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Choroid, a unique site for metastasis in Marjolin's ulcer

 Department of Cancer Surgery, VMMC and Safdarjung Hospital, New Delhi, India

Date of Submission18-Aug-2019
Date of Decision09-Oct-2019
Date of Acceptance31-Dec-2019
Date of Web Publication07-Nov-2020

Correspondence Address:
Amit Bagur Lokesh,
No. 26/4, 1B Cross, Saraswatipuram, Off Bannerughatta Main Road, Bengaluru - 560 076, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_617_19

 > Abstract 

Marjolin is an aggressive malignancy, which shows initial local aggression, followed by the rapid regional and distant dissemination during the latter part of its growth. Metastasis to the uveal tract, although infrequent, is usually secondary to the malignancies of the breast and lung. Marjolin's ulcer metastasizing to choroid is quite rare and unheard of. We intend to report one such case here. Here, we present a case report of a 55-year-old male, who developed Marjolin's ulcer over a previously injured left lower limb. He developed recurrence and re-recurrences requiring multiple surgeries, radiation, and chemotherapy cycles. He eventually developed disseminated systemic metastases. Over the course of his disease, he reported eye symptoms of pain, blurring of vision, and field defect in the left eye. On further evaluation with imaging and fundoscopy, a metastatic deposit was identified in the choroid of the left eye. Metastasis to the uveal tract is an unusual unreported event in the disease progression of Marjolin's ulcer. The treatment is usually palliative. It heralds the terminal stage of the disease, with inevitable death.

Keywords: Burns, choroid, Marjolin's ulcer, metastasis, skin neoplasms, squamous cell carcinoma

How to cite this URL:
Lokesh AB, Kumar R, Saheer N, Bhatnagar A. Choroid, a unique site for metastasis in Marjolin's ulcer. J Can Res Ther [Epub ahead of print] [cited 2021 Dec 5]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=300198

 > Introduction Top

Marjolin's ulcer of skin usually follows several years after an injury. The usual presentation is ulceration over an old-healed scar. They are known to occur in about 0.8%–2% of burn scars and may comprise about 2% of all squamous cell carcinomas (SCCs).[1] Although nodal involvement is quite rare in early lesions, as the malignant ulcer grows beyond the confines of scar, the disease is very aggressive in both locoregional spread and systemic dissemination as compared to SCC occurring de novo. Metastatic spread to the lung, bone, liver, dura, brain, and kidney has been reported.[2] Metastasis to the uveal tract from cutaneous SCC has never been reported, to the best of our knowledge in the English literature. Here, we present one such case of Marjolin's ulcer developing choroidal metastasis and aim to update our present understanding of the disease and its tumor biology.

 > Case Report Top

A 55-year-old male patient presented with 10-month history of nonhealing ulcer over the left foot. History revealed injury to the left foot 10 years ago, due to road traffic accident. Biopsy of the ulcer revealed moderately differentiated SCC, and contrast-enhanced computed tomography (CECT) showed the erosion of calcaneum without any evidence of regional lymphadenopathy. Below-knee amputation was done, following which 2 months later, he developed metastatic inguinal adenopathy. The left groin dissection was performed, which showed metastatic deposits in two out of six inguinal lymph nodes, and none among seven iliac lymph nodes. He received adjuvant radiotherapy to the groin, 54 grays (Gy) over 27 fractions, with two cycles of concomitant cisplatin and 5-fluorouracil (5-FU). Three months into the completion of radiotherapy, he developed recurrence in the popliteal fossa encasing popliteal vessels. On evaluation, he was found to have no evidence of distant metastasis, clinically and radiologically. He was further treated with left lower limb disarticulation and adjuvant chemotherapy with four cycles of cisplatin and 5-FU. Further cycles were withheld due to poor tolerability.

On further follow-up, the patient developed ulceration over stump after 3 months, with complaints of pain and diminished vision in the left eye, with nasal field defect. He had also developed contralateral inguinal nodal metastasis and noncontiguous multiple metastatic deposits within anterior abdominal wall and gluteal region. CECT thorax revealed new multiple bilateral lung nodules and mediastinal lymphadenopathy. On fundoscopy, a dome-shaped lesion was noted at the posterior pole with exudative retinal detachment around the lesion. Ultrasonogram of the left eye showed a dome-shaped lesion with a low height-to-base ratio. Magnetic resonance imaging (MRI) brain [Figure 1] and [Figure 2] revealed focal-enhancing intra-ocular lesion 7.9 mm (craniocaudal) × 4.0 mm (anteroposterior) × 8.9 mm (mediolateral), in the left eye, superior to optic disc suggestive of choroidal metastasis. Fundoscopic fine-needle aspiration of the lesion was attempted but it was unyielding. The patient was discussed in tumor board and he received palliative radiotherapy of 15 Gy over 3 fractions to the left eye. Left ocular pain was relieved after external beam radiotherapy. He succumbed 2 months after diagnosing choroidal metastasis.
Figure 1: Oblique sagittal view of magnetic resonance imaging showing enhancing lesion of 7.9 mm × 4.0 mm lesion over postero-superior aspect of the globe of left eye

