The Enigmatic Spitz Lesion

The Enigmatic Spitz Lesion

The Dawn of Spitz

S Spitz Sophie Spitz Melanomas of Childhood ; Am J Pathol 1948 1910-1956 13 children (18 mo - 12 yrs) 12/13 had a benign clinical course

Sophie Spitz Born 1910 in Nashville AFIP 1944/45: Atlas of Pathology of Tropical Diseases MSK 1939 1956

Sophie Spitz

Spitz & Allen

Am J Pathol 1948

S Spitz Sophie Spitz Melanomas of Childhood ; Am J Pathol 1948 13 children (18 mo - 12 yrs) 12/13 had a benign clinical course 1910-1956 JUVENILE MELANOMA - different from adult tumors

Sophie Spitz s Melanomas - Heterogeneous Group of Tumors Am J Pathol 1948 S Spitz 13 children (18 mo -12 yrs) All benign except for one: 12 yo girl Tumor on foot Deeply locate: plantar fascia 1910-1956 Probable correct diagnosis: Clear cell sarcoma

Juvenile Melanoma A sheep in wolf s clothes

Spitz Nevus Kernan JA, Ackerman LV. Spindle cell nevi and epithelioid cell nevi (socalled juvenile melanomas) in children and adults: a clinicopathological study of 27 cases. Cancer. 1960;13:612-25. Weedon D, Little J. Spindle and epithelioid cell nevi in children and adults. A review of 211 cases of Spitz nevi. Cancer 1977; 40: 217-25. Paniago-Pereira C, Maize JC, Ackerman AB. Nevus of large spindle and/or epithelioid cells (Spitz's nevus). Arch Dermatol. 1978; 114: 1811-23

Spitz Nevus Melanoma J Derm Surg 1975

Distinction by Microscopy Spitz Nevus Architecture Symmetric Sharply circumscribed Cytology Maturation Spindle and/or epitheloid Other Features Kamino bodies Clefts Melanoma Architecture Asymmetric Ill-defined Cytology No maturation Pagetoid, Pleomorphism Other Features No Kamino bodies Consumption of epidermis

Picasso vs DaVinci

Real Picasso vs Fake Picasso

28 F, left arm Spitz Nevus

Spitz Nevus Kamino Bodies

Pigmented Spitz Nevus

The Spitz Family Grows Spitz nevus, nos Pigmented spindle cell nevus of Reed Desmoplastic Spitz nevus Angiomatoid Spitz nevus Halo Spitz nevus Pagetoid Spitz nevus Others

Darth Spitz

Reported as Spitz Nevus 28 yo man with dark mole on chest Spitz s nevus

Junctional nests of pigmented spindle cells with cleft Maturation Mitotic figures

Spitzoid Melanoma 6 yrs later 6 yrs later: LN Metastasis

The Fog of Spitz

Atypical Spitz Tumor or Spitz Nevus?

Spitz Nevus, AST or Melanoma? Nevoid Borderline Tumor

BAP1 Diagnosis: BAP1-Deficient Nevus (aka Wiesner s Nevus)

Surgery to the Rescue

J Am Acad Dermatol 2000;42:527-30

SLN Findings for Diagnosis If any neoplasm made up of melanocytes metastasizes, it is a melanoma A Spitz-like lesion that metastasizes is a melanoma, pure and simple Mones & Ackerman Am J Dermatopathol 2004;26:310-33 AB Ackerman

Dermal Solar Elastotic Material in SLN Am J Surg Pathol 2010; 34:1492-7

Mesothelial Cells in LN

Subcapsular Melanocytes What do they mean? Mart1 Mart1 Axillary SLN from 44F with mammary adenocarcinoma

The Brave New Spitz The Molecularization of Spitz

Molecular Classification of Spitz Tumors

Desmoplastic Spitz Nevus 33 F SNP-array: 11p

Spitz Nevus with ALK Fusions 25 M ALK

Alk-Fusion Partners in Spitz lesions TPM3 DCTN1 GTF3C2 NPM1 CLIP1 TPR MLPH (1q21.3) (2p13.1) (2p23.3) (5q35.1) (12q24.31) (1q31.1) (2q37.3)

28F NTRK1 Spitz Nevus with NTRK1 expression

NTRK-Fusions LMNA-NTRK1 TP53 NTRK1 ETV6 - NTRK3 MYO5A NTRK3 MYH9 NTRK3

Atypical Spitz Tumor with ALK-Fusion ALK

Atypical Spitz with NTRK1-Fusion

Value of Molecular Findings Clarity of Terminology Adjunct Evidence for Diagnosis Possibly Useful for Prognosis and/or Treatment

Clarity of Terminology Spitzoid Resembles a Spitz Nevus Spitz/Spitzian Pathway of Spitz Nevus

Spitzoid Melanomas

Melanomas with BRAF and NRAS Mutations Conventional melanomas with minor spitzoid features

Spitzoid Melanoma vs Malignant Spitz Tumor BRAF- or NRAS- mutated conventional melanomas with spitzoid features Melanomas with genomic aberrations typical of Spitz = malignant Spitz tumors

Spitz Nevus vs Melanoma Role of Molecular Studies for Diagnostic Accuracy

19 F, rt wrist

Diagnosis in 2001 Spitz Nevus, Compound Type

LN, rt axilla, 2013 S100P

FISH for EWSR1 break apart TRANSLOCATION NORMAL

Diagnosis Compound Clear Cell Sarcoma J Cutan Pathol 2013; 40: 950-4

14 F; rt cheek Diagnosis?

Path Report: Spitzoid Neoplasm with Severe Atypia

Cytogenetics: Gain of 11p 11p

14 F, rt cheek Diagnosis: Spitz Nevus

Spitzoid Melanoma 6 yrs later FISH Results: Gains in CCDN1 (11q13) and RREB1 (6p25) in > 70% of cells Metastatic melanoma

Potential Prognostic or Therapeutic Significance Kinase fusions

Spitzoid Neoplasms Spitz Nevi Atypical Spitz Tumors (AST) Spitzoid/Spitzian Melanoma

Spitzoid Neoplasms Tools for Dx Conventional H&E IHC Molecular Studies Clinical Correlation

Spitz Nevus or Melanoma?

Spitzoid Neoplasm

Clinical Findings 68 yo woman New lesion within past year Has doubled in diameter in 3 months

Diagnosis: Melanoma

Mutation Status: NRASQ61R

Cytogenetic Analysis: Melanoma

Spitzoid Melanoma of Adults A Diagnostic Problem Wolf in Sheep s Clothing - Modern ancillary methods can reduce diagnostic errors - Better clinical correlation can reduce errors

Use of Atypical Spitz Tumor Diagnostic Problem Short Term Work-up incomplete Diagnostic Uncertainty Long Term Work-up did not yield definitive evidence Low Grade Malignant Neoplasm

Pediatric Melanomas Melanoma death rates (2007, USA): 13.5% (www.cancer.org) MSKCC: Death rate of patients with melanoma diagnosed before age 18: 12%

Is Spitzoid Melanoma of Childhood a Malignant Melanoma? Cancer 2013; 119: 3911

Spitz Rebirth From Juvenile Melanoma to Spitzoid Melanoma of Childhood

Summary Spitz nevus vs tumor vs melanoma Spitzoid vs Spitz/Spitzian Molecular Pathology (Diagnosis/Classification)

The Spectrum of Spitz Benign Spitz Atypical Spitz Malignant Spitz

MSKCC Dept of Pathology 1948

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