Modern Pathology

https://doi.org/10.1038/s41379-019-0402-x

LONG COURSE ARTICLE

Melanoma pathology reporting and staging

1,2,3
Richard A. Scolyer ●
Robert V. Rawson1,2,3 Jeffrey E. Gershenwald4 Peter M. Ferguson1,2,3 Victor G. Prieto4
● ● ●

Received: 24 October 2019 / Accepted: 24 October 2019

© The Author(s), under exclusive licence to United States & Canadian Academy of Pathology 2019

Abstract
The pathological diagnosis of melanoma can be challenging. The provision of an appropriate biopsy and pertinent history
can assist in establishing an accurate diagnosis and reliable estimate of prognosis. In their reports, pathologists should
document both the criteria on which the diagnosis was based as well as important prognostic parameters. For melanoma,
such prognostic parameters include tumor thickness, ulceration, mitotic rate, lymphovascular invasion, neurotropism, and
tumor-infiltrating lymphocytes. Disease staging is important for risk stratifying melanoma patients into prognostic groups
and patient management recommendations are often stage based. The 8th edition American Joint Committee on Cancer
(AJCC) Melanoma Staging System was implemented in 2018 and several important changes were made. Tumor thickness
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and ulceration remain the key T category criteria. T1b melanomas were redefined as either ulcerated melanomas <1.0 mm
thick or nonulcerated melanomas 0.8–1.0 mm thick. Although mitotic rate was removed as a T category criterion in the 8th
edition, it remains a very important prognostic factor and should continue to be documented in primary melanoma pathology
reports. It was also recommended in the 8th edition that tumor thickness be recorded to the nearest 0.1 mm (rather than the
nearest 0.01 mm). In the future, incorporation of additional prognostic parameters beyond those utilized in the current
version of the staging system into (web based) prognostic models/clinical tools will likely facilitate more personalized
prognostic estimates. Evaluation of molecular markers of prognosis is an active area of current research; however, additional
data are needed before it would be appropriate to recommend use of such tests in routine clinical practice.

Introduction site such as the width of excision margins and the role of
sentinel lymph node (SLN) biopsy as well as recommen-
One of the most important challenges clinicians face is to dations for the frequency and duration of clinical follow-up
estimate the risk of metastasis and death for any cancer. [1]. It has recently been demonstrated that targeted and
This is important firstly, because patients want to know immune therapies, when administered in an adjuvant setting
what is likely to happen to them and secondly, because for stage III melanoma, are associated with a 50%
management recommendations are principally based upon improvement in relapse-free survival [2–4]. It is therefore
this risk. In melanoma, these include recommendations more important than ever that patients not only receive an
related to the definitive management of the primary tumor accurate diagnosis but also an accurate estimate of prog-
nosis in order to select the correct therapy.
If melanoma is detected when it is at an early clinical
stage of disease, diagnosed accurately and treated appro-
* Richard A. Scolyer priately, it is associated with an excellent prognosis (10-year
[email protected] survival of 98% for T1a melanoma) [5]. Prior to 2009, there
1 were no effective systemic drug therapies for patients with
Melanoma Institute Australia, The University of Sydney,
Sydney, NSW, Australia advanced melanoma which at that time had a 25% 1-year
2 survival rate [6]. Underpinned by improved understanding
Sydney Medical School, The University of Sydney,
Sydney, NSW, Australia of the molecular basis of melanoma and regulation of
3 immune system [7], new effective targeted and
Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred
Hospital & NSW Health Pathology, Camperdown, NSW 2050, immune therapies have transformed the management of
Australia patients with widespread melanoma metastases. Indeed, in
4
University of Texas, MD Anderson Cancer Center, Houston, TX 2019, 1-year survival rates of ~75% have been reported in
77030, USA American Joint Committee on Cancer (AJCC) stage IV
 R. A. Scolyer et al.

melanoma patients treated with targeted or immune thera- Table 1 A synoptic or structured pathology report for primary
cutaneous melanoma
pies [8, 9].
Pathologic feature Example

