Pathologie Prof. Dr. med. Katharina Glatz

Malignant Melanoma Diagnostic Criteria of Malignant Melanoma

2014-02-25

Epidemiology of Melanoma

Melanoma Research 2013, 23:402-407 Opportunistic screening strategy for cutaneous melanoma does not change the incidence of nodular and thick lesions nor reduce mortality: a population-based descriptive study in the European region with the highest incidence. Bordoni A. et al

Incidence in Ticino/CH 1996-2003: 17.4/100’000 2004-2010: 20.6/100’000 Mortality 1996-2010: unchanged

Clinical Diagnosis

A= Asymmetry

B= Irregular Border

C= multiple Colors

D= Diameter (over 5mm)

and Dynamic

Indikationen Sentinel Lymphknoten Sentinel Lymph Node Procedure

Breslow >1mm Breslow >0.75mm & at least one of the following: - Clark Level IV-V - Ulceration - High mitotic count - Young Patient

Biologically Relevant Melanoma Subtypes

Pigment Cell Melanoma Res 2011; 24: 879-897

Acral Melanoma

Early genomic instability

with gene amplifications (Cyclin D1)

Histology: often acrolentiginous melanoma

Skin with intermittent UV exposure

Association with nevi (hereditary component)

Incidence increasing sharply. Histology: often SSM

Skin with chronic UV exposure

Very slowly growing

Incidence moderately increasing

Histology: often melanoma in situ

(lentigo maligna)

Mucosal Melanoma

Early genomic instability

with gene amplifications (CDK4)

Histology: often lentiginous growth

Uveal Melanoma

Blue nevi

Melanoma ex blue nevus

Size > 6mm

Asymmetry of Silhouette

Asymmetry of Lateral Borders

Asymmetry in Distribution of Junctional Nests

Asymmetry of

Pigment Distribution

Asymmetry of

Inflammatory Response

Asymmetry of Epidermal Alteration

Asymmetry of

Cytological Details

Poor Delimitation

Large Confluent Nests

Expansile Nodules and Solid Growth

Consumption Of Epidermis

Cellular Atypia

Mitotic Figures and Cellular Pleomorphism

Pagetoid Spread

Solar Elastosis

Patient Age

Mother’s Little

Helpers

Maturation

Epidermal Ulceration

Size > 6mm

© DermAtlas; http://www.DermAtlas.org

Patient Age

Cancer Research UK, http://www.cancerresearchuk.org/cancer-info/cancerstats/types/skin/incidence/#age, February 2014.

Solar Elastosis

Ugly Duckling Sign

Asymmetry of Silhouette

Mitoses and Cellular Pleomorphism

Asymmetry of Epidermal Alteration

Asymmetry in Distribution of Junctional Nests

Asymmetry of Lateral Borders

Left border Right border

Asymmetry of Cytological

Details

Asymmetry of Pigment Distribution

Asymmetry of Inflammatory

Response

Consumption of Epidermis

Epidermal Ulceration

Poor Delimitation

Large Confluent Nests

Pagetoid Spread

Lateral border

Expansile Nodules and Solid Growth

Absence of Maturation

Cellular Atypia

Size > 6mm

Asymmetry of Silhouette

Asymmetry of Lateral Borders

Asymmetry in Distribution of Junctional Nests

Asymmetry of

Pigment Distribution

Asymmetry of

Inflammatory Response

Asymmetry of Epidermal Alteration

Asymmetry of

Cytological Details

Poor Delimitation

Large Confluent Nests

Expansile Nodules and Solid Growth

Consumption Of Epidermis

Cellular Atypia

Mitotic Figures and Cellular Pleomorphism

Pagetoid Spread

Solar Elastosis

Patient Age

Mother’s Little

Helpers

Ugly Duckling Sign

Epidermal Ulceration

Low specificity and sensitivity of many criteria Conflicting criteria in the same lesion Vaguely defined criteria

Use criteria in groups Criteria must be sufficient in number and weight Start from differential diagnosis of well-defined

histologic entities as Spitz nevus and spitzoid melanoma

Sensitivity & Specificity of Criteria

Sensitivity and specificity of histological criteria in the diagnosis of conventional cutaneous melanoma. Urso, Carmelo; Saieva, Calogero; Borgognoni, Lorenzo; Tinacci, Galliano; Zini, Enzo Melanoma Research. 18(4):253-258, August 2008. Digital Object Identifier: 10.1097/CMR.0b013e3283043cc0

Sensitivity & Specificity of Criteria

Sensitivity and specificity of histological criteria in the diagnosis of conventional cutaneous melanoma. Urso, Carmelo; Saieva, Calogero; Borgognoni, Lorenzo; Tinacci, Galliano; Zini, Enzo Melanoma Research. 18(4):253-258, August 2008. Digital Object Identifier: 10.1097/CMR.0b013e3283043cc0

Mother’s Little

Helpers

• HMB-45

• Mib1

• p16

• FISH

Ancillary Techniques

HMB-45

Benign Nevus Spitz Nevus Blue Nevus

Malignant Melanoma

Residual Nevus

SSM ex Naevus

HMB-45: No Maturation

HMB-45: Breslow?

Residual Nevus: HMB-45 negative

Ki-67

Benign Nevus: <2% Spitz Nevus: <10% Blue Nevus: <2%

Malignant Melanoma: >10% Irregular distribution. Ki-67 + cells in the deep dermis.

Residual Nevus: negative

v

Of note: Only evaluate the dermal component! Do not count Ki-67 + inflammatory or endothelial cells!

Ki-67

0.5% 2.6% 6.9% 23.7% Average MIB1 Index

Am J Dermatopathol 2000; 222(6): 489-95

Ki-67

Residual Nevus Residual Nevus Inflammatory Infiltrate

Melanoma

Sentinel Node

Nodal Nevus: Bland cytology Involves nodal capsule or trabeculae HMB-45 mostly negative (or very focal) Melan A positive No mitoses Ki-67 negative or <0.2%

Nodal Metastasis: Atypical melanocytes (may be bland) Involves nodal parenchyma HMB-45 60-75% positive Melan A positive Mitoses Ki-67 2-82%, most >10%

Am J Surg Pathol 2002; 26(10): 1351-1357

p16

Am J Dermatopathol 2013; 35(2): 277-280. Intratumoral Heterogeneity of Chromosome 9 Loss and CDKN2A (p16) Protein Expression in a Morphologically Challenging Spitzoid Melanoma

Chr. 9p most commonly lost genomic region in melanomas: 10% homozygous loss with complete loss of p16 expression 50% heterozygous loss with retained p16 expression Methylation of promotor region with loss of p16 expression

FISH Four Colour Probe

Problems: Intratumoral heterogeneity Small dermal component Cell size Melanin pigment Residual nevus Melanoma is not a single entity Polyploidy Borderline remains borderline Chromosome 9 not included Cutoffs? Time consuming

normal nucleus

RREB1

CEP6

CCND1

MYB

Am J Surg Pathol 2009; 33:1146-56. Gerami et al. FISH as an ancillary diagnostic tool in the diagnosis of melanoma.

FISH Interpretation

Keep Cool!

A false-negative diagnosis of melanoma was the single most common reason for filing a malpractice claim against a pathologist.

Arch Pathol Lab Med. 2006 May;130(5):617-9. Medicolegal aspects of error in pathology.

Troxel DB.