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J Clin Pathol 1993;46:1071-1075 1071

HIV and the necropsy


S B Lucas

Introduction CLINICOPATHOLOGICAL FOLLOW UP


In mid-1981 reports from the USA docu- Clinicopathological follow up is the tradi-
mented clusters of homosexual men with tional role of the necropsy. As many reports
Pneumocystis caninii pneumonia and dissemi- have iterated, necropsies reveal major dis-
nated Kaposi's sarcoma, until then both rare crepancies with premortem diagnoses which
conditions. These and other early accounts of are of potential therapeutic relevance.7 The
the disease complex that was subsequently situation is no different with AIDS, in which
labelled AIDS were supported by diagnoses cytomegalovirus infection, tuberculosis, sys-
from necropsy, which also emphasised the temic Kaposi's sacoma and Mycobacterium
presence of multiple opportunistic infections avium complex infection may be missed
in these patients.lA Within two years the first before death on a substantial scale.8 The pre-
of an everlengthening list of necropsy series of valence of cerebral lesions such as primary
patients with AIDS (in this case 10 patients) cerebral lymphoma, progressive multifocal
emphasised that there was underdiagnosis leucoencephalopathy, and HIV encephalitis
during life of many opportunistic infections may be doubled by necropsy compared with
and neoplasms. Ten years on, the peroration those suggested by premortem diagnoses.9
that pathologists "are in a unique position to There are, of course, certain lesions which
facilitate research efforts by distributing necropsy does not detect well, particularly
blood, biopsy and necropsy tissues of AIDS intestinal infections with Cryptosporidium and
patients... by complete autopsy examina- the microsporidian Enterocytozoon bieneusi
tions pathologists will not only assist with (because of autolysis) and bacteraemia.
patient care but will continue to increase
understanding of this new syndrome" DESCRIPTIVE CLINICAL PATHOLOGY AND
remains true.5 EPIDEMIOLOGY OF HIV DISEASE
At the same time, regular necropsies con- The pathology of AIDS is now well described
ducted in a hospital in Miami, USA, showed in industrialised countries. In the Third
that among immigrants from Haiti who died World-where the major current and, espe-
between 1979-82, a high proportion had cially, future burdens of HIV infection will
opportunistic infections6: eight of 23 patients fall-the patterns of disease are not well
had AIDS defining conditions by existing cri- defined; and they are not predictable from the
teria (most frequently cerebral toxoplasmo- First World's experience. To supplement
sis), though in retrospect, with broadening of clinical studies of HIV disease (logistically
the surveillance criteria for AIDS, the true difficult in the tropics), systematic post
figure was 13 of 23. Not only were these pro- mortem examination of seropositive adults
portions significantly higher compared with and children dying in hospitals provides rep-
necropsy figures for African-Americans, but resentative data on the main infections and
none of the Haitian patients had the then tumours that characterise AIDS in that com-
accepted risk factors for AIDS-haemophilia, munity. This has been done in Africa,10 and
homosexual behaviour, intravenous drug mis- could provide a short-cut to the understand-
use. The fact that women were affected and ing of the clinical pathology of HIV disease in
that the incidence of tuberculosis among regions such as India and South-East Asia,
these patients was high, these observations where HIV is now spreading rapidly. In
from the mortuary presaged three of the Thailand and Hong Kong, for example, dis-
major features of AIDS in developing coun- seminated Penicillium marneffei infection will
tries: heterosexual spread; women affected as probably be a major opportunist disease in
well as men; and the importance of tubercu- HIV positive people," 12 as necropsies will
losis as an opportunistic infection. A year readily show.
