Sentinel Node Mapping in Marjolin’s Ulcers: Is it Feasible?

Introduction. This study evaluated the feasibility of sentinel node biopsy in Marjolin’s ulcers using peritumoral injection of the radiotracer and blue dye. Materials and Methods. Ten patients with Marjolin’s ulcers (5 male and 5 females) ranging in age from 39-65 years, and who were candidates for surgical removal of their tumors, were included in this study. The patients received 2 mCi technetium 99m (99mTc) antimony sulfide colloid in 2 divided doses subcutaneously in the peritumoral region. Immediately after anesthesia induction, 1 cc patent blue V in 2 divided doses was also injected in the same fashion as the radiotracer. Lymphatic mapping and sentinel node biopsy was performed using a gamma probe. Any hot and/or blue lymph nodes were harvested as a sentinel node. Primary lesions were then excised and wounds grafted with a split-thickness skin graft. Results. A sentinel node could be identified on the lymphoscintigraphy images in only 2 patients. Sentinel node mapping was successful during surgery in these 2 patients. None of the harvested sentinel nodes were blue. Conclusion. Lymphatic mapping and sentinel node biopsy do not seem feasible in Marjolin’s ulcers located in areas of extensive burn scarring due to a low detection rate. Larger studies are needed to validate the results of this study.

  Cutaneous squamous cell carcinoma (SCC) is a common skin cancer with fairly favorable prognosis. Curative treatment by surgery or local destructive therapies is achievable in most cases.^1,2 However, several studies reported a subgroup of patients with SCC who had a high risk of recurrence and poor prognosis if the carcinoma was of a large size (ie, > 2 cm) with poorly defined borders, had rapid growth, ≥ 4 mm depth, and had perineural or vascular involvement, or if the patient was immunosuppressed.^3,4

  Cutaneous SCC arising from sites of prior radiotherapy or chronic skin inflammation are among the most aggressive skin cancers with a high rate of regional nodal involvement, distant metastasis, and overall mortality.^5,6 Marjolin’s ulcers are cutaneous malignancies, the majority of which are SCC,^7-9 that arise in chronically inflamed skin due to other etiologies such as chronic sinuses of osteomyelitis, posttraumatic wounds, and pressure ulcers. Marjolin’s ulcers are aggressive tumors and necessitate an equally aggressive treatment to improve survival.^7-9

  One of the most important prognostic factors in the management of Marjolin’s ulcers is pathological involvement of the regional lymph nodes. It is reported that 5-year and 10-year survival of patients with cutaneous SCC with regional nodal involvement is 30% and 15%, respectively.^10,11 Early detection of regional nodal involvement in patients with clinically node-negative SCC is of prognostic significance and can guide the managing physicians to more aggressive therapies, such as regional nodal dissection and radiotherapy, with potential for an increased survival benefit.^12,13

  Sentinel node mapping is an accurate technique for regional nodal staging in many solid tumors. This technique has been used with promising results for patients with cutaneous SCC who are at high risk for recurrence and poor prognosis.^12-16

However, there is limited data on lymphatic mapping in Marjolin’s ulcers. In the current study, the authors evaluated the feasibility of sentinel node biopsy in Marjolin’s ulcers using a peritumoral injection of the radiotracer and blue dye.

  This study included 10 patients with Marjolin’s ulcers who were candidates for surgical removal of their tumor. The study was performed from April 2008 to December 2010. The underlying condition for all included patients was burn wounds. The study was approved by the local ethical committee of Mashhad University of Medical Sciences under approval number 89580. The patients were consecutively included in the study. They were informed about the study before participation and all gave written informed consent before entering the study.

  Patients were sent to the nuclear medicine department of Ghaem Hospital (Mashbad, Iran) for the injection of the radiotracer and lymphoscintigraphy 2-4 hours before surgery. Patients received 2 mCi technetium 99m (99mTc) antimony sulfide colloid in 2 divided doses of 0.1 mL each in the peritumoral region subcutaneously. All patients had extensive burn scars in the peritumoral area and the injections were done in the scar tissue around the tumor.

