Index

A Analytical validation, 79
Abdomen, multiple peritoneal surface masses throughout, 218 Aneuploidy, 5
ABL1 qPCR, 48 Angiocentric gliomas, 127
Acute myeloid leukemia (AML), 433 Angioimmunoblastic T-cell lymphoma (AITL), 386, 387, 389
ancillary tests, 286 Angiomatoid fibrous histiocytoma (AFH), 212, 216
APL diagnosis, clinical work up for an, 288 Array-CGH, 191
CEBPA mutations, 283, 284 Asthma, 201
diagnosis and classification of, 295, 298–300 Astroblastoma, 131
diagnosis and laboratory evaluation of, 275, 276 Atypical chronic myeloid leukemia (aCML), BCR-ABL1-negative, 311
FLT3 mutations, implications of, 281, 282 Atypical melanocytic neoplasm, 198
initial diagnostic workup of, 276, 277 8-aza-7-deazaguanosine, 30
minimal/measurable residual disease detection, 287, 288
molecular genetic/cytogenetic tests for, 277, 278
molecular testing/mutation profiling, 286 B
neoplastic clone of, 293–295, 297 B cell gene rearrangement, 341
NPM1, 288–290 B cell neoplasm, positive immunoglobulin (Ig) gene rearrangement, 342
NPM1 mutation, clinical significance of, 282, 283 B lineage cells, 341
risk stratification of, 278 B lymphoblastic leukemia, 82
adverse risks, 278 B lymphoblastic leukemia/lymphoma (B-ALL), 334
favorable risks, 278, 279 BCR-ABL1 fusion, 327
RUNX1, 290–292 BCR-ABL1 fusion and KMT2A, 326, 327
RUNX1 mutations and clinical significances, 285 BCR-ABL1-like B-ALL, 329, 330, 335
TP53 mutations, 284, 285 chromosomal numerical abnormalities in, 328
transient abnormal myelopoiesis, GATA1 mutation in, 285, 286 chromosome 21, intrachromosomal amplification of, 328, 329
types of, 279 CREBBP mutations, 331
Acute promyelocytic leukemia (APL) CRLF2 alterations, 331
morphologic and immunophenotypic features of, 279, 280 cytogenetic changes associated with poor prognosis, 328
morphologic characteristics, 279 ERG mutations, 331
morphologic features and PML-RARA FISH, 289 genetic workup of, 325, 326
with t(15;17), PML-RARα, 84 hypodiploidy in, 334, 335
Adamantinomatous craniopharyngioma, 133 IKZF1 mutations, significance of, 329, 331
Additional chromosomal abnormalities (ACAs), 307 mutational landscape of, 329
Adipocytic tumors, molecular testing in, 209 PAX5 alterations, 331
Adult spindle cell/sclerosing rhabdomyosarcoma, 212 TP53 mutations in, 328
Adult T-cell leukemia/lymphoma, 390 Balance difficulties, 215
Agarose gel electrophoresis, 30 Bannayan-Riley-Ruvalcaba syndrome, 177
Aggressive NK-cell leukemia (ANKL), 383 BAP1-inactivated melanocytic tumors (BIMT), 192
ALK gene, lymphomagenesis, 383 Basal-like subtype of breast cancer, 93
ALK+ histiocytosis, 417 B-cell (immunoglobulin gene) clonality tests
clinicopathology features of, 409 benign verus malignant lymphoproliferative disorder, 340
type of, 417, 418 clonal relationship, 340
ALK-negative anaplastic large cell lymphoma (ALK-negative ALCL), principles of, 340
385, 388 BCL2-IGH gel, 50
Allele dropout, 34 BCOR-rearranged sarcoma, 209
Allelic imbalance, 433 BCR-ABL1, 48
Allred score, 96 BCR-ABL1-like B-ALL, 329, 330, 335
ALT/WDL, MDM2 FISH for diagnosis of, 209, 210 BCR-ABL1-negative myeloproliferative neoplasms, 308
Alterations/mutations, 6 Benign melanocytic nevi, 191, 192
Alveolar rhabdomyosarcoma (ARMS), 211, 224 Benign vascular tumor, soft tissue tumors, 211
Alveolar soft part sarcoma, 212 Beta-catenin, 133
Analyte specific reagent (ASR), 77, 78 Bilateral salpingo-oophorectomy, 115

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2021 439
Y. Ding, L. Zhang (eds.), Practical Oncologic Molecular Pathology, Practical Anatomic Pathology,
https://doi.org/10.1007/978-3-030-73227-1
440 Index

