May 2007
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
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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. |
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. |
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. |
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. |
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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.
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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. Miccrosatellites 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 melanomas 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. |
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