72

myocardium showed more recent infarction, withoutevidence of fungal invasion.The lungs were oedematous, with foci of fungal

bronchopneumonia which were more pronounced inthe right lower lobe. Fungal hyphae were also seen inmultiple renal and brain abscesses.The thoracic and upper abdominal segments of the

aorta showed severe atheroma with calcification, anda synthetic graft replaced the bifurcation and thelower part of the aorta. The abdominal branches ofthe aorta were all patent, and the graft anastomoticsites were intact.The appearance of the fungus was similar at all the

sites in which it was found. The hyphae were of vari-able diameter, but in general, were rather broad.There were some folds and kinks, and branchesoccurred irregularly but typically at right angles.Septa were seen, but these were scanty in most areasand showed no particular relation to the points ofbranching (fig 4). Two rounded structures, resemblingsporangia, were seen protruding from the endo-cardium in a single section of the wall of the leftatrium. Each was borne on the end of a thick hyphaand had a well defined limiting membrane; there wereno sterigmata on the surface, and no columella couldbe identified (fig 5). A few similar structures werefound in a single tiny colony of fungus in the lung.

Benbow, McMahon

Discussion

Zygomycosis is often diagnosed on histology only;';

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Fig4 Fungal hyphae within lumen ofintramyocardial vein.Hyphae are generally broad but of varying diameter.Branching is at right angles, and both septa andpseudoseptaare seen. (Grocott's stain.) Original magnification x 120.

Fig 5 Left atrial endocardium with probable sporangium protruding into lumen. (Periodic acid Schiffstain.) Originalmagnification x375.

i ....

:4:

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Myocardial infarction in disseminated zygomycosis

cultures may not be taken because the presence of aninfection is not anticipated, and even if they are takenthe fungus may fail to grow.' In tissue sectionszygomycosis needs to be distinguished, in particular,from aspergillosis. This task may be difficult for themorphology is more variable in tissue than it is inculture, and both aspergillosis and zygomycosis may,

on occasion, produce appearances which may simu-late the other.4 8 First appearances may therefore bemisleading, and histological diagnosis in most cases

requires careful examination of those features thatpermit a distinction to be made.

In zygomycosis the hyphae branch irregularly andtypically at right angles, whereas hyphal branching inaspergillosis is regular, mainly dichotomous, and usu-

ally at about 45°. Hyphal diameter in zygomycosis isvariable and often relatively broad, in contrast to thenarrower and more regular hyphae of aspergilli; thosein zygomycosis are usually kinked to a variabledegree, and the opposite walls of any one hypha are

often not parallel with each other. Septa are commonin aspergillosis and often occur at typical sites adja-cent to the branches. In contrast, septa may be scantyin zygomycosis, and, indeed, some authors claim thata total lack of septation is typical. It is certainly truethat aseptate hyphae are consistent with zygomycosis,but the corollary of this statement is not true for it isalso known that some, if not all, species produce septain culture, especially late ones,9 and in tissue.410Pseudosepta, produced by minor kinks in the zygo-

mycete hyphae, are often difficult to distinguish fromtrue septa and lead to a false increase in the estimatedprevalence of septa. The fungi in both conditions maybe atypical when they are growing in a confined space,and it is important to assess those areas in histologicalsections where growth is relatively unimpeded, suchas within thrombus or within a well establishedinfarct. In our case we were able to assess those fea-tures of the fungus, both within thrombus, and myo-cardium, which showed well established infarction.The findings correspond well to the classical appear-ances of zygomycosis, apart from the presence ofsepta; there were, however, no areas where true septawere present with the incidence typical of asper-gillosis.The rounded structures within the left atrial lumen

and within the lung closely resemble the sporangia ofZygomycetes," though they cannot be definitely dis-tinguished from the chlamydoconidia that are occa-

sionally produced.'2 They clearly lack the ranks ofsterigmata that are so characteristic of aspergilli.Few positive cultures have been reported in pre-

viously published cases of cardiac zygomycosis, andseveral of those have been described as "Mucor,"without any specific species identification.'3 -16 In

two cases, however, the organism was identified as

73

Cunninghamella bertholletiae.f7 18 Further, one of theearly cases of cardiac zygomycosis was also due toCunninghamella sp, though the actual species was notidentified.'3 This genus is a rare cause of humaninfection, and only eight reported cases have been dueto Cunninghamella bertholletiae. 18 Although thisassociation with the heart may be mere coincidence, itmight also represent a specific organ preference.Other similar species are known to prefer certainorgans: Absidia corymbifera is associated with lunginfection. 9