Binary sequence alignment/map (BAM), 60–62 gene signature and molecular profiling, 100
Binomial calculations HER2 in situ hybridization assay, single-probe and dual-probe
false positive events, probability of, 42 assay in, 97
true positive events, probability of, 41 HER2 ISH groups, 97, 98
Bioinformatics, 55, 56 HER2 ISH testing, 97
annotator, small variants, 63, 66 HER2 testing, 96, 97
BAM, 60–62 hereditary breast cancer
base call, 56–58 genetic testing, 92, 93
clinical laboratory, 70 significance of, 92
clinical report, 69 hereditary mutations associated with breast cancer, 91
clinical significance, 68 metastatic, bone specimen, 95
FASTQ, 57, 58 molecular subclassification of, 93
for each specimen, 59 molecular testing, 100, 102
end with gz, 58 pathologic features of, 91, 92
molecular bar codes, 60, 63 pathologic findings and oncotype recurrence risk, discordance, 100
format and mate-pairs, 73, 74 PIK3CA mutation, 100
HGVS nomenclature, 65, 68 triple-negative and basal-like subtype breast cancers, 93
HGVS nomenclature and rules, 72
high-throughput massively parallel sequencing, 56, 57
laboratory testing, phases of, 56 C
NGS cancer panels, process short, 61, 65 Cancer
NGS method, processing DNA sequenced using, 56, 57 characteristics of, 3
processor utilization, 71 clonal diversity and cancer development and progression, 9
protected health information and cloud services, 75, 76 clonal evolution, 16
read depth and molecular bar coding, 72, 73 colorectal cancer, acquisition mechanism of genetic alteration, 14, 16
RefSeq accession number, 64, 67 development, cellular activities, 3, 4
variant filtering, 74, 75 epigenetics, 7, 8, 10
VCF file, 61, 64 fifth metacarpal mass, 18, 19
Bladder cancer, UroVysion FISH analysis for, 240, 241 genetic abnormalities, 10
Bone marrow, 398 molecular method for detection, 12, 13
Bone marrow engraftment analysis types of, 10, 11
chimerism, 421, 422 human cells, genes organized in, 4–6
cell lineages, 423 liquid biopsy for, 42
detection principle and parameters, 423 molecular tests, purposes of, 11, 12
methodologies, 423–425 mutation types and combination of different genetic abnormalities, 11
short tandem repeats and, 425, 426 mutations or genetic abnormalities, kinds of, 13
testing, clinical utility of, 422, 423 noncoding RNA and microRNA, 8, 9
STR analysis oncogenes, 6
biological and testing artifacts, 432, 433 TP53 mutation, myeloid neoplasm, 17, 18
multiplex STR, 431, 432 tumorigenesis, principles of, 9, 10
quantification of donor and recipient DNA, 428–431 tumor suppressor genes, 6, 7
BRAF mutations, cutaneous melanoma, 149, 193, 194 ultinucleotide variants, 19, 20
limitations, 194, 195 CAP Laboratory Accreditation program, 80
testing for, 195 Capillary gel electrophoresis (CGE), 30
BRAF V600E mutation, 83 Carcinosarcoma, 150
BRCA mutation CD117, 317
approach for, 103 CD25, 317
testing methods for, 92 CEBPA mutations, 283, 284
BRCA1 and BRCA2 genomic status, 102 Cell free DNA testing, lung cancer, 155, 156
Breast cancer, pedigree of, 258 Cell growth, 3
Breast implant-associated ALCL (i-ALCL), 385 Cellular dermal based mesenchymal neoplasm, 224
Breast tumor Central nervous system (CNS) tumors
ASCO/CAP recommend testing PR status, 93, 94 ATRX and TP53 mutations, utility of, 124
biomarker status, discordances of, 98 atypical teratoid/rhabdoid tumor, 136
biomarker test, 93, 95 BCOR, MN1, FOXR2, and CIC gene alterations, 131
BRCA mutations, testing methods for, 92 BRAF mutation and CDKN2A/2B homozygous deletion, 128
breast pathology, molecular testing in, 90, 91 chromosome 7 concurrent gain and loss of chromosome 10, 125
clinicopathologic features of, 93 CNS melanocytic neoplasms and metastatic melanomas, 133
discordant biomarker status, causes of, 98 diffuse midline glioma, H3 K27M mutation in, 125, 126
discordant HER2, causes for, 98 EGFR amplification, and/or TERT promoter mutation, 125
ER embryonal neoplasm, 136, 137
causes for, 96 ependymal tumors, molecular classification of, 128, 129
expression assays, 96 ependymomas, classification of, 135
low positivity, significance of, 96 FISH, disadvantage of, 125
and PR, immunohistochemical assessment, semiquantitative focal amplification or fusion at chromosome 19q13.42, 131, 132
scoring methods, 96 GBMs, IDH1 or IDH2 gene sequencing, 124
staining, 96 hemispheric diffuse glioma, H3.3 G34 mutation in, 126
Index 441

