This document discusses melanoma pathology reporting guidelines. It summarizes the key histologic parameters used to characterize melanoma subtypes and staging. There was variability in some required elements between different pathology reporting systems. The panel standardized 18 core elements and 4 additional elements when lymph nodes are present. Accurate reporting of features like tumor thickness, ulceration, mitoses and lymph node status are critical for prognosis and management.

1. BY EKTA JAJODIA

2.  Melanoma is a major public health problem in many
countries, particularly those with a large population of
fair-skinned individual
Histologic parameters of primary tumor are strongest
predictors of outcome in patients with clinically
localized primary melanoma and strongly influence
next stages of management
 Structured reporting aims to improve the
completeness and usefulness of pathology reports for
clinicians and improve decision making process for
cancer treatment

3. SUPERFICIAL SPREADING
MELANOMA
 Most common type
 Lesions have irregular borders
 Areas of regression common( seen as white areas)
 Microscopically 1. Proliferation of atypical
melanocytes
2. Nest formation and pagetoid
appearance(buckshot spread)
3. Melanin pigmentation shows
powdery appearance
4. Inflammatory infiltrate present
in band like distribution along superficial dermis

4. LENTIGO MALIGNA MELANOMA
 Typically occurs in sun exposed areas (MC on
cheek)
 Microscopically – 1. Proliferation of atypical
melanocytes(with fusiform cytology) in basal layers
of epidermis
2. Dendritic processes and
pericellular retraction – characteristic
3. Tendency for melanocytes to
grow along upper portion of hair follicles as far as the
level of sebaceous gland duct – can simulate invasion
(HUTCHISON FRECKLE)

5. ACRAL LENTIGINOUS MELANOMA
 Typically occurs on soles, palms, subungual
areas(melanotic whitlow), mucocutaneous
junction of oral and nasal cavities, and anus
 Microscopically -
1. Intraepidermal component is
similar to that seen in hutchison freckle
2. Long dendritic melanocytes are
characteristic
3. Involved epidermis is hyperplastic
4. Papillary dermis is widened and
inflammed

6. ACRAL MELANOMA

7. NODULAR MELANOMA
 Can present as a smooth nodule covered
by normal epidermis/ elevated blue-black
plaque/ polypoid ulcerated mass
 Affects all body surfaces
 Occurs in younger age group

8. NODULAR
MELANOMA
Ulcerated
nodular
melanoma
resembling
granuloma
pyogenicum

9. UNUSUAL MELANOMAS
 Desmoplastic melanoma
 Neurotropic melanoma
 Balloon cell melanoma
 Signet-ring cell melanoma
 Blue nevus-like melanoma
 Rhabdoid malignant nelanoma
 Borderline or minimal deviation melanoma
 Amelanotic melanoma

10. METHODS
 Round table meeting of representatives of 4
organisations were held to form International
Collaboration on Cancer Reporting (ICCR)
1. Royal college of pathologists (UK)(RCPath)
2. College of american pathologists (CAP)
3. Royal college of pathologists of Australia (RCPA)
4. Canadian association of pathologist
 GOAL – To produce evidence-based generic cancer
data sets/protocols for all organ-specific cancers
 PILOT PROJECT – To develop cancer data sets for
pathological reporting of melanoma, lung cancer,
prostate cancer and endometrial cancer

11.  Individual items in cancer data sets were classified
as-
- Required/core/mandatory/standard
- Recommended/non core/non mandatory/
guideline
 Required data elements – Those which are essential
for clinical management, staging and assessment of
prognosis
 Recommended data elements– those which are
clinically important and recommended for good
practice
 The panel compared the existing protocols for
cutaneous melanoma developed by RCPA, RCPath and
CAP

12. CONCORDANT DATA ELEMENTS – defined as :
1. Data elements included in all 3 reporting systems as
required/core element , and,
2. Have similar methodologies for its assessment and
reporting
MINOR DISCORDANCE – Defined as :
1. Inclusion as a required element in 2 out of 3 reporting
systems, or,
2. Included in all 3 but there were differences in their
assessment
MAJOR DISCORDANCE – Defined as :
1. Inclusion as required element in only 1 reporting
system , and ,
2. Included either as recommended/non core element or
not included in other 2 reporting systems

