MALIGNANT WOUNDS
The management of malignant lower
limb ulcers: clinical considerations
ABSTRACT
Lower limb malignant ulcers are an uncommon finding, making diagnosis
complex and their management costly. Yet, despite this, the increase
in skin cancers over the past 30 years means that clinicians require an
awareness and understanding of their existence, particularly in the primary
care setting. Familiarity with common aetiologies and presentations is
vital for prompt recognition, diagnosis and referral of wounds suspicious
for malignancy. Lower limb malignant wounds often develop insidiously,
with a wide variation in clinical presentation that overlap between entities.
Therefore, a fundamental algorithm for approaching lower limb ulcers that
raise suspicion of malignancy should be possessed by all clinicians. This
article reviews the clinical features of malignant wounds that should alert
clinicians to the need for further evaluation, such as atypical location
and appearance. The authors also highlight the various diagnostic and
therapeutic modalities available and review current clinical guidelines for
the referral and follow-up of suspicious lesions.
Key words: Malignant wounds ■ Wound care ■ Tissue viability
■ Lower limb ulcers
A
s clinicians, awareness of malignant wounds and
their management is important to ensure that
patients are treated in a timely fashion. Malignant
ulcers are fortunately uncommon, accounting
for 2-4% of lower limb wounds, but they often present
in insidious ways, with features overlapping with other
pathologies (eg venous changes) that can potentially delay
diagnosis (Lautenschlager and Eichmann, 1999). That said,
over the past 30 years the incidence of skin cancer incidence
rates have risen dramatically in England, with a projected
cost to the NHS in 2020 likely to be in the region of £180
million (Vallejo-Torres et al, 2014).
A high index of suspicion for wounds that ‘just don’t
seem right’ or fail to heal in a typical fashion with standard
treatments should raise suspicion for malignancy. A
Paul Ghaly, Resident, Department of Vascular Surgery, Liverpool
Hospital, Sydney, Australia
Yewon D Kim, Resident, Department of Vascular Surgery, Liverpool
Hospital, Sydney, Australia
Jim Iliopoulos, Associate Professor and Vascular and Endovascular
Surgeon, Liverpool Hospital, Sydney, Australia
Mehtab Ahmad, Clinical Superintendent, Department of
Vascular Surgery, Liverpool Hospital, Sydney, Australia,
tabbyahmad@doctors.org.uk
Accepted for publication: July 2020
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correct, early diagnosis is essential to avoid inappropriate
investigations or treatment.
When faced with a clinical conundrum, it is always useful
to take a back-to-basics approach. Revisiting the history of
a chronic wound can identify important information that
may have been overlooked in differentiating its aetiology. A
thorough history may, for example, elicit a history of deep
venous thrombosis (eg following surgery or pregnancy) or
venous symptoms (aching, throbbing and swelling of the leg(s),
that is particularly worse at the end of the day or exacerbated
by prolonged periods of standing/dependency and relieved by
elevation). There may be a history of intermittent claudication
(muscle discomfort, fatigue, aching or cramping most
commonly localised to the calf, but which may also affect the
thigh or buttocks, that is reproducible by exercise and relieved
by rest within 10 minutes (Norgren et al, 2007)), suggestive of
arterial insufficiency as the underlying problem.
For malignant ulcers, a thorough history of causative risk
factors is essential, and should include whether there is a
history of ultraviolet (UV) sunlight exposure, use of tanning
beds or a positive family history of skin cancers (Sham et al,
2016). Given the overlap of clinical presentations and features,
a thorough understanding of malignant tumours is necessary
to ensure prompt recognition and improve patient outcomes.
Clinical features of malignant wounds
The wide variation in malignant ulcers adds to the complexity
of establishing a clinical diagnosis. As such, a methodological
approach to skin ulcers can provide clues suggestive of a
malignant wound.
As a minimum, ulcer examination should include the
basics, for example the location, size and shape of the
wound, colour of the base, shape of the border, depth of
the ulcer and composition of the discharge (Lautenschlager
and Eichmann, 1999). The ‘BBEDDS’ framework for
examining an ulcer can provide structure to a basic, stepwise
approach (Box 1).
On examination, the following characteristics should raise
suspicion of malignant ulcers:
Atypical location
Ulcers of non-malignant aetiology, namely venous stasis,
arterial or neuropathic ulcers, are well-described and
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familiarity with common anatomical sites of development
of these wounds is paramount to identifying irregularities.
Venous ulcers are commonly found in the gaiter region
of the lower leg (malleoli to the mid-calf); ischaemic or
neuropathic ulcers typically occur over bony prominences
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Box 1. ‘BBEDDS’ framework for describing an ulcer