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Figure 2: Axial view of T1 magnetic resonance imaging image showing lesion of 8.9 mm over posterior aspect of the globe of left eye

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 > Discussion Top

In 1828, a French surgeon, Jean Nicholas Marjolin described warty lesions that arise from burn scar. They may also arise from discharging sinuses of chronic osteomyelitis, scars of chronic venous ulcers, skin graft donor sites, and a variety of chronic inflammatory conditions of the skin. The transformed lesions are commonly well-differentiated SCC, basal cell carcinoma, or melanoma. Although Marjolin's ulcers account for 0.05% of SCCs of lower limbs,[3] they arise in about 2% of chronic burn scars.[2] There has even been a report of multiple synchronous lesions.[4]

Many theories have hypothesized the malignant transformation. Depressed immune system, chronic irritation, and repeated trauma, subjecting to increased frequency of repair mechanisms, increased mitosis, and cellular atypia can incite malignant degeneration.[5] Their potential for late metastasis is due to the relative avascularity of the scar tissue. The latency period can range from 11 to 75 years.[6] There have been reports of acute Marjolin's ulcer, where the latency period is <12 months.[4],[7] The classical triad of nodule formation, induration, and ulceration can hint toward their earlier identification. Others being foul discharge, bleed on touch, epithelial pearls, excessive granulation, and pain.[5] In a study among 31 patients of scalp Majolin's ulcer, infiltration beyond the skull (i.e., depth of infiltration) and completeness of excision had a significant bearing on survival outcome. Incomplete healing wounds can significantly shorten the latency period, whereas longer postulceration period had better survival, though not statistically significant.[8]

Although there are no defined treatment protocols. The general therapy is surgical wide local excision with skin cover either by graft or local/regional flaps. The margins of excision been recommended with 2 cm, although some authors have accepted 1 cm.[5] Extensive lesions may require amputation. There has been further refinement with the use of free flaps, cryosurgery, and Mohs surgery. Other experimental methods have been tried, namely CO2 laser, intralesional interferon, and photodynamic therapy. There have not been much literature on intra-arterial methotrexate and topical 5-FU. Most surgeons disagree with prophylactic regional nodal dissection. Radiotherapy and chemotherapy have been advised, among those where surgery is precluded due to poor performance, metastatic or recurrent disease, unwilling for surgery.[2],[3],[6]

The overall risk of metastasis is 20%–30%.[9] Lymph nodes, lung, brain, liver, and kidney are the reported sites. There has even been a report of metastasis to the myocardium.[10] The 5-year survival rate is 40%–69%, the highest being among those who undergo amputation.[11] Survival rate is much lower among those who present with lymph node metastasis.[3]

The propensity of metastasis to uveal tract, choroid in particular, albeit rare, can be reasonably explained by the abundance of its blood supply.[12] The common primary malignant tumors that may metastasize to choroid are breast (40%–47%) and lung (20%–29%).[13] About two-thirds of patients with uveal metastasis were known cases of cancer, the rest one-third had no history of malignancy. About half of the patients in latter group had no identifiable primary malignancy even after subsequent thorough evaluation.[14] Multifocal or bilateral metastatic disease usually originates from breast cancer, whereas unifocal or unilateral disease arises from lung cancer.[13]

Metastasis of SCC is extremely rare.[12] A review of several literatures revealed certain rare instances of metastatic deposits of both squamous and nonsquamous origin, such as esophagus, thyroid (papillary carcinoma, and SCC), uterocervical, gonadal, neuroendocrine, oropharyngeal, and hypopharyngeal tumors. A large retrospective study of uveal metastasis by Shields et al. reported nine patients of skin cancer (melanoma) out of 420 patients with uveal metastases.[14] As mentioned earlier despite extensive search through various English literature databases, we could not find any reported case of cutaneous SCC with metastatic spread to the choroid. This is an unusual feature in the natural history of Marjolin's ulcer.

Blurred vision, flashes and floaters, pain, and field defects are some of the symptoms by which these metastases may present.[13],[15] Besides fundoscopy, modalities that may aid in diagnosis include ultrasonography, fluorescein angiography, MRI, computed tomography, and fine-needle aspiration.[13] Ophthalmic signs of choroidal metastasis are single or multiple yellow subretinal mass, choroidal pallor, retinal detachment with exudate, retinal edema, and hemorrhage.[14] Some authors have suggested fine-needle aspiration biopsy to confirm the diagnosis.[12] Tissue diagnosis may be omitted in a known case of previous malignancy with corroborating image findings. A diagnosis of choroidal melanoma should be considered in cases with equivocal findings.

