Diagnostic Pathology: Molecular Oncology

Mohammad A. Vasef, MD, is a Professor at the Department of Pathology and Director of MGP Fellowship Program at The University of New Mexico Health Sciences Center. He is also Medical Director of Molecular Diagnostics, and works for TriCore Reference Laboratories in Albuquerque, New Mexico. Aaron Auerbach, MD, MPH, is the senior hematopathologist at the Joint Pathology Center in Silver Spring, Maryland, where he delivers expertise in both hematopathology and gastrointestinal pathology. He is the author of the prior and upcoming editions of Diagnostic Pathology: Molecular Oncology (2019 and 2023), and the sole author of Diagnostic Pathology: Spleen (2022).

DP2 Molecular Oncology: Auerbach and Vasef

Introduction

Structure of Chromosomes and Nucleic Acids

DNA Replication, Transcription, and Translation

Gene Mutations

Common Techniques for Analysis of Alterations in Chromosomes and DNA

Cytogenetics and FISH

Chromosomal Microarray

Amplification Methods

DNA High-Resolution Melting Curve Analysis

Sequencing Technologies

High-Throughput Methods in Molecular Pathology

DNA Methylation Analysis

Molecular Genetic Tests in Hematopoietic Tumors

*BCR-ABL1* Fusion Gene

*PDGFRA*, *PDGFRB*, and *FGFR1* Rearrangements Detection

PML-RARA Fusion Gene

Reverse Transcription PCR for Other Myeloid Leukemia Transcripts

FLT3, NPM1, and CEBPA Mutations

JAK2 Mutations and Rearrangements

MPL Mutations

Calreticulin (CALR) Mutations

CSF3R Mutations

SETBP1 Mutations

KIT Mutations

IDH1 and IDH2 Mutations

Other Mutations and Gene Panel Testing in Myeloid Neoplasms

Immunoglobulin Heavy (IGH) Chain Gene Rearrangements

T-Cell Receptor Gamma (TRG) and Delta (TRD) Chain Rearrangements

T-Cell Receptor Beta (TRB) Chain Gene Rearrangements

Southern Blot Analysis of Antigen Receptor Genes

EBV-Associated Human Neoplasms

MYD88 Mutation

NOTCH1 Mutation

EZH2 Mutation

Molecular Genetic Tests in Solid Tumors, Bone and Soft Tissue Tumors, and CNS Tumors

ALK Gene Rearrangements and Mutations

FISH for ROS1 Rearrangements

RET Rearrangements

FISH for MET Amplifications

FISH for ERBB2 (HER2) Gene Amplifications

KRAS Mutations

BRAF Mutations

EGFR Mutations

Targeted Hotspot Gene Panel Using Massively Parallel Sequencing (Next Generation Sequencing)

Targeted Hotspot Gene Panel Table

MGMT Promoter Gene Methylation Assay

MET Exon 14 Skip Mutations

NGS Panels for NCI MATCH

FISH for 1p/19q Deletions

IDH1 and IDH2 Mutations

Molecular Basis of Immunotherapy in Cancer

Molecular Pathology of Myeloid Neoplasms

Molecular Pathology of Myeloid Neoplasms

Molecular Work-Up of Myeloid Neoplasms

Myeloproliferative Neoplasms

Chronic Myeloid Leukemia, BCR-ABL1 Positive

Chronic Neutrophilic Leukemia

Polycythemia Vera

Primary Myelofibrosis

Essential Thrombocythemia

Chronic Eosinophilic Leukemia, NOS

Mastocytosis

Myeloproliferative Neoplasms, Unclassifiable

Mastocytosis

Myeloid/Lymphoid Neoplasms With PDGFRA Rearrangement

Myeloid/Lymphoid Neoplasms With PDGFRB Rearrangement

Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement

Myeloid/Lymphoid Neoplasms With PCM1-JAK2

Myelodysplastic Syndrome (MDS)

Overview and Classification of MDS

Myelodysplastic Syndromes With Single Lineage Dysplasia

Myelodysplastic Syndrome With Ring Sideroblasts

Myelodysplastic Syndrome With Multilineage Dysplasia

Myelodysplastic Syndrome With Excess Blasts

Myelodysplastic Syndrome With Excess Blasts and Erythroid Predominance

Myelodysplastic Syndrome With Excess Blasts and Fibrosis

Myelodysplastic Syndrome With Isolated del(5q)

