Clinical research on the expression of three vascular regulatory factors in different morphological regions of Marjolin ulcer and their relationship with angiogenesis / 中华烧伤杂志

Objective@#To investigate the expressions of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1α), and epidermal growth factor receptor (EGFR) in different morphological regions of Marjolin ulcer and their clinical relationship with angiogenesis.@*Methods@#From January 2012 to December 2017, the patients admitted to our hospital who met the inclusion criteria were selected, including 92 patients with Marjolin ulcer [56 males and 36 females, aged (55±15) years], 100 patients with chronic non-cancerous skin ulcer [59 males and 41 females, aged (51±16) years], and 100 patients performed with other skin-related surgery [58 males and 42 females, aged (52±15) years], and they were enrolled into Marjolin ulcer group (MU), chronic non-cancerous ulcer group (CNU), and other skin surgery group (OSS) respectively. The etiology, pathogenic site, ulcer diameter, and course of patients in group MU were retrospectively analyzed. Ulcer tissue specimens from patients of group MU and group CNU and specimens of normal skin tissue attached to the tissue resected during operation from patients of group OSS were collected. The expressions of VEGF, HIF-1α, EGFR, and CD34 in the above-mentioned tissue and the surrounding normal skin, ulcer, epitheliomatous hyperplasia, and canceration areas in Marjolin ulcer tissue were detected by immunohistochemical method, and the positive expression rate and protein expression level were calculated. Data were processed with Pearson chi-square test, Mann-Whitney U test, Bonferroni method, and Bonferroni correction, and Spearman correlation analysis was used to analyze the relationship among the total protein expression levels.@*Results@#In group MU, burns accounted for 91.3% (84/92) of the causes of patients, 44.6% (41/92) of the patients had tumors in the lower extremities, 62.0% (57/92) of the patients had skin ulcer diameter of 2.1-5.0 cm, and 75.0% (69/92) of the patients had a course of disease of more than 20 years. The positive rates of VEGF, HIF-1α, and EGFR in ulcer tissue of patients in group CNU were 41.0% (41/100), 77.0% (77/100), and 83.0% (83/100), respectively, significantly higher than those of normal skin tissue of patients in group OSS [12.0% (12/100), 45.0% (45/100), and 67.0% (67/100), χ2=21.589, 21.522, 6.827, P<0.01]. The positive rates of VEGF, HIF-1α, and EGFR in ulcer tissue of patients in group MU were 91.3% (84/92), 100.0% (92/92), and 100.0% (92/92), respectively, which were significantly higher than those in corresponding tissue of patients in group CNU and group OSS (χ2=53.372, 24.772, 17.159; 120.543, 72.777, 36.661, P<0.01). In ulcer tissue of patients in group MU, the positive expression rates of VEGF in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than the rate in surrounding normal skin area (χ2=87.120, 42.368, 89.624, P<0.01); the positive expression rates of VEGF in canceration and ulcer areas were significantly higher than the rate in epitheliomatous hyperplasia area (χ2=22.586, 16.060, P<0.01). In ulcer tissue of patients in group MU, the positive expression rates of EGFR in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than the rate in surrounding normal skin area (χ2=21.679, 27.600, 27.600, P<0.01), but the positive expression rates of HIF-1α in four morphological areas were similar (χ2=3.008, P>0.05). In ulcer tissue of patients in group MU, the protein expression levels of VEGF and CD34 in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than those in surrounding normal skin area (Z=-6.765, -6.819; -6.765, -6.640; -6.765, -6.819, P<0.01), the protein expression levels of VEGF and CD34 in epitheliomatous hyperplasia area were significantly lower than those in ulcer area (Z=-4.484, -5.266, P<0.01), and the protein expression levels of VEGF and CD34 in canceration area were significantly higher than those in ulcer area (Z=-6.427, -6.723, P<0.01) and epitheliomatous hyperplasia area (Z=-6.427, -6.462, P<0.01). In ulcer tissue of patients in group MU, the protein expression levels of HIF-1α and EGFR in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than those in surrounding normal skin area (Z=-6.819, -6.393; -6.819, -6.393; -6.819, -6.393, P<0.01), the protein expression levels of HIF-1α and EGFR in ulcer area were significantly lower than those in epitheliomatous hyperplasia and canceration areas (Z=-6.118, -5.638; -6.640, -6.393, P<0.01), and the protein expression levels of HIF-1α and EGFR in canceration area were significantly higher than those in epitheliomatous hyperplasia area (Z=-6.558, -6.819, P<0.01). In ulcer tissue of patients in group MU, the total protein expression levels of VEGF, HIF-1α, and EGFR were significantly positively correlated with the total protein expression level of CD34 (r=0.772, 0.415, 0.502, P<0.01) respectively; the total protein expression level of EGFR was significantly positively correlated with that of HIF-1α (r=0.839, P<0.01), both of which were significantly positively correlated with the total protein expression level of VEGF (r=0.531, 0.440, P<0.01) respectively.@*Conclusions@#The expressions of VEGF, HIF-1α, and EGFR are the highest in Marjolin ulcer canceration area, and EGFR may promote angiogenesis through HIF-1α or directly increasing the expression of VEGF.

