MCCs are rare and aggressive neuroendocrine tumors arising from cutaneous Merkel cells. Their incidence seems to be rising; they affect more elderly and immunosuppressed people with a correlation to sun exposure. They tend to spread locally before developing distant metastasis, and at time of diagnosis up to 68% of patients already present lymph node involvement [40
]. The presence of clinically palpable nodes and visible lymphadenopathy on CT scan is an indicator of poor survival rate [13
] so that early detection of lymph node involvement is the most important prognostic factor.
MCC is known to be radiosensitive, but the systematic use of radiotherapy to the primary tumour and/or the lymph node basin is still debated. Eich et al. [41
] have reported a significant higher disease-free survival rate and Mojica et al. have reported [42
] a higher overall survival rate after adjuvant radiotherapy. However, Allen et al. could not demonstrate that an adjuvant radiotherapy was necessary if the primary tumor and the lymph node basin were surgically controlled (ELND, SLNB, and CLND) [5
]. Conversely in patient without nodal control (SLNB/ELNB) metastatic lymph node will appear in 45% of cases and radiotherapy is mandatory.
Already in 2002, Goessling et al. listed 49 patients with MCC and concluded that the SLNB could be a useful tool for their staging [43
]. Since then, the use of SLNB for MCC has been the subject of several reviews which are summarized in [5
]. The cumulated rate of positive SNs was 31% (101/326). Only half of the SN positive patients underwent a CLND, and the rate of positive NSNs after CLND was 35% (19/54). It seems that despite the absence of guidelines, the number of patients undergoing SLNB followed by CLND is increasing.
Review of studies with sentinel lymph node biopsy in patients with MCC.
Criteria for a high risk of metastatic sentinel node in Merkel cell carcinoma are presented in . However, patients without these criteria still have a 23–36% risk for positive SN [41
Criteria for a high-risk of metastatic sentinel node in Merkel cell carcinoma.
One of the largest monocentric study was presented by Fields et al. [16
]. From 153 patients who underwent SLNB, 45 of them presented positive SN. CLND was consecutively performed in 21 patients, and 6 of them presented metastatic NSNs. During a median followup of 41 months 8/99
SN-negative patients developed nodal recurrence which corresponds to a false negative rate of 15%. The presence of lymphovascular invasion (LVI) was highly predictive for the disease-free and overall survival but not for the SN status. Interestingly 71% of the patients with positive SN and 92% of the patients with negative SN did not receive any adjuvant therapy. In this study, the author recommends to perform routinely SLNB even by patients who are clinically staged as N0. However, this staging procedure remains a subject of controversies in the recent published studies [15
The use of immunohistochemistry (pancytokeratin and CK-20 antibodies) can significantly upstage false negative SNs [46
] and should be the role for SN examination.
In summary up to 68% of MCC patients present nodal metastases at time of diagnosis. 20–30% of clinically N0 patients can be upstaged if a SLNB is performed. Nodal status is an important prognostic factor. The exact role and benefit of radiation therapy on lymphatic basins are not definitively assessed (clinically negative or after SLND, CLND, and ELND) [5
]. New attempts for improving standardized histopathology report [48
] and treatment algorithm [49
] would be helpful.
MCC has a higher incidence in transplanted patients. These patients are younger and their 5-year overall survival of 46% [50
] is slightly lower than the 54% observed in a large MCC data base regarding matched population [51