IDH1 or IDH2 mutation, significance of, 123, 124 Clear cell sarcoma, 212, 224
IDH-mutant astrocytomas, grading of, 124 Clinical Laboratory Improvement Act of 1967 (CLIA ’67), 78
IDH-mutant gliomas and the practical workup, 133, 134 analytical validation and clinical validation, 79
infiltrative appearing glioma, diagnosis for, 127 requirements, 78, 79
INI1, nuclear expression of, 130, 131 Clinical validation, 79
KIAA1549-BRAF fusion, frequency and distribution of, 126, 127 Clonal cytopenia of undetermined significance (CCUS), 313, 314
medulloblastoma diagnostics, genomic alterations, 130 Clonal diversity, 9
meningiomas, genetic alterations, 132 Clonal hematopoiesis of ndeterminate potential (CHIP), 313, 314
MGMT methylation analysis, clinical utility of, 126 Clonal rearrangement positive, 340
molecular genetics, 122 Clonal T-cell receptor gene rearrangement, 203, 204
molecular methods, 122, 123 Cloud services, 75, 76
molecular signature, 138 CNS Ewing sarcoma, 131
nuclear immunoreaction with STAT6 immunostain, 133 CNS melanocytic neoplasms, 133
oligodendrogliomas, molecular signature of, 124, 125 CNS neuroblastomas, 131
papillary craniopharyngioma and adamantinomatous College of American Pathologists (CAP), 80
craniopharyngioma, 123, 133 Colorectal carcinoma (CRC)
pediatric high-grade gliomas, genetic alterations in, 128 acquisition mechanism of genetic alteration, 14, 16
pediatric low-grade neuroepithelial tumors, genetic alterations in, 127 clinical management, molecular genetic biomarkers for, 173, 174
pediatric supratentorial ependymoma, C11orf95-RELA fusion in, 129 clinical significance, 173, 174
pediatric-type diffuse gliomas, classification of, 137, 138 clinical syndromes associated with GI tract polyposis, 176, 177
phenotype-genotype correlation, 135, 136 immune checkpoint inhibitor treatment, MMR/MSI testing in, 176
posterior fossa ependymomas groups A and B, 129, 130 Lynch syndrome in, 182–184
PXA, 128 microsatellite instability, molecular methods for, 175, 176
Central nervous system/vascular cancer, 247 molecular biomarkers testing guideline recommendation, 14, 16
CHIC2 gene, 309 molecular testing algorithm, 181
Chimerism, 421, 422, 433–436 tumorigenesis, mismatch repair protein deficiency in, 174, 175
detection principle and parameters, 423 Comparative genomic hybridization (CGH), 198
methodologies, 423–425 Complete cytogenetic response (CCyR), 307
short tandem repeats and, 425, 426 Congenital spindle cell rhabdomyosarcoma, 212
testing, clinical utility of, 422, 423 Copy number variants (CNVs), 191
Chromatins, 5 CpG island methylator phenotype (CIMP), 7
Chromogenic in situ hybridization, immunoglobulin kappa and CREBBP mutations, in B-ALL, 331
lambda light chain stainings, 342 Crizotinib, 383
Chromosomal abnormalities, 5 CRLF2 alterations, in B-ALL, 331
Chromosome 7, CNS timors concurrent gain of, 125 Cronkhite-Canada syndrome (CCS), 177
Chromosome 10, CNS tumors loss of, 125 Cutaneous melanoma
Chromosome 17, disomy of, 240 BRAF mutations, 193, 194
Chromosome 19q13.42, focal amplification or fusion at, 131, 132 limitations, 194, 195
Chromosome 21, intrachromosomal amplification of, 328, 329 testing for, 195
Chronic lymphocytic leukemia (CLL) targetable mutations, 195
genetics and risk-stratified approach, 354–357 Cutaneous T-cell lymphoma (CTCL) a, 197
prognostic biomarkers, 343, 344, 354–357 Cyst bone lesion, 18
Chronic lymphoproliferative disorder of NK cells (CLPD-NK), 381 Cytologic atypia, 405, 408
Chronic myeloid leukemia (CML), 315
BCR-ABL1 fusion variants, 306
chronic neutrophilic leukemia from, 309 D
cytogenetic abnormalities for, 306, 307, 314, 315 D7S820 allele 10, 435
diagnosis of, 306, 317–319 Dedifferentiated liposarcoma (DDLPS), 210, 220
molecular techniques, 307 Deletion of chromosome 13q, 356
cytogenetic abnormalities for, 314, 315 Dendritic cell neoplasms
treatment response criteria in, 12 ALK+ histiocytosis, clinicopathology features of, 409
tyrosine kinase inhibitors therapy Erdheim-Chester disease, 407
cause of, 307, 308 follicular dendritic cell sarcoma, 408
complete response, 307 histiocytic sarcoma, 406, 407
tests recommended monitoring response, 307, 308 immunohistochemical markers, 405
Chronic myelomonocytic leukemia (CMML) indeterminate dendritic cell tumor, 409
genetic abnormalities, 309, 310 interdigitating dendritic cell sarcoma, 408, 409
prognostic significance, 310 juvenile xanthogranulomas, 408
proliferative and dysplastic, 311 Langerhans cell histiocytosis
Chronic neutrophilic leukemia (CNL), 45, 308, 309, 311 genetic changes, 405, 406
Chronic NK-cell lymphoproliferative disorder (CPLD-NK), 383 clinicopathologic features of, 405
Chronic obstructive pulmonary disease, 16 transdifferentiation, 405
CIC gene alterations, 131 Dendritic cells
CIC-rearranged sarcoma, 220 non-neoplastic macrophages, immunohistochemical
cis-regulatory elements, 36 markers of, 404
CIC sarcomas, 131 origin of, 403
Classical Hodgkin lymphoma, 354 types of, 404, 405
442 Index

