Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic,...

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Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical and Molecular Features: an Approach to Diagnosis and Reporting Session number:1000 Victor G. Prieto, MD, PhD Chair, Professor of Pathology Michael T. Tetzlaff , MD, PhD Associate Professor of Pathology Jonathan L. Curry, MD Associate Professor of Pathology University of Texas-MD Anderson Cancer Center Houston, Texas

Transcript of Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic,...

Page 1: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical

and Molecular Features: an Approach to Diagnosis and Reporting

Session number:1000

Victor G. Prieto, MD, PhD Chair, Professor of Pathology Michael T. Tetzlaff , MD, PhD Associate Professor of Pathology Jonathan L. Curry, MD Associate Professor of Pathology University of Texas-MD Anderson Cancer Center Houston, Texas

Page 2: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

SESSION NUMBER:1000 SEGMENT 3 Pathology report of the morphologic parameters: - impact staging - fulfill laboratory accreditation (Dr. Curry)

Page 3: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Speaker Disclosure In the past 12 months, I have not had a significant

financial interest or other relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) that will be discussed in my presentation.

Page 4: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Outline 1. Cancer protocol template 2. Major histologic types of melanoma 3. Primary parameters that impact staging 4. Other histologic parameters 5. Lymph node status and satellitosis 6. Distant metastasis

Page 5: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Invasive Cutaneous Melanoma

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Pathology Report

• Pathology reports have become more comprehensive – Diagnosis – Prognostic factors – Mutation information

• Include cancer protocol templates • Impact clinical decisions and treatment

modalities

Page 7: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Cancer Templates

• Attempt to better standardize pathology

• To avoid omission of critical information

• Required for accreditation – Laboratory

• College of American Pathologists – Cancer center

• National Cancer Institute

Page 8: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Histopathologic Parameters of Melanoma

Page 9: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

15 Histopathologic Parameters

Page 10: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Histopathologic Parameters of Melanoma

15

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Histopathologic Parameters of Melanoma

* * *

*

*

* *

* CAP required elements *

Page 12: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Histopathologic Parameters of Melanoma

* * *

*

*

* *

* CAP required elements * Elements for AJCC

Page 13: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Why Report all 15 Histopathologic Parameters?

• Provide complete pathology report • Glean important information from non-required

elements – Clark level (e.g. Breslow thickness and/or mitotic rate not

available) • Fragmented tissue (e.g. curettage specimens) • Maloriented specimens

• Perineural invasion – Included in Breslow thickness – May upstage T classification (e.g. change T1 to T2)

Page 14: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Why Report all 15 Histopathologic Parameters?

• Regression – Depth of regression measured in mm may impact overall survival

• Associated nevus – Aid in examination of excision specimens and/or sentinel lymph

nodes

• Cell phenotype – Aid in examination of excision specimens and/or sentinel lymph

nodes • Spindle • Nevoid

– Insight into BRAF mutation status • Spindle less likely to harbor BRAF V600E mutation than epithelioid

Page 15: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Reporting Histopathologic Parameters of Melanoma

• Provide all 15 histopathologic parameters from biopsy specimen

• Excision specimen include – Clark level – Breslow thickness – Other parameters that differ or add information – Surgical margins

• Cancer Template – Incorporates histopathologic parameters seen in biopsy and

excision specimens – “The CAP and pTNM information provided in this report is a

compilation of both this current and the prior MDACC S- #”

Page 16: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Melanoma Pathology Report

Page 17: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Cancer Template

Primary tumor

Lymph node

TNM

Page 18: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Outline 1. Cancer protocol template 2. Major histologic types of melanoma 3. Primary parameters that impact staging 4. Other histologic parameters 5. Lymph node status and satellitosis 6. Distant metastasis

Page 19: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Histologic Types of Melanoma

• 4 major histologic types – Superficial spreading melanoma – Lentigo maligna melanoma – Nodular melanoma – Acral lentiginous/mucosal melanoma

• Many morphologic variants

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Melanoma Variants

Weedon

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Superficial Spreading Type

Page 22: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 23: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Nodular Type

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Page 25: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 26: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 27: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Acral Lentiginous Melanoma

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Desmoplastic Melanoma • Morphologic feature-seen with any of the

major histologic type of melanoma

Page 29: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Desmoplastic Melanoma

Not DMM-Cellular and spindle DMM=Hypocellular

Page 30: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pure Desmoplastic Melanoma • Defined as >90 % of

tumor with uniform desmoplastic stroma and hypocellular proliferation of spindle cells