Ulcera de Marjolin, reporte de caso / Marjolin's ulcer: a case report

Se presenta el caso de una mujer de 77 años, sin antecedentes relevantes, con úlcera en tobillo izquierdo de dos años de evolución relacionada a herida previa por quemadura con agua caliente de aproximadamente 60 años de antigüedad, con crecimiento progresivo y mala respuesta a tratamiento inicial con curaciones y luego con antibióticos. Se realiza estudio con biopsia cutánea incisional que confirma cáncer espinocelular moderadamente diferenciado e infiltrante en dermis reticular, lo cual corresponde a una úlcera de Marjolin. Se deriva a cirugía oncológica en donde se realiza el estudio de etapificación con resultado de lesión ósea por contigüidad y una tomografía computada (TC) de tórax, abdomen y pelvis sin diseminación a distancia, por lo que se decide amputación infracondilea de la extremidad afectada. Debido a este caso de interés, se realiza una revisión sobre úlcera de Marjolin, con el fin de lograr un diagnóstico adecuado y un tratamiento precoz.

We present the case of a 77-year-old woman, with no relevant history, with a left ankle ulcer of two years of evolution related to previous burn injury with hot water of approximately 60 years old, with progressive growth and poor response to initial treatment with cures and then with antibiotics. A study was performed with cutaneous incisional biopsy confirming moderately differentiated and infiltrating squamous cell cancer in the reticular dermis, which corresponds to a Marjolin ulcer. It is derived to oncologic surgery where the etapification study is carried out with result of contiguous bone injury and a computed tomography (CT) thorax, abdomen and pelvis without distant dissemination, so infracondile amputation of the affected extremity is decided. Due to this interest case report, a review of Marjolin's ulcer is performed, in order to achieve an adequate diagnosis and early treatment.

Marjolin’s ulcer: A case report of chronic leg ulcer leading to squamous cell carcinoma

34 1 Department of Orthopaedic, Hospital Kuala Lipis, 27200 Kuala Lipis, Pahang, MALAYSIA 2 Department of Surgery, Hospital Kuala Lipis, 27200 Kuala Lipis, Pahang, MALAYSIA 3 Department of Pathology, Hospital Tengku Ampuan Afzan, 25300 Kuantan, Pahang, MALAYSIA 4 Department of Radiology, Hospital Kemaman, 24000 Kemaman, Terengganu, MALAYSIA Marjolin’s ulcer: A case report of chronic leg ulcer leading to squamous cell carcinoma Ren Yi Kow 1 , Dhiauddin Hai Ismail 2 , Jamaluddin Shafie 1 , Ruben Jaya Kumar 1 , Nor Hafliza Md Salleh 3 , Chooi Leng Low 4 Case Report IeJSME 2016 10(3): 34-36 Introduction Marjolin’s ulcer is a malignant cutaneous ulcer that undergoes transformation from a previously traumatized or chronically inflammed skin. 1 Causes leading to ulcerations can be burn injury, trauma, chronic osteomyelitis and varicose ulcers. 2 It is named after a French surgeon, Jean Nicolas Marjolin, who first described the condition in patients who developed malignant ulcers from burn scars. 3 We report a case of a chronic non-healing foot ulcer that has become a Marjolin’s ulcer after 12 years