Site Right upper leg

What pathologists need from clinicians to Diagnosis Melanoma, dermal
accurately diagnose end stage melanoma invasive
Breslow thickness 2.3 mm
Provision of an appropriate biopsy and pertinent clinical Ulceration (diameter in mm) Present (1.1 mm)
history are keys to the accurate diagnosis and prognostica- Dermal mitotic rate (per mm2) 8
tion of melanoma. Unless there are clinical reasons to do
Melanoma subtype Superficial spreading/
otherwise, it is usually recommended that an excision low CSD [43]
biopsy be performed for diagnosing lesions that are clini- Vascular or lymphatic invasion Absent
cally suspected to be melanoma [10]. Partial biopsies, such Neurotropism Absent
as shave and particularly punch biopsies, that do not include Desmoplastic melanoma component (% of Absent
the entire lesion, have been associated with an increased dermal invasive tumor, if present)
risk of misdiagnosis [11, 12]. Pertinent clinical information TILs
that assists pathologists when interpreting pigmented Distribution Focal
lesions includes the age of the patient and site of the lesion. Density Dense
In certain circumstances, such as following trauma, prior Microsatellites Absent
biopsy, or even biopsies taken during pregnancy, some Regression:
benign melanocytic tumors can display histologic features Intermediate (angiofibroplasia ± TILs), if Absent
that are usually associated with melanomas occurring in present
other settings [13]. Therefore, such lesions are at risk at Late (fibrosis and loss of rete ridges) Absent
being overdiagnosed as melanoma if the pathologist is not Predominant cell type Epithelioid
aware of the clinical scenario. The duration for which the Associated nevus Nil
lesion has been present and any history of recent change Solar elastosis Moderate (2+)
together with the clinical diagnosis or differential diagnosis Margins of excision
may also be of assistance to the pathologist when inter-
Invasive component—nearest 3.5 mm
preting the biopsy. Despite widespread knowledge of the peripheral margin
importance of the provision of pertinent clinical In situ component—nearest 7.6 mm
information on pathology request forms, and recommen- peripheral margin
dations in clinical practice guidelines [13], in one recent Deep margin 4.1 mm
large study, no useful clinical information whatsoever was
TILs tumor-infiltrating lymphocytes, CSD cumulative sun damage
provided in 46% of melanoma pathology request/requisition
forms (n = 1200, de Menezes and Mar unpublished data).
When there is a history of focal change within a preexisting synoptic or structured reporting format can facilitate this
lesion, it is critically important that the pathologist examines (Table 1) [15–17]. The prognosis for patients with clinically
such foci very carefully since they may represent early localized primary melanoma is principally dependent on the
melanoma arising within a preexisting nevus or other lesion. tumor thickness, which is measured as described by Bre-
Use of the so-called punch scoring technique has recently slow [18]. Other important prognostic features for primary
been demonstrated to represent a helpful way to melanoma include ulceration [19], mitotic rate [20], lym-
identify and direct pathologists to such areas of focal phovascular invasion, tumor-infiltrating lymphocytes (TILs)
change, ensuring they are carefully evaluated and can [21], melanoma subtype (e.g. desmoplastic melanoma is
facilitate melanoma diagnosis of clinically suspicious less frequently associated with nodal metastasis and has a
lesions [14]. more favorable prognosis [22, 23]), as well as patient
characteristics such as age, gender, and anatomical site of
the tumor (young patient age, female gender and melanoma
Melanoma pathology report arising on the extremities are each associated with a more
favorable prognosis).
The melanoma pathology report should include doc- It is important that synoptic reporting formats are
umentation of the features relied upon to establish a diag- reviewed and updated periodically to reflect contemporary
nosis of melanoma as well as features that are important for knowledge. Although new prognostic markers are
the prognosis and management of the patient. The use of a reported on a regular basis, many require independent
Melanoma pathology reporting and staging

validation in larger data sets before it would be appropriate locoregional metastases, and stage IV for those patients
to recommend their routine use and inclusion in pathology with distant metastases.
reports.

