Multimodality Management of Locoregionally Extensive Marjolin Ulcer: A Case Report and Review of the Literature

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MU is a rare cutaneous squamous cell carcinoma that occurs in long-standing unstable scar tissues and areas of chronic inflammation, such as post-burn scar. The incidence of MU has been reported to range from 0.77% to 2%.¹ The mean latent period between burn scar and onset of malignancy is 28 years.² Following the initial insult, repeated low-grade trauma and incomplete wound healing are the possible precipitating factors for malignant transformation. Surgical resection followed by adjuvant therapy is the treatment of choice for MU. The current case report discusses a rare case of MU metastasizing to the parotid gland, with an aggressive clinical course.

A 20-year-old male sustained burns over the left side of the scalp at 3 months of age, which was managed conservatively at that time. The scalp wound healed, with scar formation, and the patient remained symptom-free for 20 years until he developed a nonhealing ulcer over the left scalp burn wound site. The ulcer was painless and gradually progressive in size. He was diagnosed with MU over the left scalp and underwent wide local excision with split-thickness skin grafting at a different institution before being referred to the authors of the current study.

The postoperative histopathology report revealed well-differentiated squamous cell carcinoma measuring 2 cm × 2 cm × 0.7 cm with all resected margins tumor-free and negative for perineural invasion and lymphovascular invasion. A detailed history was obtained, physical examination conducted, and informed written consent obtained.

The patient received adjuvant mold brachytherapy 40 Gy in 10 fractions for 10 consecutive days beginning 1 month following surgery at the authors' institution. Two months following completion of adjuvant therapy, the patient developed a 3-cm × 2-cm firm, nodular mass with restricted mobility in the left preauricular region. Fine-needle aspiration cytology of the mass showed metastatic squamous cell carcinoma. Two FDG-avid intraparotid lymph nodes were identified on whole-body PET, with one measuring 1.6 cm × 1.7 cm (SUV_max 6.31) and the other 1.1 cm × 1.2 cm (SUV_max 3.94), along with FDG-avid bilateral cervical, supraclavicular, right suboccipital, and mesenteric lymph nodes. Due to the widespread nature of the disease, a nonsurgical treatment plan was made. The patient received 2 cycles of docetaxel and cisplatin with salvage nodal irradiation of 66 Gy in 30 fractions.

One month following treatment, the patient developed a 2-cm × 3-cm ulcer over the left parotid region. PET-CT showed resolution of all previous sites except for a 3.2-cm × 1.6-cm (SUV_max 8.8) soft tissue mass involving the left preauricular region with infiltration of the parotid gland (Figure 1). The ulcer biopsy was positive for moderately differentiated squamous cell carcinoma. The patient underwent wide local excision with left radical parotidectomy with left selective neck dissection levels I through III and spiral pectoralis major myocutaneous flap reconstruction (Figure 2). Postoperative histopathology revealed a 6-cm × 2.5-cm × 1-cm moderately differentiated squamous cell carcinoma pT3N0. The primary recipient and donor sites healed satisfactorily (Figure 3). No adjuvant treatment was given because the patient had already received irradiation within 5 months. The follow-up PET-CT at 6 months showed a 5-cm × 3.4-cm (SUV_max 17.5) mass involving the parotid bed, infratemporal fossa, and skull base with left axillary lymphadenopathy; the mass was confirmed on biopsy (Figure 4). The patient was subsequently started on triple metronomic therapy comprising methotrexate 9 mg/m², celecoxib 200 mg, and erlotinib 150 mg. At 3-month follow-up after initiation of palliative chemotherapy, the patient was alive and had stable disease.

MU was first described by Jean-Nicholas Marjolin, a French surgeon, in 1828.³ MU has been described as a highly aggressive malignant neoplasm that arises in a setting of chronic nonhealing wounds, most commonly in burn injuries.⁴ Although MUs commonly show histological features of well-differentiated squamous cell carcinoma, as in the patient in the current report, transcriptional analysis conducted by Sinha et al⁵ showed dysregulation of cell adhesion molecules such as cadherins and upregulation of platelet-derived growth factors, which increase the epithelial-mesenchymal transition, which is a key step in defining the metastatic capability of a neoplasm. MUs have a much higher metastatic rate than squamous cell carcinoma (30%–40% and 0.5%–3%, respectively).⁶ Post-burn obliteration of lymphatics and the presence of fibrotic scar tissue aid in immune surveillance evasion and account for the local aggressiveness of MU.⁷

