If your local pathologist has very carefully processed your skin specimen and carefully determined the parameters, you will be able to find out additional information on the internet or from medical contacts around the world. A FAXed, excellently informative pathology report contains essential information on which experts can give additional opinions and advice (there are usually only a few actual glass slides which could be shipped out for other opinions). Especially important is the application of exact criteria to separate RGM & VGM in cases of thin level II, see below¹⁴. There is developing genetic information⁶. All of these parameters are considered in estimating a melanoma patient's prognosis if left untreated. If it is "bad", then various treatment measures are considered.

Predicting positive SLN: One parameter for assessing prognostic risk in a melanoma patient is "node status", and there are parameters which help to select (the old one, based on survival data [see below] indicated SLN exam was justified on all lesions 0.76mm or thicker) those at risk for node positivity...tested by sentinel lymph node or other node biopsy or dissection. Especially as to melanoma "growth phase", "vertical growth phase (some think radial growth phase...RGM... rarely if ever metastasizes¹⁷) melanoma" has the ability to metastasize (13 % of VGMs have pos. SLN). So, RGM are extremely unlikely to metastasize. This 2006 study of 682 VGM SLN cases found 88 positive. Here are their SLN triage & prediction criteria: (1) if Breslow is 2mm or less & zero mitoses per square mm, 2.1% have pos. SLN & if any mitoses per square mm, 9.8% pos SLN (those negative for TILs have the highest rate in this group); and, if (2) Breslow is thicker than 2mm, then absence of significant TILs actually infiltrating through melanoma cell clusters has a 40% SLN positivity rate while infiltration by TILs only has a 20% positivity rate¹⁷. So any VGM [criteria] with no dermal-melanoma-cell mitoses and less than 2mm thick has only a 2% likelihood of a positive sentinel node¹⁷!

On finding a positive SLN, the pathologist must be careful not to interpret small node capsule melanocytic nevi (amitotic and low Ki67) as metastatic melanoma. Likewise, it is possible that a melanoma initially diagnosed in a pathological node is a capsular nevus primary [L08-3623] if the previous history is totally negative and the patient is also currently negative for a primary melanoma of skin or mucosa.

In spite of prognosis, remember that melanoma is a malignancy infamous for NOT "playing by the rules". I personally know a man who was misdiagnosed 35 years ago and only correctly diagnosed a year later when he had bulky axillary metastasis...alive and well today. We also just had a case of a patient initially diagnosed 45 years ago...a late recurrence...who had marrow metastasis appear in 2005 [S05-15202].

Unlike most of the local "competition", our group's pathology reports on the primary skin melanoma include the following numerous parameters (basic diagnostic criteria):

1. tumor location: extremities ^B vs. trunk ^Intermediate vs. other.
   ( acral [volar & subungual], scalp, ears, and mucous membrane or immediately adjacent skin⁹)^W.

2. sex of patient (survival, men ^W vs. women ^B).

3. Clark's melanoma histogenetic types: lentigo maligna ^B, SSMM, acral lentigenous, mucosal lentigenous, verrucous, desmoplastic, nodular ^W [microscopic diagnostic criteria & other pigmented lesions].

4. Breslow thickness.

5. Clark's level.

6. mitotic rate.

7. host inflammation.

8. angiolymphatic invasion.

9. tumor ulceration (not meaning traumatic excoriation [L05-517] or artifactual "ulceration"⁶)...defined as absence of epidermis over a major portion (probably 3MM or more [L-05-517]) of the melanoma & measurements should be made¹⁶. See below.

10. surgical margin status.

11. lymp node status:we are now working up about 1-2 sentinel lymph node cases per week (our department is regularly involved in breast cancer sentinel node cases and a large experience of detailed and focused skill at lymph node dissection in search of metastatic malignancies). It is vital to not mistake a nodal nevus for metastatic melanoma...even taking care to discern a nodal nevus in a completion dissection in a case with positive sentinel node [L07-5254]!

A file on melanoma types and skin lesions which might clinically be melanoma

An overview page with link to melanoma on-line prognostic calculator

Below: B=better, W=worse.

Naked-eye (dermatologist) parameters:

• is it located on an extremity ^B (arm or leg) or non-extremity ^W?

• is it in a sun-exposed ^B or covered location ^W?

• is it small ^B or large ^W?

• is it nodular ^W or not completely nodular ^B?

• is it pigmented ^B (melanotic) or not pigmented ^W (amelanotic)?