AJCC T category criteria

8th edition AJCC melanoma staging system
The T category is divided into T1–T4 based on the tumor
For several decades, the established benchmark for risk thickness. Each category is subdivided into a and b on the
stratification for patients into prognostic groups has been the basis of the absence or presence of ulceration, respectively.
AJCC staging system. This is updated periodically and the In addition, nonulcerated tumors 0.8–1 mm thick are cate-
most recent (8th) edition became operational in 2018 [24]. gorized at T1b tumors (Table 2).
The staging system is also important for eligibility, strati- When reporting tumor thickness, it is recommended in
fication, and analysis of clinical trials. The 8th edition the 8th edition that the thickness be recorded to the nearest
AJCC Melanoma Staging System is underpinned by ana- 0.1 mm. The principal reason for this is because it is gen-
lysis of more than 46,000 stage I–III melanoma patients erally impractical and imprecise to measure to the nearest
who were diagnosed and managed since 1998, a period after 100th of a millimeter for tumors > 1 mm thick. Whilst for
which SLN biopsy was routinely used in most melanoma thinner tumors they may be measured to the nearest 100th
treatments centers worldwide. In November 2015, the of a millimeter, it is recommended that they be rounded up
International Melanoma Pathology Study Group (IMPSG) or down to the nearest 0.1 mm for recording in the pathol-
met at the University of California, San Francisco, and ogy report to be used in the AJCC scheme. The 8th edition
considered, discussed, debated, and voted upon various provides clear guidance for the application of rounding up
pathology staging issues. The consensus recommendations and down. For example, any melanoma measuring
from the IMPSG were subsequently taken to the AJCC 0.75–0.84 mm in thickness would be rounded to 0.8 mm
melanoma expert panel and were incorporated into the 8th and recorded as a T1b melanoma. Similarly, a melanoma
edition Staging System. measuring 1.04 mm thick would be recorded as 1.0 mm in
Similar to the staging of other cancers, melanoma staging the pathology report and designated as T1b for staging.
is divided into four stages with stages I and II for clinically Data from a number of large independent data
localized primary melanoma, stage III for patients with sets supported the selection of 0.8 mm as an appropriate

Table 2 Definition of primary

T Category Thickness Ulceration status
tumor (T)
TX: primary tumor thickness cannot be assessed (e.g., Not applicable Not applicable
fragmented biopsy)
T0: no evidence of primary tumor (e.g., unknown primary Not applicable Not applicable
or completely regressed primary melanoma)
Tis (melanoma in situ) Not applicable Not applicable
T1 ≤1.0 mm Unknown or unspecified
T1a <0.8 mm Without ulceration
T1b <0.8 mm With ulceration
0.8–1.0 mm With or without ulceration
T2 >1.0–2.0 mm Unknown or unspecified
T2a >1.0–2.0 mm Without ulceration
T2b >1.0–2.0 mm With ulceration
T3 >2.0–4.0 mm Unknown or unspecified
T3a >2.0–4.0 mm Without ulceration
T3b >2.0–4.0 mm With ulceration
T4 >4.0 mm Unknown or unspecified
T4a >4.0 mm Without ulceration
T4b >4.0 mm With ulceration
Adapted with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The
original and primary source for this information is the AJCC Cancer Staging Manual, 8th edition (2017)
published by Springer International Publishing
Modified from ref. [24]
 R. A. Scolyer et al.

presents with nodal metastasis and no known primary

melanoma. Tis is used to designate melanoma in situ. TX is
used when tumor thickness cannot be determined. The latter
might occur because of perpendicular sectioning in a
curettage-type or fragmented specimen (see also next
section).

