INTRODUCTION
Worldwide, about 6 million people require medical care because of burns; in Brazil,
this number is about 1 million patients per year1,2. Such lesions can be caused by thermal, chemical, electrical, biological, or radioactive
agents and are divided into three degrees according to their complexity.
In addition to the physical damage, many burn victims suffer from psychological and
economic problems due to a prolonged recovery time3,4. Given that this pathology requires long and painful treatment, it may, in some cases,
be neglected and evolve into a process of lesion malignancy.
Malignant skin lesions are the most frequent form of cancer in Brazil and worldwide,
being subdivided into melanoma and non-melanoma, which is the most common, representing
95% of tumors. Exposure to solar radiation is a predisposing factor for squamous cell
carcinogenesis and basal cell carcinomas5,6.
In 1828, the French surgeon Jean Nicolas Marjolin associated the inadequate treatment
of Marjolin’s ulcer with burns that were not treated due to their malignancy. However,
the term Marjolin’s ulcer was first recognized in 1903 in a description by Da Costa
of a malignant process resulting from a burn8. The term is currently used more generally for any chronic malignancy in scars, although
burns remain the main precursor lesion, with the incidence of burn scar evolving to
carcinoma being 0.77-2%8.
Although it is possible to identify other malignant neoplasms, such as sarcoma, melanoma,
and basal cell carcinoma, the main histopathological sample of the tumor is spinocellular9. Thus, 76% of patients with a history of burn scar have squamous cell carcinoma10.
Furthermore, this pathology is classified as acute or chronic, lesions that became
malignant within or beyond a 12-month period after the injury, respectively7.
This study provides knowledge about the above-mentioned problems and the tools used
for the effective diagnosis, treatment, and prognosis of Marjolin’s ulcer. Thus, it
is necessary to use therapeutic tools and medical knowledge to better manage patients,
prevent the development of this disease in burn patients, and awaken the interest
of clinicians about its early identification.
OBJECTIVE
The objective of this study is to review the literature on Marjolin’s ulcer resulting
from burn injuries.
METHODS
This is an integrative review of burn scar carcinoma, classically known as Marjolin’s
ulcer. The Virtual Health Library (VHL), PubMed (Publisher Medicine), Scientific Electronic
Library Online (SciELO), and Cochrane databases were used. The following controlled
keywords were used: “Queimadura/Burn” and “Úlceras de Marjolin/Marjolin’s Ulcers.”
The inclusion criteria established were studies published in the last 5 years of humans
and full availability on the web in English or Portuguese.
Moreover, integrative reviews, literature reviews, systematic reviews, and letters
to the editor were defined as the exclusion criteria.
RESULTS
By using the inclusion criteria, we found 31 studies in the databases, of which only
six met the inclusion criteria after the analytical reading being included in the
final sample of this study (Tables 1 and 2). Of the 11 studies found in the VHL, two letters to the editor, two studies that
were not available on the web, and two articles that did not address burns were excluded.
Thus, five studies were included in the sample. Eighteen studies were found in PubMed,
eight of which were already found in the VHL, three were not available on the web,
and six studies were excluded because they did not address burns, one of which addressed
trauma-related injuries in general. Thus, only one study of this database was included
in the sample. Two studies using the previously determined keywords were found in
SciELO, but none of them addressed burns. No study was found in the search of the
Cochrane database.
Table 1 - Distribution of articles addressing the development of Marjolin's ulcer in burn scars
by article title; study type; and publication year, language, and origin. Fortaleza
- Ceará, 2019.
| Study Title |
Study Type |
Year |
Language |
Origin |
| Úlcera de Marjolin: relato de caso (Marjolin's ulcer: case report) |
Case Report |
2015 |
Portuguese |
Brazil |
| Multiple Marjolin's ulcers arising from irradiated post-burn hypertrophic scars: a
case report
|
Case Report |
2014 |
English |
Canada |
| Acute Marjolin's ulcers: a nebulous diagnosis |
Case Report Series |
2014 |
English |
United States |
| Incidences of malignancy in chronic burn scar ulcers: experience from Bangladesh |
Prospective and Observational Study |
2015 |
English |
Bangladesh |
| Epidemiology and predictors of recurrence of Marjolin's ulcer: experience from Mansoura
University
|
Retrospective Study |
2017 |
English |
Egypt |
| Úlcera de Marjolin: revisão de literatura e relato de caso – (Marjolin's ulcer: literature
review and case report)
|
Case Report |
2016 |
Portuguese |
Brazil |
Table 1 - Distribution of articles addressing the development of Marjolin's ulcer in burn scars
by article title; study type; and publication year, language, and origin. Fortaleza
- Ceará, 2019.
