Dr prieto lesiones melanocíticas

Application of Immunohistochemistry to the Diagnosis of Melanocytic Lesions PerĂş 2013 Victor G. Prieto, MD, PhD Professor Depts. of Pathology and Dermatology University of Texas MD Anderson Cancer Center Houston TX, USA

Index • Introduction • Immunohistochemistry • Differential diagnosis • New techniques (in the case discussion) • Conclusions

Introduction • Growing incidence of

melanoma • Growing number of biopsies • Gray areas (black / white) • Need for additional techniques

Immunoperoxidase in Dermatopathology

• Multiple applications • Several antibodies

S100 protein

HMB45 Nevus

Melanoma

MART1

Ki67

MITF

SOX10

IPOX in Dermatopathology: Special Situations

• Diagnosis (melanocytic differentiation)

• Depth of invasion • Distinction between benign/ malignant

Detection of Melanocytic Differentiation

• Poorly differentiated lesions • Pan-melanocytic cocktail (HMB45, anti-MART1, MelanA, anti-tyrosinase) • Keratin • SMA • 2nd line: SOX10, S100

MART1

S100 protein

Detection of Level of Invasion

• Questionable dermal invasion

• Desmoplastic melanoma

Keratin

Scar-like, but epidermal hyperplasia

S100

Differentiation between benign and malignant lesions

Blue Nevus Family vs. Melanoma • Mitotic figures • Patchy HMB45 • Necrosis • Increased MIB1 • Cytologic atypia • Biphenotypic pattern (nevus + mel.)

• “Atypical” BN: – (Scalp) – Scattered mitotic figures OR – Necrosis OR – Cytologic atypia Tran et l. J Cutan Pathol 1998; 25: 252-258

Large lesion Uniform pigmentation

Elongation of rete ridges, small junctional component

Uniform cells, small nucleoli

Ki67

HMB45, Cellular blue nevus

Irregular pigmentation

Pleomorphism, irregular pigmentation

Nuclear pleomorphism

Cellular blue nevus with atypical features

Ki67/MART1

HMB45

Large nodule, originally called metastatic melanoma

Melanoma arising in a blue nevus

Necrosis, mitotic figures

Pigmented Epithelioid Melanocytoma • a.k.a. animal melanoma (pejorative term) • Epithelioid cells • Cytologic atypia • Relatively benign behavior

Zembowicz, Carney, Mihm. Am J Surg Pathol 2004;28:31-40"

Pigmented Epithelioid Melanocytoma

• Of 24 cases with LNs, 11 met and 1

liver metastasis • Follow-up (mean 32 months, range up to 67 months): No DOD • Ulceration rare; in epithelioid blue nevi of the Carney complex • Protein kinase a regulatory subunit 1α

Marked pigmentation Ulceration

Marked pigmentation Apparently densely cellular

Pigmented epithelioid melanocytoma

Melanocytes Macrophages

Key Points Blue Nevus-Type Lesions • Cellularity • Distribution of pigment • No or very rare mitotic figures • Diffuse expression of HMB45 antigen and MART1 • Low proliferation rate

• PEM Low-grade melanoma?

Spitzoid Lesions

• Current trend to designate these lesions as tumors

• Likely a spectrum between benign and malignant

• Mostly a histologic diagnosis

Spitz Nevus • Originally described as

Juvenile melanoma (Sophie Spitz) • Histologic similarities with melanoma • Mostly children and young adults

Histologic Features – Circumscription

– Maturation

– Symmetrical

– No dermal mitotic figures

– Absent or central pagetoid migration – Uniformly atypical – Vertically oriented cells nests

– Kamino bodies – IPOX

Histologic Features – Circumscription

– Maturation

– Symmetrical

– No dermal mitotic figures

– Absent or central pagetoid migration – Uniformly atypical – Vertically oriented cells nests

– Kamino bodies – IPOX

Wedge shape Papular

Infiltration of adipose tissue

Kamino bodies

Maturation

HMB45

Differential Dx: Spitzoid melanoma • Older patients (but not an exact science!)

• Asymmetry • Poorly circumscribed

No junctional component No clear maturation

Vascular invasion

Irregular pigment deposition

HMB45

Metastatic melanoma

HMB45

• Irregular nests • No maturation

• Marked pleomorphism

• Confluent pattern • Atypical mitotic figures

HMB45: top bottom

Spitzoid melanoma

MIB1 (deep)

Key Points Spitzoid Lesions • Age only partially helpful • Symmetrical • Wedge shaped • No or very rare mitotic figures • Maturation (H&E and IPOX)

Desmoplastic Nevus vs.

Desmoplastic Melanoma

• Head and neck • Mitotic figures • High expression of Ki67 • Expression of gp100 in the

deep region • Patchy MART1 expression

35 yo W trunk

Dense cellular infiltrate

Called melanoma at another institution

Lymphoid aggregates Focal atypia

55-yo W, shoulder

Dense cellular infiltrate

Junctional component Cellular atypia

HMB45 MART1

S100

Nevus

Melanoma

S100

MART1

Distinction Between Scar and Desmoplastic Melanoma

S100

S100

Lentigo Maligna vs. SunDamaged Skin

• Diffuse, confluent growth of atypical melanocytes in the epidermis

• HMB45 / pan mel cocktail • MiTF1 (nuclear)

MART1 HMB45

MART1 HMB45

MiTF1

Margins of Lentigo Maligna

• Discourage use of frozen sections Prieto et al, AJCP 2003; 120: 203

• “Slow” Mohs (rapid processing in paraffin to allow wound closure)

Unexpected IPOX results

Bleaching Technique • Allows better analysis of morphology in heavily pigmented lesions • Modifies some of the antigens: – HMB45 in macrophages – Melan A in macrophages • Requires standardization in each laboratory

Densely cellular neoplasm

Marked atypia

Partial loss of S100

S100

PanMel

S100 CD68 Outside Dx: Atypical fibroxanthoma

S100

MART1 CTL

S100

MART1

Primary, invasive melanoma

MART1 • Majority of melanocytes (except for

desmoplastic / spindle cell melanoma) • MART1 artefactually positive: – Diffuse labeling of dendrites in sundamaged skin – Macrophages (then use HMB45 or anti-MITF1) Trejo O, Reed JA, Prieto VG. J Cutan Pathol 2002; 29: 397-406 El Shabrawi-Caelen L, Kerl H, Cerroni L. Am J Dermatopathol. 2004;26:364-6 Wiltz KL et al. J Cutan Pathol. 2007;34:601-5

HE

MART1

CD68

HMB45 in Nevi

• Superficial cells (Spitz, blue) • Usually not in nodal nevi • Interlaboratory variation • Traumatized nevi Biddle DA, et al. Intraparenchymal nevus cell aggregates in lymph nodes: a possible diagnostic pitfall with malignant melanoma and carcinoma. Am J Surg Pathol 2003; 27: 673-681

MART1

Outside HMB45

HMB45

Irregular HMB45 in traumatized nevi Adeniran, Prieto, Chon, Duvic, Diwan. JAAD 2009

Final Summary • Melanocytic benign and malignant lesions: Histologic diagnosis

• Correlation with special studies and clinical features

• Expect the unexpected!