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Melanoma Staging

Mitotic rate now recognized as the most powerful predictor

Vol. 4 • Issue 5 • Page 31

Dermatology/Oncology

Melanoma can be a frightening diagnosis for both patients and providers. An understanding of the most current melanoma staging guidelines issued by the American Joint Committee on Cancer (AJCC)1 is crucial for discussing prognoses with patients and developing multidisciplinary plans for appropriate treatment.

The committee recently published updates to its melanoma staging criteria, naming mitotic rate the single most powerful predictor of prognosis.

Types of Melanomas

Four major types of melanoma have been identified. They are classified as Types 1 through 4. Type 1 is superficially spreading melanoma. It is the most common type, comprising 70% of all melanomas.2 Type 2 is known as lentigo maligna, and it accounts for 10% of all melanomas. Type 3 is known as acral lentiginous melanoma, and it accounts for 2% to 8% of melanoma in white patients and 29% to 72% of melanoma in dark-skinned patients.2 Type 4 is nodular melanoma; 10% to 15% of cases are in this stage.3

Any lesion that is suspicious for melanoma should be entirely removed. Currently, the technique of choice is an excisional biopsy with a narrow 1-mm to 2-mm margin of adjacent normal-appearing skin. An extra deep saucerization biopsy is sufficient only if the lesion is flat.4

Pathology Reports

The pathology report for melanoma includes a measurement for tumor thickness called Breslow thickness. Tumor thickness is measured as the total vertical height of the melanoma, from the top of the skin to the deepest level of tumor penetrations.5 The higher the Breslow thickness value, the worse the prognosis.5

A pathology report for melanoma also includes a Clark level. This reflects tumor penetration depth into the skin.5 Although Clark levels are not included in the AJCC staging guidelines, they are important for melanomas measuring less than 1.0 mm. A Clark level of 4 or 5 indicates a worse prognosis in a thin melanoma. It is therefore usually reported with Breslow thickness.

Staging

Staging for all melanomas is labeled in a system with categories of T (primary tumor), N (regional lymph nodes) and M (distant metastasis). Each category has a grading system. Become familiar with each definition to ensure confidence while discussing pathology reports with patients.

Primary Tumor

The primary tumor is the pathologically confirmed melanoma lesion that underwent biopsy. The primary tumor thickness and ulceration are examined and determined by a dermatopathologist, who provides this information in the pathology report that aids in developing a treatment plan. Staging for localized melanomas (Stages 1 and 2) are dependent on three things: primary tumor thickness, primary tumor ulceration and primary tumor mitotic rate.1

Archive ImageA

Figure 1: Diagnosis: Melanoma in situ. Clinical Staging: Stage 0 Tis. All photos courtesy the author

Archive ImageA

Figure 2: Diagnosis: Malignant melanoma.
Pathology report: Breslow's Thickness: 0.9 mm; Clark Level III/Early IV; Mitotic Index:* 2 mm2; Ulceration: Not identified; Melanoma contained within one lymph node. Final clinical staging: T1bN1a = Stage 3.
*Skin cancers require an immediate referral for sentinel lymph node biopsy if mitotic activity is ≥ 1. This is quite different from any other type of cancer. Therefore, any patients with T1b melanomas should be recommended for a sentinel lymph node biopsy as a staging procedure. This will further assist in devising a treatment plan and follow-up regimens. 

Archive ImageA

Figure 3: Diagnosis: Metastatic melanoma. This photo shows metastases to skin after an excision 60 days prior. Prognosis of 6 months has been given. Stage IV.

Ulceration refers to tumor breakage and ulceration, allowing melanoma cells to escape and travel easily to other locations. Tumor mitosis is a measurement of how fast cells are dividing. The higher the rate of division, the higher the chance of invasion into blood or lymphatic vessels.

The AJCC recently identified mitotic rate as a powerful and independent predictor of survival. Previous melanoma staging did not include mitotic rate but now is required for melanoma staging.1

In the list below, a and b subcategories of T are assigned based on ulceration and mitotic rate measured as number of mitoses per mm2.

Tx: Primary tumor cannot be assessed

T0: No evidence of primary tumor

Tis: Melanoma in situ (Figure 1)

T1: Melanomas 1 mm or less in thickness

a. without ulceration and mitosis < 1/mm2

b. with ulceration or mitosis ≥ 1/mm2 (Figure 2)

T2: Melanomas 1.01 mm to 2.0 mm in thickness

a. without ulceration

b. with ulceration

T3: Melanomas 2.01 mm to 4.0 mm in thickness

a. without ulceration

b. with ulceration

T4: Melanomas more than 4.0 mm

a. without ulceration

b. with ulceration

Regional Lymph Nodes

Any nodal involvement requires a Stage 3 classification. Any metastases to skin, subcutaneous or distant lymph nodes is a Stage 4 classification. Patients are typically referred to an oncology center for lymph node mapping.

NX: Regional nodes cannot be assessed (for example, previously removed for another reason)

NO: No regional metastases detected

N1: 1 node

Subcategories of N1 (detected by immunohistochemical staining)

a. micrometastasis

b. macrometastasis

N2: 2 or 3 nodes

Subcategories of N2 (Figure 3)

a. micrometastasis

b. macrometastasis

c. in transit met(s)/satellite(s) without metastatic nodes

N3: 4 or more metastatic nodes, or matted nodes, or in transit met(s)/satellite(s) with metastatic node(s) (Figure 3).

Distant Metastatis

Patients with metastases in any other visceral sites and an elevated lactic acid dehydrogenase (LDH) are classified as M1c and have the worst prognosis. LDH is an enzyme that becomes elevated in response to cell damage. It is widely used as a marker to detect how well chemotherapy is working.

The overall 5-year survival rate for patients whose melanoma is detected early, before the tumor has spread to regional lymph nodes or other organs, is about 98%.1

The rate falls to 62% when the disease reaches the lymph nodes and 15% when the disease metastasizes to distant organs.1

MO: No detectable evidence of distant metastases

M1a: Metastases to skin, subcutaneous or distant lymph nodes

M1b: Metastases to lung

M1c: Metastases to all other visceral sites or distant metastases to any site combined with an elevated serum LDH. â– 

References

1. Balch CM, et al. Final Version of 2009 AJCC Melanoma Staging and Classification. J Clin Oncol. 2009;27(36):6199-6206.

2. Odomr JW, Berger T. Melanocytic nevi and neoplasms. In: Andrews Diseases of the Skin Clinical Dermatology. Philadelphia, PA: W.B. Saunders Company; 2000: 881-889.

3. McPhee S, Papadakis M. Current Medical Diagnosis & Treatment 2009. 48th Ed. New York, NY. McGraw-Hill; 2009.

4. Homsi J. Cutaneous Melanoma: Prognostic factors. Cancer Control: Journal of the Moffitt Cancer Center. 2005;12(4):223-229.

5. Seattle Cancer Care Alliance. Melanoma. Seattle Cancer Care Alliance. http://www.seattlecca.org/diseases/melanoma-facts.cfm http:/www.medscape.com/viewarticle/516206_8

Amy Gouley is a physician assistant at Rosario Skin Clinic in San Juan Islands, Wash. She is the founder of Project Happy Face, a nonprofit corporation dedicated to treating disadvantaged teenagers with acne. Gouley has completed a disclosure statement and reports no relationships related to this article.




     

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