malignant melanoma - · pdf file04.02.2014 · pathologie prof. dr. med. katharina...
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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.