Research

Committee. The authors thank the National HIV Surveillance
Committee and the doctors who reported AIDS cases
under national surveillance procedures.
References
1. National Working Group on HIV Projections. Estimates
and projections of the HIV epidemic in Australia, 1981-
1994. Internal technical report 1. Sydney: National
Centre in HIV Epidemiology and Clinical Research,
April 1992.
2. Valuing the past ... investing in the future. Evaluation
of the National HIV/AIDSStrategy 1993-94 to 1995-96.
Canberra: Commonwealth Department of Human Ser-
vices and Health, 1995.
3. National Centre in HIV Epidemiology and Clinical
Research. Estimates and projections of the HIV epi-
demic in Australia, 1981-1997. In: Technical appendix
no. 1: An epidemiological assessment of the HIV epi-
demic in Australia. Evaluation of the National HIV/AIDS
Strategy 1993-94 to 1995-96. Canberra: Common-
wealth Department of Human Services and
Health,1996.
4. National Centre in HIV Epidemiology and Clinical
Research. Australian HIV Surveillance Report, Vol. 12,
NO.1. Sydney: National Centre in HIV Epidemiology
and Clinical Research, 1996.
5. Brookmeyer R, Gail MH. A method for obtaining short-
term projections and lower bounds on the size of the
AIDS epidemic. J Am Stat Soc 1988; 3: 301-308.
6. Taylor JM. Models for the HIV infections and AIDS epi-
demic in the United States. StatMed 1989; 8: 45-58.
7. Becker NG, Watson LF, Carlin JB. A method of non-
parametric back-projection and its application to AIDS
data. StatMed 1991; 10: 1527-1542.
8. Rosenberg PS. Backcalculation models of age-specific
HIV incidence rates. Stat Med 1994; 13: 1975-1990.
9. Brookmeyer R, Liao J. The analysis of delays in dis-
ease reporting: methods and results for the acquired
immunodeficiency syndrome. Am J Epidemio/1990;
132: 355-365.
10. Rosenberg PS, Goedert JJ, Biggar RJ, for the multi-
center Hemophilia Cohort Study and the International
Registry of Seroconverters. Effect of age-at-serocon-
version on the natural AIDS incubation distribution.
AIDS 1994; 8: 803-810.
11. Biggar RJ and the International Registry of Serocon-
verters. AIDS incubation in 1891 HIV seroconverters
from different exposure groups. AIDS 1990; 4:
1059-1066.
12. Selik RM, Buelher JW, Karon JM, et al. Impact of the
1987 revision of the case definition of Acquired
Immune Deficiency Syndrome in the United States. J
AIDS 1990; 3: 73-82.
13. Kaldor JM, French MAK. When do patients present
with HIV infection? Med J Aust 1993; 158: 37-38.
14. Volberding PA, Lagakos SW, Koch MA, et al. Zidovu-
dine in asymptomatic human immunodeficiency virus
infection: A controlled trial in persons with fewer than
500 CD4-positive cells per cubic millimeter. N Engl J
Med 1990; 322: 941-949.
15. Cooper DA, Gatell JM, Kroon S, et al. Zidovudine in
persons with asymptomatic HIV infection and CD4+
cell counts greater than 400 per cubic millimeter. N
EnglJ Med 1993; 329: 297-303.
16. Concorde Coordinating Commitee. Concorde:
MRC/ANRS randomised double-blind controlled trial of
immediate and deferred zidovudine in symptom-free
HIV infection. Lancet 1994; 343: 871-881.
17. Rosenberg PS, Biggar RJ, Goedert JJ. Declining age
at HIV infection in the United States [letter]. N Engl J
Med 1994; 330: 789-790.
18. Miller E, Waight PA, Tedder RS, et al. Incidence of HIV
infection in homosexual men in London, 1988-94. BMJ
1995; 311: 545.
19. Australian Bureau of Statistics. Australia in profile. Can-
berra: ABS, 1993. (Catalogue No. 2821.0.)
(Received 13 Nov 1995, accepted 2 April 1996) 0
An unedited version of this paper was published on
the World Wide Web on 23 April 1996. URL:
htlp:/Iwww.library.usyd.edu.au/MJAlpapers/law/law.html
and will be available at that address until 1 July.