Myelodysplastic Syndrome, Unclassifiable

Childhood Myelodysplastic Syndrome and Refractory Cytopenia of Childhood

Myelodysplastic/Myeloproliferative Neoplasms

Overview of Myelodysplastic/Myeloproliferative Neoplasms

Chronic Myelomonocytic Leukemia

Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative

Juvenile Myelomonocytic Leukemia

Myelodysplastic/Meloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

Myeloid Neoplasms With Germline Predisposition

Acute Myeloid Leukemia

Overview of Acute Myeloid Leukemia

Acute Myeloid Leukemia With t(8;21); RUNX1-RUNX1T1

Acute Myeloid Leukemia With inv(16) or t(16;16); CBFB-MYH11

Acute Promyelocytic Leukemia With t(15;17); PML-RARA

Acute Myeloid Leukemia With t(9;11); MLLT3-KMT2A

Acute Myeloid Leukemia With t(6:9); DEK-NUP214

Acute Myeloid Leukemia With inv(3) or t(3;3); RPN1-MECOM

Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22); RBM15-MKL1

Acute Myeloid Leukemia With BCR-ABL1

Acute Myeloid Leukemia With Gene Mutations

Acute Myeloid Leukemia With Mutated NPM1

Acute Myeloid Leukemia With Biallelic Mutation of CEBPA

Acute Myeloid Leukemia With Mutated RUNX1

Acute Myeloid Leukemia With Myelodysplasia-Related Changes

Acute Myeloid Leukemia, NOS

Therapy-Related Myeloid Neoplasms

Myeloid Sarcoma

Myeloid Proliferations Associated With Down Syndrome

Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic Plasmacytoid Dendritic Cell Neoplasm