Deoxynucleotide triphosphates (dNTP), 28 F

Dermatofibrosarcoma protuberans (DFSP), 197, 198, 214 Familial adenomatous polyposis (FAP), 176
Dermis, 199 Familial B-lymphoblastic leukemia (B-ALL), 252
Desmoid-type fibromatosis, 214 FASTQ, 57, 58
Desmoplastic small round cell tumor (DSRCT), 213, 218 and BAM files
Detecting deficient mismatch repair (dMMR), significance of, 104 molecular bar codes, 60, 63
Dideoxynucleotides, 30 for each specimen, 59
Differentiate translocation associated TCC (tRCC), molecular assays, 235 end with gz, 59
Diffuse large B-cell lymphoma, 392 format and mate-pairs, 73, 74
Diffuse leptomeningeal glioneuronal tumor, 127 Favor malignant melanoma, 198
Diffuse midline glioma, H3 K27M mutation in, 125, 126 FFPE specimens, 39
DNA-based analysis, 36 Fibroblastic/myofibroblastic tumors, 213–215
DNA methylation, 7, 34, 122 Fine needle aspiration (FNA), 83
Droplet digital PCR (ddPCR), 33 Flow cytometry, 295, 297
Dual-probe assays, 97 FLT3, 281
Ductal carcinoma in situ of breast, 115 Fluorescence in situ hybridization (FISH), 122, 125, 306, 424
DUSP22-IRF4 gene, 384 Fluorometry, 27
Dyserythropoiesis, 293 FNA cytology, 84
Dysplastic CMML, 311 Focal epidermotropism, 203
Follicular dendritic cell sarcoma (FDCS), 415
clinicopathologic features of, 408
E morphologic features of, 411, 413
Early T-cell precursor lymphoblastic leukemia (ETP-ALL), 336 Formalin-fixed, paraffin-embedded (FFPE) tissues, 155
molecular genetic changes in, 332 FOXR2, 131
molecular profiling study, 335, 336
EGFR T790M mutation, lung cancer, 159, 160
Electropherogram, 48–51, 202 G
Electrophoresis, 27 Gastric adenocarcinoma
Endocrine cancer predisposition syndromes, 247 HER2 expression/amplification in, 171, 172
Endometrial adenocarcinoma, 105, 106 HER2 testing algorithm for, 184–186
Endometrial carcinoma Gastrointestinal stromal tumors (GIST), 172, 173
biomarker tests, 110 Gastrointestinal tumors
TCGA molecular classification of, 109 gastric adenocarcinoma, HER2 expression/amplification in, 171, 172
Endometrial stromal sarcoma, 116 gastrointestinal stromal tumors and clinical significance, 172, 173
Endometrial stromal tumors, 110 molecular classification systems of, 172
Endometrioid adenocarcinoma, 117 Gene expression analysis, 123
Engraftment, 422 Gene expression profiling (GEP) assay
Enteropathy-associated T-cell lymphoma (EATL), 387 prostate cancer, 242
Eosinophilic cytoplasm, 227 prostatic cancer, 237, 238
Ependymal tumors, molecular classification of, 128, 129 Generalized tonic clonic seizures, 135
Ependymomas, 129, 135 Gene signature, 100
Epigenetic regulation, 7, 8 Genetic abnormalities, types of, 10, 11
Epimutations, 260 Genitourinary neoplasms
Epithelioid cells, basaloid population of, 215 bladder cancer, UroVysion FISH analysis for, 240, 241
Epithelioid hemangioendothelioma (EHE), 211 differentiate translocation associated TCC, 235
Epithelioid hemangioma, 211 hereditary RCC syndrome, 235, 236
ERBB2 (HER2)-enriched tumors, 93 molecular assays, 233, 234
Erdheim-Chester disease (ECD), 414, 417 papillary renal cell carcinoma, molecular assays, 234, 235
clinical and radiologic features of, 407 papillary renal neoplasm, immunophenotypic and molecular
clinical and radiologic findings of, 411 features of, 238, 240
molecular genetic changes in, 407 prostate adenocarcinoma, diagnosis of, 237
morphologic and immunophenotypic features of, 407, 411 prostate cancer
ER expression assays, 96 gene expression profiling (GEP) assay, 237, 238, 242
ERG mutations, in B-ALL, 331 molecular genetic abnormalities in, 237
ER low positivity, significance of, 96 screening algorithm, 237, 238
Erlotinib, 159 renal cell carcinoma, VHL mutations or 3p deletions, 233, 234
Essential thrombocythemia, molecular basis of, 315, 316 testicular germ cell tumors, molecular changes in, 238
Essential thrombocytosis, 219 urothelial carcinoma screening, 235, 236
ETS gene fusions, in prostate adenocarcinoma, 237 Wilms tumor, genetic alterations in, 235
Ewing sarcoma (EWS), 208, 209 Genodermatoses, 247
Ewing sarcoma with EWSR1-FLI1 fusion, 215 Germ cell tumors (GCT), 238
EWSR1 FISH, 224 Gestational trophoblast disease (GTDs), 112
EWSR1-SMAD3-positive fibroblastic tumor, 213 GI tract polyposis, 176, 177
Extranodal NK/T-cell lymphoma, nasal type (ENKTL-nasal), 382, 383 Giant cell fibroblastoma/dermatofibrosarcoma protuberans, 214
Extraskeletal myxoid chondrosarcoma, 213, 226 Graft failure, 422
EZH2 mutation, clinical implications for, 344, 345 GVHD, 436
Index 443