• Pure DM with 2.2 % positive SLN

• Mixed DM with 15.8% positive SLN

• Non-DM with 17.5% positive SLN

Pawlik, Ross, Prieto, et. al. Cancer, 2005

Page 31: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Outline 1. Cancer protocol template 2. Major histologic types of melanoma 3. Primary parameters that impact staging 4. Other histologic parameters 5. Lymph node status and satellitosis 6. Distant metastasis

Page 32: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

TNM • T = Primary tumor

(Stage I and II) – Breslow (Tumor)

thickness – Mitotic rate – Ulceration

• N = Regional

metastasis (Stage III) – Lymph node

• Microscopic • Macroscopic

– Skin/subcutaneous tissue (Intransit metastasis/satellites)

• M = Distant metastasis (Stage IV) – Lymph node – Skin/subcutaneous

tissue – Visceral metastasis

• Pulmonary • Non-pulmonary

– Serum LDH

Page 33: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Impact on T Stage • T = Primary tumor (Stage I and II)

– Breslow (Tumor) thickness – Mitotic rate – Ulceration

Page 34: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Breslow (Tumor) Thickness • Powerful predictor of survival • T category for thickness

– Defined in even integers: 1.0, 2.0, and 4.0 mm • 10 year survival

T1 (≤ 1.0 mm): 92% T2 (1.01-2.0 mm): 80% T3 (2.01-4.0 mm: 63% T4 (> 4.0 mm): 50%

Page 35: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Breslow Thickness

Fills and expands papillary dermis

Extend into papillary dermis

Epidermis

Papillary dermis

Reticular dermis

Subcutaneous fat

Intra-epidermal

Reticular dermis

Subcutaneous fat

I

II

III

IV V

Breslow thickness Clark level

Page 36: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Tumor Thickness Measured From Center of Follicle

Breslow thickness

Tumor thickness

Page 37: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Microanatomic Compartment

Papillary dermis

Reticular dermis

Page 38: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Breslow thickness

Clark level

Breslow Thickness and Clark Level

Page 39: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfalls in Measurement of Breslow Thickness (BT)

• Follicle/adnexal structures • Satellite lesion • Tangential sections • Combine BT from two separate biopsies • Nevus cells • Artifact spaces or tears in tissue • We do include Breslow thickness

measurement to area of perineural invasion

Page 40: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 41: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfalls in the Measurement of Breslow Thickness

Adnexal structure

Breslow thickness

Overestimate Breslow thickness

Page 42: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 43: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfalls in the Measurement of Breslow Thickness

Page 44: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Breslow Thickness

Breslow thickness

Satellite lesion

Page 45: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 46: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Tangential Section

Page 47: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfalls in the Measurement of Breslow Thickness

Page 48: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Specimen 1

Specimen 2

Page 49: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Breslow Thickness Are Not Additive

BT1 BT2 BT3

Page 50: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Breslow thickness

Breslow Thickness in Melanoma with Associated Nevus

Do not include nevus cells in Breslow thickness

Do not report Breslow thickness at least, since nevus cells at the base of shave

Page 51: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Breslow Thickness Reported “At Least”

Breslow thickness, at least, base transected

Page 52: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 53: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Breslow thickness

Do include Breslow thickness to area of perineural invasion (PNI)

PNI

Page 54: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Perineural Invasion • Seen more frequently

in LMM and ALM with desmoplastic features

• Presence of PNI may be indicator for further adjuvant therapy with XRT

• Include area of PNI in Breslow thickness measurement

Page 55: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Impact on T Stage • T = Primary tumor (Stage I and II) • Breslow (Tumor) thickness • Mitotic rate • Ulceration

Page 56: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

T= Primary Tumor

2001 2010

Mitotic rate (MR)

Page 57: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Mitotic Rate • Important predictor of survival • 5 year survival rate non-ulcerated T1

melanoma – Mitosis: < 1=98%; 1-2=95%; 3-5=87%; 6-

10=78%; 11-19 =70%; >20=59% • T1 > 0.76 mm with at least 1 mitosis

– 10% risk of occult metastasis • 78% of ulcerated T1 melanomas were

associated with mitotic rate of at least 1/mm2

Page 58: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Mitotic Rate

Dermal mitosis Junctional mitosis

Page 59: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Mitotic Rate • Do’s

– Try to find highest mitosis per mm2

– Examine all sections and levels for mitosis or “hot spot”

– Search for mitosis in invasive melanoma

– Look for mitosis by morphology

• Don’ts – Average mitotic count in

more than one mm2 area (1/2mm2 = 0.5/mm2)

