case 1 in salivary gland neoplasia 50-year-old male with a ... on molec… · 1 fusion transcripts...
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Fusion Transcripts that Characterize Epithelial Malignancies of Salivary Gland Origin
Joaquín J. García, M.D. Department of Laboratory Medicine and Pathology
Division of Anatomic Pathology Mayo Clinic, Rochester, MN
USA
Objectives
Detail histomorphologic overlap in salivary gland neoplasia
Discuss shortcomings of current
grading schema in salivary gland neoplasia
Evaluate diagnostic and prognostic utility of fusion transcript identification in salivary gland neoplasia
Histomorphologic Overlap in Salivary Gland Neoplasia
Case 1
50-year-old male with a cheek mass
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Lymphoepithelial Cyst
Case 2
51-year-old male with a cheek mass
3
Oncocytic Papillary Cystadenoma
Case 3
52-year-old male with a cheek mass
Warthin’s Tumor
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Case 4
50-year-old female with a cheek mass
Adenosquamous Carcinoma
Case 5
51-year-old female with a cheek mass
Salivary Duct Carcinoma
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Case 6
52-year-old female with a cheek mass
Mucoepidermoid Carcinoma
LEC OPC WT
Ad Sq Ca SD Ca MEC
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Shortcomings of Current Grading Schema in Salivary Gland Neoplasia
Ideal Features of Histopathologic Grading Schema
• Simple
• Reproducible
• Accurately predicts behavior/outcome
• Stratifies patients into distinct management categories
Adenoid Cystic Carcinoma Adenoid Cystic Carcinoma
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Adenoid Cystic Carcinoma Adenoid Cystic Carcinoma
H&E AE1/AE3 p63
Shortcomings in the Grading of Adenoid Cystic Carcinoma
• Challenging
• Poor reproducibility due to mixed histology
• Does not accurately predict behavior/outcome
• Does not stratify patients into distinct management categories
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Mucoepidermoid Carcinoma Mucoepidermoid Carcinoma
Mucoepidermoid Carcinoma Mucoepidermoid Carcinoma
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Grading Mucoepidermoid Carcinoma
AFIP Brandwein
Cystic component (<20%) 2 (<25%) 2
Perineural invasion 2 3
Necrosis 3 3
>4 Mitoses per 10 hpf 3 3
Anaplasia/Nuclear atypia 4 2
Pattern of infiltration (nests/islands)
2
Angiolymphatic invasion 3
Bone Invasion 3
Grade
0-4 LG
5-6 IG
> 7 HG
0-1 LG
2-3 IG
>4 HG
Grading Mucoepidermoid Carcinoma
AFIP Brandwein
Cystic component (<20%) 2 (<25%) 2
Perineural invasion 2 3
Necrosis 3 3
>4 Mitoses per 10 hpf 3 3
Anaplasia/Nuclear atypia 4 2
Pattern of infiltration (nests/islands)
2
Angiolymphatic invasion 3
Bone Invasion 3
Grade
0-4 LG
5-6 IG
> 7 HG
0-1 LG
2-3 IG
>4 HG
Grading Mucoepidermoid Carcinoma
AFIP Brandwein
Cystic component (<20%) 2 (<25%) 2
Perineural invasion 2 3
Necrosis 3 3
>4 Mitoses per 10 hpf 3 3
Anaplasia/Nuclear atypia 4 2
Pattern of infiltration (nests/islands)
2
Angiolymphatic invasion 3
Bone Invasion 3
Grade
0-4 LG
5-6 IG
> 7 HG
0-1 LG
2-3 IG
>4 HG
Grading Mucoepidermoid Carcinoma
AFIP Brandwein
Cystic component (<20%) 2 (<25%) 2
Perineural invasion 2 3
Necrosis 3 3
>4 Mitoses per 10 hpf 3 3
Anaplasia/Nuclear atypia 4 2
Pattern of infiltration (nests/islands)
2
Angiolymphatic invasion 3
Bone Invasion 3
Grade
0-4 LG
5-6 IG
> 7 HG
0-1 LG
2-3 IG
>4 HG
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Grading Mucoepidermoid Carcinoma
AFIP Brandwein
Cystic component (<20%) 2 (<25%) 2
Perineural invasion 2 3
Necrosis 3 3
>4 Mitoses per 10 hpf 3 3
Anaplasia/Nuclear atypia 4 2
Pattern of infiltration (nests/islands)
2
Angiolymphatic invasion 3
Bone Invasion 3
Grade
0-4 LG
5-6 IG
> 7 HG
0-1 LG
2-3 IG
>4 HG
Grading Mucoepidermoid Carcinoma
AFIP Brandwein
Cystic component (<20%) 2 (<25%) 2
Perineural invasion 2 3
Necrosis 3 3
>4 Mitoses per 10 hpf 3 3
Anaplasia/Nuclear atypia 4 2
Pattern of infiltration (nests/islands)
2
Angiolymphatic invasion 3
Bone Invasion 3
Grade
0-4 LG
5-6 IG
> 7 HG
0-1 LG
2-3 IG
>4 HG
Shortcomings in the Grading of Mucoepidermoid Carcinoma
• Simple but time consuming
• Poor reproducibility due to lack of standardization
• Does not accurately predict IG behavior/outcome
• Does not stratify IG patients into distinct management categories
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Low grade
Intermediate
Grade
High Grade
Low grade
Intermediate
Grade
High Grade
Adenoid Cystic carcinoma Mucoepidermoid carcinoma
Shortcomings in Grading Schema
Low grade
Intermediate
Grade
High Grade
Low grade
Intermediate
Grade
High Grade
Adenoid Cystic carcinoma Mucoepidermoid carcinoma
Shortcomings in Grading Schema
Low grade
Intermediate
Grade
High Grade
Low grade
Intermediate
Grade
High Grade
Adenoid Cystic carcinoma Mucoepidermoid carcinoma
Shortcomings in Grading Schema
Diagnostic & Prognostic Utility of Fusion Transcript Identification
in Salivary Gland Neoplasia
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Fusion Transcript Generation Mucoepidermoid Carcinoma
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Warthin’s lacking MAML2 rearrangement
MEC with MAML2 rearrangement Mammary Analogue Secretory Carcinoma
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Mammary Analogue Secretory Carcinoma Mammary Analogue Secretory Carcinoma
Adenoid Cystic Carcinoma
t(6;9)(q22-23;p23-24)
MYB-NFIB
Fusion Transcript Detection in Salivary Gland Malignancies
Diagnostic Accuracy
Reproducible Grading
Appropriate Management
Targeted Therapy
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Objectives
Detail histomorphologic overlap in salivary gland neoplasia
Discuss shortcomings of current
grading schema in salivary gland neoplasia
Evaluate diagnostic and prognostic utility of fusion transcript identification in salivary gland neoplasia
Joaquín García, M.D.
Department of Pathology
Mayo Clinic
200 1st Street SW
Rochester, MN 55905
(507) 538-4357 (office)
(507) 284-1599 (fax)