A PRACTICAL APPROACH TO THE

DIAGNOSIS OF MELANOCYTIC
LESIONS

KURSUS DERMATOPATHOLOGY PPDS

NOVEMBER 2021
Melanoma Maligna
CLUES FROM THE REQUEST FORM

• The age of the patient :

Melanoma is very uncommon <10 years (with the exception of specific rare scenarios, such as lesions
arising within large congenital melanocytic nevi), and mimics of melanoma, such as Spitz nevi
• The site of the lesion
benign melanocytic nevi in certain areas of the body can display atypical morphologic features: acral
locations, the genital skin, the milk line (from the axillae over the breast to the genitalia), the umbilicus, the
flexural skin, the scalp, the ears, and the back and shoulder of elderly patients
• Clinical Diagnosis
• Size
 CLUES FROM LOW-POWER EXAMINATION

• size, symmetry, circumscription, and sun damage (4S)

1. Size: small lesion < 4mm
Within the broad category of lesion size, depth might also be considered. Although congenital nevi, deep penetrating nevi,
cellular blue nevi, and some Spitz nevi may extend deeply into the dermis
2. Symmetry
The growth pattern, cellular density, and cytologic features, pigment, lymphocyte infiltrate should all be similar across
equivalent horizontal levels of the lesion
3. Circumscription
Closely related to the concept of symmetry is the presence of good circumscription
4. Sun damage
Junctional or compound melanocytic lesions arising in sun-damaged skin
CLUES FROM MEDIUM TO HIGH-POWER EXAMINATION

• Nevus: , junctional melanocytes are arranged in a predominantly nested pattern, with the
nests being of even size and regular distribution
• MM: nests may appear enlarged, uneven, and irregularly distributed, perhaps with some
located at the sides of rete ridges or over the tops of dermal papillae , single cell, lentiginous
• Imaginary dermal papilla line: below à benign, above à should be viewed with concern
• Epidermal consumption

• Cytology atypia, manifested by enlarged, pleomorphic nuclei with a coarse, clumped

chromatin pattern and large, prominent nucleoli
Melanoma
Worrisome histologic features
• Asymmetry
• Poor circumscription
• Cytologic atypia
• Multiple phenotypes
• Predominance of single cells over nests
• Pagetoid upward migration
• “Epidermal consumption”- “zipper effect”
Worrisome histologic features
• Lack of dermal maturation
• Expansile growth “puffy shirt”
• Mitoses / atypical mitoses in dermal melanocytes
• Ulcerated lesions
• Regression (fibrosis, melanophages, flattening of the
epidermis)
• REMEMBER- NOT ALL OF THESE FEATURES NEED TO BE PRESENT TO
ESTABLISH THE DIAGNOSIS
Asymmetry
Poor circumscription
“Epidermal consumption”- “zipper effect”
Histopathologic features of a dysplastic nevus
Symmetry, minimal
Symmetry, minimal inflammation inflammation
or stromal changes or stromal changes

Symmetry, lack of pagetoid upward migration, elongation of

rete ridges
Cytologic atypia
Multiple phenotypes
Predominance of single cells over nests
Pagetoid upward migration 14

“Epidermal consumption”- “zipper effect” Cytologic atypia

1
Courtesy: Dr. Ivan

3
Page 48
Damsky and Bosenberg
Author Manuscript Author Manuscript Author Manuscript
Necrosis 13

Lack of maturation
 2

1
Expansile growth
(puffy shirt)
 Summary: Distinguishing Histopathologic Features
Nevus Melanoma
Symmetry Present Absent
Circumscription Present Absent
Host response Uniform/Absent Asymmetric/present
Confluence (DEJ) Absent Present
Single cells/Nests (DEJ) Nests>Single cells Single cells>Nests
Pagetoid spread Absent/focal Extensive/High level
Ulceration Absent May be present
Growth pattern Well-spaced nests Expansile sheets
Maturation Present Absent
Cytologic atypia Minimal Extensive
Necrosis Absent May be present
Mitotic figures Absent, few Numerous
Imunohistokimia
HMB45 dan Ki67
 Melanocytic Lesions
➢ Gold standard for diagnosis:
H&E histologic examination
➢ Grey-zone melanocytic lesions: melanocytic proliferations
whose histopathologic features overlap both benign and
malignant proliferations.
➢ IHC may be helpful