later, the main viral agent of AIDS was dis- In industralised countries the HIV
covered. Human immunodeficiency virus necropsy can still reveal hitherto unknown
type 1 (HIV-1) is the major virus, prevalent infections. A recent example is a new
in virtually all countries of the world; HIV-2, microsporidian parasite which, unlike intesti-
Department of identified subsequently, is restricted mainly to nal Enterocytozoon infection, spreads to the
Histopathology, UCL West Africa. kidney, respiratory tract, and liver
Medical School, parenchyma.13 14
Rockefeller Building,
University Street In addition to cross-sectional studies, long
London WClE 6JJ The present value of the necropsy in HIV term comparisons of findings at necropsy of
S B Lucas disease HIV positive patients can indicate very
Correspondence to: There are six major reasons for performing important changes in the pattern of HIV dis-
Dr S B Lucas
Accepted for publication necropsies on HIV positive patients, in addi- ease. These may reflect the use of specific
29 July 1993 tion to any forensic requirement: prophylaxis-for example, reducing the over-
1072 Lucas

all prevalence of P carinii pneumonia at P carinii pneumonia has been very thoroughly
necropsy while increasing the proportion who studied, not all patients are successfully
have extra-pulmonary pneumocystosis."5 On treated for it. Drug reactions in HIV positive
the basis of point prevalences over several patients are of increasing concern. Many are
years, it has been suggested that use of the cutaneous and readily evaluated in life2l but
antiretroviral agent azidothymidine (AZT) is necropsy material is needed for the study of
associated with a reduction in the proportion damage of deep organs such as the pancreas:
of patients with AIDS whose brains had antimicrobial and antiretroviral agents are
multinucleate giant cell encephalitis (a associated with pancreatitis.22
marker of productive HIV infection in the
brain).'6 As HIV positive people in industri- SPECIFIC ORGAN BANKS
alised countries patients live longer due to Davies et al23 document the benefits of accu-
better medical care while severely immuno- mulating tissue banks of brain specimens.
compromised, it is predicted that more of Studies on the epidemiology and pathology of
them will develop non-Hodgkin's lym- HIV related brain disease are done optimally
phoma'7; again, the necropsy will be the most in such special centres using uniform
sensitive means of detecting this. Finally, methodologies. These tissue banks are also a
tuberculosis is globally the most important resource for basic scientists wishing to study
opportunistic infection associated with the mechanisms of damage in the central ner-
AIDS.'8 At present it is a relative rarity at vous system associated with HIV. Similar col-
necropsy in patients with AIDS in the United lections of spinal cords and eyes from HIV
Kingdom. But given the difficulties in the positive patients will greatly aid the evalua-
premortem diagnosis of disseminated tuber- tion of myelopathies and retinopathies in
culosis and the likelihood of mortality if infected patients.24
untreated, a high necropsy rate of HIV posi-
tive patients could provide an early indication EDUCATION
of increasing coinfection of HIV and M tuber- The wealth of macroscopic pathology found
culosis, which would have important public at necropsy in most patients with AIDS pro-
health implications. vides excellent material for teaching medical
Finally, necropsies on HIV positive people students and postgraduates. With histology,
who do not have clinical AIDS and who have these necropsies make valuable clinicopatho-
died from unnatural causes (such as intra- logical conferences, emphasising the patholo-
venous drug misuse, and trauma) provide gist's role in the management of HIV disease.
useful data on the early stages and pathogene- The proceedings of several such conferences
sis of HIV disease, particularly in the central at our hospital have been published which
nervous system.'9 highlight specific diagnostic and therapeutic
problems.25 29
ENDPOINTS IN CLINICAL TRIALS The quantity of HIV related diagnostic
Studies of antiretroviral agents and drugs material arriving at histopathology laborato-
directed against opportunistic infections and ries varies regionally, so that pathologists have
tumours in cohorts of HIV positive patients a wide range of experience of the lesions asso-
require the validation of endpoints. Once ciated with HIV. The study of necropsy histo-
HIV disease has progressed to AIDS it is logy helps greatly in learning-for example,
probably always fatal; the necropsy will indi- the variations in the patterns of Kaposi's sar-
cate whether the patient died with an AIDS- coma and the various types of intracerebral
defining illness or from an incidental event.20 lesions that may be biopsied.
DRUG EFFICACY AND TOXICITY
There is no antiretroviral drug that has been Risks of performing necropsies on HIV
proved to have sustained efficacy, so the man- positive cadavers
agement of patients withi HIV disease Among pathologists and anatomical patho-
depends to a large extent on optimising the logy technicians, globally, there is a good deal
prophylactic and therapeutic range of treat- of concern over the likelihood of becoming
ment against infections and tumours. Clinical infected with HIV by performing necropsies
response provides data on drug efficacy, but on HIV positive cadavers. It is important to
the necropsy will give information on the ulti- be aware of the real risks. Infection might
mate response of many specific lesions. The arise: (1) from contact of infected blood or
activity of M avium complex infection, the body fluids on skin, eyes, mouth or nose; (2)
resolution or not of lymphoma, and the from penetrating percutaneous injuries from
extent of P carinii pneumonia are instances of infected bone spicules, scalpel blades, syringe
this. In our hospital, for example, we needles, and sewing-up needles; or (3)
encounter patients with known pulmonary inhaled aerosols of infected fluids or sawn
Kaposi's sarcoma who worsen and die bone dust.