Challenges with measuring tumor thickness

Pathologists may be faced with a number of challenges

when measuring tumor thickness. Occasionally, it can be
difficult to determine whether atypical nevoid cells within
the dermis represent maturing, benign-appearing melanoma
cells or part of a preexisting nevus. In such instances, it may
Fig. 1 Melanoma with multiple mitotic figures. High mitotic rate is an be problematic to determine the deepest dermal cell to
independent predictor of adverse outcome in melanoma patients measure the tumor thickness. Comparison of the cytological
features to both the clearly invasive component as well as
cut-off point for subcategorizing nonulcerated T1 melano- any associated benign nevus can assist. Nevertheless, this
mas [25–27]. usually requires careful and reasoned judgment.
Mitotic rate was removed as a T1 subcategory criterion If the specimen is received as two separate fragments
in the 8th edition. This represents a change from the 7th (usually two shaves or one punch and a shave), the tumor
edition. Nevertheless, mitotic rate represents a very strong thickness should not be provided as the addition of the
independent predictor of outcome across its dynamic range thickness in each fragment, since it is not possible to
in clinically localized primary melanoma patients and determine how the fragments spatially relate to each other.
should be recorded in all melanoma pathology reports When there is deep periadnexal extension of melanoma
(Fig. 1). There were a number of reasons for removing as a “tongue” of tumor that extends much more deeply than
mitotic rate as a staging parameter in the 8th edition. the main, more superficial part of the dermal invasive
Importantly, using an international database that informed melanoma, it is not recommended that such extension be
the 8th edition, in T1 analyses that included tumor thickness included in the measurement of tumor thickness, unless this
stratified by <0.8 mm versus ≥ 0.8 mm −1.0 mm, presence represents the only focus on invasion. Recently published
or absence of ulceration, and mitotic rate as a dichotomous data by Dodds et al. [29] provided evidence based on out-
variable, the latter factor, mitotic rate, was no longer sig- come data that periadnexal extension should not be included
nificant [5]. Concern has also been expressed that pathol- in tumor thickness measurements. When periadnexal mel-
ogists may be looking more carefully for a single mitotic anoma represents the only focus of invasion, tumor thick-
figure following its introduction as a staging parameter in ness should be measured from the middle of the adnexal
the 7th edition, which may have resulted in fewer mela- structure from where it has likely risen.
nomas being identified with zero mitotic figures than were Microsatellites or foci of neurotropism or lymphovas-
identified in the data sets upon which its prognostic sig- cular invasion should not be included in the measurement of
nificance was originally assessed. Furthermore, it was on the Breslow thickness.
occasion erroneously stated that mitotic rate was only
prognostically significant as a dichotomous variable (less
than or greater than or equal to 1/mm2) when in fact it is Ulceration
strongly prognostic across its full dynamic range [5]. It is
likely that mitotic rate will be a key prognostic parameter in The presence of ulceration is an adverse prognostic para-
prognostic calculators currently being developed. meter in primary cutaneous melanoma. It is important to
Mitotic rate should be assessed using the “hot spot” distinguish true ulceration from separation of the epidermis
method in all T1–T4 primary melanomas [28]. This method from the underlying tumor as a result of sectioning or other
has been shown to have excellent interobserver reproduci- artefactual disruption. The presence of a tissue reaction to
bility amongst pathologists with varying experiences in the loss of epidermis with fibrin and acute inflammation are
assessment of melanomas. important histopathologic hallmarks of true ulceration
In the 8th edition, T0 designates patients in whom no (Fig. 2). Not only is the presence or absence of ulceration
evidence of a primary tumor is identified, e.g., a patient who important prognostically but also the width of ulceration is
Melanoma pathology reporting and staging

Fig. 3 a Desmoplastic melanoma of pure subtype involving severely

Fig. 2 a, b Ulcerated nodular melanoma. A fibrinopurulent exudate is
sun damaged skin. b A focus of neurotropism (intraneural invasion) is
present on the surface
present

strongly associated with outcome. Patients with more

extensively ulcerated melanomas have a poorer prognosis melanoma. It typically occurs in the head and neck region in
than minimally ulcerated tumors [19]. severely sun-damaged skin of elderly patients. It may be
associated with a lentigo maligna in the overlying epidermis
or an atypical epidermal melanocytic proliferation. In most
Melanoma subtype studies, other melanoma subtypes (apart from desmoplastic
melanoma) are not independently associated with
Desmoplastic melanoma is an uncommon subtype of mel- prognosis.
anoma (1–4%) characterized by the presence of spindled
melanoma cells within fibrosclerotic stroma (Fig. 3a). It
often has a subtle appearance both clinical and pathological Neurotropism
and might not be diagnosed until it is at an advanced clinical
stage. Compared with other melanoma subtypes, it is The two major forms of neurotropism are perineural inva-
associated with less frequent nodal metastasis, better overall sion and intraneural invasion (Fig. 3b). Neurotropism is
survival and better response rates to immune therapy [22, most commonly seen associated with desmoplastic mela-
23, 30]. This is particularly true for the “pure” subtype of noma where it is termed “desmoplastic neurotropic mela-
desmoplastic melanoma, where the desmoplastic compo- noma.” However, neurotropism occasionally also occurs in
nent (malignant spindle cells separated by fibroblastic non-desmoplastic melanoma. Neurotropic melanoma may
stroma often with accompanying myxoid change and lym- extend well beyond on the edge of the primary tumor. For
phoid aggregates) accounts for >90% of the invasive this reason, it is associated with an increased risk of local
 R. A. Scolyer et al.

recurrence [31]. At some, but not all, melanoma treatment

centers, the presence of neurotropism instigates the appli-
cation of postoperative radiotherapy to reduce the risk of
local occurrence [31].

