Patterns of Metastasis in Merkel Cell Carcinoma

Song, Yun; Azari, Feredun S.; Tang, Rebecca; Shannon, Adrienne B.; Miura, John T.; Fraker, Douglas L.; Karakousis, Giorgos C.

BACKGROUND: Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied. METHODS: Patients with American Joint Committee on Cancer (8th edition) stage I–IV MCC treated at our institution were identified (1/1/2008–2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated. RESULTS: Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20–66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, P = 0.001) and stage IV disease with worse MSS (hazard ratio 6.30, P = 0.002). CONCLUSIONS: Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.