Malignant Transformation in Chronic Stage IV Sacral Pressure Ulcer: A Case of Marjolin Ulcer

Marjolin ulcer (MU) refers to cutaneous malignant growth that occurs in a chronic wound and can be of heterogenous origin. Malignant transformation to an MU is most common and well-documented within old burn scars, especially those allowed to heal by secondary intention.¹ However, transformation also can occur within pressure sores, venous ulcers, osteomyelitis wounds, and nearly any chronic, poorly healing wound.^1,2 These ulcers most commonly present in the lower extremity, with the plantar surface of the foot the most common anatomic location. In addition, the most common tumor type identified via tissue biopsy is a well-differentiated squamous cell carcinoma (SCC); basal cell tumors and melanomas have also been identified.² 

The incidence of MU is rare, with malignant transformation occurring in an estimated 0.1% to 2.5% of wounds and scars caused by chronic inflammatory instigation or traumatic insult.³ However, MU is a highly aggressive malignancy with an overall metastatic rate of 27.5%, and it is associated with higher rates of recurrence, mortality, and poorer prognosis relative to other SCCs.^4-6 The exact pathophysiology and mechanism of transformation of MU have yet to be identified, and thus, there is an incomplete understanding of its heightened metastatic potential and overall aggression. The rarity of MU and the heterogeneity of wounds from which it arises contribute to this lack of understanding. Certain risk factors are understood, however, and it has been posited that patients who are immunocompromised or elderly are at increased risk for malignant transformation.² Values published in the literature vary but generally indicate that average patient age at the time of diagnosis of MU is approximately 50 years.^5,7 The latency period from initial insult to malignant transformation is variable, with a reported range of 11 years to 75 years and an average of approximately 30 years.^4,5 In addition, there is evidence that this latency period is shorter in the elderly and is inversely correlated with age—that is, the younger the patient at the time of injury, the longer the latency period.⁴ 

In this report, the authors present a case involving a 63-year-old patient with a history of paraplegia since birth, spina bifida, and a chronic, unhealed stage IV sacral pressure ulcer that underwent a malignant transformation resulting in MU. This is an uncommon setting for MU; the more frequent presentation is of MU in a burn scar. 

The patient was a 63-year-old male with a history of spina bifida and paraplegia since birth (Figure 1). At age 25 years, the patient developed a stage IV pressure ulcer of the sacrum and right buttock. Because of the patient’s nonadherent status concerning previous treatment recommendations, this ulcer never healed. The patient periodically underwent treatment at the wound center to address the sacrococcygeal ulcer and recurrent lower extremity lymphedema ulcers. Seven months prior to the diagnosis of MU, the patient declined wound care to the sacrum. The patient was also known to have a 2-year history of chronic lymphocytic lymphoma managed with chemotherapy by an oncologist. On a recently obtained follow-up chest radiograph, 2 small metastatic spots were discovered on the patient’s lungs. According to the oncologist, these were too small to be primary tumors. As part of the metastatic workup, the authors were contacted by the patient’s oncologist to view the chronic wound and perform biopsies to identify a primary source. 

At the time of consultation at the wound center, the sacral ulcer measured 17 cm × 9 cm × 7.2 cm and was covered with 80% slough; in addition, the left lateral edge of the wound bed was raised, indurated, thickened, and suspicious for malignant transformation (Figure 2). Three 3-mm punch biopsies were performed in the wound clinic and all were positive for invasive, poorly differentiated SCC (Figures 3, 4). One biopsy was obtained from the wound bed, and the other 2 were obtained from the wound edge at the 7-o’clock and 8-o’clock positions. Each biopsy donor site was marked with an arrow in Figure 2. 

Wound care of the sacrum was started immediately after the biopsies were performed and included wet and moist dressing changes twice a day using a woven gauze (Kerlix; Cardinal Health) and quarter-strength Dakin solution with a collagenase ointment (Santyl Ointment; Smith and Nephew) applied to the slough areas. The patient was moved to a low air loss mattress and was frequently repositioned. Consultation with a nutritionist was obtained.

The metastatic workup included computed tomography imaging of the pelvis, which showed chronic osteomyelitis of the right hip, right pubic ramus, and pubic symphysis with bone destruction. The tumor mass was invading the pelvic floor bilaterally but predominantly on the right side. A metastatic lesion was identified in the lower sacral canal. The perirectal space was involved, with metastatic lymphadenopathy. Additionally, the internal and external iliac lymph node chains were involved and enlarged.