Table 2 - Epidemiological characteristics and treatment reported in case reports. Fortaleza
- Ceará, 2019.
| Study |
Number of cases studied |
Age at burn |
Age at diagnosis |
Sex |
Treatment |
| Úlcera de Marjolin: relato de caso (Marjolin's ulcer: case report) |
2 |
Not reported |
Case 1: 59 years |
Cases 1 and 2: Male |
Cases 1 and 2: Exeresis with wide margin of safety |
| Case 2: 82 years |
| Multiple Marjolin's ulcers arising from irradiated post-burn hypertrophic scars: a
case report
|
1 |
4 years |
61 years |
Male |
Exeresis with wide margin of safety |
| Graft for radial artery reconstruction |
| Acute Marjolin's ulcers: a nebulous diagnosis |
3 |
Not reported |
Case 1: 42 years |
Case 1: Female |
Case 1: Exeresis with wide margin (3.5 × 1.8 cm) |
| Case 2: 50 years |
Case 2: Male |
Case 2: Surgical debridement |
| Case 3: 60 years |
Case 3: Male |
Case 3: Exeresis with wide margin |
| Úlcera de Marjolin: revisão de literatura e relato de caso (Marjolin's ulcer: literature
review and case report)
|
1 |
27 years |
52 years |
Male |
Wide margin exeresis and local graft |
Table 2 - Epidemiological characteristics and treatment reported in case reports. Fortaleza
- Ceará, 2019.
It should be noted that although the last selected study has the term “Literature
Review” in its title, a type of study that was considered an exclusion criterion,
the “Úlcera de Marjolin: Revisão de literatura e relato de caso (Marjolin’s Ulcer:
Literature Review and Case Report)” article was actually a case report.
DISCUSSION
After analyzing the results, we decided to divide the study into the following topics
to facilitate understanding.
Risk Factors and Topography
Although chronic pressure lesions are reported in 2.6% of cases of Marjolin’s ulcer,
they are more common in old burn scars, representing 76% of cases, and venous stasis
ulcers, representing 6.3% of cases11.
A study conducted of 140 patients showed that, on average, 80% of the malignant transformations
of burns scars were caused by flames, mainly due to the ability of this etiological
agent to deepen the lesion, causing greater stiffness and consequent cracking of the
lesion scar12.
Moreover, although Marjolin’s ulcers may occur in any location, the upper and lower
limbs were the most affected topographies, which is explained by the high incidence
of venous stasis burns and ulcers, and the higher propensity to repeated damage in
these sites, especially in the joints12.
In addition to burn scars with a long healing time, other important risk factors are
reported in the literature, such as second intention scars and scars that are easily
traumatized, confirming the relevance of topography for assessing lesion malignancy13. Skin grafts in deeper burns is mentioned as a protective factor against malignancy14.
A study conducted in China demonstrated that easily traumatized scars are a risk factor
for the development of Marjolin’s ulcer. Of the 17 patients with Marjolin’s ulcer
(35%) they assessed, six reported recurrent ulcers within the lesion15.
Etiology
Although Marjolin’s ulcer is not carcinogenic, its etiology appears to include several
factors that are influenced by the trauma that occurs within the region. This trauma
makes the lesion more malignant since it intensifies some carcinogenic factors, such
as UV rays, due to the greater sensitivity of traumatized skin13. It also causes prolonged cell proliferation due to inefficient healing, which can
cause mutations in the DNA of these cells16.
Another factor that may contribute to carcinogenesis of these lesions is the reduction
in vascularization in the region where the healing process occurs, making the immune
response to these cells with mutated DNA less efficient16. It also includes lymphatic obliteration due to healing, impairing the presentation
of the antigen and the activation of the defense cells17.
At the molecular level, some studies have attributed the malignancy process of Marjolin’s
ulcer to mutations in the p53 and FAS genes17.
Diagnosis and Latency
The diagnostic approach begins with clinical suspicion of Marjolin’s ulcer based on
the lesion’s characteristics, i.e., chronic ulcerative lesions with unhealed high
and hardened edges, an unpleasant odor, a budding appearance, and occasional purulent
discharge18.