GVHD post-solid organ transplantation, 435 hematologic malignancies, germline predisposition for, 257
Gynecologic tumors myeloid neoplasm, indications of, 252
BRCA mutation, approach for, 103 pathogenic variant, 255, 257
BRCA1 and BRCA2 genomic status, 102 somatic findings, 262, 263
detecting deficient mismatch repair, significance of, 104 somatic testing
endometrial carcinoma cancer predisposition genes, 253, 254
biomarker tests, 110 variant interpretation and reporting, guidelines for, 255
TCGA molecular classification of, 109 variants, types of, 254
endometrial stromal tumors, molecular testing in, 110 somatic tumor testing, germline pathogenic variant in, 263–266
germline, risk evaluation, counseling and genomic testing for, 103 variant allele frequency, 254
gestational trophoblast disease, diagnosis of, 112 Hereditary mixed polyposis syndrome (HMPS), 177
homologous recombination deficiency, 102, 103 Hereditary RCC syndrome, 235, 236
Lynch syndrome HGVS nomenclature, 65, 68
advantages and disadvantages, 108, 109 High grade papillary urothelial carcinoma, 241
pathologic features of, 104 High-throughput massively parallel sequencing, 56, 57
screening, 104 HIPAA business associate agreement (BAA), 71
testing methods for, 104 HIPAA privacy rule, 75
microsatellite instability, 107 Histiocyte-rich rhabdomyoblastic tumor, 212
mismatch repair protein, 104 Histiocytes
mismatch repair protein testing, 107 non-neoplastic macrophages, immunohistochemical markers of, 404
MLH1 promoter methylation, 107, 108 origin of, 403
MMR proteins, immunohistochemical stains for, 105, 107 types of, 404, 405
molecular human papillomavirus (HPV) testing, cervical cytology Histiocytic cell neoplasms
specimen, 110 ALK+ histiocytosis
molecular testing, roles of, 102 clinicopathology features of, 409
p16 immunostaining, 110, 111 molecular genetic changes in, 409
sex cord-stromal tumors, molecular testing in, 111, 112 Erdheim-Chester disease
tissue testing, causes for, 108 clinical and radiologic features of, 407
uterine serous carcinoma, HER2 testing in, 110 molecular genetic changes in, 407
morphologic and immunophenotypic features, 407
follicular dendritic cell sarcoma
H clinicopathologic features of, 408
Hematologic malignancies syndromes from inflammatory myofibroblastic tumor, 408
genetic predispositions to, 251, 252 recurrent molecular genetic changes in, 408
germline predisposition for, 257 histiocytic sarcoma
Hematopathology, 339 clinicopathologic features of, 406, 407
Hematopoietic progenitor cell transplantation (HPCT), 421 lymphoma and transdifferentiated, clonal relationship, 407
Hemispheric diffuse glioma, H3.3 G34 mutation in, 126 molecular genetic changes in, 407
Hepatocellular carcinoma (HCC) transdifferentiation, lymphomas, 407
molecular classification of, 178, 179 indeterminate dendritic cell tumor
molecular targeted therapies for, 177, 178 clinicopathologic features of, 409
Hepatosplenic T-cell lymphoma (HSTL), 380 recurrent genetic changes in, 409
Hepatosplenomegaly, 388 interdigitating dendritic cell sarcoma
HER2 immunohistochemistry, 114 clinicopathologic features of, 408, 409
HER2 in situ hybridization assay, 97 Juvenile xanthogranulomas
HER2 ISH groups, breast tumor, 97, 98 clinicopathologic features of, 408
HER2 ISH testing, breast tumor, 97 molecular genetic changes in, 408
HER2 mutations, 149 Langerhans cell histiocytosis
HER2 testing, breast tumor, 96, 97 genetic changes, 405, 406
Hereditary breast cancer Langerhans cell histiocytosis, clinicopathologic features of, 405
genetic testing, 92 transdifferentiation, 405
limitations of, 92, 93 Histiocytic sarcoma (HS), 412
significance of, 92 clinicopathologic features of, 406, 407
Hereditary breast cancer, genetic testing for, 92 differential diagnosis of, 410, 411
Hereditary cancer syndromes, 245–250 lymphoma and transdifferentiated, clonal relationship, 407
cellular pathways, molecular events of, 250, 251 molecular genetic changes in, 407
features of, 251 morphologic and immunophenotypic features of, 410, 411
germline cancer predisposition, 257 Hodgkin lymphoma, clonality assay in, 348, 351, 354
germline cancer predisposition, laboratories, 257 Homologous recombination deficiency (HRD), 102
germline testing, 252 diagnosis, 103
ordering, counseling, and interpreting, 252, 253 HRDetect test, 103
techniques for, 253 Human androgen receptor X-assay (HUMARA), 382
variant interpretation and reporting, guidelines for, 255 Human papillomavirus (HPV) testing
variants, types of, 254 cervical cytology specimen, 110
hematologic malignancies syndromes, genetic predispositions to, Human retrovirus, 390
251, 252 Human T-cell lymphotrophic virus type 1 (HTLV-1), 391
444 Index

Hybrid capture assays, 36 molecular genetic changes in, 406

Hybridization technologies, 36 morphology of, 409
Hypercholesterolemia, 201 Lenalidomide, 313, 365, 371
Hyperparathyroidism, clinical and family history of, 259 Light chain (AL) amyloidosis, molecular and genetic testing is useful
Hypodiploidy, 328, 334 for, 365, 366
Hysterectomy, 115 Lipoma, 220
Lipomatous neoplasms, 209
Liquid biopsy, 42, 155
I Lower anogenital squamous terminology (LAST), 110
iAMP21, 328 Low-grade fibromyxoid sarcoma (LGFMS), 215
IDH-mutant astrocytomas Lower leg nodule, 224
grading of, 124 Lung adenocarcinoma, 161
IDH-mutant gliomas, 133, 134 significant genetic abnormalities seen in, 148, 149
Idiopathic cytopenia of undetermined significance (ICUS), 313, 314 Lung cancer
IHC HER2, 99 ALK1 rearrangements, 164
IHC method, advantages and disadvantages of, 108 cell free DNA testing, 155, 156
IKZF1 mutations, in B-ALL, 329 EGFR T790M mutation, 159, 160
Imatinib, 173, 198 FISH method, 163
Immune checkpoint inhibitor, MMR/MSI testing in, 176 genetic aberrations of, 152–154
Indeterminate dendritic cell tumor (IDCT), 416 immunotherapy, guidance for, 157
clinicopathologic features of, 409 lesions and/or multiple metastatic tumors, 152
morphologic and immunophenotypic features of, 413, 415 lung adenocarcinoma, 161
recurrent genetic changes in, 409 MET exon 14 skipping, 164
Individualized quality control plan (IQCP), 82 metastatic bone lesion, histologic feature of, 161
Infantile fibrosarcoma, 214 molecular genetic testing for, 151
Infiltrative appearing glioma, diagnosis for, 127 molecular test, re-biopsy sampling for, 163
Inflammatory myofibroblastic tumor (IMT), 408 mutation profile, 152
Inherited breast cancer syndrome, clinical and family history risk mutation profiling, specimen types acceptable for, 155
factors, 257–259 NGS test, 157, 158, 161
Interdigitating dendritic cell sarcoma (iDCS), 416 non-small cell lung cancer, genes/mutations, 151, 152
clinicopathologic features of, 408, 409 non-small cell lung cancer, next generation sequencing-based tests
differential diagnosis, 413 for, 154, 155
morphologic and immunophenotypic features of, 413 NSCLC, pathologic characterization, 153
Intermediate cluster region (ICR), 48–49 significant genetic abnormalities, 148, 149
Intermediate/low-grade vascular neoplasms, 211 significant genetic alterations, 150, 151
International Prognostic Index for Chronic Lymphocytic Leukemia small cell carcinoma of the lung, 150
(CLL-IPI), 344 splice site mutation, 164
Intervening fibrous septa, 221 squamous cell carcinoma
Intimal sarcoma, 213 mutation testing for, 150
Invasive ductal carcinoma, 91, 114, 115 squamous cell carcinoma, mutation landscape of, 149, 150
Invasive malignant melanoma, 200 subset of, 160
Isochromosome 7q, 380 synchronous multifocal lung cancers, 160
ITD fragment analysis, 43 tumor mutational burden, 156, 157
types of, 147, 148
Lymph node, 398
J metastatic deposit in, 217
JAK/STAT pathway, 380, 382, 385 Lymphadenopathy, 388, 392
Juvenile myelomonocytic leukemia (JMML) Lymphoid neoplasms, molecular techniques in, 339, 340
genes, 311, 312 Lymphomagenesis, ALK gene in, 383
Juvenile polyposis syndrome (JPS), 177 Lynch syndrome, 117
Juvenile xanthogranulomas (JXG) colorectal carcinoma
clinicopathologic features of, 407, 408 tumorigenesis of, 174, 175
CRC, 182–184
IHC method, PCR-based MSI testing and NGS-based MSI testing
K advantages and disadvantages, 108, 109
Karyotype, 300 pathologic features of, 104
KIT mutations, 195 screening, 104
KMT2A/MLL translocation testing methods for, 104
cytogenetic features of, 327, 328
Knudson’s two-hit theory of carcinogenesis, 250
KRAS mutation, 151 M
Major molecular response (MMR), 307
Malignant melanoma, 201
L molecular studies, 193
Langerhans cell histiocytosis (LCH), 405, 410 proliferative nodules and molecular findings, 193
clinicopathologic features of, 405 MALT lymphoma, 346
genetic mutations, 409 Mammogram, 112, 114
Index 445

