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Prognostic Parameters of Melanoma

Dr Sampurna Roy MD

 

                                                                                                                      

 

In addition to establishing the diagnosis, it is essential to document a number of management and prognostic indicators.

 
Diagnostic Checklist:

1. Tumour location;  

2. Histological subtype;

3. Growth phase;      

4. Breslow's thickness;

5. Clark's level;         

6. Mitotic rate /mmsq;

7. Host immune response; 

8. Vascular invasion;

9. Perineural infiltration;   

10. Predominant cell type;

11.Tumour ulceration;     

12. Regression;

13. Desmoplasia;            

14. Microsatellites;

15. Surgical margin status.

 


Tumour location:

High risk site include the so called 'BANS area' of the body .

B (back),

A (posterior upper arm),

N (posterior neck),

S (scalp) and feet and genitalia.

 

Histological subtype:


I.  Superficial spreading melanoma

 
II. Nodular melanoma

 
III. Lentigo maligna melanoma

IV. Acral lentiginous melanoma

 

 

Growth phase:



Radial growth phase- 

In-situ or invasive component (microinvasive melanoma. - Clark level:  I - II.

Single or small clusters of melanocytes  are present in the papillary dermis  (< 10 cells wide).

The cells  have similar features to those in the epidermis.

The nests should not be larger than any of the epidermal nests.

Mitotic figures are not usually present. There is a prominent host lymphocytic response.

Vertical growth phase-

Clark level: III - IV.  

The tumour infiltrates as nodules of tumour cells filling the papillary dermis with or without extension into the reticular dermis. 

A dermal nest of tumour cells is larger than the largest intraepidermal nest. 

There is variation in epidermal and dermal cell cytology.

Dermal mitoses is present.

This lesion has potential for metastasis.

 

Mitotic rate:

Number of mitotic figures per square millimeter of tumour tissue is equivalent to ten high powered fields using x40 objective. 

The counts are given as an absolute number/mmsquare or as absent, low (<6/mmsq) or high.

 

Clark's Levels of Invasion:

It has been demonstrated that increasing levels of invasion are associated with diminished survival.

Level 1- Melanoma cells confined to the epidermis-  (in-situ, non invasive)- Radial growth phase

Level 2-  Invasion of the papillay dermis by melanoma cells- Homogeneous, widely spaced, small nests (less than 10 cells wide)- Radial growth phase.

Level 3- Tumour cells expand and fill the papillary dermis.

( Note: A line of subpapillary blood vessels marks the junction of the papillary and reticular dermis.)- Vertical growth phase.

Level 4- Tumour cells infiltrate the reticular dermis. - Vertical growth phase.

Level 5-  Tumour cells infiltrate the subcuaneous tissue. - Vertical growth phase.

 

Breslow's thickness:

Thickness is the most important prognostic feature.

Depth of invasion is measured in millimetres from the top of the granular layer ( ulcer base- if present) to  the deepest melanoma cell.
 

Note:

1. Involvement of adnexal structures by melanoma cells should not be included.

2. Epidermal hyperplasia should be mentioned in the  description. (The depth of invasion may be  overestimated)

3. Measurement can be difficult in the presence of regression and when a benign naevus is present.

Less than 1.0 mm - lymphnode usually
negative. (Small number of patients with thin melanoma may develop metastasis).

Greater than 4.0 mm - high risk that nodes are positive.

Host immune response:

Tumour infitrating lymphocytes are defined as lymphocytes extending between individual tumour cells.

The presence of lymphocytes correlates with improved survival.

Brisk: (++)  

I. The lymphocytes are diffusely present throughout the substance of the vertical growth phase component.

II. At the periphery lymphocytes are layered across the entire base of the tumour.

Nonbrisk : (+) 

I.  One or more foci of lymphocytes in the substance of the tumour 

II. At the periphery, focally the lymphocytes are layered at the base of the tumour.

Absent: (0) No lymphocytic reaction present.

Note:   Heavy infiltrate of plasma cells may be present. (suggestive of tumour deposits in lymphnode).

 

Regression:

Regression is defined as lymphocytic response with fibrosis, vascular telangiectasia and presence of melanophages in the dermis. 

There is destruction of melanoma cells (this is particularly important to make a distinction from the stromal response of an atypical naevus).

It has been reported that the rate of metastasis  is higher in thin melanomas with extensive regression.

 

Microsatellites:

Microsatellites are nodules of melanoma cells  (0.05 mm or more in diameter) away from the main body of the tumour by a distance of atleast 0.05 mm. 

To rule out any connection with the main mass serial sections should be undertaken.

Microsatellites are indicators of poor prognosis and are associated with increased local recurrence.

 

Vascular invasion:

Vascular invasion may be difficult to identify on haematoxylin and eosin stained slides. 

Use of an endothelial immunostain such as CD34 may help to confirm vascular structure.

 

Perineural invasion:

Infiltration of nerves by tumour cells is usually noted  in desmoplastic and neurotropic melanoma and is usually associated with high recurrence rate.

 

Ulceration:

Ulceration should not be traumatic or artifactual.

Microscopically ulceration is defined as the absence of intact epidermis overlying a portion of primary melanoma. 

It is an independent prognostic indicator particularly when it is  more than 3 mm in diameter.

Ulceration has been associated with decreased survival (less than 5 years).

 

Excision margin:

Distance of the tumour from lateral and deep excision margins should be recorded in millimetres.

 

         

 


 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)


 

 

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