Lymphatic mapping and sentinel node biopsy in a patient with upper limb Merkel Cell Carcinoma: a case report and brief review of literature
Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
[Received 19 IX 2014; Accepted 3 IX 2015]
Abstract
Sentinel node mapping is an integral part of regional lymph node staging in many solid tumors and plays an important role in surgical oncology. This technique has been used with excellent results for non-melanoma skin cancers including Merkel Cell Carcinoma (MCC). In the current study, we reported our first MCC patient who underwent successful sentinel node mapping. We also reviewed the available literature regarding the prognostic significance of sentinel node mapping in cN0 MCC patients.
KEY words: lymphoscintigraphy, radiotracer, Tc-99m-Phytate, Merkel Cell Carcinoma, sentinel node, lymphatic mapping
Nuclear Med Rev 2016; 19, 1: 42–45
Background
Merkel Cell Carcinoma (MCC) is a rare aggressive neuroendocrine skin tumor with high rate of recurrence and distant metastasis [1]. Pathological status of regional lymph nodes is one of the most important prognostic factors in MCC. Patients with clinically involved regional nodes have far worse prognosis compared with cN0 patients [2, 3].
However there is a group of cN0 patients with occult lymph node metastasis which also have poor prognosis and outcome. Sentinel node mapping is an important technique for regional lymph node staging in many solid tumors which has also been used for MCC [4].
We reported a cN0 MCC of the upper limb which was treated with sentinel node mapping and briefly reviewed the available literature regarding the prognostic importance of sentinel node mapping in MCC.
Case report
A 65-year-old male presented with a 0.8 cm painless erythematous mass over the lateral aspect of the left elbow. The mass had been present for more than 1 year and slowly growing. He didn’t have any history of trauma or previous skin lesions. He didn’t have any history of malignancy.
The patient underwent excisional biopsy of the lesions. Hematoxylin and Eosin and cytokeratin 20 staining lead to the diagnosis of MCC.
The patient was referred to the nuclear medicine department for sentinel node biopsy the morning of the surgery. The patient received two injections of 0.5 mCi/0.2 mL 99mTc-phytate subcutaneously around the scar of the tumor biopsy, 30 minutes before surgery. Ten minutes post-injection, lymphoscintigraphy images of the patient was performed (ANT-POST views, 5 minutes/view, using 99mTc photopeak and a dual head variable angle gamma camera (E.CAM Siemens) equipped with high resolution low energy collimator). Hue of the patient (scatterogram) was imaged simultaneously by the technique of Momennezhad et al. [5]. Scatterogram is imaging of the scatter photons of the Tc-99m simultaneous with the original lymphoscintigraphy images. In this technique, no additional time or radiation is needed and a hue of the patient can be imaged. As scatterogram can be done without any additional time, radiation and cost; it can be recommended with all planar lymphoscintigraphy imaging.
Lymphoscintigraphy images of the patient showed a single sentinel node in the axillary region (Figure 1). Intra-operatively the tumor site was excised with a wide margin and an axillary sentinel node was harvested by a gamma probe (EUROPROBE, France). The sentinel node was not pathologically involved by frozen section examination and axillary dissection was not performed. Permanent H&E examination of the sentinel nodes was done after serial sectioning and was also pathologically negative.
Figure 1. Lymphoscintigraphy images of the patient. The lower row images are scatterograms of the corresponding upper row lymphoscintigrams. A sentinel node could be identified in the left axilla. Injection site is out of the field of imaging
The patient underwent local radiotherapy for the primary site of the tumor. At 7 months follow up the patient didn’t have any evidence of local or regional recurrence.
Literature review and discussion
Sentinel node mapping is the standard method of regional lymph node staging in breast cancer and melanoma [6, 7]. Its application in other solid tumors such as gynecological and urological cancers is growing with very promising results [8, 9].
Lymphatic mapping and sentinel node biopsy has also become very common in the high risk squamous cell carcinoma (SCC) of the skin [10, 11] including SCC of the genital area [12, 13].