  Lymphoscintigraphy of the regional nodal basin was performed 30 minutes post-injection in anterior-posterior projections (ie, 128 × 128 matrix size, 99mTc photopeak, and low energy high resolution collimator using a dual head variable angle gamma camera [E.CAM, Siemens, Erlangen, Germany]).¹⁷

  After completion of the lymphoscintigraphy imaging, patients were sent to the operating room. Immediately after anesthesia induction, 1 cc of patent blue V in 2 divided doses was injected in the same fashion as the radiotracer. Lymphatic mapping and sentinel node biopsy were performed using a gamma probe (Europrobe, Lyon, France). Any hot and/or blue lymph nodes were harvested as a sentinel node. Primary lesions were then excised and wounds grafted with a split-thickness skin graft. Pathological examination of the harvested sentinel nodes was done using frozen section, step sectioning, and hemotoxylin-eosin staining.

  Patients with noninvolved sentinel nodes did not undergo regional lymph node dissection. For patients with sentinel node harvesting failure, regional lymph node dissection was left to the discretion of the surgeon. The authors also searched the medical literature for cases of patients with Marjolin’s ulcers who underwent sentinel node mapping for regional lymph node staging and presented their results for comparison with the results of this study.

  Ten patients, 5 male and 5 female, ranging in age from 39-65 years, were included in this study. In addition to these 10 patients, the authors found 9 cases in the medical literature in which lymphatic mapping and sentinel node biopsy were performed for the treatment of Marjolin’s ulcers.^18-21

  The details of sentinel node mapping results of the patients in the current study and the 9 patients of the other institutions found in the medical literature are provided in Table 1.

  As shown in Table 1, a sentinel node could be identified on the lymphoscintigraphy images in only 2 patients in the current study (Figure 1). Only in these 2 patients was sentinel node mapping successful during surgery. None of the harvested sentinel nodes were blue.

  The concept of sentinel node mapping is based on an orderly spread pattern of lymphatic drainage from tumors and is an accurate method for regional lymph node staging of many solid tumors, best known for its use in breast cancer and melanoma.^22-24 This technique has also been used for mucosal^25-27 and cutaneous SCC. This is especially true for anogenital SCCs, including anal, penile, and vulvar.^14-16,28 The accuracy of sentinel node mapping for diagnosis of subclinical regional lymph node involvement in cutaneous SCC is high for all types of tumors.^29,30

  Not all patients with cutaneous SCC are at high risk of local recurrence or metastasis. Several high-risk groups have been identified including: patients with tumors located in the anogenital area, patients with tumors measuring > 2 cm, and patients with tumors with a depth > 4cm.³¹ Cutaneous SCCs that originate in the chronic inflammation and scar area (ie, Marjolin’s ulcers) carry a high risk of local recurrence and metastasis.^32,33 The optimal surgical management of lymph nodes in Marjolin’s ulcers for clinically node-negative patients is highly debated. Elective lymph node dissection or observation both have advocates in the medical literature.^34-37 The fact that there is disagreement about the best method of treatment is the reason sentinel node mapping can be useful in this group of patients. However, there are few cases of lymphatic mapping in Marjolin’s ulcers in the medical literature.

  In the largest report thus far, Eastman and colleagues²¹ reported the results of sentinel node mapping in 6 Marjolin’s ulcers. They reported successful sentinel node procedures in 5 patients and the harvested sentinel nodes were pathologically involved in 4 patients.²¹

  The other 3 cases of sentinel node mapping in Marjolin’s ulcers are case reports.^18-20 All reported successful harvesting of sentinel nodes during surgery, none of them were pathologically involved, and no regional recurrence was observed during follow-up.