because of undiagnosed P carinii pneumonia. The quantities of HIV present in blood
Similarly, patients have presented with con- peak at the time of seroconversion, are then
firmed or suspected P carinii pneumonia and low for years, and rise again during the final
died rapidly, despite maximal appropriate illness of AIDS.30 HIV-1 virus is recoverable
chemotherapy. Necropsy showed that they from cadaveric blood and tissue samples.
died with severe P carinii pneumonia: all this The largest study to date found virus in 21
reminds us that although the management of of 41 (51%) serum specimens or blood
HIV and the necropsy 1073

mononuclear cell fractions from cadavers.3' tions with the attendant potential for trans-
The longest post mortem time tested was mission to staff in the mortuary. Cryptococcus
37-5 hours, but virus was found only up to neoformans, P carinii, Candida, M avium and
21-5 hours. In other smaller investigations, other non-tuberculous mycobacteria may be
HIV-1 virus has been recovered 18 hours to inhaled during the necropsy. But as they are
11 days after death.'2 34 Skull bone contained ubiquitous, they will not cause disease unless
HIV six days after death, but no samples of the pathologist or technician is already
sawn bone dust did. HIV was recovered from immunosuppressed (and therefore should not
spleen specimens stored for up to 14 days.34 be working in a mortuary). Hepatitis B virus
Refrigeration of cadavers did not seem to (HBV) infection is common in HIV positive
diminish the recovery of virus. HIV-2 has patients, and far more transmissible than
been cultured from cadaveric blood 16-5 days HIV, but with vaccination against HBV,
after death.35 infection is minimised. More worrying is the
Necropsies are usually performed within a possibility of infection with hepatitis C virus,
few days of death, so for practical purposes, particularly from the cadavers of intravenous
all HIV positive cadavers must be assumed to drug misusers. We need studies on the preva-
contain viable infectious HIV. None the less lences of this infection among HIV positive
many thousands of necropsies have been per- and HIV negative cadavers, and on the risk of
formed on HIV positive adults, children, and acquisition by prosectors.
on cases of perinatal death. There are no Tuberculosis is a special concern. As yet,
reports of a pathologist acquiring HIV infec- the proportion of HIV positive patients (and,
tion from a necrospy.'6 Three "morgue tech- implicitly, cadavers) in the United Kingdom
nicians/embalmers" in the USA are stated to with M tuberculosis infection is low. However,
have possible occupation-related HIV-1 it is likely that the prevalence of tuberculosis
infection, but no further details are avail- in HIV positive cadavers is greater than that
able.37 in HIV negative cadavers. This is certainly
Global data up to December 1992, on the true in sub-Saharan Africa where about 50%
risk of occupational transmission of HIV, of cadavers with AIDS may have active tuber-
indicate that 52 health care workers have HIV culosis, and the lesions contain vast numbers
seroconversion documented after a specific of bacilli with the concomitant potential of
exposure. Most of these occurred after nee- inhalation. Because of international travel,
dle-stick injuries (needles may contain 1 pl of several other virulent infections that are
blood), and the estimated HIV transmission prevalent outside the United Kingdom may
rate after a single percutaneous exposure is be encountered in HIV positive cadavers,
0-27% (95% confidence interval 0-12- such as Histoplasma capsulatum and
0 42%). For a single mucocutaneous expo- Coccidioides immitis.
sure, the HIV transmission rate is estimated
to be 0.04%.38 Transmission by aerosol
inhalation has not been documented. Mortuary practices
It is arguable whether a scalpel injury The principles of safe practice for working
incurred whilst dissecting a cadaver carries a with HIV positive cadavers are no different
greater or lesser risk of HIV transmission than from those that should be used for all cases.