 The head and neck region is the second most common site of MU after the lower limb.² Among the head and neck subsites, MU of the scalp has a reported incidence of approximately 15%.⁸ A long, stable pre-ulceration period, followed by rapid deterioration and features of malignant transformation post-ulceration, is a unique characteristic of MU of the scalp,¹ as evident in the current case. Lymph node metastases portend poor prognosis, apart from the type and grade of the tumor.⁹ Parotid nodes are considered the prime nodal basin for cutaneous squamous cell carcinomas that predominantly involve the fronto-temporal region.¹⁰ The incidence of lymph node metastases at presentation varies from 7% to 19%.^11,12 There are limited data on elective nodal clearance in the absence of clinico-radiological evidence of nodal involvement. Sentinel lymph node mapping is also of limited importance due to lymphatic obstruction in the post-burn fibrotic scar.¹³ The short treatment-free interval in the patient in the current study indicates the highly aggressive nature of the disease and the limited response to chemoradiotherapy. Having exhausted 2 major treatment modalities, salvage radical surgery was the remaining option. A depth of invasion of 12 mm, presence of perineural invasion, and lymphovascular invasion were the major negative prognostic factors. Two significant risk factors as described in the guidelines published by the European Dermatology Forum, the European Association of Dermato-Oncology, and the European Organisation for Research and Treatment of Cancer—namely, tumor diameter greater than 20 mm and a depth of invasion greater than 6 mm—were present in the current case.¹⁴ Therein lies the importance of adjuvant radiotherapy, which was already exhausted in the patient in the current case report. The TROG 05.01 trial showed no benefit of adjuvant chemotherapy and thus, was not considered for the patient described herein.¹⁵ The locoregional control rate of squamous cell carcinoma metastatic to lymph nodes with surgery alone has been reported to be 40% to 45%.^16,17

Immune checkpoint inhibitors hold promise in the management of primary cutaneous recurrent/metastatic squamous cell carcinoma. PD-1 inhibitors such as cemiplimab and pembrolizumab have shown overall response rates of 47% to 50% in phase I and II clinical trials.¹⁸ However, affordability is the major limiting factor in resource-limited settings, as in the patient in the current report. Additionally, considering the distinct tumor biology of MUs, further studies of the efficacy of such therapy are needed.

In a systematic review by Abdi et al,¹⁹ the incidence of local recurrence of MU varied from 6% to 67%, with a mean survival of 13.3 months reported in 1 study included in the review. The distant recurrence rate was reported to be as high as 12%.¹⁹ Given the propensity of locoregional and distant recurrence, a stringent follow-up protocol is imperative in the management protocol of patients with MU. The 2023 National Comprehensive Cancer Network guidelines recommend clinical evaluation every 2 to 3 months in the first year, every 2 to 4 months in the second year, every 4 to 6 months in the third year, and every 6 to 12 months thereafter for life in patients with cutaneous squamous cell carcinoma with regional disease.²⁰

The current study has limitations. It involves a single patient treated at a single institution. MU of the scalp with such a grave clinical presentation is a rare clinical scenario; however, this case underscores the invasive disease biology. In the absence of consolidated management guidelines specific to MU, a personalized treatment approach was used. Such treatment may vary from center to center.

Despite the use of multimodal therapy, MU in the head and neck region may have an aggressive clinical course with a short disease-free interval and a high propensity for locoregional and distant metastases.

Authors: Sandipta Mitra, MS, MRCS, DNB¹; Smriti Panda, MS, MCh¹; Kapil Sikka, MS, DNB¹; Supriya Mallick, MD, DNB, MNAMS²; and Alok Thakar, MS, FRCSED¹

Affiliations: ¹Department of Otorhinolaryngology and Head and Neck Surgery, All India Institute of Medical Sciences, New Delhi, India; ²Department of Radiation Oncology, National Cancer Institute, All India Institute of Medical Sciences, Jhajjar, India

ORCID: Mallick, 0000-0003-4228-5211; Mitra, 0000-0001-9311-9200; Panda, 0000-0003-1257-8611; Thakar, 0000-0002-5691-8932

Disclosure: The authors disclose no financial or other conflicts of interest.

Correspondence: Smriti Panda; Department of Otorhinolaryngology and Head and Neck Surgery, Room No. 4075, 4th Floor, Teaching Block, All India Institute of Medical Sciences, New Delhi 110029, India; smriti.panda.87@gmail.com

Manuscript Accepted: April 1, 2024