Acute Leukemias of Ambiguous Lineage

Overview of Ambiguous Lineage Leukemias

Acute Undifferentiated and Mixed Phenotype Acute Leukemias

Molecular Pathology of Lymphoid Neoplasms

Overview of Lymphoid Neoplasms

Molecular Work-Up of Lymphoid Neoplasms

Precursor Lymphoid Neoplasms

B-Lymphoblastic Leukemia/Lymphoma, Not Otherwise Specified

B-Lymphoblastic Leukemia/Lymphoma With Recurrent Genetic Abnormalities

B-Lymphoblastic Leukemia/Lymphoma, BCR-ABL1-Like

T-Lymphoblastic Leukemia/Lymphoma

Mature B-Cell Neoplasms

Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia

Monoclonal B-Cell Lymphocytosis

B-Cell Prolymphocytic Leukemia

Splenic Marginal Zone Lymphoma

Hairy Cell Leukemia

Splenic B-Cell Lymphoma/Leukemia, Unclassifiable

Lymphoplasmacytic Lymphoma

IgM Monoclonal Gammopathy of Undetermined Significance

Heavy Chain Disease

µ-Heavy Chain Disease

?-Heavy Chain Disease

a-Heavy Chain Disease

Plasma Cell Myeloma

Marginal Zone Lymphoma

Follicular Lymphoma

Large B-Cell Lymphoma With IRF4 Rearrangement

Mantle Cell Lymphoma

Diffuse Large B-Cell Lymphoma

T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation

Burkitt Lymphoma

High-Grade B-Cell Lymphoma

Mature T- and NK-Cell Neoplasms

T-Cell Prolymphocytic Leukemia

Chronic Lymphoproliferative Disorder of NK Cells

Aggressive NK-Cell Leukemia

Extranodal NK-/T-Cell Lymphoma, Nasal Type

Adult T-Cell Leukemia/Lymphoma

Intestinal T-Cell Lymphoma

Hepatosplenic T-Cell Lymphoma

Subcutaneous Panniculitis-Like T-Cell Lymphoma

Mycosis Fungoides/Sezary Syndrome

Primary Cutaneous CD30-Positive T-Cell Lymphoproliferative Disorders

Primary Cutaneous Peripheral T-Cell Lymphoma, Rare Subtypes

Peripheral T-Cell Lymphoma, Not Otherwise Specified

Angioimmunoblastic T-Cell Lymphoma

Anaplastic Large Cell Lymphoma, ALK-Negative

Anaplastic Large Cell Lymphoma, ALK-Positive

Breast Implant-Associated Anaplastic Large Cell Lymphoma

Determination of Clonality in B-, T-, and NK-Cell Neoplasms

Lymphoma-Associated Chromosomal Translocations

Molecular Pathology of Dendritic Cell and Histiocytic Neoplasms

Histiocytic Sarcoma

Tumors Derived From Langerhans Cells

Interdigitating Dendritic Cell Tumor

Interdigitating Dendritic Cell Sarcoma

Follicular Dendritic Cell Neoplasm

Fibroblastic Reticular Cell Tumor

Disseminated Juvenile Xanthogranuloma

Erdheim-Chester Disease

Molecular Pathology of Solid Tumors

Head and Neck, Including Sinonasal Tumors and Salivary Glands

HPV-Related Squamous Cell Carcinoma

Head and Neck Mucosal Squamous Cell Carcinoma, Non-HPV-Related

Important Alterations in Non-HPV-Related Head & Neck SCC

Translocation-Specific Salivary Gland Tumors

Nasopharyngeal EBV-Related Squamous Carcinoma

Other Head and Neck Tumors

Thyroid

Papillary Thyroid Carcinoma

Follicular Thyroid Carcinoma

Poorly Differentiated Thyroid Carcinoma

Undifferentiated Thyroid Carcinoma

Medullary Thyroid Carcinoma

Lung

Adenocarcinoma, Lung

Squamous Cell Carcinoma, Lung

Small Cell Neuroendocrine Carcinoma

Mesothelioma

Luminal GI Tract

Gastric Adenocarcinoma

Colorectal Adenocarcinoma and Precancerous Lesions

Gastrointestinal Stromal Tumor

Liver

HNF1a-Inactivated Hepatocellular Adenoma

ß-Catenin-Activated Hepatocellular Adenoma

Inflammatory Hepatocellular Adenoma

Hepatocellular Carcinoma

Pancreaticobiliary

Pancreatic Ductal Adenocarcinoma

Pancreatic Mucinous Cystic Neoplasm

Pancreatic Intraductal Papillary Mucinous Neoplasm

Cholangiocarcinoma

Testis

Testicular Germ Cell Tumors

Kidney

Clear Cell Renal Cell Carcinoma

Chromophobe Renal Cell Carcinoma

Papillary Renal Cell Carcinoma

MiT Family Translocation Renal Cell Carcinoma

Wilms Tumor

Clear Cell Sarcoma of Kidney

Oncocytoma

Rhabdoid Tumor of Kidney

Bladder

Urothelial Carcinoma

Adrenal

Pheochromocytoma/Paraganglioma

Adrenal Cortical Carcinoma

Neuroblastoma

Adrenal Cortical Adenoma

Prostate

Prostatic Adenocarcinoma, Acinar Type and High-Grade Prostatic Intraepithelial Neoplasia

Breast

ADH and DCIS (Dysplastic, Premalignant)

Ductal Carcinomas

Lobular Carcinoma

Carcinoma With Medullary Features, Breast

Metaplastic Breast Carcinoma

Phyllodes Tumors

Basal-Like and Triple-Negative Carcinomas

Cervix/Vulva/Vagina

Preneoplastic Conditions, Cervix/Vulva/Vagina

Squamous Cell Carcinoma, Cervix/Vulva/Vagina

Adenocarcinoma, Cervix/Vulva/Vagina

Uterus

Endometrial Intraepithelial Neoplasia

Uterine Endometrioid Carcinoma

Uterine Serous Carcinoma

Clear Cell Carcinoma, Uterus

Uterine Sarcomas

Ovaries/Fallopian Tube

Serous Tumors of Ovary and Fallopian Tube

Other Surface Epithelial Tumors of the Ovary

Sex Cord-Stromal Tumors of the Ovary

Germ Cell Tumor, Ovary

Skin

Preneoplastic Conditions, Skin

Melanoma

Squamous Cell Carcinoma, Skin

Basal Cell Carcinoma, Skin

Other Skin Conditions

Bone

Osteosarcomas

Overview of Molecular Pathology of Bone and Soft Tissue Tumors

Ewing Sarcoma

Other Small Round Blue Cell Sarcomas

Giant Cell Tumor of Bone

Intermediate and Malignant Cartilaginous Tumors of Bone

Soft Tissue

Overview

Intermediate and Malignant Myofibroblastic/Fibroblastic Tumors

Liposarcomas

Muscle Sarcomas

Intermediate and Malignant Vascular Tumors

Malignant Peripheral Nerve Sheath Tumor

Representative Genetic Findings in Bone and Soft Tissue Tumors

Sarcomas of Uncertain Differentiation

Rare Sarcomas of Uncertain Differentiation With Specific Molecular Alterations

CNS

High-Grade Astrocytoma

Low-Grade Astrocytoma

Pilocytic Astrocytoma

Oligodendroglioma

Ependymoma

Medulloblastoma

Choroid Plexus Tumors

Meningioma

Retinoblastoma

Quality Assurance and Regulatory Issues

Federal Agencies and Regulation of Laboratories

FDA Regulations

Proficiency Testing and Accreditation