• is it "tumor ulcerated" ^W (a scab or crust may cover the ulcer) or not ulcerated ^B? [don't misdiagnose traumatic or excoriative defects...they have hemorrhage and brightly eosinophilic fibrin exudation on the site surface...which are not really tumor-necrosis ulcerations⁶] True ulceration tends to be thick melanomas⁹.

• is the patient young ^W or old ^B?

• could it be a cutaneous metastasis from a previous melanoma (be sure to warn the pathologist if you previously had a melanoma)?

• Predicting Metastatic Potential:

  The various Clark levels, followed later by designations of radial growth or vertical growth melanoma, are a staging attempt to separate those which are highly unlikely (RGM & Clark levels I & II) to metastasize from the rest of melanomas which are more likely to metastasize. The Breslow thickness is thought to be a more reliable parameter, less subject to inter-observer variation. Warning¹³: Dr. Ackerman has collected a small group of cases of very thin melanomas which metastasized; we have seen one which was daignosed as MIS turn up later with brain mets [LMC-01-8112]...never guarantee a melanoma patient of a complete cure!

Microscopic (pathologist) parameters:

• Ulceration: true tumor ulceration seems related to "explosive" upward intra-epidermal melanoma cell scattering (whereas, the epidermis tends to bulge over non-ulcerated melanomas¹⁵). In thin melanomas (1MM or less thick), the level of invasion is more powerful prognostically than in thicker stage I-II where presence of ulceration indicates a 50% 10 year survival rate & without ulceration, a 78% survival rate.

• what is the exact thickness (the Breslow thickness³ is measured in millimeters from the granular epidermal layer to the deepest point of tumor penetration)...thinner ^B or thicker ^W? A carefully interpreted marker stain such as MART-1 can help discern vague deeper cells as well as "early" progression of cells into the next deeper Clark level [S-01-9973; S-01-9340]. There is greater inter-observer agreement on thickness than on Clark level¹².

• less than 1.0 mm, lymph nodes usually negative¹  

  • AJC TNM    pT1=  0.75 mm. or thinner (likely Clark I-II)

  • AJC TNM    pT2=  0.76-1.5 mm (likely Clark III or worse)

  • AJC TNM    pT3=  1.5-4.0 mm
    1.            pT3a= 1.5-3.0 mm
    2.            pT3b=  >3 but not more than 4 mm
  1. greater than 4.0 mm, high risk that nodes are positive¹  

     • AJC TNM    pT4=   > 4 mm. and/or invades subcutaneous fat

• what is the Clark level (I-V)...I ^B....V ^W?

is it radial growth phase (RGP/RGM) ^B or vertical growth phase (VGP/VGM) ^W?

Presence of this type of cluster and/or dermal mitosis...especially presence of any dermal mitosis makes it VGP/VGM!!!

• what is the mitotic rate^{10, 11} (number of mitotic figures per square millimeter of tumor tissue)...is it low ^B or high ^W? In Clark's study of 23 variables, 6 were independently prognostic; and the mitotic rate was the most powerful!

  • 8-year survival if zero mitoses/mm²: 95.1%

  • 8-year survival if 0.1-6.0 mitoses/mm²: 79.4%

  • 8-year survival if >6.0 mitoses/mm²: 38.2 %

• what is the Schmoeckle & Braun-Falco prognostic index¹⁰ (PI) (product of Breslow thickness x mitotic rate)...low ^B or high ^W?

• the Clark 6-parameter (with mitotic rate) prognostic model for stage I cases: if tumor is strictly radial growth phase, there is 100% 8 year survival. If  VGM.

• the Clark 4-parameter (without mitotic rate) prognostic model for stage I cases:

  Table 3. Probabilities of 10-Year Survival in Patients with Primary Cutaneous Melanoma

• Are there any dermal or subcutaneous metastatic cell clusters  within 5 cm. ^W (satellitosis)...or not ^B?

• what is the host inflammatory cell response in VGM..."brisk" ^B vs. "non-brisk" ^W?

does the host inflammation contain plasma (plasmas) ^W cells or not (few) ^B? [yes (especially if heavy ) is more likely to have gone to lymph nodes] ¹

• is there any visible venous or lymphatic embolic lumenal tumor ^W or not ^B? ["yes" is awful²]

• is there any visible perineural (neurotropism) space invasion ^W or not ^B? If so, may be (strongly recommend consideration [L07-132], NOTE HERE) a candidate for local control radiation.

• are the surgical margins free of visible tumor ^B (did the surgery seem to get all of the tumor out?) or positive ^W for tumor?