a needle-stick injury.39 The incidence of cuts They are appropriate training and experience,
during necropsy does depend on the experi- good work practices, the use of safe imple-
ence of the operator. One study found that ments, and a safe working environment.'9
pathology trainees sustained a cut or needle- In addition to standard guidelines on
stick injury once out of every 11 necropsies; necropsy and mortuary practice,424' there are
for the more experienced consultant patholo- specific recommendations for HIV necrop-
gists, the rate was one out of 53 necropsies.40 sies.4A6 Although in principle a policy of
Although there is evidence that the rate of adopting such special precautions may be
cuts to the hands among surgeons is not advocated for all necropsy work, in the
affected by prior knowledge of the patient's United Kingdom, where the prevalence of
HIV infection status,4' there are no data on HIV infection is currently low,47 this is unre-
this point regarding pathologists. Anecdotal alistic. The Health Services Advisory
and personal observations, however, indicate Committee guidelines adopt a two-tier
that pathologists performing necropsies on approach on safety measures with regard to
HIV positive cadavers, in the United HIV and other high risk infections.42 A similar
Kingdom at least, rarely if ever cut them- approach is advocated by the Clinical
selves as they take great care not to. It is most Pathology Accreditation Scheme. This strati-
unlikely that statistically useful data on the fication may seem to be illogical and unsatis-
occupational risk of HIV infection for pathol- factory, but with the current very low
ogists will accumulate. We should therefore prevalence of previously unknown HIV infec-
accept the theoretical risk and proceed using tion in cadavers for necropsy, there is no con-
sensible and appropriate practices. sensus among pathologists for advocating
special precautions for all necropsies. In the
United Kingdom at present, the only group
Other risks of infections of cadavers with a substantial likelihood of
The emphasis hitherto has been on HIV unknown HIV infection is intravenous drug
infection, but HIV infected cadavers often misusers coming to medicolegal necropsy;
have multiple opportunistic and other infec- 15-38% of such cadavers are HIV positive
1074 Lucas

(Dr I West, personal communication),4"8 but positive patients in 1990/91 .23 The major
the numbers studied have been small. In a reason cited for not doing so was lack of
study in London and Cardiff of cadavers for requests. However, AIDS is not going to go
medicolegal necropsy, which excluded the away in industrialised countries like the
"high risk" categories of homosexual men, United Kingdom,49 and the amount of HIV
prisoners, and intravenous drug misusers, necropsy work will increase over the decades
only one in 264 was found to be HIV positive to come.
(Drs P Vanezis and S Leadbeatter, personal
communication).
The recommendations for performing HIV
necropsies include: wearing a face mask and 1 Centers for Disease Control and Prevention. Pneumo-
glasses to protect mucosal surfaces; wearing a cystis carinii pneumonia-Los Angeles. Morbid Mortal
Week Rep 1981;30:250-2.
water-impermeable gown or body suit to 2 Centers for Disease Control and Prevention. Kaposi's sar-
cover the arms, and a plastic over-apron; and coma and Pneumocystis carinii pneumonia among
homosexual men-New York city and California.
wearing two pairs of gloves (latex inner gloves Morbid Mortal Week Rep 1981;30:305-8.
and outer thicker household rubber gloves); 3 Gottleib MS, Schroff R, Schanker HM, et al.
some pathologists also opt for cut-resistant Pneumocystis carinii pneumonia and mucosal candidia-
sis in previously healthy homosexual men. N Engl Jf Med
glove liners. The instruments used should be 1981;305:1425-31.
4 Masur H, Michelis MA, Greene JB, et al. An outbreak of
kept to a minimum, and blunt-ended imple- community-acquired Pneumocystis carinii pneumonia.
ments used in preference to sharp-pointed- Initial manifestation of cellular immune dysfunction.
for example, round-ended scissors, and NEnglJMed 1981;305:1431-8.
5 Reichert CM, O'Leary TJ, Levens DL, Simrell CR,
non-pointed body-opening knife blades and Macher AM. Autopsy pathology in the acquired
immune deficiency syndrome. Am J? Pathol 1983;
organ-slicing knives. It is ideal to have a sepa- 112:357-82.
rate "infectious disease" suite available within 6 Moskowitz LB, Kory P, Chan JC, Haverkos HW, Conley
a mortuary, but it is not essential. FK, Hensley GT. Unusual causes of death in Haitians
residing in Miami: high prevalence of opportunistic
infections. JAMA 1983;250:1 187-91.
7 Royal College of Pathologists. The autopsy and audit.
London: Royal College of Pathologists, 1991.