Favor Favor
Nevus Benign ? Malignant Melanoma

Ancillary techniques
Immunohistochemistry in Melanocytic Lesions
Most commonly used ancillary technique
Applications:
Confirm melanocytic differentiation
Differentiate between benign and malignant lesions
Identify the presence of invasion in melanoma
Determine the depth of invasion
Determine extent of melanocytic lesion / margin status
Identify therapeutic targets

Prieto, JCP 2008; Prieto, Arch Pathol Lab Med. 2011; Tetzlaff, Clin Cos Inv Derm 2015
 HMB45
A mouse monoclonal antibody that recognizes gp100 or Pmel17, a
premelanosome protein
Also positive in perivascular epithelioid cell tumors, renal cell carcinomas with
t(6:11), rare steroid producing tumors of ovary
95-100% specific for melanocytic differentiation
Sensitivity: 70-100% in primary melanomas and <80% in metastases
Usually negative in most spindle cell and all desmoplastic melanomas
Patchy expression in traumatized melanocytic nevi
HMB-45
Adema, JBC 1994; Wood, JCB 1991; Skelton, AJDP 1991

• BEST USE: to show maturation (i.e., greater reactivity in the top

HMB45
as compared to the deep aspect)
• Melanoma-PATCHY
• Exceptions: Blue nevi, Spitz nevi (diffuse)
• If a spindled melanocytic lesion is diffusely HMB45, it is more
likely to be benign.
Nevi: dermal component is negative or shows progressive loss of expression with
dermal descent: maturation pattern

Patchy HMB45 expression in melanoma

Nevi: dermal component is negative or shows progressive loss

of expression with dermal descent: maturation pattern
 Melanoma: HMB45
MB45 expression in blue nevus
HMB-45 labels only cells in the epidermis and upper dermis of the nevus while it highlights sca=ered melanoma cells throughout the lesion

Melanoma: HMB45
Diffuse HMB45 expression in blue nevus
 Ki67 Ki-67 (MIB1)
• Surrogate marker of proliferation (nuclear expression in
cells in G1, M, G2 and S phases, not in G0)
• Look for increased proliferation and maturation of
proliferation
• Look for “hot-spots” – foci where in contrast to the rest of
the lesion, there are more numerous positive nuclei
Uguen et al. Diagnostic Pathology (2015) 10:195 Page 5 of 10
• Don’t count lymphocytes as positive!
• Double labeling (Mart1/Ki67)

Nevi <4
Table 3 Proposed three parameters scoring system
Parameter Score 0 Score 1 Score 2 Score 3 Score 4 Total scores
Ki-67 <2 % 2–5 % 6–10 % 11–20 % >20 % p16-Ki-67 score: 0–7
p16-Ki-67-HMB45 score: 0–9
p16 >50 % 11–50 % 1–10 % 0% -
HMB45 Gradient present Gradient doubtful or inconclusive Gradient absent - -

A p16-Ki-67-HMB45 immunohistochemistry scoring system as an ancillary diagnos>c tool in the diagnosis of melanoma
Arnaud Uguen1,2,3,4*, MaEhieu Talagas2,3,4, Sebas>an Costa2, Sandrine Duigou2, Stéphanie Bouvier2, Marc De Braekeleer1,3,5 and Pascale
Marcorelles2,3,4
 Distinguishing Immunohistological Features
Nevus Melanoma
HMB45 Maturation pattern, negative or Patchy
diffusely positive
MART1 Diffuse Rarely patchy
Ki67 Low-absent High