Tumor-infiltrating lymphocytes

The presence of TILs signifies that the host immune system

recognizes and reacts to the tumor. As such, it is a favorable
prognostic parameter in primary melanoma. Various grad-
ing schemes have been described for the quantification of
TILs [32] in melanoma. In general, the more TILs that are
present, the better the prognosis is for the patient [21].

Fig. 4 Lymphatic invasion by melanoma. The melanoma cells have

Regression been stained positively with MelanA/MART1 (red chromogen) whilst
the lymphatic endothelium is stained with the lymphatic marker D2-40
(brown chromogen)
As is commonly observed clinically in primary melanomas,
the immune system can react against a primary melanoma and
result in loss of part or all of the tumor. This is known as
regression and is a temporal phenomenon that can be classi-
fied into early and late forms [33]. Early regression is char-
acterized by immature fibrous tissue and increased
vascularity, usually accompanied by a chronic inflammatory
cell infiltrate. Late regression is characterized by the presence
of mature dermal fibrosis usually with accompanying loss of
rete ridges in the overlying epidermis. In some studies,
regression has been an adverse prognostic parameter, whilst in
others it has been a favorable prognostic parameter [34, 35].

Lymphovascular invasion

The presence of tumor cells within lymphatics (or blood

Fig. 5 Microsatellite metastasis identified in a primary melanoma wide
vessels) at or near the primary melanoma site is an adverse excision specimen
prognostic parameter in melanoma. The use of Immuno-
histochemical staining for lymphatic and/or vascular mar-
kers (such as D2-40 and CD31) accompanied by markers of
melanoma cells can be useful for identifying and high- when considering a diagnosis of the presence of micro-
lighting lymphovascular invasion (Fig. 4). satellites, it is often prudent to examine additional levels of
the block of tissue to ensure that the microsatellite is indeed
discontinuous from the primary tumor.
Microsatellites

In the 8th edition, the definition of microsatellites was AJCC N category

revised. It is defined as a microscopic metastasis adjacent or
deep to a primary tumor site identified on pathological There are three criteria that define the N category in the 8th
examination. It must be discontinuous from the primary and edition:
separate by normal stroma, without fibrosis or inflammation
(Fig. 5). The previous minimum size and distance from the (1) the presence of clinically occult regional lymph node
primary tumor that formed part of the 7th edition definition metastases identified by sentinel lymph node (SLN)
are not applicable in the 8th edition. It is recommended that biopsy;
Melanoma pathology reporting and staging

Table 3 Definition of regional lymph node (N)

Extent of regional lymph node and/or lymphatic metastasis
N Category Number of tumor-involved regional lymph node Presence of in-transit, satellite,
and/or microsatellite metastases

NX Regional nodes not assessed (e.g., SLN biopsy not performed, regional nodes No
previously removed for another reason)
Exception: pathological N category is not required for T1 melanomas, use cN, if
regional lymph nodes not assessed for patient with T1 melanoma
N0 No regional metastases detected No
N1 One tumor-involved node or any number of in-transit, satellite, and/or microsatellite
metastases with no tumor-involved nodes
N1a One clinically occult (i.e., detected by SLN biopsy) No
N1b One clinically detected No
N1c No regional lymph node disease Yes
N2 Two or three tumor-involved nodes or any number of in-transit, satellite, and/or
microsatellite metastases with one tumor-involved node
N2a Two or three clinically occult (i.e., detected by SLN biopsy) No
N2b Two or three, at least one of which was clinically detected No
N2c One clinically occult or clinically detected Yes
N3 Four or more tumor-involved nodes or any number of in-transit, satellite, and/or
microsatellite metastases with two or more tumor-involved nodes, or any number of
matted nodes without or with in-transit, satellite, and/or microsatellite metastases
N3a Four or more clinically occult (i.e., detected by SLN biopsy) No
N3b Four or more, at least one of which was clinically detected, or presence of any number No
of matted nodes
N3c Two or more clinically occult or clinically detected and/or presence of any number of Yes
matted nodes
Adapted with permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original and primary source for this
information is the AJCC Cancer Staging Manual, 8th edition (2017) published by Springer International Publishing
Modified from ref. [24]