Massive parallel sequencing, 425 Microchimerism, 422

Mastocytosis, 309 Microglandular adenosis, 113, 114
Mature B cell neoplasms MicroRNAs (miRNAs), 8, 9, 381
B cell neoplasm, positive immunoglobulin (Ig) gene Microsatellite instability (MSI)
rearrangement, 342 colorectal carcinoma
B-cell (immunoglobulin gene) clonality tests molecular methods for, 175, 176
benign verus malignant lymphoproliferative disorder, 340 gynecologic tumors, 107
clonal relationship, 340 Minimal residual disease testing, 364, 365
principles of, 340 Minimal/measurable residual disease (MRD) detection
chromogenic in situ hybridization, immunoglobulin kappa and acute myeloid leukemia, 287, 288
lambda light chain stainings, 342 ALL, 331, 332
chronic lymphocytic leukemia Mismatch repair protein, 104
genetics and risk-stratified approach, 354–357 Mitogen activated protein kinase (MAPK) pathway, 126
prognostic biomarkers, 343, 354–357 Mitoses, 405
clonality determination, methods, 341 MLH1 promoter methylation, 107, 108
clonality test MMR proteins, immunohistochemical stains for, 105, 107
indication of, 345–347 MN1, 131
limitations of, 341, 342 Molecular alterations, vascular lesions, 210
diagnosis, molecular techniques, 339, 340 Molecular diagnostic laboratories
diagnosis, prognosis and treatment, 345 bone marrow aspirate revealed frequent blasts, 83
EZH2 mutation, clinical implications for, 344, 345 fine needle aspiration, 83
Hodgkin lymphoma, clonality assay in, 348, 351, 354 FNA cytology, 84
lymphoid neoplasms, molecular techniques in, 339, 340 individualized quality control plan, 82
mucosa-associated lymphoid tissue, extranodal marginal zone peripheral blood smear reveals scattered abnormal promyelocytes,
lymphoma of, 344, 345 85
MYD88 L265P potential sources of error, 82, 83
clinical implications for, 343, 344 proficiency testing, 81, 82
methods, 344 QNS, potential sources of error, 83–85
NGS based clonality tests, advantages of, 342, 343 quality assurance and quality control in, 81
NGS-based clonality assay, 345–347 analyte specific reagent, 77, 78
PCR based clonality assay, 345–347 analytical validation and clinical validation, 79
clonal relationship, determination of, 348, 351, 354 CAP Laboratory Accreditation program, 80
positive clonality, IGH and IGK clonal gene rearrangement, 342 CLIA requirements, 78, 79
Mature T- and NK-cell neoplasms College of American Pathologists and professional
ALK-negative anaplastic large cell lymphoma, diagnosis and organizations, 80
prognosis of, 385 instruments and systems, 78
angioimmunoblastic T-cell lymphoma, 386, 387 next generation sequencing tests, quality control challenges for,
breast implant-associated anaplastic large cell lymphoma, 385 80
chronic NK-cell lymphoproliferative disorder, 383 quality control samples, 80
enteropathy-associated T-cell lymphoma, 387 U.S. Food & Drug Administration, 77
extranodal NK/T-cell lymphoma, nasal type, 382, 383 quality management and improvement initiatives, 81
FISH molecular markers, prognostic significance of, 388 standard operation procedure, 81
lymphomagenesis, ALK gene in, 383 Molecular diagnostic methods
monomorphic epitheliotropic intestinal T-cell lymphoma, 387 AML
mycosis fungoides, molecular testing, diagnosis and prognosis, FLT3 D835/I836 and ITD mutations, 42, 43
381 cancer, liquid biopsy for, 42
NK-cell neoplasms–aggressive NK-cell leukemia, 383 electropherogram
peripheral T-cell lymphomas, not other specified, 386 endpoint PCR and recognizing, 48–51
primary cutaneous anaplastic large cell lymphoma, 384, 385 hybrid capture based and multiplex PCR amplicon, 39, 40
subcutaneous panniculitis-like T-cell lymphoma, 387, 388 microsatellite instability, 37
T-cell large granular lymphocytic leukemia, 381, 382 multiplex PCR, 36, 37
T-cell prolymphocytic leukemia, characteristic genetic alterations, next generation sequencing
378, 379 errors and sequencing artifacts, processes cause, 39, 41
T-cell receptor gene rearrangement, 377, 378 and molecular diagnostics, 37
Mature T-cell lymphoma, 390 sequencing chemistries, 39
Mature T-cell neoplasms, T-cell leukemia/lymphoma among, 379, 380 workflow for, 37, 38
Mayo molecular model (MMM), 310 NGS, myeloid neoplasms, 43–46
M-bcr breakpoints, 306 pre-analytical variables, sample integrity and nucleic acid
Medulloblastomas, 130 extraction
Melanocytes, 198 diagnostic sensitivity, 26
Melanoma, prognosis for, 195, 196 DNA and RNA quality, 26
Meningiomas, genetic alterations, 132 extraction, DNA and RNA quality, 26, 27
MET exon 14 skipping, 149, 164 nucleic acid extraction, methods, 25, 26
Metastatic angiomatoid fibrous histiocytoma, 216 nucleic acids, yield and quality of, 24, 25
Metastatic melanomas, 133 PCR and mechanism of inhibition, 24
MGMT methylation analysis, clinical utility of, 126 specimen requirements, 24
Microarray technology, 36 tissue/samples, types of, 24
446 Index

