MALIGNANT MELANOMA
Staging:
AJCC Staging System — The AJCC staging system is based upon evaluations of the
primary tumor (T) and the presence or absence of regional lymphatic (N) and distant
metastases (M) . The AJCC staging system divides patients into four stages:
Stage I — Stage I is limited to patients with low-risk primary melanomas, without
evidence of regional or distant metastases. Stage I is divided into stages IA and IB:

Stage IA primary lesions are 1 mm thick, without either ulceration of the
overlying epithelium or invasion of the reticular dermis or subcutaneous fat
(Clark level IV or V)

Stage IB includes primary lesions 1 mm thick with epithelial ulceration or
invasion into Clark's levels IV or V. Stage IB also includes primary lesions 1
mm and 2 mm thick without ulceration or invasion into Clark's levels IV or V.
Stage II — Stage II disease includes high-risk primary tumors without evidence of
lymphatic disease or distant metastases. Stage II is divided into three subsets:

Stage IIA includes lesions 1 mm and 2 mm thick with ulceration of the
overlying epithelium and those >2 mm and 4 mm thick without epithelial
ulceration.

Stage IIB lesions are >2 mm and 4 mm thick with epithelial ulceration or >4 mm
without ulceration.

Stage IIC consists of primary lesions >4 mm with epithelial ulceration.
Stage III — Pathologically documented involvement of regional lymph nodes or the
presence of in transit or satellite metastases defines a lesion as stage III.
Within stage III, patients with involvement of 1, 2 to 3, and 4 or more lymph nodes are
sub-classified as having N1, N2, and N3 disease, respectively. Patients with in transit or
satellite metastases are classified as having N2 disease if lymph node involvement is not
present, and as having N3 disease if lymph node involvement is present. In addition,
lymph node involvement is divided based upon whether disease is microscopic or
macroscopic (eg, N1a versus N1b). Among patients with stage III disease, the presence of
ulceration in the primary tumor remains an independent negative prognostic factor.
Using these parameters, patients with stage III disease are sub-classified as follows:

Stage IIIA includes patients with one to three microscopically involved lymph
nodes (N1a or N2a) in a patient whose primary tumor is not ulcerated.
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
Stage IIIB includes patients with one to three microscopically involved lymph
nodes (N1a or N2a) in a patient whose primary tumor is ulcerated, or one to three
macroscopically involved lymph nodes (N1b or N2b) in a patient with a nonulcerated primary tumor, or patients with in transit and/or satellites without
metastatic lymph nodes (N2c).