In most cases, the diagnosis of choroidal metastasis heralds the last leg of the disease process with a dismal prognosis. The treatment is mostly palliative. It aims to optimize the quality of life with an attempt at the preservation of vision. The treatment options include enucleation for blind painful eye, systemic chemotherapy, immunotherapy, hormonal therapy, radiotherapy, photodynamic therapy depending on the number, location, and laterality of metastases, histology of primary tumor, and performance status.[13]

 > Conclusion Top

Marjolin's ulcer, we know as of today has a high propensity of local spread with a tendency to involve the regional lymph nodes. The most common site of distant metastasis is lungs. Uveal tract so far, is an exceptional site of metastatic spread in Marjolin' ulcer, and carry poor prognosis. This report helps us in better understanding the tumor biology and the nature of the disease process.

Consent for publication

The patient provided informed consent to publish the article.


We would like to acknowledge Dr. Simran Singh (Radiologist) for providing findings on imaging and Dr. Vikas (Radiation Oncologist) for planning and contributing in the management of the patient.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

Copcu E. Marjolin's ulcer: A preventable complication of burns? Plast Reconstr Surg 2009;124:156e-64e.  Back to cited text no. 1
Aydoǧdu E, Yildirim S, Aköz T. Is surgery an effective and adequate treatment in advanced Marjolin's ulcer? Burns 2005;31:421-31.  Back to cited text no. 2
Bauer T, David T, Rimareix F, Lortat-Jacob A. Marjolin's ulcer in chronic osteomyelitis: Seven cases and a review of the literature. Rev Chir Orthop Reparatrice Appar Mot 2007;93:63-71.  Back to cited text no. 3
Hobbs M, Campbell E, Braun KA, Wong L. Multiple synchronous acute marjolin ulcer: A report of 2 cases and literature review. JAAD Case Rep 2019;5:511-3.  Back to cited text no. 4
Pekarek B, Buck S, Osher L. A comprehensive review on marjolin's ulcers: Diagnosis and treatment. J Am Col Certif Wound Spec 2011;3:60-4.  Back to cited text no. 5
Agale SV, Kulkarni DR, Valand AG, Zode RR, Grover S. Marjolin's ulcer – A diagnostic dilemma. J Assoc Physicians India 2009;57:593-4.  Back to cited text no. 6
Chang JB, Kung TA, Cederna PS. Acute marjolin's ulcers: A nebulous diagnosis. Ann Plast Surg 2014;72:515-20.  Back to cited text no. 7
Xiao H, Deng K, Liu R, Chen Z, Lin Y, Gao Y, et al. A review of 31 cases of marjolin's ulcer on scalp: Is it necessary to preventively remove the scar? Int Wound J 2019;16:479-85.  Back to cited text no. 8
Baskara A, Sikka L, Khan F, Sapanara N. Development of a marjolin's ulcer within 9 months in a plantar pressure ulcer. Eur J Dermatol 2010;20:225.  Back to cited text no. 9
Efendizade A, Kobayashi D, Forbes TJ, Liu S, Lieberman R, Afonso L. Myocardial metastasis of cutaneous squamous cell carcinoma in a burn patient. Case (Phila) 2019;3:6-10.  Back to cited text no. 10
Chiang KH, Chou AS, Hsu YH, Lee SK, Lee CC, Yen PS, et al. Marjolin's ulcer: MR appearance. AJR Am J Roentgenol 2006;186:819-20.  Back to cited text no. 11
Mendez CAM. Squamous Cell Carcinoma Metastatic to the Choroid. J Cytol Histol [Internet] 2014;05. Available from: http://www.omicsonline.org/open-access/squamous-cell-carcinoma-metastatic-to-the-choroid-2157-7099.1000225.php?aid=25752. [cited 2015 May 3].  Back to cited text no. 12
Arepalli S, Kaliki S, Shields CL. Choroidal metastases: Origin, features, and therapy. Indian J Ophthalmol 2015;63:122-7.  Back to cited text no. 13
[PUBMED]  [Full text]  
Shields CL, Shields JA, Gross NE, Schwartz GP, Lally SE. Survey of 520 eyes with uveal metastases. Ophthalmology 1997;104:1265-76.  Back to cited text no. 14
Asteriou C, Konstantinou D, Kleontas A, Paliouras D, Samanidis G, Papadopoulou F, et al. Blurred vision due to choroidal metastasis as the first manifestation of lung cancer: A case report. World J Surg Oncol 2010;8:2.  Back to cited text no. 15


  [Figure 1], [Figure 2]


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