Clinical Efficacy of Pre-operative 18F-FDG-PET/CT in Marjolin's Ulcer

PURPOSE: Marjolin's ulcer is a rare malignancy that occur in chronic wounds or scars. Marjolin's ulcers tend to infiltrate adjacent tissue more extensively than squamous cell carcinoma that occurs in normal skin, and it is prone to recurrence and metastases, leading to a poor prognosis. Hence, its accurate diagnosis and treatment is very important. The aim of this study was to investigate the diagnostic value and clinical efficacy of preoperative 18F-FDG-PET/CT. METHODS: The study population consisted of 27 patients who were suspected to have Marjolin's ulcer who visited this hospital between January 2009 and June 2012, and who had also received preoperative PET/CT. To confirm the diagnostic efficacy of preoperative PET/CT, the PET/CT findings of the primary lesion and the lymph node, as well as the post-operative histology results were compared to investigate the sensitivity, specificity, false-positive and false-negative rates. RESULTS: The sensitivity and the specificity for the primary lesion of the Marjolin's ulcer in the preoperative PET/CT were 93.3% and 100% respectively. The false-positive rate and the false-negative rate here were 0% and 6.7% respectively. The sensitivity and the specificity for the lymph node metastases of the Marjolin's ulcer in the preoperative PET/CT were 100% and 66.7% respectively. The false-positive rate and the false-negative rate here were 33.3% and 0% respectively. The histological results of Marjolin's ulcer showed that 14 patients had squamous cell carcinoma and 1 had sarcoma. CONCLUSION: Preoperative PET/CT used for the assessment of Marjolin's ulcer and its primary lesion showed a high level of sensitivity and specificity. It was also useful because it allowed the assessment of the primary lesion, lymph node metastases, and distant metastases with a single test. However, the specificity for lymph node metastases was relatively lower, and more research would be needed to improve this.

Squamous Cell Carcinoma Showing Rapid Metastasis after Leg Amputation due to Chronic Osteomyelitis / 대한피부과학회지

Marjolin's ulcer is a malignant lesion, which arises in a chronic wound. When squamous cell carcinoma occurs in Marjolin's ulcer, the prognosis is known to be worse than that of cutaneous squamous cell carcinoma, due to other etiologies. A 56-year-old male who was diagnosed as chronic osteomyelitis was recommended for a surgical amputation of the left lower leg. After amputation, the histology of chronic ulcer revealed squamous cell carcinoma. In a few months period, multiple suppurative ulcers and nodules appeared near the amputation stump, as well as the proximal sites of the left leg, which appeared to spread rapidly. Biopsy of a representative lesion and positron emission tomography-computed tomography revealed a metastatic squamous cell carcinoma and malignant lymphadenopathy. Aggressive amputation without appropriate preoperative evaluation to detect the locoregional metastasis may be an inadequate option of the treatment for the patient due to a rapid spread of cancer metastasis, which may happen immediately after an amputation. Therefore, it is important to obtain a thorough preoperative evaluation of recalcitrant ulcer from osteomyelitis before the decision to undergo an amputation.

Marjolin's Ulcer Secondary to Tuberculous Tenosynovitis of the Wrist: A Case Report

Tuberculous tenosynovitis usually presents as a chronic, slowly progressive disease. It is difficult to detect in early phase and diagnosis frequently requires biopsy in addition to stain or culture. Authors describe a case who had a Marjolin's ulcer secondary to tuberculous tenosynovitis of the wrist.

Outcomes of Treatment for Squamous Cell Carcinoma Originating as a Marjolin's Ulcer / 대한골관절종양학회지

PURPOSE: The purpose of this study was to analyze the results of treatment and prognosis of Marjolin's ulcer compared with primary squamous cell carcinoma. MATERIALS AND METHODS: Fourteen patients treated for Marjolin's ulcer were analyzed. Twenty patients with primary squamous cell carcinoma treated during the same time period was the control group. Mean age was 61.2 years. There were 24 males and 10 females. The locations, TNM stages, histological grades, recurrence, metastasis, and survival rate were analyzed and compared between two groups. RESULTS: The mean follow-up period was 54.8 months (range, 12-168 months). Local recurrences were found in 6 cases, 5 ones in Marjolin's ulcer patients, and one case in primary squamous cell carcinoma patients. The mean time interval between the initial presentation and occurrence of local recurrences was 9 months (range, 2-20 months). There were 6 metastases. 2 (14.3%) metastases were found in Marjolin's ulcer patients, and 4 (20.0%) metastases in primary squamous cell carcinoma patients. Total events (metastasis or local recurrence) were found in 10 pateients, 6 of them in Marjolin's ulcer group, and the remaining four in primary group. 5-year disease-free survival rate was 64.3% in Marjolin's ulcer group and 95.0% in primary squamous cell carcinoma group. CONCLUSION: Squamous cell carcinomas originating as Marjolin's ulcers revealed higher recurrence rate and lower survival rate despite of aggressive treatment. Therefore, new treatment modalities should be developed for improving outcomes.