  Overall, the literature is not rich regarding the utility and feasibility of sentinel node mapping in Marjolin’s ulcers and, to the extent of the authors’ knowledge, in additional to the author’s cases described herein, only the 9 cases mentioned in this paper exist in the medical literature. Contrary to the previous cases, the authors in this study identified sentinel nodes in only 2 out of 10 included patients (a 20% detection rate) which is not a promising result. The clinicians at the Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran, have 10 years experience in sentinel node mapping in various malignancies,^17,28,38,39 so the poor results of lymphatic mapping in Marjolin’s ulcers should not be attributed to the learning curve effect.

  Successful identification of sentinel nodes during surgery depends on patient-related and mapping material-related variables. Mapping material is an important factor in successful lymphatic mapping. Traditionally, blue dyes and radiotracers are used alone or in combination, but it seems that the combined method is optimal for sentinel node mapping with a high detection rate in surgical oncology.^40,41 Some authors dispute the added value of blue dyes and stress the life-threatening complications of blue dyes, such as anaphylaxis and other hypersensitivity reactions, to advocate the radiotracers alone.^42-44 The radiotracer attributes—mainly the particle size—are also an important factor associated with sentinel node mapping success. Small-sized particles usually move fast in the lymphatic pathways with a high intraoperative yield of sentinel node harvesting.^45-47

  In the current study, the authors used the combination of patent blue V and 99mTc antimony sulfide colloid, which has a proven high detection rate for sentinel node mapping.^48-50 In addition, a low volume of radiotracer was used, which has a proven effect on increasing the detection rate of sentinel nodes in breast cancer.⁵¹

  In addition to variables in mapping material, patient-related factors also play an important role in the success of sentinel node mapping. It has been reported that edema associated with previous surgical manipulation of breast lesions can hamper the movement of the radiotracers in the lymphatic system.^{52, 53} Marjolin’s ulcers are located in areas of previously damaged skin with chronic inflammation and scarring. Although regeneration of the lymphatic tissue has been documented within the scars,⁵⁴ the lymph vessels in the scar tissue are scant and less developed compared to the normal skin.⁵⁵ The lymphatics in the relatively avascular scars are usually obliterated⁵⁶; even malignant degeneration has been attributed to the relative inaccessibility of the immune system to the scar tissue.⁵⁷

  In the authors’ opinion, the reason for the low detection rate in this study was the less-developed lymphatic tissue in the scar tissue surrounding the Marjolin’s ulcers which hampered the movement of the radiotracer in the lymphatics. All of the patients included in this study had extensive burn scars with no area of normal skin tissue near the malignant lesions and, consequently, the radiotracer and blue dye were injected into the scar tissue around the tumor.

  None of the cases from the literature reported the extent of the patient’s underlying condition or disease from which the malignancy arose. The extent of the underlying disease can be associated with success of the sentinel node mapping. With a less-extensive condition, injection of the mapping material can be done in less-involved or noninvolved areas of the skin with the potential chance of a more successful sentinel node detection. As mentioned in this paper, all of the patients in this study had extensive underlying diseases and all injections were in the scar tissue around tumor. Future studies should explore the relation of disease extent with the sentinel node mapping success.

  Lymphatic mapping and sentinel node biopsy do not seem to be feasible in Marjolin’s ulcers located in areas of extensive burn scarring due to low detection rate. Larger studies are needed to validate the results of this study.

This study is the result of a residency thesis under approval number 89580, and was conducted in the Nuclear Medicine and Vascular and Endovascular Surgery Research Centers of Mashhad University of Medical Sciences, Mashhad, Iran.

The authors are from the Mashhad University of Medical Sciences, Mashhad, Iran.

Address correspondence to:
Ramin Sadeghi, MD
Nuclear Medicine Research Center
Mashhad University of Medical Sciences
Mashhad, Iran
sadeghir@mums.ac.ir

Disclosure: This study was supported financially by the Vice Chancellery of Research of Mashhad University of Medical Sciences.