B – Basics (eg site, size, shape)
B – Base (eg colour)
E – Edge (eg flat, rolled, undermined, everted, punched-out)
D – Depth (in mm)
D – Discharge (serous, blood, purulent)
S – Surrounding (eg skin changes, colour, scars)

Box 2. Uncommon aetiologies for primary skin ulcers

■ Malignant vascular tumours (eg Kaposi’s sarcoma,
angiosarcoma)
■ Cutaneous lymphomas
■ Rare adnexal tumours
■ Cutaneous metastases

Source: Isoherranen et al, 2019

that experience pressure (Figure 1); while ulcers on the calf are
not commonly associated with vascular pathology and should
raise suspicion for vasculitic, infective or malignant aetiology
(Hayes and Dodds, 2003; Spentzouris and Labropoulos, 2009).
Chronic venous stasis ulcers in the gaiter region that are
refractory to standard treatments, however, should undergo
Figure 1. Neuropathic ulcer with ‘punched out’ appearance
evaluation for malignancy, due to their potential for malignant
transformation (Labropoulos et al, 2007).

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Atypical appearance
Further to its location, the appearance of an ulcer provides
invaluable clinical clues to its aetiology. Long-standing ulcers
with features of excessive granulation tissue in the ulcer base
with, or without, extension beyond the ulcer margins, raised
or rolled wound edges and changes in shape or size are
atypical and suggestive of malignancy (Hayes and Dodds, 2003;
Isoherranen et al, 2019).
Other, less specific, clues for malignant ulcers include
irregular wound borders, malodour, increasing pain severity
and associated bleeding (Isoherranen et al, 2019). Despite
the overlap in signs and symptoms with other aetiologies,
one cardinal features of malignant wounds are their poor
tendency to heal despite standard treatment such as
compression therapy for venous stasis ulcers (Lautenschlager Figure 2. Lower limb basal cell carcinoma with characteristic rolled edge
and Eichmann, 1999). Consequently, interval examination
is highly recommended, with a delay in wound healing or Basal cell carcinoma
changes in ulcer morphology alerting the clinician to the BCC is the most common type of skin cancer, accounting
possibility of a malignant wound. for about 75% of all NMSC (Chintamani and Tandon, 2016).
About 8% of BCC arise in the lower extremity (Labropoulos
Primary skin tumours et al, 2007). These tumours are slow growing, locally
Malignant ulcers can be subclassified as primary or secondary destructive, painless and arise from a subset of basal cells
skin tumours. within the epidermis. Their typical clinical course involves
■ Primary malignant ulcerating skin tumours refer to those superficial dome-shaped nodules that progress to central areas
arising in previously normal skin, most commonly basal of ulceration (Figure 2). Despite the low rate of metastasis,
cell carcinoma (BCC) and squamous cell carcinoma BCCs can invade local tissue, causing destruction. Fair skin
(SCC), collectively called non-melanoma skin cancers and red hair (Fitzpatrick skin type 1 or 2), exposure to ionising
(NMSC). Less common causes of primary malignant radiation, immunosuppression and genetic predisposition are
tumours include malignant melanoma (Box 2) all important associated risk factors.
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■ Secondary ulcerating malignant tumours, collectively

referred to as Marjolin’s ulcers, are rare and refer to those Squamous cell carcinoma
that develop in chronic leg wounds secondary to, for SCC of the lower extremity has a spectrum of presentations
example, burn scars or osteomyelitis sinuses (Pavlovic et and is the second most common skin cancer after BCC,
al, 2011). with an increasing incidence (Alam et al, 2018). This rise is