13. COMPARISON OF RCPA, RCPath AND CAP
PATHOLOGY REPORTING PROTOCOLS
 There were 8 concordant data elements – all
included as required/core elements
 6 elements showed minor discordance – 5 included
as required elements; 1 (melanoma subtype) included
in recommended elements
 Few parameters showed major discordance – some
included as required, some as recommended and not
included at all

14.  Eg : LYMPH NODE STATUS – Both RCPA and
RCPath did not include this element ( presumably
because LN specimen are not received at the time of
primary cutaneous biopsy)
 But in the 7th edition of AJCC, regional LN is
included as key staging parameter for cutaneous
melanoma.
 So, the review panel included this under required
elements and recommended that it should be
reported only if LN are received.
 If not received , data elements relating to LN
should not be included in pathology report

15.  Some elements were not included as
required by any reporting system, but the
panel included as core items on the basis of
sufficient evidence eg : desmoplastic
melanoma component

16.  There are 16 required/core elements and
additional 4 required elements for
specimens received with lymph nodes
 Total 18 recommended elements

17.  Important to accurately identify anatomic
site of primary melanoma
 Melanomas in head and neck area, upper
back and axial skeleton have worse prognosis
than extremity-based lesions
 RESPONSE VALUES : not provided/ specify
1. TUMOUR SITE

18.  RESPONSE VALUES- not provided/ midline/ left/
right
2. SPECIMEN LATERALITY
3. SPECIMEN TYPE
 RESPONSE VALUES –
excision/incision/punch/shave/currette/re-
excision/others
 Excision biopsy with narrow clearance margins-
most appropriate method of biopsy of a clinically
suspected melanocytic tumor

19. Incomplete biopsies may cause pathological
misdiagnosis because –
1. Partial biopsy may sample only benign part of
lesion and miss a co-existing melanoma in
heterogenous tumor
2. Lesion may regrow from residual nevocytes after
incomplete removal
 Regenerating nevi display histological features
similar to those in melanomas ( pagetoid epidermal
invasion, cytologic atypia. HMB-45 positivity, mitotic
figures). Such lesions are k/a pseudomelanomas
/recurrent nevus and are prone to over diagnosis as
melanomas

20. Nevertheless partial biopsies are performed quite
frequently in following conditions -
1. Very low suspicion of melanoma
2. Very large lesion
3. Located in cosmetically sensitive area (face /
eyes / digits)

21.  Must document relationship of both in situ and
invasive components to nearest resection margins
 For invasive component, both deep and peripheral
margin must be recorded separately
 The pathology report should document the:
(1)In situ component: peripheral margin
(2)Invasive component: peripheral margin
(3) Invasive component: deep margin
 Recorded in (mm)
4. SURGICAL MARGIN/TISSUE EDGES

22. RESPONSE VALUES – not identified/ present/
indeterminate
 In recently biopsied lesions and in cases
with only focal loss of epidermis; it is
difficult to determine whether the epidermal
deficiency is due to ulceration or to
sectioning artifact
 Absence of fibrin or granulation tissue
from areas of ulceration suggest sectioning
artifact
5. ULCERATION

23.  The number of mitotic figures can vary greatly
between different parts of a tumor
 It is recommended to determine number of high-
power fields that equates to 1mm²
 In the seventh edition of the AJCC melanoma
staging system, the recommended method is to find
an area in the dermis with obvious mitotic activity
(“hot spot”)
 Begin counting in this area, then count in the
adjacent nonoverlapping high-power fields in area
1mm²
6. MITOTIC COUNT

24.  If no hot spot identified and mitotic figures are
sparse and randomly scattered, begin counting in a
field containing a mitosis, then count in adjacent
nonoverlapping high-power fields until a 1mm² area
is assessed
 Number of mitotic figures should be listed as a
whole number/mm2
 If no mitotic figures identified, the mitotic count
may be recorded “none identified” or “0/mm²”
 No additional sections should be cut and
examined for the purpose of determining the mitotic
rate( in case no mitotic figures are identified on the
initial, routinely examined sections)

25.  Measured from top of granular layer of epidermis
(or, if the surface is ulcerated, from base of ulcer) to
the deepest invasive tumour cell
 Can only be evaluated accurately in sections cut
perpendicular to epidermal surface
 Otherwise, a note should be included
indicating that “the section is cut tangentially and
an accurate Breslow thickness cannot be provided.”
7. BRESLOW THICKNESS

