- Incidence 0.4/100,000 in 2001 (up from 0.1/100,000 in 1986)
- Stage (SEER data, 1973-2002)
- Stage I: 55%
- Stage II: 31%
- Stage III: 6%
- Median survival: 4 years
- Incidence of cancer linked to Merkel cell polyomavirus. Virus DNA detected in 75% to 80% of Merkel Cell carcinoma specimens.
- Cutaneous malignancy of neuroendocrine origin
- Initially described in 1972 as "trabecular carcinoma"
- Nomenclature changed to MCC due to structural and IHC similarities to Merkel cells
- Merkel cells were initially described as non-dendritic, non-keratinocyte epidermal cells that function as tactile skin receptors
- High rate of local failure and regional recurrence (50-80%)
- Considered highly radiosensitive
- Management is controversial; surgery tends to be mainstay, with some investigators suggesting margins of 3cm
- Role of adjuvant RT is not well defined. However, a recent retrospective SEER analysis shows a significant survival benefit for all patients, and particularly for tumors >2cm
- Only one prospective trial has been conducted to date (TROG 96:07), which suggests a benefit for concurrent chemo-RT in N+ patients
AJCC 7th Edition (2009)
Note: This is a new staging system for MCC beginning with the 7th Edition. In previous versions, was included in non-melanoma skin cancer staging.
Excludes: MCC of the eyelid
- T0 - no evidence of primary tumor
- Tis - in situ
- T1 - tumor <= 2 cm
- T2 - >2 cm and <= 5 cm
- T3 - > 5 cm
- T4 - invades bone, muscle, fascia, or cartilage
Regional Lymph Nodes:
- N0 - none
- N1a - micrometastasis
- N1b - macrometastasis
- N2 - in transit metastasis
- defined as a tumor distinct from the primary tumor and either 1) between the primary and the nodal basin or 2) distal to the primary
- M0 - none
- M1a - metastasis to skin, subcutaneous tissues, or distant lymph nodes
- M1b - metastasis to lung
- M1c - metastasis to all other visceral sites
- IA - T1 pN0
- IB - T1 cN0
- IIA - T2-3 pN0
- IIB - T2-3 cN0
- IIC - T4 N0
- IIIA - N1a
- IIIB - cN1/N1b/N2 *(corrected in erratum)
- IV - M1
Note: prognostically, pN0 is better than cN0 (without pathologically confirmed node negativity) and thus pN0 vs cN0 is incorporated into overall staging, as is N1a vs N1b
Older staging systems
AJCC 6th Edition (2002)
Was staged as a Non-melanoma skin cancer
Lymph Node Assessment
- 95 pts undergoing SLN biopsy for MCC.
- 2011: PMID 21300936 -- "Features Predicting Sentinel Lymph Node Positivity in Merkel Cell Carcinoma." (Schwartz JL, J Clin Oncol. 2011 Mar 10;29(6):1036-1041.)
- SLN identified in 93 of 97 primary tumors. SLN + associated with increasing clinical size, tumor thickness, mitotic rate, and infiltrative tumor growth pattern.
- Conclusion: no subgroup of patients could be identified who had a < 15-20% likelihood of positive LN. SLN biopsy should be recommended in pts with localized disease.
- SEER, 2007 (1973-2002) PMID 17369567 -- "Adjuvant radiation therapy is associated with improved survival in merkel cell carcinoma of the skin." (Mojica P, J Clin Oncol. 2007 Mar 20;25(9):1043-7.)
- Retrospective. 1665 patients in SEER registry. Surgery in 89% cases, adjuvant RT 40%. Median F/U 40 months
- Median survival: 49 months (surgery only 45 months vs. adjuvant RT 63 months)
- RT benefit: for all patients, but highly significant if tumor size >2 cm (median OS 21 vs. 50 months). For tumors <1cm (48 months vs. 93 months), for tumors 1-2cm (52 months vs. 86 months)
- Conclusion: "The use of adjuvant radiation therapy is associated with improved survival in patients with MCC."
- Comment & author reply: PMID 17906216
- Sydney; 2007 (Australia)(1992-2004) PMID 17356954 -- "Merkel cell carcinoma: assessing the effect of wide local excision, lymph node dissection, and radiotherapy on recurrence and survival in early-stage disease--results from a review of 82 consecutive cases diagnosed between 1992 and 2004." (Jabbour J, Ann Surg Oncol. 2007 Jun;14(6):1943-52.)
- Retrospective. 82 patients with early-stage
- Outcome: Recurrence rate 51%,
- Predictors: LN+ status negative, lymphadenectomy prolonged DFS (28 months vs. 12 months, SS) but not OS. SM- not associated with better outcome. RT in 58%, improved DFS (24 months vs. 12 months); improved OS for both primary site (54 months vs. 46 months) and N+ (103 months vs. 34 months)
- Conclusion: Adjuvant RT recommended for early-stage disease; involved regional LN should be treated
- Brown University; 2006 PMID 16785371 -- "Adjuvant local irradiation for Merkel cell carcinoma." (Lewis KG, Arch Dermatol. 2006 Jun;142(6):693-700.)