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MALIGNANT WOUNDS
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Figure 3. Squamous cell carcinoma with characteristic central scale and
erythematous nodule appearance
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Figure 4. Nodular lesions on the posterior aspects of both calves. Note the
irregularity and atypical location of the lesions
thought to be due to an increase in cumulative exposure to
UV light, which is the greatest environmental risk factor for
development (Xiang et al, 2014). This relationship is evident
by SCCs of the lower limb being more prevalent in women
than men, with higher rates over the anterior surface of the
leg, and is likely to be due to lifestyle and clothing choices
(Kim et al, 2014). Other risk factors for SCC are similar to
those for BCC.
SCCs are characterised by indurated, nodular, keratinising
or crusted tumours that ulcerate or ulcers without
keratinisation (Motley et al, 2020) (Figure 3). Among the
African American population SCC is the most common type
of skin cancer (Labropoulos et al, 2007), classically affecting
non-chronically sun exposed areas. SCCs can grow rapidly,
with a higher incidence of metastasis compared with BCC.
Malignant melanoma
Malignant melanomas (MMs) are cancerous tumours arising
from the melanocytes (pigment-producing cells) of the skin
(Figure 4). They comprise a small proportion of cutaneous
tumours, yet are the most lethal, accounting for the majority
of skin cancer deaths. Lower-extremity malignant melanomas
are more common in women (Ganguly and Sarkar, 2016).
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Secondary skin tumours
Marjolin’s ulcers
In the 19th Century, French surgeon Jean Nicolas Marjolin
described the phenomenon of chronic ulcers undergoing
malignant transformation, hence their collective name.
Marjolin’s ulcers describe rare, malignant cancers originating
from chronic non-healing wounds.
The malignant transformation is most commonly
associated with burn wounds, however other non-healing
ulcers, such as pressure sores, venous stasis ulcers, traumatic
wounds and osteomyelitis, have been reported to undergo
malignant transformation. Marjolin’s ulcers develop slowly,
with an average latency period of 25 years.
Most commonly, Marjolin’s ulcers are histopathologically
SCCs followed by BCC. They tend to be more aggressive
with higher rates of metastases and mortality, highlighting
the importance of periodic surveillance for chronic non-
healing wounds (Pavlovic et al, 2011).
Diagnosis
Wounds that generate a high index of suspicion should
undergo biopsy for histological analysis. Although an
objectively defined ‘observation period’ for chronic wounds
prior to referral for biopsy does not exist, much of the
literature suggests a period of 12-17 weeks (Hayes and
Dodds, 2003; Labropoulos et al, 2007).
Biopsies can either be in the form of a punch biopsy
(3‑4 mm), shave biopsy or deep wedge-shaped incisional
biopsy. A minimum of two biopsies, taken from different
areas of the wound, ideally the wound edge and wound bed,
should be performed. Overall, biopsies are safe procedures,
commonly performed under local anaesthesia with good
wound healing.
With regards to BCCs and SCCs, a ‘single-best-biopsy’
technique has not been published in the literature and
choice of biopsy therefore remains dependent on factors,
such as clinical characteristics, suspected malignancy,
tumour morphology and patient-specific factors (eg
patient preference and bleeding diathesis) (Alam et al,
2018). Contrastingly, the recommended biopsy modality
for a suspected MM is an excisional biopsy with inclusion
of the whole tumour and an additional 2 mm margin of
normal epithelium. Shave biopsies are not recommended
for MM and may lead to misdiagnosis (Marsden et al, 2010).
On certain occasions punch biopsies are acceptable, such
as in cases of suspected lentigo malignant melanoma on
the face.
If an ulcer continues to raise suspicion despite previous
negative biopsies, repeated interval biopsies may be
required to ensure that a malignant diagnosis is not missed
(Isoherranen et al, 2019).
Treatment
Over the years, a wide array of non-surgical treatment
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modalities have entered clinical practice to treat malignant
wounds, however surgical excision remains the mainstay for
high-risk lesions (Telfer et al, 2008).
Surgical treatment includes standard excision,
histologically controlled excision, known as Mohs
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micrographic surgery (MMS), and curettage and
electrodessication (C&E). Standard surgical excision with
4-5 mm margins of normal skin to the depth of the mid-
subcutaneous adipose tissue and follow-up histological
assessment is a good treatment for primary BCC, and
is associated with 95% clearance rates (Bichakjian et al,
2018). Slightly wider margins (4–6 mm) are recommended
with standard excision for low-risk primary SCCs (Alam et
al, 2018).
MMS, a technique pioneered by Dr Frederic Mohs in
the 1940s, was developed on the principles of maximal tissue