(2) clinically detected regional lymph nodes (detected specific survival ranges from 88% for stage IIIA to 24% for
either via by physical examination or on radiological stage IIID melanoma [5].
imaging); and
(3) the presence of in-transit, satellites, or microsatellite
metastases. SLN biopsy

The various N categories are presented in Table 3. In the 8th edition staging system, SLN biopsy is required
In the univariate analyses that were performed for the 8th for pathological staging of all patients whose primary
edition, the prognosis of patients with non-nodal regional melanomas is greater than 1 mm thick. Many clinical
metastasis (in-transit, satellite, and microsatellite metastasis) practice guidelines also recommend SLN biopsy be con-
were almost identical [5]. For this reason, these three sub- sidered in patients with tumors 0.8–1 mm thickness when
categories were grouped together for staging purposes in the other high-risk features are present such as the presence of
8th edition. In patients with stage III melanoma, the number ulceration, a high mitotic rate, young patient age (<40), or
of locoregional metastases as well as the tumor burden lymphovascular invasion. SLN tumor harboring status
strongly correlates with outcome, i.e., the various N sub- represented the strongest predictor of outcome in patients
categories correlate with survival. In addition, data analyses with clinically localized primary melanoma. Furthermore, it
performed for the 8th edition also demonstrated that pri- may also be helpful in identifying some patients who may
mary tumor characteristics (i.e., the T subcategory) were benefit from adjuvant systemic therapy.
also strongly associated with outcome even in patients who The SLN tumor burden predicts both the risk of non-
had locoregional disease [5]. It is for this reason that both SLN metastasis within the regional node field as well as
the T and N categories were combined to define the stage III survival in patients with sentinel node metastasis [35–38].
groupings in the 8th edition (Table 4). Ten year melanoma Various surrogates for quantifying SLN tumor burden have
 R. A. Scolyer et al.

Table 4 Melanoma stage III subgroups AJCC M category

AJCC Eighth Edition
Patients with distant metastasis are categorized as M1 in the
Melanoma Stage III Subgroups 8th edition and are subcategorized into M1a, b, c, or d on
the basis of the site(s) of distant metastasis. Suffixes are
N T Category
added for the M category for elevated (1) or non-elevated
Category T0 T1a T1b T2a T2b T3a T3b T4a T4b (0) serum lactate dehydrogenase (LDH) levels (Table 5).
N1a N/A A A A B B C C C

N1b B B B B B B C C C AJCC staging rules

N1c B B B B B B C C C In the 8th edition, clinical staging is defined as being based
N2a N/A A A A B B C C C upon assessment of the initial primary tumor biopsy as well
as clinical examination of regional lymph nodes. This
N2b C B B B B B C C C means that for clinical staging pathological features of the
N2c C C C C C C C C C
primary tumor biopsy are incorporated. For pathological
staging, pathological features of the definitive treatment of
N3a N/A C C C C C C C D the primary tumor site is utilized (both the primary tumor
biopsy and wide excision specimens). Pathological staging
N3b C C C C C C C C D
should be based on the worst features of either the primary
N3c C C C C C C C C D tumor biopsy or wide excision specimen. For example, if an
ulcerated T2 melanoma is identified on initial biopsy, it
Instructions Legend
should be designated as cT2b. However, even if there is no
(1) Select patient’s N category at left of chart. A Stage IIIA ulceration present in the subsequent excision specimen, the
associated primary melanoma should still be designated as
(2) Select patient’s T category at top of chart. B Stage IIIB
pT2b. In such unusual instances, it is recommended that
(3) Note letter at the intersection of T&N on pathologists add a note to their report to explain how the
staging categorization was derived. It is also specified in the
grid.
C Stage IIIC staging system that tumor thickness measured on an initial
(4) Determine patient's AJCC stage using biopsy and subsequent incision should not be added toge-
ther to derive the tumor thickness. Rather, the thickest
legend.
portion of the tumor in either specimen should be used in
N/A=Not assigned, please see manual for staging purposes, even in situations when the initial biopsy
D Stage IIID has a tumor-involved deep biopsy margin.
details.3