– Cut additional sections only to evaluate for mitosis

– Junctional mitosis – Report Ki-67 positive cells

as mitotic rate

Page 60: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfalls in Identification of Mitotic Figure

• Report mitotic figure of inflammatory cell or endothelial cell as positive

• Resolve with IHC studies

Page 61: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Impact on T Stage • T = Primary tumor (Stage I and II) • Breslow (Tumor) thickness • Mitotic rate • Ulceration

Page 62: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

T= Primary Tumor

2001 2010

Ulceration

Page 63: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Ulceration

• Defined as absence of intact epidermis overlying primary invasive melanoma

• Based on microscopic examination

• Distinguish from artifactual or traumatic disruption of epidermis

Page 64: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Ulceration

Page 65: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfalls in the Assessment of Ulceration

• Transepidermal elimination of tumor • Incomplete sections • Prior trauma or biopsy site • Detached epidermis

Page 66: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 67: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Not ulcerated

Detached epidermis

Page 68: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 69: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 70: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Not ulcerated

In tact epithelium

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Page 72: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Not ulcerated from melanoma

Ulcerated Basal cell

Page 73: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters
Page 74: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Not ulcerated

Ulcer from trauma Absence of melanoma beneath ulcer

Page 75: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfalls of Ulceration

Page 76: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Outline 1. Cancer protocol template 2. Major histologic types of melanoma 3. Parameters that impact staging 4. Other histologic parameters 5. Lymph node status and satellitosis 6. Distant metastasis

Page 77: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Histopathologic Parameters of Melanoma

* * * * * * *

*

* CAP required elements

Page 78: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Vascular Invasion

Page 79: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Detection of Vascular Invasion in Primary Melanoma with D2-40

• (+) LVI with D2-40 – 67% positive SLN

• (-) LVI with D2-40 – 19% positive SLN

• Patients with LVI – Decreased

disease specific survival

Petersson et. al. J Cutan Pathol. 2009

Page 80: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Detection of Vascular Invasion

D2-40

Page 81: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Histopathologic Parameters of Melanoma

* * *

*

*

* *

* CAP required elements * Elements for AJCC

not required elements in cancer checklist

RADIAL (NON-TUMORIGENIC) GROWTH PHASE, PRESENT VERTICAL (TUMORIGENIC) GROWTH PHASE, PRESENT

REGRESSION, NOT IDENTIFIED

TUMOR-INFILTRATING LYMPHOCYTES, NON-BRISK

PREDOMINANT CYTOLOGY, EPITHELIOIOD ASSOCIATED MELANOCYTIC NEVUS, NOT IDENTIFIED

Page 82: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Radial and Vertical Growth Phase • Radial growth phase (RGP)

– Expansion of tumor parallel to the epidermis • invasive tumor cells are not proliferative • in situ and/or invasive components

• Vertical growth phase (VGP) – Expansion of tumor perpendicular to the

epidermis • invasive tumor cells are proliferative • mitogenic-presence of dermal mitosis • tumorigenic-dermal nest lager than junctional nests

Page 83: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Radial Growth Phase (RGP)

Page 84: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Vertical Growth Phase (VGP)

Page 85: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Regression • Defined as replacement of melanoma cells in

the dermis with fibrosis, vascular proliferation, lymphocytic infiltrate, and melanophages

• Changes of epidermis with loss of rete ridges • Regression reported as focal or extensive

(>50% or >75%) • Nagarajan et. al.

– Depth of regression measured in mm associated with worse prognosis

Page 86: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Regression

Page 87: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Tumor-infiltrating Lymphocytes (TIL) • Brisk:

lymphocytes infiltrate entire base of invasive melanoma

• Non-brisk: lymphocytes infiltrate focally

• Absent: lymphocytes not associated with tumor

Page 88: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Predominant Cytology

Page 89: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Surgical Margins

• “Present” • “Uninvolved” • Distance of residual tumor to margins in

excision specimens – Not required element in template – Measured distance from pathology specimens

may differ from distance of “clinical” surgical margins

Page 90: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Primary Tumor Parameters • Initial histologic evaluation is critical in

diagnosis and T staging – Breslow thickness – Mitotic rate – Ulceration

• Clinically suspected melanoma – Excise entire lesion – Deep saucerization – Punch biopsy

• Superficial shave biopsy or curettings should be avoided

Page 91: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Outline of Presentation