conservation with complete tumour excision through the
utilisation of real-time micrographic analysis. MMS is the
recommended modality for high-risk BCC and SCCs, with
superior curative rates over traditional excisions. However,
MMS is superseded by wide excisions, with or without flap
reconstruction, in the lower limbs, due to the ease of access
and typically concomitant presence of chronic inflammation
limiting microscopic analysis (Sham et al, 2016).
C&E is an effective, easily performed treatment modality
that has long been employed for the treatment of low-risk
BCCs and SCCs, however, results are highly operator and
location dependent (Bichakjian et al, 2018).
Non-surgical therapy remains second line to surgical
treatment of BCCs and SCCs. If surgical therapy is not
feasible for BCCs, non-surgical methods for their treatment
include cryotherapy, topical therapy (eg imiquimod),
photodynamic therapy or radiation therapy (Telfer et
al, 2008). Topical and photodynamic therapies are not
recommended for the treatment of SCCs, largely due to lack
of available data (Alam et al, 2018).
Radiotherapy can be considered for some tumour entities
or as a palliative therapy, however consideration of the
associated poor wound healing and pain when employed for
treatment of lower limb malignant wounds must be given,
particularly in patients with peripheral vascular disease(Alam
et al, 2018; Bachakjian et al 2018).
Referral and follow-up
On encountering a suspected SCC or MM, appropriate
referral should be promptly initiated using locally endorsed
suspected cancer referral pathways. These ensure patients are
seen within the current national target for cancer referrals
(within 2 weeks) by a specialist (typically a dermatologist).
This is due to their rapidly progressive nature and high risk of
metastases (National Institute of Health and Care Excellence
(NICE), 2015).
Routine referral is appropriate for patients with suspicion
of low-risk BCC, with suspected cancer pathway referrals
to the local skin cancer multidisciplinary team reserved for
patients with BCC raising suspicion of squamoproliferative
processes (NICE, 2010).
The ABCD rule (Box 3) or the 7-point checklist (Box 4)
can aid the early identification and referral of suspicious
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lesions. A score of 3 or more on the 7-point checklist
indicates a need for urgent referral under the 2-week rule
to local skin cancer services, typically a dermatologist.
Suspicious lesions for melanoma should not be removed in
the primary care setting (Marsden et al, 2010).
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MALIGNANT WOUNDS
Box 3. ABCD features of melanoma
A. Asymmetry of a mole
B. Border irregularity of a mole
C. Color variability
D. Diameter increase more than 6mm
Source: Ganguly and Sarkar, 2016
Box 4. Weighted seven-point checklist
Major features (scoring 2 points each):
■ Change in size
■ Irregular shape
■ Irregular colour
Minor features (scoring 1 point each)
■ Diameter ≥ 7mm
■ inflammation
■ Oozing
■ Sensory change
Source: Marsden et al, 2010; National Institute for Health and Care
Excellence, 2015
Follow-up is paramount for the effective treatment of
lower limb malignant ulcers, to ensure early detection of
tumour recurrence or metastases. Some 75% of recurrent
SCCs occur within the first 2 years of diagnosis. Therefore,
current practices recommend biannual follow-up for low-
risk SCCs and more frequent, quarterly, follow-up of high-
risk SCCs for the first 2 years (Isoherranen et al, 2019), with
consideration of imaging for metastases on clinical suspicion.
Conclusion
In summary, malignant wounds are uncommon yet complex
disease processes due to their overlap in aetiology and
presentations. Observer familiarity of common lower limb
ulcers is crucial for the early detection and prompt referral
of malignant wounds, ultimately reducing their associated
morbidity and mortality. BJN
Conflict of interest: none
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KEY POINTS
■ An awareness of malignant lower limb wounds is essential for all clinicians.
A high index of suspicion should exist for chronic, non-healing wounds
■ Familiarity with commonly encountered non-malignant ulcers, namely arterial,
venous-stasis and neuropathic ulcers, can aid the clinician in recognising
atypical ulcers
■ Surgical procedures such as standard excision, Mohs micrographic surgery
(MMS), and curettage and electrodissection (C&E) remain the mainstay
treatment choice for high-risk lesions
■ Early referral and regular follow-up are the cornerstone of good outcomes for
suspicious lower limb wounds
CPD reflective questions
■ When approaching an atypical wound, do you have a preferred style of
approach?
■ What are the two commonest primary skin tumors to consider with
atypical wounds?
■ When deciding on the appropriate referral pathway for a malignant
wound, do you consult National Institute for Health and Care
Excellence guidelines?
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Motley R, Kersey P, Lawrence C. Multiprofessional guidelines for the
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