Malignancy in chronic leg ulcers

Danian Yang, Brendan D Morrison, Yvonne K Vandongen, Amarjeet Singh and Michael C Stacey

he prevalence of chronic ulcera-

T
Abstract
tion of the lower limbs in urban
Objective: To evaluate the frequency of malignant ulcers in patients presenting Australians is estimated to be 1.1
with leg ulcers. per 1000 population.' Venous disease or
Design: A descriptive study from data collected between July 1988 and June 1995 arterial disease, or a combination of the
from 981 patients (2448 ulcers) attending a leg ulcer clinic. two, are thought to be the main causes of
Setting: A specialised leg ulcer clinic at a tertiary teaching hospital. leg ulcers.' Although malignancy has
been reported to be uncommon.>s in the
Subjects: 43 patients with 55 malignant skin lesions.
past few years we have been impressed
Outcome measures: Tissue biopsies in ulcerated lesions that suggested by the increasing number of malignant
malignancy or were not responding to appropriate treatment. leg ulcers. Most are atypical in appear-
Results: Forty-three patients were found to have malignant lesions on the legs, ance, which often causes delays in the
giving a frequency of malignant ulcers of 4.4 per 100 leg ulcer patients, or 2.2 per diagnosis and subsequent treatment.
100 leg ulcers. Seventy-five per cent of the malignant ulcers were basal cell We identified all patients with malig-
carcinoma and 25% were squamous cell carcinoma. nant ulcers at a specialised leg ulcer
Conclusions: Malignant skin changes are common in chronic leg ulcers. A biopsy clinic at Fremantle Hospital, estimated
should be taken from all suspicious ulcers or ulcers that do not respond to the frequency of malignancy in leg
appropriate treatment. ulcers, and identified some of the clini-
cal features of these lesions to facilitate
MJA 1996; 164: 718-720 rapid recognition.

Fremande Hospital, Fremande, WA. Patients and methods

Danian Yang, MB BS, Research Registrar, Department of Surgery. Brendan D Morrison, MB BS,
Research Registrar, Department of Surgery. Yvonne K Vandongen, BA, Research Assistant, Over a period of seven years (july 1988
Department of Surgery. Amarjeet Singh, MD, FRCPA, Consultant Pathologist, Department of to June 1995), 981 patients (1122
Histopathology. Michael C Stacey, DS, FRACS, Associate Professor of Surgery.
Reprints: Associate Professor M C Stacey, University Department of Surgery, Fremantle Hospital,
ulcerated limbs) with 2448 chronic leg
GPO Box 480, Fremantle, WA 6160. ulcers were referred to the leg ulcer
E-mail: dmulcahy@cyllene.uwa.edu.au clinic at Fremantle Hospital. Of these