26.  Cannot be determined if superficial
biopsy transects a melanoma and includes
only its superficial portion
 In such instances, the pathologist can
only report the melanoma to be “at
least” a certain thickness

27.  Vascular invasion is identified by
demonstration of melanoma cells within the
lumina of blood vessels or lymphatics or
both
 Regarded as a marker of poor prognosis
 RESPONSE VALUES – not identified/
present/indeterminate
8. LYMPHOVASCULAR INVASION

28.  Identified by presence of –
-melanoma cells around nerve sheaths (perineural
invasion), or
-within nerves (intraneural invasion) , or
-tumor itself may form neuroid structures (termed
“neural transformation”)
 Infiltration along nerve sheaths (or occasionally
within the endoneurium) may be associated with an
increased local recurrence rate
 Neurotropism is common in DM (desmoplastic
neurotropic melanoma)
 RESPONSE VALUES – not identified/present/
indeterminate
9. NEUROTROPISM

29.  Satellites (micro- or macro-) is any nest of
metastatic tumor cells discontinuous from
primary tumor (not just separated by fibrosis
or inflammation)
Should be within 2cm of primary tumor
 In-transit metastases – tumor nests
beyond 2cm of primary tumor but not
beyond regional lymph nodes
 RESPONSE VALUES – not identified/
present/indeterminate
.
10. SATELLITES

30.  Presence of a melanoma satellite
metastasis at a peripheral excision margin
may be an indication for reexcision
 It implies that there may be further
melanoma in the skin beyond the visible
margins
 RESPONSE VALUES – cannot be
assessed/not involved by satellite/involved
by satellite
11. SATELLITES: MARGINS

31. 4yjkrdf
 Rare subtype of melanoma characterized by
malignant spindle cells separated by prominent
fibrocollagenous or fibromyxoid stroma.
 2 types- 1. Pure DM : entirely or almost entirely
desmoplastic (≥ 90% of tumor shows desmoplasia)
2. Mixed DM : mixed desmoplastic and
nondesmoplastic component (DM component > 10%
and < 90% of tumor )
 In pure DM –
- Survival rate is better
- Regional lymph node metastasis is lesser
12. DESMOPLASTIC MELANOMA
COMPONENT

32.  If lymph nodes NOT received, this element should
NOT be reported
 If lymph nodes submitted, the following must be
recorded:
1. Number of sentinel nodes examined
2. Number of positive sentinel nodes
3. Total number of nodes examined (sentinel and non
sentinel)
4. Total number of positive nodes examined (sentinel
and non sentinel)
13. LYMPH NODES

33. Pitfalls in the microscopic examination of SLNs :
distinguishing nodal nevus cells from a melanoma
metastasis
NODAL NEVI MELANOMA METS
1. Usually located in fibrous
capsule and trabeculae
2. c/o small bland cells
3. Devoid of mitotic activity
4. IHC - strong diffuse
positivity for S-100 and
Melan-A with minimal
staining for HMB-45
5. Low (<2%) Ki-67
proliferative index
1. Located in subcapsular sinus
and parenchyma
2. Large atypical cells with
prominent nucleoli
3. Mitotic activity present
4. HMB-45 positivity
5. Ki-67 >2%

34.  T2, T3 and T4 is defined by tumor thickness
and ulceration
 T1 also includes dermal mitotic rate
 Clark level IV or V is referred to by the AJCC
as a tertiary criterion for T1b in cases with no
ulceration and “if mitotic rate cannot be
determined”
14. AJCC Staging—Primary Tumor T
Category
(Seventh Edition)

35. Classification Thickness (mm) Ulceration Status/Mitoses
T
Tis NA NA
T1 ≤ 1.00 a: Without ulceration and
mitosis < 1/mm
2
b: With ulceration or
mitoses ≥ 1/mm
2
T2 1.01-2.00 a: Without ulceration
b: With ulceration
T3 2.01-4.00 a: Without ulceration
b: With ulceration
T4 > 4.00 a: Without ulceration
b: With ulceration
TNM Staging Categories for Cutaneous Melanoma

36.  When insufficient information is available to determine
the N staging subcategory these should be recorded with an
“x” (ie, Nx)
 N1 and N2 categories remain for microscopic and
macroscopic nodal disease, respectively (with SLN biopsy
recommended for pathologic staging)
 M staging is determined both by site of distant metastases
and serum lactate dehydrogenase
 Patients with regionally isolated metastasis from an
unknown primary site should be categorized as stage III
rather than stage IV
15. AJCC STAGING—REGIONAL LYMPH NODES N
CATEGORY (SEVENTH EDITION)

