Five competing staging systems have been used to describe Merkel cell carcinoma (MCC) in most publications.

Table 3. Five Currently Used Competing Merkel Cell Carcinoma Staging Systems

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First Author	Publication Date	Institution(s)	No. of Patients in Case Series	Dates of Cases
Yiengpruksawan et al.[2]	1991	MSKCCa	77	1969–1989
Allen et al.[3]	1999	MSKCCa	102	1969–1996
Allen et al.[4]	2005	MSKCCa	250	1970–2002
American Joint Committee on Cancer[5]	2002	N/A	N/A
Clark et al.[6]	2007	Westmead Hospital, Sydney, Australia	110
		Princess Margaret Hospital/University Health Network, Toronto, Canada
		Sydney Head and Neck Cancer Institute/Royal Prince Alfred Hospital, Sydney, Australia

MSKCC = Memorial Sloan Kettering Cancer Center

N/A = Not applicable

aThe MSKCC system has evolved over time. MSKCC authors have published one additional case series with 256 patients.[1]

These staging systems are highly inconsistent with each other. Indeed, stage III disease can mean anything from advanced local disease to nodal disease to distant metastatic disease. Furthermore, all MCC staging systems in use have been based on fewer than 300 patients.

To address these concerns, a new MCC-specific consensus staging system was developed by the American Joint Committee on Cancer (AJCC).[7]

Table 4. Primary Tumor (T)^a

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aMerkel Cell. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 318-9.
TX	Primary tumor cannot be assessed
T0	No evidence of primary tumor (e.g., nodal/metastatic presentation without associated primary)
Tis	In situ primary tumor
T1	≤2 cm maximum tumor dimension
T2	>2 cm but ≤5 cm maximum tumor dimension
T3	>5 cm maximum tumor dimension
T4	Primary tumor invades bone, muscle, fascia, or cartilage

Table 5. Regional Lymph Nodes (N)^a

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NX	Regional lymph nodes cannot be assessed
N0	No regional lymph nodes metastasis
cN0	Nodes negative by clinical examb (no pathologic node exam performed)
pN0	Nodes negative by pathologic exam
N1	Metastasis in regional lymph node(s)
N1a	Micrometastasisc
N1b	Macrometastasisd
N2	In transit metastasise

aMerkel Cell. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 318-9.

bClinical detection of nodal disease may be via inspection, palpation, and/or imaging.

cMicrometastases are diagnosed after sentinel or elective lymphadenectomy.

dMacrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or needle biopsy.

eIn transit metastasis: a tumor distinct from the primary lesion and located either (1) between the primary lesion and the draining regional lymph nodes or (2) distal to the primary lesion.

Table 6. Distant Metastasis (M)^a

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aMerkel Cell. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 318-9.
M0	No distant metastasis
M1	Metastasis beyond regional lymph nodes
M1a	Metastasis to skin, subcutaneous tissues or distant lymph nodes
M1b	Metastasis to lung
M1c	Metastasis to all other visceral sites

Patients with primary Merkel cell carcinoma with no evidence of regional or distant metastases (either clinically or pathologically) are divided into two stages: stage I for primary tumors no more than 2 cm in size and stage II for primary tumors larger than 2 cm in size. Stage I and stage II are further divided into A and B substages based on method of nodal evaluation. Patients who have pathologically proven node negative disease (by microscopic evaluation of their draining lymph nodes) have improved survival (substaged as A) compared with those who are evaluated only clinically (substaged as B). Stage II has an additional substage (IIC) for tumors with extracutaneous invasion (T4) and negative node status regardless of whether the negative node status was established microscopically or clinically. Stage III is also divided into A and B categories for patients with microscopically positive and clinically occult nodes (IIIA) and macroscopic nodes (IIIB). There are no subgroups of stage IV Merkel cell carcinoma.[7]

Table 7. Anatomic Stage/Prognostic Groups^a

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aMerkel Cell. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 318-9.
Stage 0	Tis	N0	M0
Stage 1A	T1	pN0	M0
Stage 1B	T1	cN0	M0
Stage IIA	T2/T3	pN0	M0
Stage IIB	T2/T3	cN0	M0
Stage IIC	T4	N0	M0
Stage IIIA	Any T	N1a	M0
Stage IIIB	Any T	N1b/N2	M0
Stage IV	Any T	Any N	M1

Before the new AJCC consensus staging system was published, the most recent MSKCC four-stage system was favored because it was based on the largest number of patients and was the best validated.[1] The stages in the MSKCC system included:

• Stage I: local disease <2 cm.
• Stage II: local disease ≥2 cm.
• Stage III: regional nodal disease.
• Stage IV: distant metastatic disease.

One group has suggested a list of 12 elements that should be described in pathology reports of resected primary lesions and nine elements to be described in pathology reports of sentinel lymph nodes. The prognostic significance of these elements has not been validated prospectively.[8] The 2009 AJCC staging manual also specifies a variety of factors which should be collected prospectively on pathology reports.

References

1. Andea AA, Coit DG, Amin B, et al.: Merkel cell carcinoma: histologic features and prognosis. Cancer 113 (9): 2549-58, 2008.  [PUBMED Abstract]
   
   
2. Yiengpruksawan A, Coit DG, Thaler HT, et al.: Merkel cell carcinoma. Prognosis and management. Arch Surg 126 (12): 1514-9, 1991.  [PUBMED Abstract]
   
   
3. Allen PJ, Zhang ZF, Coit DG: Surgical management of Merkel cell carcinoma. Ann Surg 229 (1): 97-105, 1999.  [PUBMED Abstract]
   
   
4. Allen PJ, Bowne WB, Jaques DP, et al.: Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol 23 (10): 2300-9, 2005.  [PUBMED Abstract]
   
   
5. American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002. 
   
   
6. Clark JR, Veness MJ, Gilbert R, et al.: Merkel cell carcinoma of the head and neck: is adjuvant radiotherapy necessary? Head Neck 29 (3): 249-57, 2007.  [PUBMED Abstract]
   
   
7. American Joint Committee on Cancer.: AJCC Staging Manual. 7th ed. New York, NY: Springer, 2010. 
   
   
8. Bichakjian CK, Lowe L, Lao CD, et al.: Merkel cell carcinoma: critical review with guidelines for multidisciplinary management. Cancer 110 (1): 1-12, 2007.  [PUBMED Abstract]