• NODES: do sentinel or other regional nodes contain ^W  metastatic cells or not ^B?

1. S100 is the most sensitive  IHC marker⁷ (but it also marks nodal dendritic cells) while HMB-45 & MART-1 are more specific; HMB-45 can have some IHC positive mononuclear cells in which the nuclei are discordantly non-melanomatous [LMC-01-6340]. Watch out for nodal nevi, present even in cases with melanoma mets, in fibrous septae & capsule & with benign cytology & lacking nucleoli [L07-5254].
2. if not, be sure to note whether the melanoma shows signs of regression⁶: papillary dermal deposition of loose, edematous collagen containing increased numbers of  melanophages & possibly ectatic vessels plus MAYBE some lichenoid vacuolar change in overlying basal keratinocytes⁸.
3. it is the number of positive nodes (met = 0.2 mm or larger tumor cell cluster) and the percentage of the node occupied by the met (not the size of the met) that is better or worse¹⁵. Therefore, watch out for nodal nevi, present even in cases with melanoma mets, in fibrous septae & capsule & with benign cytology & lacking nucleoli [L07-5254]. Node capsule nevi have a very low Ki67 proliferation of around 1% & are HMB45 negative, while both melanoma, nevus cells, & nodal dendritic cells are S100 positive, and nodal nevi & melanoma are MART-1 positive¹⁸.

• serum LDH repeatedly elevated (not just one time) is a stage independent prognostic factor for decreased survival¹⁵.

• serum albumin at or less than 3.5-4.0 is an independent prognostic factor for decreased survival in stage IV cases¹⁵.

REFERENCES: [melanoma diagnostic criteria] [skin diseases index]

1. The American J. of Dermatopathology, A. B. Ackerman, editor, 6(supplement):1-352, 1984 [EBS's office]
2. A Trial in Philadelphia, a combined reprint,  A. B. Ackerman (compiler), Dermatopathology: Practical & Conceptual, 6(3):236-250, 2000; 7(1):21-27, 2001; 7(2):165-170, 2001. [EBS's office]
3. Principles & Practice of Surg. Path. and Cytology, [3 vol. text] Silverberg, SC, 3rd Ed. 1997.
4. Prognostic factors for Cutaneous Melanoma [editorial], Wick, Mark R., AJCP, 110:713-717, 1998.
5. Prognostic Value of Tumor Infiltrating Lymphocytes in the Vertical Growth Phase of Primary Cutaneous Melanoma, Clemente, Mihm, et. al., Cancer 77:1303-10, 1996.
6. Journal of Clinical Oncology, Mihm MF (et. al.) 19(16):3635-3646, 15 Aug. 2001 [EBS's office], Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma.
7. Archives of P. & L. M., 125:1295-1306, Mihm MF (et. al.), October 2001, Malignant Melanoma, an Update.
8. Murphy GF, Dermatopathology, 1995 [textbook].
9. Maize JC, et. al., Cutaneous Pathology, 1998 [textbook, WRA's office]
10. Fitzpatrick TB (et. al.), Dermatology in General Medicine [text], vol. I, 4th Ed. (1993) Chapter 12 (Dr. Mihm, et. al.)
11. Clark WH, J. Natl. Ca. Inst. 81:1893-1904, 1989.
12. Fletcher A, et. al., J. of Pathology, 163:245-250, 1991.
13. Ackerman AB, 9th Annual (Pittsburgh) Seminar in Pathology, 4 May 2002.
14. Relevance of Vertical Growth Pattern in Thin Level II Cutaneous Superficial Spreading Melanomas, Lefevre M et. al., A. J. Surg. Path. 27(6):717-724, 2003 (an excellent case-controlled study in search of features predictive of relatively poor prognosis in thin melanomas). Abstract also in CAP Today October 2003, page 80.
15. Compton CC, et. al., Protocol for the Examination of Specimens from Patients With Malignant Melanoma of the Skin, Arch. Path. & Lab. Med. 127(10):1253-1262, Oct. 2003.
16. McKee, Calonje, & Granter, Pathology of The Skin...
17. Kruper LL, Spitz FR, Czerniecki BJ, Fraker DL, Blackwood-Chirchir A, Ming ME, Elder DE, Elenitsas R, Guerry D, Gimotty PA, "Predicting sentinel node status in AJCC stage I/II primary cutaneous melanoma" Cancer 107(10):2436-45, 15 November 2006.
18. Biddle DA, et. al., AJSP 27(5):676, 2003.

(posted 9 February 2002; latest additions 11 August 2008)