Cardiac zygomycosis is usually seen as a com-ponent of disseminated zygomycosis.5 The heart israrely the only organ affected in zygomycosis.20 21Virmani et al reviewed 115 cases of systemic zygo-mycosis from the files of the Armed Forces Instituteof Pathology (AFIP) in Washington DC, and foundonly five with cardiac disease.5 All had widespreaddisease of other organs, particularly of the lungs.They also reviewed the published reports, apparentlyin a selective manner, and found four examples ofdisseminated zygomycosis with cardiac disease in anolder report from the AFIP,3 together with six casesin reports from other centres.2' 23 Their selectivityenhances the apparent rarity of cardiac zygomycosis,for at least 15 other cases were available in the litera-ture at that time. 13 - 15 24 - 29 Several more have beenadded more recently.6 16 -18 30

Heart disease in zygomycosis may be endocardial,myocardial, or both. In addition, lesions in the lungmay give rise to pericardial disease as a result of directspread. Endocardial zygomycosis often overlies anarea of myocardial infection and infarction and maythus be a consequence of invasion of a mural throm-bus by hyphae from the wall of the heart.22 Alterna-tively, endocardial zygomycosis may precede and leadto myocardial zygomycosis. When the intramuralcomponent comes first, it is a consequence ofembolism of hyphae to the coronary arteries. Whensuch embolism causes infection and growth within anepicardial artery, there may be extensive myocardialinfarction without invasion of the infarcted area bythe fungus.'5 This, however, seems to be the excep-tion rather than the rule, for it is more usual to seethrombosis induced by fungus within small intra-mural arteries and for prominent growth of hyphae tooccur within the infarcted myocardium.21 22 In ourcase there were extensive areas where the presence ofa well defined polymorph reaction suggested aninfarct of some days' duration. The polymorphs weredisposed in between the dead fibres in a pattern typi-cal of myocardial infarction rather than that of anabscess, though the coincidence of such areas withhyphal invasion makes interpretation difficult. Otherareas showed typical very recent infarction, withincreased myocardial fibre eosinophilia and loss of

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74 Benbow, MecMahonnuclei and cross striations, but without a polymorphinfiltrate or fungal invasion. This seems to be consis-tent with progressive infarction caused by thrombosisinduced by fungus, followed by invasion of theinfarcted stroma in each area by the fungus.

All of the reported cases of coronary and myo-cardial zygomycosis that we found were diagnosed assuch only at necropsy. Most, like ours, were clinicallyunsuspected. Many of the previous reports provide aconsiderable amount of clinical detail, and so it isinteresting to realise that no symptoms or signs ofcardiac or major vessel disease could be found onreview of the clinical notes in most of thesecases. 3 5 13 16 17 21 - 24 27 In others cardiologicalfindings were non-specific,' or dominated by endo-cardial events.22 ECG findings have rarely beenreported, presumably because they have been negli-gible or unhelpful. In two cases where they weredetailed the ECG findings were entirely non-specific,5and in another two they were limited to changingheart blocks and arrhythmias.3 6 In only one previousreport was there clear ECG evidence of myocardialinfarction: Kolbeck et al describe a new right bundlebranch block, associated with Q waves in severalleads. 1 8Zygomycosis is an opportunistic infection, which is

clearly being recognised more often than pre-viously.23 One of the earlier reports of zygomycosis inthe British literature came from a health district adja-cent to ours,3' though the first case identified in thisdepartment was seen in 1984.32 Others have been seensince then, and zygomycosis now seems to be a wellestablished opportunistic infection. Myocardial dis-ease is an unusual complication of the disseminatedform of zygomycosis but should be included withinthe differential diagnosis when evidence of myo-cardial ischaemia or infarction occurs in a patient atrisk of such opportunistic infection.

We are grateful to Dr HG Love for reviewing theelectrocardiograms and to Dr RW Stoddart for hisinvaluable comments. We thank the universitydepartment of medical illustration and Mrs JaneCrosby for help with the photographs.

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Requests for reprints to: Dr EW Benbow, Department ofPathology, Stopford Building. University of Manchester,Oxford Road, Manchester, M139PT, England

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doi: 10.1136/jcp.40.1.70 1987 40: 70-74J Clin Pathol

 E W Benbow and R F McMahon zygomycosis.cardiac disease in disseminated Myocardial infarction caused by

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