The patient was nearing the end of chemotherapy treatment for B-cell chronic lymphocytic leukemia, which included obinutuzumab prescribed by specialists in hematology and oncology. The patient then began immunotherapy, including pembrolizumab, to manage the primary and metastatic SCC disease.

Soft tissue culture from the wound bed grew multi-drug resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). A peripherally inserted central catheter (PICC) line was placed, and an infectious disease specialist prescribed a 6-week course of meropenem (after culture and sensitivity showed P aeruginosa to have become resistant to cefepime) and vancomycin. 

After a long discussion with the patient and his mother, and owing to the poor prognosis, the patient was shifted to primarily palliative and hospice care. At the time of this writing, the patient is receiving daily wound care, including application of collagenase to the wound bed with subsequent packing using a moist gauze roll with quarter-strength Dakin solution covered with border dressing. The patient was also provided a low-air-loss mattress and is receiving side-to-side repositioning, along with nutritional support. Owing to spina bifida and paraplegia, pain was not an issue that needed to be addressed.

This case is a unique example of MU that occurred in a chronic pressure ulcer and metastasized to the patient’s lungs. In a case report, Khan et al⁶ noted that, similar to what is presented herein, the prognosis for MU in chronic pressure ulcers is even poorer than for the more common presentation of MU in burn scars. Those authors reported a metastatic rate of 61% for MU in pressure sores and attributed this poor prognosis to lack of awareness of this condition among health care providers, resulting in delayed management.⁶ In addition, the fact that this malignancy had metastasized further downgraded the prognosis and outlook for survival for the patient reported herein. The literature indicates that in the absence of metastasis, the 3-year post diagnosis survival rate ranges from 65% to 75%, whereas with metastasis the 3-year post diagnosis survival rate ranges from 35% to 50%.^2,6 This finding emphasizes the importance of early detection in the overall prognosis of MU; biopsy should be performed, especially in the setting of a chronic pressure sore, in which MU is exceedingly rare and may go undetected or misdiagnosed. 

The occurrence rate of SCC in pressure sores may be as low as 0.5%.⁸ Additionally, MU in this setting is often considered a disease of economically developing, low-income nations in which health care access and resources are limited. This complication is rarely reported in economically developed, high-income, industrialized Western countries, and as of 2010 only approximately 10 reported cases of MU complicating a pressure ulcer in a patient with spina bifida had been reported in the English-language literature.⁹ Because of the rarity of this particular finding and the fact that malignant transformation may be entirely asymptomatic and painless, especially for a patient with paraplegia such as the one presented in this case, awareness and proactive action by the health care professional are of paramount importance.⁶

Wound excision and primary closure, when possible, are the best prophylaxis against malignant transformation. In cases like the one reported here, in which complete primary closure is not possible, it is critically important that providers regularly inspect the chronic wound and perform histological analysis in response to suspicious markers.¹⁰ Various indications for malignant degeneration have been described in the literature, several of which are noted in this case and shown in Figure 2. Indications include indurated wound edges, a friable ulcer bed, odorous discharge, and chronic ulceration lasting longer than 3 months.^2,8 Any one of these indications in a chronic wound warrants suspicion of malignant degeneration and should result in a tissue biopsy to make a definitive diagnosis and avoid delays in treatment.⁶ Biopsies should be performed at several different locations around the suspected ulcer, including the center and the borders as was done in this case, to mitigate the potential for false-negative results. In addition to wound inspection, regional lymph nodes should be closely monitored for any changes that could indicate metastasis.¹⁰ This is the recommended course of action to ensure early detection and the most favorable prognosis possible.