Final note 8 Wilkes MS, Felix JC, Fortwin AH, Godwin TA,
In November 1992, 30 pathologists from Thompson WG. Value of necropsy in acquired
immnodeficiency syndrome. Lancet 1988;ii:85-8.
Great Britian and Ireland, representing most 9 Monforte Ad'A, Vago L, Lazzarin A, et al. AIDS-defining
of those interested in necropsy work on HIV diseases in 250 HIV-infected patients; a comparative
study of clinical and autopsy diagnoses. AIDS 1992;6:
disease, met at the Royal College of 1159-64.
10 Lucas SB, Hounnou A, Peacock C, et al. The mortality
Pathologists. They included forensic patholo- and pathology of HIV in a West African city. AIDS
gists and neuropathologists in addition to 1993 (in press).
11 Li PCK, Tsui WMS, Ma KF. Penicillium marneffei: indi-
general histopathologists. The issues dis- cator disease for AIDS in South East Asia. AIDS 1992;
cussed included fears among pathologists and 6:240-1.
technical staff in general; screening before 12 Tsui WMS, Ma KF, Tsang DNC. Disseminated
Penicillium marneffei infection in HIV-infected subject.
necropsy for HIV positivity; the problems in Histopathology 1992;20:287-91.
13 Orenstein JM, Dieterich DT, Kotler DP. Systemic dis-
obtaining consents for necropsy (in many semination by a newly recognised intestinal
units, the major limiting factor for HIV microsporidia species in AIDS. AIDS 1992;6:1143-50.
14 Schwartz DA, Bryan RT, Hewan-Lowe KO, et al.
necropsies); the cost of HIV necropsies, Disseminated microsporidiosis (Encephalitozoon
which are more expensive than non-HIV hellem) and acquired immunodeficiency syndrome.
Arch Pathol Lab Med 1992; 116:660-8.
cases as they occupy more of the pathologists' 15 Coker RJ, Clark D, Claydon EL, et al. Disseminated
time and generate more tissue blocks; and Pneumocystis carinii infection in AIDS. J Clin Pathol
199 1;44:820-3.
pathologists' actual practices for performing 16 Gray F, Geny C, Doumon E, Fenelon G, Lionnet F,
HIV necropsies. The latter showed a wide Gherardi RK. Neuropathological evidence that zidovu-
dine reduces incidence of HIV infection of brain. Lancet
range of safety measures adopted, but as in 1991;337:852-3.
other fields of histopathology uniformity is 17 Gail MH, Pluda JM, Rabkin CS, et al. Projections of the
not a notable behavioral characteristic. But all incidence of non-Hodgkin's lymphoma related to
acquired immunodeficiency syndrome. JNCI 1991;83:
agreed that HIV necropsy work was safe 695-701.
18 De Cock KM, Soro B, Coulibaly I-M, Lucas SB.
when carried out sensibly, and that special Tuberculosis and HIV infection in sub-Saharan Africa.
precautions over and above those required for JAMA 1992;268:1581-7.
non-infectious cases should be taken, as out- 19 Gray F, Lescs M-C, Keohane C, et al. Early brain changes
in HIV infection: neuropathological study of 11 HIV-
lined earlier. seropositive, non-AIDS cases. J Neuropathol Exp Neurol
The aim of this editorial is emphatically to 1992;51:177-85.
20 Esiri MM, Scaravilli F, Millard PR, Harcourt-Webster
encourage pathologists to perform necropsies JN. Neuropathology of HIV infection in haemophiliacs:
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1312-15.
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fulness, it is the experience of those who have sensitivity reactions due to thiacetazone in HIV-1 sero-
positve patients treated for tuberculosis. Lancet 1991;
done many HIV necropsies that they provide 337:627-30.
22 Jost R, Stey C, Salomon F. Fatal drug-induced pancreati-
very interesting cases. It is the pathologist's tis in HIV. Lancet 1993;341:1412.
privilege to take aesthetic and intellectual 23 Davies J, Everall IP, Lantos PL. Post mortem examination
of HIV infected patients: a nationwide survey in the
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The multiplicity of hitherto unusual gross and 24 Budka H, Wiley CA, Kleihues P, et al. HIV-associated
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26 Anderson J, George RJD, Weller IVD, Lucas SB, Miller
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HIV and the necropsy 1075

27 Scoular A, Moxham J, Lucas SB, Miller RF. Adult respi- December 1992. London: PHLS AIDS Centre, 1993.
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