Molecular diagnostic methods (cont.) chromosomal abnormalities in, 312, 313

qPCR and components, 46–49 classification for, 320, 321
sequencing depth and confident mutation identification, 41, 42 clinical presentation and diagnostic criteria for, 310, 319, 320
single gene molecular profiling molecular abnormalities, 313, 314
allele dropout, 34 typical clinicopathological findings in, 312, 313
benefits of, 28 Myelodysplastic syndrome with single lineage dysplasia
cross-contamination/sample identification issues, 33, 34 (MDS-SLD), 320
delta Ct value, quantitative Polymerase Chain Reaction, 32 Myelodysplastic/myeloproliferative neoplasm
detection methods, quantitative Polymerase Chain Reaction, 32 molecular genetic abnormalities with, 312
DNA methylation, 34 Myeloid cells, 423
Droplet Digital PCR, 33 Myeloid neoplasm
hybrid capture assays, 36 indications of, 252
hybridization technologies, 36 Myeloid neoplasms, 252
microarray technology, 36 Myelomagenesis, primary and secondary genetic events, 362, 363
nucleic acid analogs, PCR reactions, 30 Myeloproliferative neoplasms, BCR-ABL1-negative, 308
nucleic acidresolve and detect, PCR reactions, 30, 31 Myxoid liposarcoma, 210, 220, 221
polymerase chain reaction, 28, 29 Myxoid spindle lesion, 227
proto-oncogenes and cis-regulatory elements, 36
quantitative polymerase chain reaction, 31
RNA analysis and reverse transcription, molecular applications, N
35 Neoplasm, 215
RNA-based analyses, 35 Neoplastic B cell neoplasms, 342
Sanger sequencing, 33 Neoplastic macrophages
target-based amplification method, 36 immunohistochemical markers of, 405
Molecular profiling, of cancer, 100 Neurofibromatosis type 2 (NF2), 132
Molecular tests, purposes of, 11, 12 Nevoid malignant melanoma, skin tumors, 191, 192
Monoclonal B-cell lymphocytosis (MBL), 346 Next generation sequencing (NGS), 37, 425
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), errors and sequencing artifacts, processes cause, 39, 41
387 hybrid capture based and multiplex PCR amplicon, 39, 40
Monophasic synovial sarcoma, 223 myeloid neoplasms, 43–46
Mosaicism, 260, 262 qPCR and components, 46–49
Mucosa-associated lymphoid tissue (MALT) quality control challenges for, 80
extranodal marginal zone lymphoma of, 344, 345 sequencing chemistries, 39
Muir-torre syndrome (MTS), 196, 197, 201 workflow for, 37, 38
Multicellular organisms, 4 NGS-based clonality assay, 350, 355
Multifocal extramedullary multiple myeloma (EMM), 367 NGS based clonality tests, advantages of, 342, 343
Multilineage dysplasia, 286 NGS-based MSI testing
Multiple endocrine neoplasia type 1 (MEN1) cancer syndrome, 259 advantages and disadvantages, 108
Multiple lung nodules, 264 NGS-based testing, 28
Multiple myeloma Nodal T-cell lymphomas, 398
copy number-single nucleotide polymorphism microarrays, 365 Nodular fasciitis, 213
diagnostics tests, 361, 362 Nodular myxoid lesion, 222
extramedullary plasma cell neoplasms differ from, 366, 367 Noncoding DNA (ncDNA) segments, 10
genetic features, 366 Noncoding RNA, 8, 9
genetic findings impact, treatment of, 364 Non-small cell lung cancer (NSCLC), 263
genetic studies, 364 with EGFR somatic mutations, 266
genetic tests, 363 genes/mutations, 151, 152
genomic markers for, 367 next generation sequencing-based tests for, 154, 155
risk stratification of, 363 pathologic characterization, 153
therapy-related myeloid neoplasms, 365 Non-template nucleotide, 433
uncertain significance and smoldering, 363, 364 Noonan syndrome, 312
Multiple soft tissue masses, 219 NPM1, 288–290
Multiple synchronous lung nodules, 160 NPM1 mutation, 286
Multiplex PCR, 36, 37 clinical significance of, 282, 283
Multiplex STR NPM-TYK2 gene, 385
advantages and disadvantages, 431, 432 NRAS mutations, 195
Mutation analysis guide therapy, 367 NTRK fusions, 149
MYB-QKI fusion, 127, 128 Nucleic acid extraction methods, 25, 26
Mycosis fungoides (MF) Nucleic acids, 24
diagnosis of, 197 yield and quality of, 24, 25
mature T- and NK-cell neoplasms Nucleophosmin (NPM1), 282
molecular testing, diagnosis and prognosis, 381 NUT carcinomas, 151
MYD88, 343, 344
MYD88 L265P
clinical implications for, 343, 344 O
methods, 344 Oligoastrocytoma, 133
Myelodysplastic syndrome (MDS), 313, 314, 398 Oligodendrogliomas, molecular signature of, 124, 125
Index 447