Sentinel node mapping for MCC has been performed with excellent accuracy since 1998 [14]. By identifying subgroup of patients with regional lymph node involvement in clinically node negative patients, sentinel node mapping can help planning treatment in MCC patients. Our department has an extensive experience in sentinel node mapping in different solid tumors since ten years ago [15]. The current case was the first MCC patient who underwent sentinel node mapping in our department. An axillary sentinel node could be harvested successfully intra-operatively and was not pathologically involved. Axillary node dissection was not performed and the patient didn’t receive any specific treatment for axillary area. Thus far the patient is recurrence free.
Nuclear medicine plays a pivotal role in the lymphatic mapping of solid tumors and nuclear physicians are the integral part of sentinel node mapping team. Pre-operative lymphoscintigraphy is also an integral part of lymphatic mapping in surgical oncology. Lymphoscintigraphy can help the surgeons to plan the surgery due to sentinel node localization before surgery, can identify the unusual locations of sentinel nodes and may decrease detection failure and false negative rate [16, 17].
Thus far three systematic reviews have addressed lymphatic mapping in MCC [4, 18]. Mehrany et al. in the 2002 systematic review gathered all cases of sentinel node mapping in MCC by comprehensive search of the literature. They could gather information of 60 patients, 67% of whom had pathologically negative sentinel nodes. These sentinel node negative patients had no evidence of regional nodal recurrence at follow up visits (no false negative case) [18]. In the 2006 systematic review, Gupta et al. gathered information of 122 MCC patients with lymphatic mapping. They reported that sentinel node mapping upstaged 39 patients (32%) due to pathologically involved sentinel node. This finding has an important clinical implication as these patients may not have received treatment to the involved node bed. Recurrence rate (overall regional and distant) was three times higher in sentinel node positive patients as compared with the sentinel node negative ones [4]. The last systematic review by Sadeghi et al. in 2014 showed the prognostic importance of SLN mapping in cN0 MCC patients as sentinel node mapping can improve disease free and overall survival in cN0 MCC patients as compared with nodal observation [19].
Thus far, six studies reported survival benefit of sentinel node mapping in cN0 MCC patients [20–25]. Table 1 summarizes the characteristics of these studies in addition to their main prognostic findings. Overall, these prognostic studies showed that operative nodal staging with sentinel node biopsy is associated with improved overall and disease free survival as compared with nodal observation in cN0 MCC patients. In addition, 3 studies evaluated the prognostic significance of pathological involvement of the sentinel nodes in MCC [26–28] . Brief prognostic data of these studies are available in Table 2.
Table 1. Characteristic of the studies evaluated prognostic significance of sentinel node mapping in MCC
| First author | Publication year | Total number of patients | Duration of follow up | Major findings |
|---|---|---|---|---|
| Tarantola | 2013 | 114 | 3.3 year (mean) | OS in the patients underwent SLN mapping was higher, HR: 1.04 [0.51–2.15], p = 0.91 |
| Kachare | 2014 | 1193 | Median of 21 months | DFS was higher in patients underwent SLN mapping, HR: 1.43 [1.01–2.05], p = 0.04 |
| Bajetta | 2009 | 63 | Median of 65 months | Operative nodal staging with SLN biopsy (HR 3.44 [1.17–10]; p = 0.023) predicted better DFS |
| Sattler | 2013 | 47 | Median 20 months | SLN mapping predicted better DFS and OS as compared with nodal observation |