Stage IIIC is defined by the involvement of four or more lymph nodes, matted
lymph nodes, or the presence of in transit metastases or satellite lesions in
conjunction with lymph node involvement (ie, N3), or patients with one to three
macroscopically involved lymph nodes (N2b) in a patient whose primary tumor is
ulcerated.
Patients with clinical evidence of regional lymph node without a full regional lymph node
dissection are classified as clinical stage III, and no further staging is applied.
Stage IV — The presence of distant metastases defines stage IV disease. Patients with
metastases are divided into three categories: disease limited to distant skin, subcutaneous
tissues, or lymph nodes (M1a), lung metastases (M1b), or involvement of all other
visceral sites (M1c). In addition, the presence of an elevated serum LDH in conjunction
with any distant metastasis classifies a patient as having M1c disease.
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AJCC 2002 TNM classification for melanoma
Tumor (T) classification
TX
Primary tumor cannot be assessed (eg, shave biopsy, regressed primary)
Tis
Melanoma in situ
T1
< or = 1.0 mm
A: without ulceration and level II/III*
B: with ulceration or level IV or V*
T2
1.01-2.0 mm
a: without ulceration
b: with ulceration
T3
2.01-4.0 mm
a: without ulceration
b: with ulceration
T4
>4.0 mm
a: without ulceration
b: with ulceration
Node (N) classification
N1
One lymph node
a: micrometastases (clinically occult)
b: macrometastases (clinically apparent)
N2
2-3 lymph nodes
a: micrometastases
b: macrometastases
c: in-transit met(s)/satellite(s) without metastatic lymph nodes
N3
4 or more metastatic lymph nodes, or matted lymph nodes, or in-transit
met(s)/satellite(s) with metastatic lymph node(s)
Metastasis (M) classification
M1a
Distant skin, subcutaneous, or lymph node metastases, normal LDH
M1b
Lung metastases, normal LDH
M1c
All other visceral metastases, normal LDH
Any distant metastases, elevated LDH
* Clark's levels: level II: invades the papillary dermis; level III: invades to the papillary-
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reticular dermal interface; level IV: invades the reticular dermis; level V: invades
subcutaneous tissue.
Micrometastases are diagnosed after elective or sentinel lymphadenectomy.
Macrometastases are defined as clinically detectable lymph node metastases confirmed
by therapeutic lymphadenectomy or when any lymph node metastasis exhibits gross
extracapsular extension.
Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago,
Illinois. The original source for this material is the AJCC Cancer Staging Manual, Sixth
Edition (2002) published by Springer-Verlag New York, Inc.
Stage
AJCC 2002 stage groupings for cutaneous melanoma
Clinical stage grouping*
Pathologic stage grouping
0
Tis
N0
M0
pTis
N0
M0
IA
T1a
N0
M0
pT1a
N0
M0
IB
T1b
N0
M0
pT1b
N0
M0
T2a
N0
M0
pT2a
N0
M0
T2b
N0
M0
pT2b
N0
M0
T3a
N0
M0
pT3a
N0
M0
T3b
N0
M0
pT3b
N0
M0
T4a
N0
M0
pT4a
N0
M0
IIC
T4b
N0
M0
pT4b
NO
M0
III
Any T
N1-3
M0
pT1-4a
N1a
M0
pT1-4a
N2a
M0
pT1-4b
N1a
M0
pT1-4b
N2a
M0
pT1-4a
N1b
M0
pT1-4a
N2b
M0
pT14a/b
N2c
M0
IIA
IIB
IIIA
IIIB
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IIIC
IV
Any T
Any N
Any M1
pT1-4b
N1b
M0
pT1-4b
N2b
M0
Any T
N3
M0
Any T
Any N
Any M1
* Clinical staging includes microstaging of the primary melanoma and
clinical/radiologic evaluation for metastases. By convention, it should be used after
complete excision of the primary melanoma with clinical assessment for regional and
distant metastases.
Pathologic staging includes microstaging of the primary melanoma and pathologic
information about the regional lymph nodes after partial or complete
lymphadenectomy. Pathologic Stage 0 or Stage IA patients are the exception; they do
not need pathological evaluation of their lymph nodes.
There are no Stage III subgroups for clinical staging.
Used with the permission of the American Joint Committee on Cancer (AJCC),
Chicago, Illinois. The original source for this material is the AJCC Cancer Staging
Manual, Sixth Edition (2002) published by Springer-Verlag New York, Inc.
Staging Work-up:
1.
2.
Stage I-II A
Stage II B – III-IV




Baseline:
CBCD, SP, LDH, CXR
CBCD, SP, LDH
Chest X-ray
CT abdomen
CT or MRI head and Neck: with head and neck melanoma
CT pelvis: with melanoma below the waistline
CT brain or bone scan only if patient is symptomatic
CT chest, if chest X-ray is abnormal
Biopsy:
Full thickness into the subcutaneous tissue must be performed. Shave or curette
biopsies are absolutely contra-indicated, since the tumor thickness cannot be
ascertained.
Types:1. Excisional biopsies- For small tumor <1.5cm, included narrow margins 2mm.
The biopsy incision should be oriented so that it can be re-excised with
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optimal skin margins and minimal skin loss if the lesions prove to be
malignant.
2. Incisional biopsies- For large lesions or when the amount of skin removed is
critical, e.g. face, hand or feet. It should not be taken at the periphery of the
lesion.
Treatment:
Summary and Recommendations — The definitive treatment for primary cutaneous
melanoma is wide local excision. The available data, taken in aggregate, allow general
recommendations to be made regarding the optimal extent of resection based upon the
histologic depth of the melanoma.