The efficacy of chemotherapy and radiation in the management of MU is the subject of ongoing debate. Some authors, such as Ozek et al,¹¹ provide clear indications concerning situations in which  radiotherapy should be used, while others have ruled the use of chemotherapy and/or radiation therapy to be ineffective overall in the management of MU.¹²  Amputation of the affected limb or surgical resection of the ulcer are considered definitive treatments, but those options are not always possible. Adjuvant radiation therapy and/or chemotherapy is used widely, however, and is generally supported in cases in which surgical resection is impossible or is refused, in cases of recurrent disease, and/or in the setting of metastatic disease.^2,5 The patient in this case study exhibited metastasis to the lungs as well as a relatively large ulcer in a surgically challenging anatomic location. Thus, chemotherapy was strongly indicated, and treatment by an interdisciplinary team of specialists in wound care and oncology was necessary. A typical chemotherapy regimen for metastatic MU such as this would involve topical or intravenous 5-fluorouracil in conjunction with methotrexate, cisplatin, and bleomycin.^12,13,14

Another important consideration in treating the patient in this case is the diagnosis of sacral osteomyelitis. Osteomyelitis is a bacterial infection that takes hold within bone and eventually results in the degradation of bone tissue. Chronic wounds associated with osteomyelitis are among the most common settings for malignant degeneration and MU formation, although a less common setting than old burn scars.¹ Bacterial colonies proliferate and invade bone under the protection of a biofilm that they secrete, presenting a barrier for antibiotic and/or disinfectant therapy. Amputation is generally considered the definitive treatment, especially for late-stage osteomyelitis in which there is considerable invasion and osteolysis, and in the presence of skin defects.^15,16 In the case reported herein, however, surgical intervention and amputation were not  viable options, and a team-based approach involving specialists in wound care and infectious diseases was necessary. Staphylococcus aureus is the most common bacterial culprit in osteomyelitis, but other bacteria, including enterobacteriaceae, pseudomonas, and streptococcus may cause it as well.¹⁷ Cultures must be obtained by infectious disease specialists to determine the proper course of antibiotics while the wound care team simultaneously clears the wound bed and, if necessary, an orthopedic specialist addresses the bone defect.¹⁵ It is important to note that although antibiotics can be used to manage chronic osteomyelitis, their use is often unsuccessful owing to factors such as bacterial antibiotic resistance, bacterial biofilm barrier, and various so-called elusion mechanisms, which is why amputation is the definitive treatment when possible.^15-17 

This case study is limited in its assessment of the efficacy of the treatment measures that were discussed because MU was identified after it had already metastasized. It has been noted that MU metastasis to regional lymph nodes is predictive of death within just 2 to 3 years.¹⁰ This finding in combination with a complex setting of multiple comorbidities in the patient reported on herein led the authors to believe the prognosis was not strong from the time MU was first diagnosed. As a result, the patient eventually elected to receive hospice care. Although health care professionals from a multitude of specialties collaborated on this case, it is difficult to gauge the efficacy of these treatments in a way that could be useful to future cases because the patient’s prognosis was poor from the beginning. Future studies that present cases of MU that have not reached this level of progression prior to discovery may provide stronger guidelines on treatment modalities that are effective in addressing this uniquely challenging disease. 

This case report presented a patient with spina bifida and paraplegia since birth who developed MU within a 38-year-old chronic sacrococcygeal pressure ulcer with chronic osteomyelitis. In addition, the SCC metastasized and spread to the pelvis, lymph nodes, and lungs. This is a rare and relatively undocumented presentation for MU, which typically occurs in burn and traumatic scars. Owing to the complex set of challenges involved in this patient’s presentation and the surgically challenging location of the ulcer in the sacrococcygeal/perineal region, a combination approach to treatment involving specialists in wound care, oncology, and infectious disease was required. This case also emphasizes the importance of performing biopsy of chronic nonhealing wounds, especially in patients who are immunocompromised and undergoing treatment with chemotherapy or immunosuppressive medications. 

The authors would like to thank the Conrad and Caroline Jobst Foundation. The authors also thank Mariam Abouahmed for administrative assistance. 

Authors: Richard Simman, MD, FACS, FACCWS^1,3; Fuad Abbas, BS²; and Surendra P. Singh, MD³

Affiliations: ¹Jobst Vascular Institute, ProMedica Health Network, Toledo, OH; ²Wayne State University School of Medicine, Detroit, MI; ³University of Toledo College of Medicine and Life Sciences, Toledo, OH

Correspondence: Richard Simman, MD, FACS, FACCWS, Jobst Vascular Institute, 2109 Hughes Drive, Suite 400, Toledo, OH 43606; richard.simmanmd@promedica.org 

Disclosure: The authors declare no conflicts of interest.