| Tseng | 2014 | 4038 | N/A | DFS was higher in patients underwent SLN mapping, HR: 1.72 [1.37–2.14]; p = 0.000001 |
| Asgari | 2014 | 218 | 2.4 years | Both OS and DFS were better in the SLN mapping group as compared with nodal observation (HR = 2.5 for both) |
OS — Overall Survival; SLN — Sentinel Lymph Node; HR — Hazard Ratio; DFS — Disease Free Survival
Table 2. Characteristic of the studies evaluated the prognostic significance of sentinel node pathological involvement in MCC
| First author | Publication year | Total number of patients | Duration of follow up | Major findings |
|---|---|---|---|---|
| Fields | 2011 | 153 | 41 months (median) | OS and DFS in the patients without involved SLN was higher, HR: 1.86 [0.22–15.6], p = 0.56; and 1.69 [0.37–7.68], p = 0.49 |
| Kouzmina | 2013 | 28 | 3.6 years (mean) | OS was higher in patients without SLN involvement, HR: 4.8 [0.79–29.37], p = 0.08 |
| Fritsch | 2014 | 721 | 34 months | DFS was higher in patient without SLN involvement especially in non-head and neck locations: HR: 2.2 [0.84–5.86], p = 0.1 for head and neck, and 3.01 [1.77–5.11], p = 0.0001 for non-head and neck locations |
OS — Overall Survival; DFS — Disease Free Survival; SLN — Sentinel Lymph Node; HR — Hazard Ratio
In conclusion, sentinel node mapping is an important method for regional lymph node staging in cN0 MCC patients. Medical literature supports that sentinel node mapping in cN0 MCC patients is associated with improved overall and disease free survival.
References
- Senchenkov A, Moran SL. Merkel cell carcinoma: diagnosis, management, and outcomes. Plast Reconstr Surg 2013; 131: 771e-778e.
- Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol 2005; 23: 2300–2309.
- Yiengpruksawan A, Coit DG, Thaler HT, Urmacher C, Knapper WK. Merkel cell carcinoma. Prognosis and management. Arch Surg 1991; 126: 1514–1519.
- Gupta SG, Wang LC, Penas PF, Gellenthin M, Lee SJ, Nghiem P. Sentinel lymph node biopsy for evaluation and treatment of patients with Merkel cell carcinoma: The Dana-Farber experience and meta-analysis of the literature. Arch Dermatol 2006; 142: 685–690.
- Momennezhad M, Zakavi SR, Dabbagh Kakhki VR, Jangjoo A, Ghavamnasiri MR, Sadeghi R. Scatterogram: a method for outlining the body during lymphoscintigraphy without using external flood source. Radiol Oncol 2011; 45: 184–188.
- Aliakbarian M, Memar B, Jangjoo A et al. Factors influencing the time of sentinel node visualization in breast cancer patients using intradermal injection of the radiotracer. Am J Surg 2011; 202: 199–202.
- Mehrabibahar M, Forghani MN, Memar B et al. Sentinel lymph node biopsy in melanoma patients: An experience with Tc-99m Antimony Sulfide Colloid. Iran J Nucl Med 2010; 18: 1–6.
- Ansari M, Rad MA, Hassanzadeh M et al. Sentinel node biopsy in endometrial cancer: systematic review and meta-analysis of the literature. Eur J Gynaecol Oncol 2013; 34: 387–401.
- Sadeghi R, Tabasi KT, Bazaz SM et al. Sentinel node mapping in the prostate cancer. Meta-analysis. Nuklearmedizin 2011; 50: 107–115.
- Tartaglione G, Potenza C, Caggiati A et al. Lymphatic mapping and sentinel node identification in squamous cell carcinoma and melanoma of the head and neck. Tumori 2002; 88: S39–41.
- Leong SP. Selective sentinel lymphadenectomy for malignant melanoma, Merkel cell carcinoma, and squamous cell carcinoma. Cancer Treat Res 2005; 127: 39–76.
- Hassanzade M, Attaran M, Treglia G, Yousefi Z, Sadeghi R. Lymphatic mapping and sentinel node biopsy in squamous cell carcinoma of the vulva: systematic review and meta-analysis of the literature. Gynecol Oncol 2013; 130: 237–245.
- Sadeghi R, Gholami H, Zakavi SR, Kakhki VR, Tabasi KT, Horenblas S. Accuracy of sentinel lymph node biopsy for inguinal lymph node staging of penile squamous cell carcinoma: systematic review and meta-analysis of the literature. J Urol 2012; 187: 25–31.