Abdominoplasty Combined with Wide Excision in Marjolin's Ulcer: Report of 2 Cases

Advances in medical science have produced significant progress in the area of wound healing. Yet, despite proper administration of initial medical treatment, burns or radiation induced wounds often develop into chronic wounds or develop other complications such as scar contractures. In these type of patients, chronic wounds and the potential accompanied ulcers are difficult to heal as malignant changes may occur to the wounds especially in the absence of or in the delay in timely medical treatment. In our beauty oriented society today people have shown great interest in improving their image and many obese patients want to undergo suction-assisted lipectomies or abdominoplasties. Abdominoplasty is an effective procedure to remove locally accumulated fat and to reshape abdominal contours by tightening the muscles of the relaxed abdominal wall. Our medical research conducted on two patients, one with contact burn injuries accompanied by upper abdominal ulcers suffered for fifty years and another with radiation impaired wounds accompanied by lower abdominal ulcers due to cancer treatment for seven years, has shown that through the proper use of abdominoplasty. We have eliminated all possibilities that may trigger the re-occurrence of Marjolin's ulcers which may become malignant. Additionally, we have been able to heal chronic wounds and functionally improve our patient's restrictions of movement caused by the scar contractures by completely removing the lesions, erythemas and discharges from the ulcer areas by performing upper and lower abdominoplasties while still obtaining cosmetically satisfactory results.

A Case of Carcinosarcoma of Skin Developed on Marjolin's Ulcer

PURPOSE: Carcinosarcomas are rare neoplasms in which both malignant epithelial and mesenchymal elements are identified. We have found only twenty one cases of primary cutaneous carcinosarcoma in the English language literature. Therefore it has been difficult to diagnosis because its unclear etiology and low frequency. METHODS: A 31-year-old young man with a protruding mass on his ankle dorsum was examined. The tumor was 7 x 6 x 3 cm sized and arose from a burn scar. The mass was wide excised and applied split thickness skin graft. Characteristic pathologic finding was a mixture of squamous cell carcinoma and malignant fibrous histiocytoma. RESULTS: Three months after the operation, the patient died of multiple metastasis to the liver, lung and finally of sepsis despite adjuvant chemotherapy and adjuvant radiotherapy. CONCLUSION: If a metastatic cutaneous carcinosarcoma is diagnosed, wide excision is required. There should be more aggressive management to minimize the risk of recurrence. Further research into the etiology and pathophysiology of the disease and a more careful differential diagnosis may allow improvement in treatment.

Malignant Fibrous Histiocytoma Arising in Old Burn Scar on the Anterior Chest

PURPOSE: Malignant changes of Marjolin's ulcer arising from chronic burn scar are rare. The majority of them are squamous cell carcinoma and basal cell carcinoma. Malignant fibrous histiocytoma is a deep seated pleomorphic sarcoma, which occurs principally as a mass of the extremities, abdominal cavity, or retroperitoneum in adults. METHODS: We report a 58-year-old male patient who was admitted due to 3.5x5cm chronic ulceration of anterior chest wall on the center of old burn scar. His scar had been occurred by boiling oil and treated with conservative treatment 45 years ago. Preoperative punch biopsy showed suspicious malignant changes and contrast enhanced chest CT showed well-defined, irregular shape enhancing lesion on anterior chest wall without intrathoracic metastasis. RESULTS: The tumor was widely excised and defect was covered with skin graft without infection, necrosis and any other complication. The pathologic findings are compatible with malignant fibrous histiocytoma(storiform - pleomorphic type). The patient underwent 3 cycles of chemotheraphy. Although distant metastasis to the lung developed 6 months later and the patient died 9 month later, there was no local reoccurrence. CONCLUSION: Aggressive and early excision is needed because malignant fibrous histiocytoma has characteristics of high malignancy with a propensity for early and distant spread. Furthermore, the patient's education about disease entity and postoperative regular follow-up for local recurrence or metastasis is very important. To prevent malignancy from secondly healing burn scar, early skin graft is recommended for patients with deep second degree burn.