37. N No. of Metastatic Nodes Nodal Metastatic Burden
N0 0 NA
N1 1 a: Micrometastasis
b: Macrometastasis
N2 2-3 a: Micrometastasis
b: Macrometastasis
c: In transit
metastases/satellites
without metastatic nodes
N3 4+ metastatic nodes, or
matted nodes, or in
transit
metastases/satellites
with metastatic nodes

38. M Site Serum LDH
M0 No distant metastases NA
M1a Distant skin,
subcutaneous, or nodal
metastases
Normal
M1b Lung metastases Normal
M1c All other visceral
metastases
Normal
Any distant metastasis Elevated
 Micrometastases are diagnosed after sentinel lymph node
biopsy.
 Macrometastases are defined as clinically detectable nodal
metastases confirmed pathologically.

39. Differences Between the 6th Edition (2002) and the Recommended
7th Edition (2009) of the Melanoma Staging System
FACTOR SIXTH EDITION SEVENTH EDITION COMMENTS
MITOTIC
RATE / MM2
Immunoc
hemical
detection of
nodal
metastases
0.2 mm
threshold of
defined N+
NOT USED
Not included
implied
USED FOR
CATEGORIZING T1
MELANOMA
Included
No lower
threshold of
staging N+ disease
Mitosis >1/mm2 defines t1b
melanoma
Must include at least one
melanoma-associated
marker (eg, HMB-45, Melan-
A, MART-1) unless diagnostic
cellular morphology is
present
Isolated tumor cells or
tumor deposits < 0.1 mm
meeting the criteria for
histologic or
immunohistochemical
detection of melanoma
should be scored as N+

40. 1. SPECIMEN DESCRIPTION
2. SPECIMEN ORIENTATION – Information
received from surgeon regarding orientation
by marking sutures or clips
Specify/not provided
3. SPECIMEN DIMENSIONS – given in
numeric(mm)
length/width/depth
4. MACROSCOPIC PRIMARY LESION
DIMENSION – given in numeric(mm)
length/width/depth(optional)/indeterminate

41. 5. MACROSCOPIC PRIMARY LESION DESCRIPTION –
should include shape, color, border, contour, e/o
ulceration and proximity to resected margins
6. BLOCK IDENTIFICATION KEY – indicates the nature
and origin of tissue
7. OTHER LESIONS – not identified/present
8. MACROSCOPIC DESCRIPTION OF OTHER LESIONS
– should include shape, color, border, contour, e/o
ulceration, proximity to resected margins and
proximity to primary lesion
9. ASSOCIATED MELANOCYTIC LESION – not
identified/present(describe)

42. 9. MELANOMA SUBTYPE
A. Superficial spreading melanoma
B. Nodular melanoma
C. Lentigo maligna melanoma
D. Acral-lentiginous melanoma
E. Desmoplastic melanoma
F. Melanoma arising from blue nevus
G. Melanoma arising in giant congenital nevus
H. Melanoma of childhood
I. Naevoid melanoma
J. Persistent melanoma
K. Melanoma, not otherwise specified
L. Other(specify)

43.  Molecular genetic evidence suggests there are
subgroups of melanoma that are associated with specific
genetic alterations
 Mutations identified in melanomas are BRAF (50%),
NRAS (15-20%), KIT (2%), and GNAQ/GNA11 (50% of uveal
melanomas)
Melanomas associated with lentigo maligna
melanomas commonly have NRAS mutation
 Superficial spreading melanomas often have BRAF
mutations
KIT mutated melanomas most often involve acral (acral
lentiginous melanoma) and mucosal sites
 Nevertheless, the degree of accuracy of mutation
status for predicting the melanoma subtype is not
sufficient to replace mutation testing for the purposes of
patient care

44.  Extent of ulceration (measured either
as diameter or percentage of tumor
width)
 Prognostically more significant than
mere presence of ulceration
10. EXTENT OF ULCERATION

45. 11. CLARK LEVEL
LEVEL CRITERIA
I Confined to epidermis
ll Infiltrates butdoes not fill
papillary dermis
lll Fills/expands the papillary
dermis
lV Infiltrates into reticular
dermis
V Infiltrates into
subcutaneous fat