718 MJA Vol 164 17 June 1996

 Research

patients, 14 1 had bilateral leg Ulcers var ied in size from 0.0 6 to
Comparison of patients with malignant leg ulcers
ulce rs , and 395 had multiple 57. 5c m l (m ed ian , 3. 9 4cm 2) .
di agnosed in the initIal asses sment period and
ulcers on the sa me leg. For our In 27 pa tient s (63%) malig-
those in whom th e di agn osi s was delayed
study, a leg u lcer whic h faile d to nancy was diagnosed during th e
hea l within one month was con- Diagnosis of malignant ulcers initial p eriod of assess m e nt
side red ch ronic." Pa tient s with <: 4 we eks > 4 we ek s (which may have taken u p to four
u lcera tio n co nfi ne d to th e foot Numb er of p atients 27 16 wee ks) . Seve n patients (16 %)
were also incl uded . The presen ce Median age 77 years 76 years h ad cl inica l feature s wh ich
of malignan cy was not co nside red Past history of malignant stro ngly sugges ted malignancy
by the refe rring practitioners. leg ulcers 12 o and pr om pted biopsy as th e first
On referral to the clinic, a Diagnosis inves tigation. M ali gn an cy was
nu mber of inves tigations were Venous insufficiency d iagnosed in 16 patient s (37%)
pe rformed to assess th e aetiology + ma lignanl ulcers 18 8 after treatment for presum ed non-
of th e ulcers . If th ere were any (2 diabetes. (1 diabel es) malignant chro nic leg ulceration
features suggestive of m align an cy 1 rheuma toid) had been in itiated . The time
(e.g., irregular nod ul ar ap pear- Venous + arterial from first assessme nt to diagnosis
insufficiency +
ance of th e ulcer surface, raised or in these pa tients ranged from six
ma lignant ulcers 2 8
ro lled edge, fir m surrounding ( 1 diabetes. (1 diabetes .
wee ks to two years (med ian, 12
skin with little lipodermatoscle- 1 rheumatoid) 1 rheumatoid) wee ks). A co mpariso n of th e two
ros is o r raised granulation tissu e Malignant skin ulcers 7 o gro ups is given in th e Table.
in an area of the u lcer base) , a Forty-one of the 48 lim bs were
biop sy was performed unde r local fully investi gat ed and ven ous
anaesthesia ( I % lignoca ine with ad ren- n ant ulcers, giving a freq ue ncy of at least abnormalities on photoplethysmography
alin) . Biop sies were also perform ed 4.4 m alignant ulc er s per lOa pa tie nts wer e the o nly finding in 29 limbs, both
later if treatment ha d been initia ted for with leg ulcer s (or 4.3% of ulcerated venous and arte rial disease were present
a d iagnosis othe r tha n ma lignancy, and limb s) . When considered in terms of th e in 10 lim bs, and th e remaining two had
the ulcer eithe r failed to respond to total n umber of ulcers th e frequen cy was ne ithe r veno us nor arter ial disease . In
treatme nt or developed features sug- 2.2 pe r 100 leg ulcers. seven limbs of seven patient s th e ulcer s
gesting a neoplasti c lesion. There were 27 wom en an d 16 men appe ared to be skin ca ncers on initial
Bio psies were either incisiona l or (m ale ; female rati o, 1 : I. 7), with an age exa m inati o n and no D oppler or pho to-
punch biopsies. Both types of biopsy were range of 5 1- 9 4 yea rs (m ed ian, 76 plethys mo graphy investig ati ons wer e
ta ken from the edge of the ulce r and yea rs) . Ninet een patients (44%) were performed . O f 29 limbs with venou s
included both ulcer base and adja cent referr ed to the leg ulc er clinic for a first abnormalities, mo st also had m an ifes-
skin. Incisional biopsies co ns isted of an episode of ulceration. The rem aining 24 tations of chro nic veno us insuffi cien cy,
ellipse of tissue 5 m m long; a 3-mm patients (56 %) had a history of previou s suc h as obvious varicose veins, ankle
punch was used to obtain punch biopsies. ulce ration: 15 had had multiple leg and/or calf oed em a, an kle flar e, li po-
Re s t in g a n kle/brac hia l arteria l ulcers and eight b ilateral leg ulcers. The derm ato sclerosis or atrophie blan ch e.
D oppler index and veno us refilling time nu m ber of previo us ulcer episo des
with photopl eth ysmography were the ran ged fro m two to abo ut 50 (m ed ian Discussion
main investigations used to establish th e episodes, five) . In ou r patients the prop ort ion of leg
cause of ulceration . In our clinic , ulcers ulcers which proved to be malignant was
were att ributed to venous d isease if Ulcers much high er th an in previou s stud ies;
pho to plethys mography showed th e refill-
O f 43 pat ient s with 48 limbs with reported frequen cies for m aligna ncy
ing tim e to be less th an 25 secon ds ," and
m align ant ulc ers, 36 limb s (75%) had have ranged from nil to less than I % of
significant arterial ischaem ia was co n- patients with leg ul cers.w O nly th ree
sidered to be present when the arte rial basal ce ll carci noma, and 12 limbs m alignant ulcer s wer e found in one
Doppler rat io was less than 0.9. R La bo- (25%) had sq uamo us cell carcino ma . series of 2000 lower-limb u lcers, " and
T hirty-seven ma lign ant skin lesions
rato ry tests for haem oglobin, urea, elec- ano ther study reported on ly five m alig-
involved th e left lower lim b and 18 were
tro lyte an d blood glucose levels, and for nant ulcers encounte red in 25 years of
auto antibod ies, were performed to iden - on the right lower limb. Seven pat ien ts pr acti ce.'?
had two m alignant ulce rs on th e same
tify possible underlying causes for the The higher proportion of m alignant
leg, and five patient s had ma ligna nt
ulcers. ulcer s we found ma y relate to the fact
ulcers bilate rally. Forty -three malignant
lesions (78% ) were in the gaiter area, six tha t Australia has the world's highest
Results ( I I %) were above th e gaiter region and inci den ce of ncn- m elanocyt ic skin
six (1 1%) were on the foot. cancer. Eleven per cent of th ese cancers
Patients
Available clinical infor m ation in 37 have bee n shown to occur on th e lower
Biopsies were performed in 187 patient s. lim bs ind ica ted th at th e ulc erat ed limb, a relatively high proportion wh en
For ty-th ree patie nt s (48 ulcerated limbs ) lesio ns had been prese nt for from two compared with th e United States, where
were found to have a total of 55 m alig- week s to 7.2 yea rs (m ed ian , 20 wee ks). one study yielded a figure of on ly 2.8%