- Literature survey. 333 reports published between 1966-2004 reviewed
- Outcome: With RT, local recurrence reduced HR 0.27 (SS); regional recurrence reduced HR 0.34 (SS). 1-year OS 87%, 5-year OS 49%; 1-year CSS 90%, 5-year CSS 62%. No difference in CSS or OS with RT, though if single patient case reports excluded, found CSS benefit (p=0.04) and OS benefit (p=0.02) for adjuvant RT
- Conclusion: Surgery plus local adjuvant RT associated with lower local and regional recurrence
- Cologne; 2002 (1990-2000) PMID 11823697 -- "Role of postoperative radiotherapy in the management of Merkel cell carcinoma." (Eich HT, Am J Clin Oncol. 2002 Feb;25(1):50-6.)
- Retrospective. 31 patients, 13 H&N, 13 limbs, 5 trunk. Stage I 26, Stage II 4, Stage III 1. Surgery alone 14/31, adjuvant RT 16/31, definitive RT 1/31
- Outcome: median OS 2.7 years; local recurrence 20%, regional LN mets 30%, DM 23%. RT decreased locoregional reccurence from 36% to 6%
- Negative predictive factors: H&N location, lack of post-op RT
- Conclusion: Post-op RT to primary tumor and regional lymphatics effective
- MD Anderson; 2001 (1945-95) - PMID 11177031 — "Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival." Gillenwater AM et al. Arch Otolaryngol Head Neck Surg. 2001 Feb;127(2):149-54.
- Retrospective. 66 pts. No difference in local relapse for surgical margins <1 vs 1-2cm vs >2cm. Improved local recurrence (12% vs 44%) and regional recurrence (27% vs 85%) rate for addition of RT. No difference in OS. Distant disease developed in 36% of pts regardless of treatment.
- Queensland Radium Institute; 1995 (1981-91) - PMID 7836086 — "The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma." Meeuwissen JA et al. Int J Radiat Oncol Biol Phys. 1995 Jan 15;31(2):325-31.
- Retrospective. 80 pts. 38 of 38 pts treated with surgery alone relapsed, versus 10 of 34 pts with S+RT.
Chemotherapy + RT
- Queensland Radium Institute / TROG; 2006 PMID 16125873 — "Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?" Poulsen MG et al. Int J Radiat Oncol Biol Phys. 2006 Jan 1;64(1):114-9.
- Retrospective. Compared 53 pts from TROG 96:07 (chemo + RT) to 144 pts treated at Queensland from 1988-96 (RT only).
- Chemotherapy does not improve survival.
- TROG 96:07 (1996-2001)
- Phase II. Pts with disease limited to the primary and nodes with at least 1 risk factor: recurrence after initial therapy, involved nodes, size > 1 cm, gross residual disease, or occult primary with nodes. N+ in 62%. 50 Gy in 25 fx with concurrent carboplatin/etoposide on days 1-3 on weeks 1, 4, 7, and 10.
- 2001 PMID 11516865 — "Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group study." Poulsen M et al. Int J Radiat Oncol Biol Phys. 2001 Sep 1;51(1):156-63. Median F/U 1.8 years
- Toxicity: Grade 3-4 skin 63%; neutropenia 40%
- Conclusion: Toxicity acceptable. No outcome measures reported
- 2003 PMID 14645427 -- "High-risk Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study--TROG 96:07." (Poulsen M, J Clin Oncol. 2003 Dec 1;21(23):4371-6.). Median F/U 4 years
- 3-year outcome: OS 76%, LR control 75%, DM control 76%
- Conclusion: Addition of chemo to RT resulted in high control
- New Zealand; 2008 PMID 18391627 -- "Management of Merkel tumours: an evidence-based review." (Henness S, Curr Opin Oncol. 2008 May;20(3):280-6.)
- High propensity for recurrence post treatment. 5-year OS 23-80%
- Addition of RT can confer significant benefit in reducing local and regional recurrence rates, and prolonging DFS. Current literature does not support role of chemotherapy
- Stage-specific treatment regimens outlined
- U. Michigan; 2007 PMID 17520670 -- "Merkel cell carcinoma: critical review with guidelines for multidisciplinary management." (Bichakjian CK, Cancer. 2007 Jul 1;110(1):1-12.)
- NCCN; 2006 - PMID 16884673 — "Role of radiotherapy in the management of merkel cell carcinoma of the skin." Decker RH and Wilson LD. J Natl Compr Canc Netw. 2006 Aug 4;(7):713-8.
- http://www.merkelcell.org - run by Seattle Cancer Care Alliance
- Resource for physicians + patients. General info. Useful photographs and contains a few good publications in PDF format