AJCC 8th Edition Head & Neck Staging Guidelines

Merkel Cell Carcinoma

Overview

Merkel Cell Carcinoma

  • Merkel Cell Carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine carcinoma.
  • Overall mortality rate (33%) is twice that of cutaneous melanoma (15%).
  • Pathogenesis is thought to be associated with clonal integration of Merkel cell polyomavirus (MCPyV).
  • UV radiation and immunosuppression are significant predisposing factors. In one study, 89% of all patients with Merkel Cell carcinoma had 3 or more of the following AEIOU features:1
    1. A – Asymptomatic (no tenderness)
    2. E – Expanding rapidly
    3. I – Immunosuppressed
    4. O – Older than 50 years old
    5. U – UV exposed area of skin affected
  • Findings on Immunohistochemistry:
    1. Paranuclear dot pattern of CK20 staining
    2. Positive staining for neuroendocrine markers: Chromogranin A, Synaptophysin, CD56
T-Categorization
T Category Criteria
TX

Primary tumour thickness cannot be assessed (eg. if the diagnosis was by curettage)
T0

No evidence of primary tumour (eg. unknown primary, or if the primary has completely regressed)
Tis

Carcinoma in-situ (has not broken through basement membrane)
T1

Maximum tumour diameter ≤ 2 cm
T2

Maximum tumour diameter > 2 cm but ≤ 5 cm
T3

Maximum tumour diameter > 5 cm
T4

Tumour invades fascia, muscle, cartilage, or bone
N-Categorization

Clinical Nodal Categorization

N Category Criteria
NX

Regional lymph nodes cannot be assessed.
N0

No regional lymph node metastasis detected clinically or radiographically.
N1

Metastasis in regional lymph node(s)
N2

In-transit metastasis WITHOUT lymph node metastasis
N3

In-transit metastasis WITH lymph node metastasis

Pathologic Nodal Categorization

N Category Criteria
NX

Regional lymph nodes cannot be assessed.
N0

No regional lymph node metastasis detected pathologically (such as after sentinel lymph node biopsy).
N1

Metastasis to regional nodes WITHOUT in-transit metastasis
N1a(sn)

Clinically occult nodal metastasis identified only on sentinel lymph node biopsy.
N1a

Clinically occult nodal metastasis identified following lymph node dissection.
N1b

Clinically or radiologically detected nodal metastasis confirmed microscopically.

N2

In-transit metastasis WITHOUT lymph node metastasis
N3

In-transit metastasis WITH lymph node metastasis

General Rules

  • In-transit metastasis is defined as cutaneous metastasis discontinuous from the primary tumour between the primary tumour and draining regional nodal basin. Unlike in melanoma, there is no differentiation between satellite metastasis (within 2 cm of primary tumour) and in-transit metastasis (> 2 cm away from primary tumour).
  • Nodal metastasis without in-transit metastasis up-categorizes you to N1
  • In-transit metastasis without nodal metastasis up-categorizes you to N2
  • In-transit metastasis with nodal metastasis up-categorizes you to N3
M-Categorization

Clinical Metastasis Categorization

M Category Criteria
M0

No evidence of distal metatasis on clinical or radiologic examination
M1 Evidence of distal metastasis on clinical or radiologic examination
M1a
  • Metastasis to distant skin, distant subcutaneous tissue, or distant lymph nodes.
M1b
  • Metastasis to lung
M1c
  • Metastasis to all other distant sites

Pathologic Metastasis Categorization

M Category Criteria
M0

No evidence of distal metatasis on clinical or radiologic examination
pM1 Distant metastasis microscopically confirmed
pM1a
  • Metastasis to distant skin, distant subcutaneous tissue, or distant lymph nodes, microscopically confirmed
pM1b
  • Metastasis to lung, microscopically confirmed
pM1c
  • Metastasis to all other distant sites, microscopically confirmed

General Rules

  • Conceptually very similar to the categorization of distant metastasis with cutaneous melanoma, except there is no M1d for CNS metastasis.
    1. Non-visceral metastasis classifies you as M1a. (eg. distant skin, distant subcutaneous tissue, or distant lymph node(s)
    2. Lung metastasis classifies you as M1b.
    3. Visceral metastasis classifies you as M1c.
  • The pathologic classification is identical except with the confirmation of distal metastasis microscopically versus solely clinically or on radiologic examination.
Group Staging

Clinical Group Staging

N0
M0		 N1-3
M0		 Any N
M1
Tis 0
T0 III IV
T1 I III IV
T2 IIA III IV
T3 IIA III IV
T4 IIB III IV

Pathological Group Staging

N0
M0		 N1a(sn)
1a, M0		 N1b-3
M0		 Any N
M1
Tis 0
T0 IIIA IV
T1 I IIIA IIIB IV
T2 IIA IIIA IIIB IV
T3 IIA IIIA IIIB IV
T4 IIB IIIA IIIB IV

General Rules

  • Clinical group staging is very similar to that of cutaneous melanoma:
    • Any nodal metastasis upstages to stage III
    • Any distal metastasis upstages to stage IV
  • With pathologic staging, N1a disease (any clinically occult disease detected either on sentinel lymph node biopsy or on neck dissection) upstages to stage IIIA
  • N1b-N3 disease is upstaged to Stage IIIB with the exception of T0 T1b-3 M0, which is Stage IIIA.

  1. Heath, Michelle et al. “Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features.” Journal of the American Academy of Dermatology vol. 58,3 (2008): 375-81. doi:10.1016/j.jaad.2007.11.020 ↩

CHAPTER 15. Mucosal Melanoma of the Head & Neck CHAPTER 17. Thyroid (Differentiated)