A margin of 0.5 cm of normal skin is recommended for in situ melanomas
A 1 cm margin is recommended for melanomas <1 mm thick
A 1 cm margin is appropriate for melanomas 1-2 mm thick. Wider margins have not
been proven to result in lower local recurrence or mortality.
For thicker melanomas, appropriate trials do not exist showing the benefit of margins
widths greater than 2 cm; therefore, a 2 cm margin is recommended for melanomas
2 mm thick.
Others recommend a surgical margin of 3 cm for T3 (2.1 to 4.0 mm) or T4 (>4 mm)
primary tumors, based upon the findings of the British trial discussed above
Recommendation for ELND:
Value of ELND remains unproven, as randomized trials have not demonstrated a
statistically significant improvement in overall survival. There may be subgroups of
patients who benefit from ELND, but consensus is lacking on this issue.
The availability of lymphatic mapping with SLNB has obviated a possible role for ELND.
Stage III melanoma (node positive or intransit metastases)
a.
WLE 2-3 cm margin with skin (grafting, if necessary)
b.
Regional lymph node dissection of clinically involved lymph node
Recommendation for adjuvant IFN Alpha-2b:
Not to be given outside clinical trial, until further clear data is available.
Recommendation for ILP (Isolated limb perfusion)
Not to be done outside clinical trial
Stage IV:
a. Multiple metastases: Palliative care and symptomatic therapy
c. Solitary metastases, e.g. regional lymph node, lung, GI, or brain may be
palliated by resection in selected patients.
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Recurrent Melanoma:
1.
Local or intransit recurrent confined to extremity or treated with resection for
clear margins.
2.
Distant cutaneous or soft tissue or parenchymal recurrence can be resected, if
isolated lesions. Positive margins can be radiated.
Variants
1.
Ocular Melanoma: Diagnosis clinical – no biopsies are performed
 Ultrasound and MRI of the eye are useful in determining extent
 Treatment:a) For asymptomatic patients with small tumors (<10 mm in diameter and <2 mm in
height), we recommend observation, rather than active intervention, until
evidence of growth is documented
For patients with larger tumors and those with symptoms, we recommend active treatment
with either radiation therapy (RT) or enucleation
b) For patients who present with metastatic disease or who develop metastatic
disease after treatment of their primary tumor, the prognosis is poor. Therapy is
generally palliative and experimental
2.
Conjunctival melanoma
For patients with melanoma arising in the conjunctiva, initial management focuses upon local
control of disease. For most patients this includes wide local excision, supplemented by
cryotherapy and alcohol application.
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Reference:
1. Cosimi AB, Sohar AJ, Mihm MC. Conservative surgical management of
superficially invasive cutaneous melanoma. Cancer 1984; 53:1256.
2. Karakonsis C, Balch, Uricht M. Local recurrence in malignant melanoma. Long
term result of surgical trial (Abstract) 48th Annual Conference Symposium, 1995.
3. Buzaid, Tinocol, Ross M, et al: The role of computed tomography in the staging
of patients with local-regional metastases of melanoma. J Clin Oncol 1995; 13:
2104- 2108.
4. Varonesi U, Cascinello N: Narrow excision (ICM margin): A safe procedure for
thin cutaneous melanoma. Archives of Surgery 1991; 126 (4): 438-441.
5. Balch C, Soong S, Basolucci A, et al: Efficacy of an elective regional lymph node
dissection of 1-4 mm thick melanoma for patients 60 years or younger. Ann Surg
1996; 224: 255-263.
6. Warnom IL, Soong SJH, Krist MM, et al: Surgery as palliative treatment for
distant metastases of melanoma. Annals of Surgery 1986; 204 (2): 181-185.
7. Overette TK, Stiu MH: Surgical treatment of distant metastatic melanoma:
Medications and results of cancer. 1985; 56(5): 1222-1230.
8. Manshof W, Van Peperzeel H: Choroidal melanoma: Enucleation and
observation? A new approach. Arch Ophthalmol 1980; 98: 71-77.
9. Creagan E, Dalton R, Ahmann D, et al: Randomized surgical adjuvant clinical
trial of R-EFN Alpha 2A. JCO 1995; 13: 2776-2778.
10. Ringburg U, Andersson R Eldh J: Resection margins of 2 versus 5 cm, for
cutaneous malignant melanoma with a tumor thickness of 0.8 – 2.0 mm. Cancer
11. 1996; 77(9): 1809-1814.
12. Lienard D. Regional therapy in melanoma. 23rd ESMO Congress November
1998. Educational book 35-36.
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