- Ames SE, Krag DN, Brady MS. Radiolocalization of the sentinel lymph node in Merkel cell carcinoma: a clinical analysis of seven cases. J Surg Oncol 1998; 67: 251–254.
- Sadeghi R, Alesheikh G, Zakavi SR et al. Added value of blue dye injection in sentinel node biopsy of breast cancer patients: Do all patients need blue dye? Int J Surg 2014; 12: 325–328.
- Balasubramanian Harisankar CN, Mittal BR, Bhattacharya A, Dhaliwal LK. Utility of SPECT/CT in Sentinel Lymph Node Detection in a Case of Vulvar Carcinoma. Mol Imaging Radionucl Ther 2013; 22: 106–108.
- Kraft O, Havel M. Detection of Sentinel Lymph Nodes in Gynecologic Tumours by Planar Scintigraphy and SPECT/CT Mol Imaging Radionucl Ther 2012; 21: 47–55.
- Mehrany K, Otley CC, Weenig RH, Phillips PK, Roenigk RK, Nguyen TH. A meta-analysis of the prognostic significance of sentinel lymph node status in Merkel cell carcinoma. Dermatol Surg 2002; 28: 113–117; discussion 117.
- Sadeghi R, Adinehpoor Z, Maleki M, Fallahi B, Giovanella L, Treglia G. Prognostic significance of sentinel lymph node mapping in Merkel cell carcinoma: systematic review and meta-analysis of prognostic studies. Biomed Res Int 2014; 2014: 489–536.
- Tarantola TI, Vallow LA, Halyard MY et al. Prognostic factors in Merkel cell carcinoma: analysis of 240 cases. J Am Acad Dermatol 2013; 68: 425–432.
- Kachare SD, Wong JH, Vohra NA, Zeivos EE, Fitzgerald TL. Sentinel Lymph Node Biopsy is Associated with Improved Survival in Merkel Cell Carcinoma. Ann Surg Oncol 2014; 21: 1624–1630.
- Bajetta E, Celio L, Platania M et al. Single-institution series of early-stage Merkel cell carcinoma: long-term outcomes in 95 patients managed with surgery alone. Ann Surg Oncol 2009; 16: 2985–2993.
- Sattler E, Geimer T, Sick I et al. Sentinel lymph node in Merkel cell carcinoma: to biopsy or not to biopsy? J Dermatol 2013; 40: 374–379.
- Tseng J, Dhungel B, Mills JK et al. Merkel cell carcinoma: what makes a difference? Am J Surg 2014; 2015; 209: 342–346.
- Asgari MM, Sokil MM, Warton EM, Iyer J, Paulson KG, Nghiem P. Effect of host, tumor, diagnostic, and treatment variables on outcomes in a large cohort with Merkel cell carcinoma. JAMA Dermatol 2014; 150: 716–723.
- Fritsch VA, Camp ER, Lentsch EJ. Sentinel lymph node status in Merkel cell carcinoma of the head and neck: Not a predictor of survival. Head Neck 2014; 2014; 36: 571–579.
- Fields RC, Busam KJ, Chou JF et al. Recurrence and survival in patients undergoing sentinel lymph node biopsy for merkel cell carcinoma: analysis of 153 patients from a single institution. Ann Surg Oncol 2011; 18: 2529–2537.
- Kouzmina M, Leikola J, Bohling T, Koljonen V. Positive sentinel lymph node biopsy predicts local metastases during the course of disease in Merkel cell carcinoma. J Plast Surg Hand Surg 2013; 47: 139–143.
Correspondence to:
Ramin Sadeghi, MD
Nuclear Medicine Research Center,
Mashhad University of Medical Sciences, Mashhad, Iran
Tel: +98 915 311 77 34; fax: +98 513 893 31 8
E-mail: sadeghir@mums.ac.ir