Furthermore, it is important to pay attention to the patient’s history since many
reports show that the transformation to carcinoma was associated with poorly healing
burns during childhood19.
Although the diagnosis can be directed by lesion characteristics and anamnesis, it
is only made histopathologically18. Ulcers persisting for more than 3 months should be biopsied20.
A common problem found in health services is the patient’s delay in seeking care,
which makes it difficult to make the early diagnosis that is essential for a favorable
prognosis. Another problem eventually reported is underestimation of the patient’s
condition, postponement of the therapeutic approach, and possible confusion with an
infected ulcer18,14.
The latency period between injury and malignancy is 11-75 years, with a mean of 30-35
years. Moreover, the patient’s age when the first lesion occurred, such as the burn
injury, is inversely proportional to the latency period, i.e., individuals who developed
this lesion at an early age have a longer latency period21.
Treatment and Recurrence
Although treatment should be individualized, since it depends on several factors,
such as age, comorbidity, and tumor characteristics, surgical excision is considered
the gold standard when the tumor has a margin at least 2 cm18,22. However, limb amputation and radiotherapy or chemotherapy may also be indicated.
Amputation is convenient when Marjolin’s ulcer infiltrates more deeply, affecting
bones and great vessels, with imaging examinations eventually being useful for detecting
the degree of bone involvement14,20, infectious processes, and significant hemorrhage, and when excision of the lesion
may generate greater functional disability17.
Radiotherapy may be indicated in cases of metastasis that cannot be surgically corrected,
tumors larger than 10 cm with positive lymph nodes after dissection, and head and
neck lesions with positive lymph nodes after dissection23.
Although chemotherapy is not always indicated, it may be convenient in situations
in which the patient does not consent to surgical treatment, has distant metastasis,
or experiences disease recurrence23.
A study analyzing 412 cases observed Marjolin’s ulcer after surgical excision in 16%
of reports. This result may be associated with some factors, such as male sex, cooking
oil burn, and treatment neglect during the first injury and recurrence13,24.
A study in Egypt analyzing 26 cases of Marjolin’s ulcer identified other factors as
predictors of recurrence, such as young age at the time of diagnosis, malignancy in
the nodal groups of lymphatic drainage, and the use of a flap or graft after wide
excision20.
CONCLUSION
This study analyzed the literature on Marjolin’s ulcer resulting from malignancy of
burn scars and discussed risk factors and topography, etiology, diagnosis and latency,
and treatment and recurrence.
From the discussion of this review, it was possible to conclude that Marjolin’s ulcer
presents as malignant skin neoplasms that appear most frequently after thermal burns
that require specific and individualized treatment since several factors influence
the therapeutic plan.
Despite the need for histopathological confirmation, clinical suspicion together with
anamnesis becomes necessary for an early diagnosis, which is essential due to the
highly aggressive nature, metastatic potential, and high recurrence rate of Marjolin’s
ulcer, which in most cases is treated surgically. In more extreme cases of bone involvement,
amputation becomes necessary to avoid worse conditions.
Thus, the knowledge of health professionals about Marjolin’s ulcers is essential for
a better prognosis so that possible cases of malignancy are not underestimated, appropriate
therapy is implemented, recurrence is avoided, and prophylactic measures are implemented
to effectively avoid burn and mitigate risk factors for malignancy.
Limitations of the present study include the low number of articles describing an
epidemiological analysis with a more considerable sample in the analyzed period and
the consideration of only Portuguese and English articles, which may have limited
the search. Therefore, clinical studies and trials are needed to gain more comprehensive
knowledge of Marjolin’s ulcer.
COLLABORATIONS
|
TMV
|
Data Curation, Methodology, Writing - Original Draft Preparation, Writing - Review
& Editing
|
|
MPFFA
|
Writing - Original Draft Preparation
|
|
BMC
|
Writing - Original Draft Preparation
|
|
SLC
|
Writing - Original Draft Preparation
|
|
MCFA
|
Writing - Original Draft Preparation
|
|
NGSO
|
Review & Editing
|
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1. Universidade de Fortaleza, Fortaleza, CE, Brazil.
Corresponding author: Thiago Maciel Valente Rua Bento Albuquerque, 1133, Cocó, Fortaleza, CE, Brazil. Zip Code: 60192-055. E-mail:
maciel.thiago@edu.unifor.br
Article received: January 29, 2019.
Article accepted: July 8, 2019.
Conflicts of interest: none.