Limitations of staging
Original source: ref. [5]

By necessity, the AJCC staging system can only take into

been proposed, and in general, all correlate with disease account a limited number of prognostic parameters.
outcomes. The IMPSG and the AJCC melanoma expert Nevertheless, many additional well-established prognostic
panel both recommend that, at a minimum, the largest factors are not incorporated into the staging system.
dimension of the largest metastasis should be recorded in Incorporation of additional prognostic parameters into
the pathology report. Other parameters that may also be computerized prognostic algorithms is likely to
useful for prognosis include the location of the metastases provide more individualized and accurate prognostic
(subcapsular, intraparenchymal, or both), the tumor pene- estimates [40].
trative depth (centripetal thickness), and the percentage Prognostic estimates associated with the various AJCC
cross-sectional area of the lymph node involved by tumor. staging categories are defined at the time of initial diagnosis
The presence of extranodal metastasis, although uncommon and do not consider changes (improvements) in prognosis
in SLNs, is also an adverse prognostic parameter; thus its that may occur with survival over time in the absence of
presence or absence should be recorded in pathology reports disease recurrence. The latter is known as a conditional
of all regional lymph node specimens derived from mela- survival estimate. For example, in one study, a patient with
noma cases [39]. AJCC 8th edition stage IIID disease had a 5-year survival of
Melanoma pathology reporting and staging

Table 5 Definition of distant metastasis (M) employing a structured pathology report. More accurate
M criteria personalized predication of prognosis is likely to be possi-
ble in the future utilizing web-based or other computerized
M Category Anatomic site LDH level
tools, the integration of additional prognostic factors and
M0 No evidence of distant metastasis Not applicable complex molecular data as well as molecular predictive and
M1 Evidence of distant metastasis See below diagnostic biomarkers.
M1a Distant metastasis to skin, soft Not recorded or
tissue including muscle, and/or unspecified Compliance with ethical standards
M1a(0) nonregional lymph node Not elevated
M1a(1) Elevated Conflict of interest RAS reports receiving fees for professional ser-
vices from Merck Sharp & Dohme, GlaxoSmithKline Australia,
M1b Distant metastasis to lung with or Not recorded or
Bristol-Myers Squibb, Dermpedia, Novartis Pharmaceuticals Australia
without M1a sites of disease unspecified
Pty Ltd, Myriad, NeraCare GmbH, and Amgen. The other authors
M1b(0) Not elevated declare that they have no conflict of interest.
M1b(1) Elevated
M1c Distant metastasis to non-CNS Not recorded or Publisher’s note Springer Nature remains neutral with regard to
visceral sites with or without M1a unspecified jurisdictional claims in published maps and institutional affiliations.
or M1b sites of disease
M1c(0) Not elevated
M1c(1) Elevated References
M1d Distant metastasis to CNS with or Not recorded or
without M1a, M1b, or M1c sites of unspecified 1. Thompson JF, Scolyer RA, Kefford RF. Cutaneous melanoma.
disease Lancet. 2005;365:687–701.
M1d(0) Normal 2. Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V,
M1d(1) Elevated Dalle S, et al. Adjuvant pembrolizumab versus placebo in resected
stage III melanoma. N Engl J Med. 2018;378:1789–801.
Suffixes for M category: (0) LDH not elevated, (1) LDH elevated. No 3. Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM,
suffix is used if LDH is not recorded or is unspecified Cowey CL, et al. Adjuvant nivolumab versus ipilimumab in resected
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(AJCC), Chicago, Illinois. The original and primary source for this 4. Long GV, Hauschild A, Santinami M, Atkinson V, Mandala M,
information is the AJCC Cancer Staging Manual, 8th edition (2017) Chiarion-Sileni V, et al. Adjuvant dabrafenib plus trametinib in
published by Springer International Publishing ref. [24] stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:
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10%, however, if the patient was still alive in 5 years, they 5. Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV,
Ross MI, et al. Melanoma staging: evidence-based changes in the
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