehensive review of HIV-related cytopathology.

Owing to the progressive reduction of the host immunesystem, HIV infected individuals are susceptible to manyopportunistic infections. As the paper that stems from SouthAfrica on primary oral tuberculosis shows, these often serveas an indicator for HIV infection. The article on Penicilliummarneffei makes the point that in endemic areas like HongKong, disseminated penicilliosis is now included in thelist of AIDS-indicator conditions. Human polyomavirusfrequently reactivates in individuals infected with HIV, whichtypically manifests with sinister pathological consequences.This issue is addressed in the paper about novel human

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polyomavirus-associated cerebral disorders seen primarily inthe era of highly active antiretroviral therapy (HAART). AsHIV+ patients are increasingly qualifying for transplants, thecomplications of concomitant infection and management inthis setting are manifold. The case report of zygomycosisassociated with HIV infection and liver transplantation dealswith just this conundrum.

The oncogenic viruses associated with HIV infectionhave incited much interest in the field over the years. Kapo-si’s sarcoma-associated herpesvirus/Human herpesvirus-8(KSHV/HHV-8) was first found in 1994 by isolating DNAfragments of this virus from a Kaposi sarcoma (KS) tumor inan AIDS patient [2]. KSHV was subsequently found to causeseveral other diseases, such as primary effusion lymphomaand multicentric Castelman′s disease (MCD). The casereport describing HHV-8 infection associated with KS,MCD, and plasmablastic microlymphoma in a single lymphnode of a Kenyan man with AIDS commendably reviews thepathology of this oncogenic process. The number of reportedcases of Epstein-Barr virus-(EBV) related smooth muscletumor arising in patients with AIDS has been increasing sincethe mid 1990s. The epidemiology, clinical manifestations,pathologic features, prognosis, and management of thisfascinating entity are methodically reviewed in this specialedition.

HIV-infected patients are at increased risk of devel-oping cancer. Despite the advent of HAART, malignancyin this population is a leading cause of morbidity andmortality. Like KS, AIDS-related non-Hodgkin lymphoma(AIDS-NHL) is one of the most common AIDS-definingmalignancies. One of the articles in this edition is a five-yearretrospective case series in which the authors review theirinstitutions experience with numerous lymphoproliferativelesions in the setting of HIV infection. The pathologicalheterogeneity of AIDS-NHL reflects the heterogeneity oftheir associated molecular lesions [3]. Even though newmolecular evidence continues to emerge regarding AIDS-NHL, several biological features about these AIDS-NHLremain perplexing. This is exemplified in the case report of a47-year-old HIV+ man with a diffuse large B-cell lymphomaobserved to undergo an immunophenotypic switch froma germinal center to nongerminal center origin. Theseauthors offer several plausible explanations to explain thisphenomenon.

The incidence and spectrum of non-AIDS-defining can-cers (NADCs) continues to grow [4, 5]. As HIV-infectedindividuals live longer due to HAART, their risk of dyingfrom one of these cancers is increased. The role of HIV-induced immunosuppression in the development of theseNADCs appears to be less important than coinfection withcertain viruses such as human papilloma virus (HPV). Thisedition offers an interesting review of the various carcinomasarising in the head and neck region in HIV+ patients,several of which are related to oncogenic viruses. Whileseveral NADCs are on the rise, it remains unclear why otherssuch as breast cancers are decreased in this population [6].The case report of an invasive ductal carcinoma of thebreast surrounded by an intense lymphocytic response in thesetting of HIV provides some insight into this interesting

association, demonstrating the unique interplay betweenbreast cancer and the HIV+ host’s immune response. It is ofgreat interest that the two hormonally driven tumors, breastand prostate cancers, may have a decreased incidence in thesetting of HIV. Of course, many of the studies about HIV-associated breast and prostate cancer are small, and this maybe a statistical aberration.

Apart from the direct and indirect effects related to HIVinfection, treatment of HIV+ patients too has untowardside effects. For example, HAART may be associated withlipodystrophy, gynecoamastia, insulin resistance, hyperlipi-demia and increased cardiovascular risk. Glitazones, a novelclass of insulin-sensitizing antidiabetic agents, have beeninvestigated in the management of HAART-associated lipiddisorders. The effect of rosiglitazone, an agonist of per-oxisome proliferator-activated receptor (PPAR), on skeletalmuscle gene expression with regard to insulin sensitivity inindividuals with HIV-insulin resistance is presented in thisspecial AIDS-related edition of the journal. Additional basicscience articles provide unique perspectives on osteoim-munopathology in HIV/AIDS and nanotherapeutics using aHIV-1 poly A and transactivator of the HIV-1 LTR-(TAR-)specific siRNA.

The challenges for diagnosis and management of sickpeople with HIV remains, despite the remarkable successof HAART. We should keep in mind that fewer than onemillion HIV-infected individuals are currently receivingantiretroviral therapy. Present anti-retroviral therapy costsbetween $10,000 and $20,000 per year, which providesexcellent value for money in developed countries with acost of about $10,000 per life-year saved; the lives saved areessentially the young and potentially economic productivesection of the population. This compares very favorablywith many other drugs for chronic therapies in current use.The limitations of anti-retroviral treatment strategies at aphysical (suppression of viremia) and political (widespreadavailability) level have underscored the need to develop moreeffective strategies to control the spread and pathogenesis ofHIV and the diseases related to it that we describe herein.In recent years, the demand for new antiviral strategies hasincreased markedly. There are many contributing factorsto this increased demand, including the ever-increasingprevalence of chronic viral infections and other pathogensindividuals are coinfected with, many of which are describedin these papers.

While this great collection of papers certainly bearstestimony to how much we have learned about HIV/AIDS todate, these papers also serve to remind us of how much westill do not understand.

Liron PantanowitzAntonino Carbone

Justin Stebbing

References

[1] AVERT, http://www.avert.org/worldstats.htm.[2] Y. Chang, E. Cesarman, M. S. Pessin et al., “Identification of

herpesvirus-like DNA sequences in AIDS-associated Kaposi’ssarcoma,” Science, vol. 266, no. 5192, pp. 1865–1869, 1994.

Pathology Research International 3

[3] A. Carbone and A. Gloghini, “AIDS-related lymphomas: frompathogenesis to pathology,” The British Journal of Haematology,vol. 130, no. 5, pp. 662–670, 2005.

[4] L. Pantanowitz, H. P. Schlecht, and B. J. Dezube, “The growingproblem of non-AIDS-defining malignancies in HIV,” CurrentOpinion in Oncology, vol. 18, no. 5, pp. 469–478, 2006.

[5] J. Stebbing, O. Duru, and M. Bower, “Non-AIDS-definingcancers,” Current Opinion in Infectious Diseases, vol. 22, no. 1,pp. 7–10, 2009.

[6] L. Pantanowitz and B. J. Dezube, “Reasons for a deficit ofbreast cancer among HIV-infected patients,” Journal of ClinicalOncology, vol. 22, no. 7, pp. 1347–1348, 2004.

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