Surgical Treatment of Squamous cell Carcinomas Arising in Scalp Burn Wounds: Two Case Reports

Marjolin's ulcer is a rare and often-aggressive cutaneous malignancy that arises in previously traumatized or chronically inflamed skin, particularly after burns. We experienced two cases after burns. Case I involved a forty eight year-old man who had suffered from a flame burn at the parietal scalp area, where had been initially described three years earlier as a full-thickness wound including the pericranium. The man consulted us for a persistent ulcerative and infected wound on the burned lesion during the last 24 months, which turned out on the contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) to be the squamous cell carcinoma with involving the skull and the dura mater. Although the posterior auricular lymph node was enlarged on the ipsilateral side, recent positron emission tomography (PET) CT did not show any metastatic lesion. It was impossible for us to resect the intracranial involvement of the tumor radically, and the postoperative PET CT still showed a focal fluorodeoxyglucose (FDG) uptake around the wall of the superior sagittal sinus. We think that an aggressive combined approach is essential for treatment in early stages for a high success rate, before the intracranial structures are involved because there is no consensus on the treatment for advanced disease, and the results are generally poor. Case 1 also did not involve a radical resection because of the intracranial invasion to the wall of superior sagittal sinus and the possibility of damage to the major cortical veins. He received adjuvant radiotherapy and must be followed periodically. Case 2 involved an eighty six year-old women who suffered from a painful scalp ulcer lesion after flame burns three years earlier. Unlike case 1, neither tumor infiltration into the dura nor lymph node enlargement was observed on the contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) CT. We did a radical resection of the tumor, including the involved bone, and a cranioplasty with bone cement.

Clinical study of Marjolin's ulcer

Marjolin's ulcer is the malignant lesion which develops in a burn scar or chronic fistula. Due to the low prevalence of this lesion, there has been disagreement regarding its clinical features, methods of treatment, and prognosis. We evaluated 19 cases of patients who had been admitted to Severance Hospital from Jan. 1970 to Dec. 1985. The results were as follows: The previous lesion was a burn scar in 52% of the cases and a fistula of chronic osteomyelitis in 32%. The mean latent period was 31.5 years. The initial symptoms were increased pain (74%), discharge with foul odor (68%) and bleeding (58%). Upon histological examination, all of the cases were squamous cell carcinoma. The rate of metastasis at the time of diagnosis was 32%. Of the 16 patients treated by surgery, local recurrence was noted in 4 cases. Three of these cases were patients who had been treated by excision and split thickness skin graft. The time interval for local recurrence ranged from 6 months to 11 months (average 8.8 months). In conclusion, the squamous cell carcinoma of marjolin's ulcer seems to have a worse prognosis than other squamous cell carcinomas and it requires aggressive treatment. The burn scar or chronic fistula that occurs in elderly patients especially requires more adequate treatment and close observation.

Clinical Study on Marjoli's Ulcer / 대한정형외과학회잡지

The Marjolin's ulcer is the malignant lesion developed in a burn scar or chronic fistula. Due to the low prevlalence of this lesion, there has been disagreement in its clinical features, methods of treatment, and prognosis. We evaluated 19 cases of patients who had been admitted to Severence Hospital from Jan. 1970 to Dec. 1958. The results were as follows : 1. The previous lesion was burn scar in 52% of the cases and fistula of chronic osteomyel-itis in 32%. 2. The mean latent period was 31.5 years. 3. The initial symptoms were increased pain(74%), discharge with foul odor(68%) and bleeding(58%). 4. Upon histological examination, all of the cases were squamous cell carcinoma. 5. The rate of recurrence of metastasis at time of diagnosis was 32%. 6. Of the 16 patients treated by surgery, local recurrence was noted in 4 cases. Three of these cases were patients who had been treated by excision and split thickness skin graft. 7. The time interval for local recurrence ranged from 6 months to 11 months(average 8. 8 months). In conclusion, the squauious cell carcinoma of the Marjolin's ulcer seems to have a worse prognosis than other squamous cell carcinoma and it requres aggressive treatment. The burn scar or chronic fistula that occured in elderly patients especially required more adequste treatment and close observation.