46.  Clark level IV or V invasion is referred to as
tertiary criterion for T1b in cases with no
ulceration and “if mitotic rate cannot be
determined”
 May provide useful prognostic information
if accurate Breslow thickness cannot be
determined

47. TUMOUR INFILTRATING
LYMPHOCYTES(TIL)
EARLY REGRESSION
 Regression is immune mediated phenomenon
wherein cytotoxic lymphocytes eliminate
malignant melanocytes
 Results in grey-white areas among pigmented
areas (due to fibrosis and infiltration of
melanophages)
 Categorized into 3 temporal stages: early,
intermediate, and late
 Early regression is signified by the presence
of TILs

48.  RESPONSE VALUES – not
identified/brisk/non brisk
 Presence of “brisk” or dense TILs is
associated with a more favorable prognosis

49.  Result in partial or complete loss of
melanoma
 Characterized by immature (intermediate)
and mature (late) dermal fibrosis
 Presence of melanophages and effacement
of the rete architecture
 RESPONSE VALUES – not identified/present/
indeterminate
TUMOR REGRESSION
( INTERMEDIATE AND LATE)

50. Prognostic significance of it is
controversial
Some studies report that it is associated
with a worse prognosis whereas others report
that it is associated with a more favorable
outcome
 WHO reports that complete regression
(disappearance of all melanocytes) is
associated with metastatic disease (thus a
bad prognostic sign)

51. Regression at a peripheral excision margin is
an indication for reexcision
 It implies there may be further melanoma in
skin beyond visible margins
 RESPONSE VALUES – cannot be
assessed/not involved by regression/involved
by regression
TUMOR REGRESSION
( INTERMEDIATE AND LATE): MARGINS

52. MELANOMA WITH PROMINENT
REGRESSION

53.  The grey pigmentation is due to heavy infiltrates
of melanophages within a fibrotic papillary dermis
Complete regression of melanoma

54. SENTINAL LYMPH NODE
 If submitted SLNs contain metastatic
melanoma, pathology report should
document:
(a)location of the tumor within the lymph
node (subcapsular,intraparenchymal, or
both)
(b) maximum single dimension of the largest
discrete metastasis
(c)presence or absence of extranodal extension

55. SLN parameters predictive of non-SLN status and
survival include –
1. Size of metastases
2. Tumor penetrative depth/maximal subcapsular
depth - defined as maximum distance of melanoma
cells from nearest inner margin of lymph node
capsule)
3. Location of tumor deposits in SLN (small number of
tumor cells in subcapsular area – good prognosis and
less chances of non-SLN metastasis/ large number of
tumor cells in central part- worse prognosis)
4. Percentage cross-sectional area of the SLN that is
involved
5. Presence of extracapsular spread

56. Prognostic factor Most favourable when
 Breslow thickness Thin (<1.51 mm)
 Histology Superficial spreading
melanoma
 Age Young
 Sex Female
 Body site Not on the trunk,
hands, feet
 Ulceration Absent
 Mitotic index Low
Prognostic indicators for melanoma

57.  The pathology report is critical in determining
management of patients with primary cutaneous
melanoma.
 Melanoma patients with suboptimal pathology
reports may be staged inadequately and managed
poorly
 In addition, structured pathology report facilitates
efficient extraction of information for registries, data
collection, and research purposes
 It by no means restricts pathologist to documenting
only features mentioned in protocol; all structured
pathology reports include the facility for free text
comments
CONCLUSION

58.  Molecular pathology mutation testing for
BRAF, NRAS, KIT, and other mutations has
become common in many melanoma treatment
centers
 Presently, routine mutation testing is
recommended only in patients with inoperable
AJCC stage III or stage IV disease (and will
therefore usually not be performed at the time
of diagnosis of primary cutaneous melanoma)
Mutation testing is also not recommended in
the ICCR protocol

62. 1. A. Scolyer Richard et al. Data Set for Pathology
Reporting of Cutaneous Invasive Melanoma
Recommendations From the International
Collaboration on Cancer Reporting (ICCR). Am J
Surg Pathol Volume 37, Number 12, December 2013
2. WHO skin tumors
3. ICCR –melanoma- bookmarked-guide-1st edition
4. Rosai and Ackerman’s surgical pathology ; 10th
edition
REFERENCES