MJA Vol 164 17 June 1996 719

Research
of non-melanocytic skin cancer on the
lower limb. ll ,12 It is also possible that the
thorough data collection undertaken in
our clinic has enabled a much more
accurate assessment of the frequency of
this problem than has been possible
previously.
Three-quarters of the malignant
ulcers we found were basal cell carcin-
oma, whereas a recent review of pub-
lished reports found malignant change
within existing chronic ulcers to be pre-
dominantly squamous cell carcinoma
(157 out of 182).6 Whether the malig-
nant lesions identified in our study orig-
inated as skin cancers or reflected
malignant change in pre-existing chronic
leg ulcers is open to speculation. Only
one patient had an ulcer that fitted the
description of a Marjolin's ulcer (the
degeneration of a chronic ulcer into a
carcinomatous ulcer). He had had a leg
ulcer for more than three years. Multiple
biopsies had initially shown it to be non-
malignant; however, it was eventually
diagnosed as a squamous cell carcinoma
by tissue biopsy.
It has also not been established
whether the development of malignant
ulcers is a complication of venous ulcer-
ation. Traditionally, the incidence of
basal cell carcinoma on the lower limb
was thought to be low. However, recent
reports'>" have shown that basal cell
carcinoma is the most common type of
skin malignancy on the lower limb.
Black and Walkden have postulated that
the changes in dermal connective tissue
occurring in venous stasis may predis-
pose to the development of basal cell
carcinoma. 16 Chronic venous skin
changes need to be present for a mini-
mum of two to three years before skin
cancers arise as a complication of
venous ulcers.' Changes in the dermis
(such as hyperplasia) induced by venous
stasis have been proposed to explain
cases of synchronous tumours.!?
In almost two-thirds of our patients
with malignant ulcers, the diagnosis was
suspected at the initial evaluation, even
though it had not been suspected by the
referring practitioner. However, in the
remaining patients the diagnosis was not
suspected even on reassessment in our
clinic and these patients frequently had
other identified causes of leg ulceration.
This difficulty in differentiating ulcer-
720
ating skin cancers on the lower leg from
chronic leg ulcers due to other causes
has been reported previously.Pi'" We,
and others,'! have found that some
ulcerating skin cancers do not have all
the clinical features characteristic of skin
malignancy. Moreover, 40% of our
patients had multiple ulcers, and it is
important in assessment to consider that
not all ulcers on the leg are due to the
same cause, and some could be skin
cancers.
A number of features of the ulcer itself
may help to raise suspicions that it is a
neoplasticulcer; these have been used
for this purpose by previous investiga-
tors. 15, 19 Some- studies have also docu-
mented an offensive odour associated
with malignant ulcersjv'? however, this
is not a feature that we have found to be
of great value. The failure of an ulcer to
respond to appropriate treatment, espe-
cially in patients with evidence of
venous disease, is another indicator that
the lesion may be a malignant ulcer. A
study in our department indicated that
75% of venous leg ulcers heal within
three to six months with our standard
treatment. 1 Our patients with malignant
ulcers had a median duration of ulcera-
tion of 20 weeks, with the longest time
being 7.2 years. Many patients present-
ing to our clinic with chronic venous
ulceration have not had optimal com-
pression therapy. However, if healing or
signs of healing do not occur within two
months once therapy is introduced, a
biopsy is performed.
In our experience, biopsy of chronic
leg ulcers can be performed under
local anaesthesia with minimal risk. The
ulcer margin and base may be sampled
with either a scalpel or a biopsy punch.
Haemostasis can usually be achieved by
direct local pressure. Suturing is unde-
sirable and generally unnecessary. We
have found, as have others.v that heal-
ing of the biopsy site occurs quickly with
minimal complications.
Malignant change within a leg ulcer
has been considered uncommon. Our
results indicate, however, that almost
5% of patients presenting with a "leg
ulcer" actually have a malignant ulcer,
regardless of whether the lesion arose as
a skin cancer or whether it represents a
neoplastic change in an existing ulcer. It
is therefore imperative that biopsies are
performed on all suspicious ulcers and
ulcers not responding to appropriate
treatment to avoid long delays in
diagnosis.
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(Received 3 Nov 1995, accepted 27 Mar 1996) 0
An unednedversion of Ihis paper was publishedon the
Wo~d Wide Web on 24 May 1996. URL:
http://www.library.usyd.edu.auIMJAlpaperslyangiyang.html
and will be available at that address until 1 July.
MJA Vol 164 17 June 1996