1. Cancer protocol template 2. Major histologic types of melanoma 3. Primary parameters that impact staging 4. Other histologic parameters 5. Lymph node status and satellitosis 6. Distant metastasis

Page 92: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

TNM • T = Primary tumor

(Stage I and II) – Breslow (Tumor)

thickness – Mitotic rate – Ulceration

• N = Regional

metastasis (Stage III) – Lymph node

• Microscopic • Macroscopic

– Skin/subcutaneous tissue (Intransit metastasis/satellites)

• M = Distant metastasis (Stage IV) – Lymph node – Skin/subcutaneous

tissue – Visceral metastasis

• Pulmonary • Non-pulmonary

– Serum LDH

Page 93: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Regional Metastatic Melanoma

Page 94: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Sentinel Lymph Node (SLN)

• Sentinel lymph nodes in melanoma – Positive in ∼20% of patients

• 15% > 1.0 mm • 5% < 1.0 mm • 16% detected on initial H&E • 4% detected with additional sections/IHC

– <5% with extracapsular extension • Frozen section of SLN not recommended

Page 95: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

SLN Isolated Melanoma Cell

• Criteria for positive lymph node – Any tumor deposit size – Isolated tumor cell on IHC acceptable – H&E confirmation no longer required – Positive for one melanocytic marker (HMB45,

Melan-A/Mart-1) – Cells have malignant morphology

Page 96: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Detection of Micrometastasis

Metastatic melanoma

H&E Panmelanocytic cocktail (HMB-45, tyrosinase, Mart-1)

Page 97: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfall in Interpretation

Melan-A positive macrophages in SLN

H&E Melan A

Page 98: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfall in Interpretation

Sentinel lymph node

Melan A HMB-45

Page 99: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Template for Lymph Nodes • Number of lymph nodes

(SLN and non-SLN) • Number containing

metastasis • Tumor location

– Subcapsular – Intraparenchymal

• Tumor size – Reported in mm – Measured gross exam or slide

• Extracapsular extension • Matted lymph node

Page 100: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Extracapsular Extension

Page 101: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

In-transit Metastasis/Satellites (N2c)

• 2.0 cm distance • Arbitrary

measurements – >0.05 mm – 0.3 mm from primary

component • Deposit separated

by normal tissue

Page 102: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Microscopic Satellitosis

Normal dermis

Page 103: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Pitfalls in the Assessment of Microscopic Satellitosis

• Colonization of adnexal structures • Intravascular deposit • Lesion contiguous on deeper sections • Incidental nevus

Page 104: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Colonization of ducts

Intravascular collection of tumor

Pitfalls of Satellitosis

Page 105: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Satellitosis

Page 106: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Outline 1. Cancer protocol template 2. Major histologic types of melanoma 3. Primary parameters that impact staging 4. Other histologic parameters 5. Lymph node status and satellitosis 6. Distant metastasis

Page 107: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

TNM • T = Primary tumor

(Stage I and II) – Breslow (Tumor)

thickness – Mitotic rate – Ulceration

• N = Regional

metastasis (Stage III) – Lymph node

• Microscopic • Macroscopic

– Skin/subcutaneous tissue (Intransit metastasis/satellites)

• M = Distant metastasis (Stage IV) – Lymph node – Skin/subcutaneous

tissue – Visceral metastasis

• Pulmonary • Non-pulmonary

– Serum LDH

Page 108: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Distant Melanoma Metastasis (M)

Page 109: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Template for Distant Metastasis

• pMX-removed from AJCC-TNM system • pM0 stage defined clinically • Pathologists should not report pMx or pM0 • pM1 reported only when metastases

documented by pathology examine • Report: pM Not applicable

Page 110: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Therapy Related Tumor Regression

Page 111: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

TNM Descriptors

• Post-therapy state (y) pTNM • Retreatment classification (r) pTNM

– Recurrent tumor – Not change original stage

• Autopsy classification (a) pTNM – Disease only recognized post mortem

• R classification (residual tumor) – RX, R0, R1 (micro), R2 (macro)

Page 112: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

Summary of Melanoma Parameters • Elements for cancer template • Primary tumor characteristics that impact

AJCC-TNM staging • Breslow thickness

– Pitfalls in measurement – Include PNI in Breslow thickness

• Pitfalls in evaluation – Mitotic figures – Ulceration – Satellitosis – SLN

Page 113: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters

THANK YOU

Page 114: Diagnosing Melanocytic Lesions - Amazon S3Diagnosing Melanocytic Lesions: Integrating Morphologic, Immunohistochemical ... Major histologic types of melanoma 3. Primary parameters