Oncogenes, 6, 250, 251 Ploidy analysis, 112

Ovarian cancer, pedigree of, 258 Polyacrylamide gel, 203
Polymerase Chain Reaction (PCR), 28, 29
nucleic acid
P acidresolve and detect, 30, 31
Pancreatic cancer, genetic landscape and clinical nucleic acid analogs, 30
significance, 179, 180 Polymorphous low-grade neuroepithelial tumor, 127
Pancreatic cysts, 180 Polyploidy, 5
Pancreatobiliary lesions, molecular diagnostics, cytologic samples of, p53 protein, 7
180, 181 PR status, breast tumor, 93, 94
Papillary craniopharyngioma, 123, 133 Precursor lymphoid neoplasms
Papillary renal cell carcinoma (PRCC), molecular assays, 234, 235 ALL
Papillary renal neoplasm, 239 CAP/ASH and NCCN guidelines for, 332, 333
immunophenotypic and molecular features of, 238, 240 minimal residual disease, 331, 332
Papillary thyroid carcinoma, 83 B lymphoblastic leukemia/lymphoma
PAX5 alterations, in B-ALL, 331 genetic workup of, 325, 326
PCR-based clonality assay, 349 B-ALL
PCR-based MSI testing, advantages and disadvantages of, 108 BCR-ABL1 fusion and KMT2A, 326, 327
PDGFRA rearrangement, molecular abnormality of, 309 BCR-ABL1-like B-ALL, 329, 330, 335
Pediatric high-grade gliomas, genetic alterations in, 128 BCR-ABL1-like B-ALL, molecular genetic changes in, 329
Pediatric low-grade neuroepithelial tumors, genetic alterations in, 127 chromosome 21, intrachromosomal amplification of, 328, 329
Pediatric supratentorial ependymoma, C11orf95-RELA fusion in, 129 CREBBP mutations, 331
Pediatric-type diffuse gliomas, classification of, 137, 138 CRLF2 alterations, 331
Pelvic pressure, 115 cytogenetic changes associated with poor prognosis, 328
Pembrolizumab, 224 ERG mutations, 331
Peripheral T-cell lymphomas, not other specified hypodiploidy in, 334, 335
(PTCLs-NOS), 386, 398 IKZF1 mutations, significance of, 329, 331
Perivascular affinity, 127, 128 mutational landscape of, 329
Personalized cancer treatment, 9 PAX5 alterations, 331
Peutz-Jeghers syndrome (PJS), 177 t(12;21)/ETV6-RUNX1 in, 328
PFH6 mutation, 19 B-ALL, chromosomal numerical abnormalities in, 328
Philadelphia chromosome-negative myeloproliferative B-ALL, TP53 mutations in, 328
neoplasms, 308 early T-cell precursor lymphoblastic leukemia, molecular genetic
PIK3CA mutation, 100 changes in, 332
Pilocytic astrocytomas, 126 ETP-ALL
P57 immunohistochemistry, 112 molecular profiling study, 335, 336
p16 immunostaining, 110, 111 KMT2A/MLL translocation, cytogenetic features of, 327, 328
Plasma cell leukemia (PCL), 366 T lymphoblastic leukemia
definition of, 369, 370 molecular genetic changes in, 332, 336
Plasma cell neoplasms Predominant small lymphocytes, 356
high-risk myeloma, genetic markers of, 368, 369 Preferential amplification, 424, 433
light chain amyloidosis, molecular and genetic testing is useful for, Primary cutaneous anaplastic large cell lymphoma
365, 366 (PC-ALCL), 384, 385
minimal residual disease testing, 364, 365 Primary peripheral T-cell lymphoma, not other specified
multiple myeloma (PTCL-­NOS), 386
copy number-single nucleotide polymorphism Proficiency testing (PT), 81, 82
microarrays, 365 Programed cell death, 4
diagnostics tests, 361, 362 Proliferative CMML, 311
extramedullary plasma cell neoplasms differ from, 366, 367 Promoters, 6
genetic features, 366 Prostate adenocarcinoma, diagnosis of, 237
genetic findings impact, treatment of, 364 Prostate cancer
genetic studies, 364 gene expression profiling (GEP) assay, 237, 238, 242
genomic markers for, 367 molecular genetic abnormalities in, 237
risk stratification of, 363 pedigree of, 258
therapy-related myeloid neoplasms, 365 screening algorithm, 237, 238
uncertain significance and smoldering, 363, 364 Prostatic atrophy, 242
multiple myeloma, genetic tests, 363 Protected health information, bioinformatics, 75, 76
mutation analysis guide therapy, 367 Proto-oncogenes, 6, 36
myelomagenesis, primary and secondary genetic events, 362, 363 Pruritis, 388–390
plasma cell leukemia, definition of, 369, 370 Pseudoclonality, 341
relapsed and refractory myeloma, secondary genetic events in, 371 Pseudomyogenic hemangioendothelioma (PMHE), 211
symptomatic myeloma, work up and diagnostic criteria for, 367, PTEN hamartoma tumor syndromes, 177
368 Pulmonary adeno-squamous carcinoma, 164
therapy-related myeloid neoplasms, molecular testing of, 370, 371 Pulmonary blastoma, 151
Pleomorphic xanthoastrocytomas (PXAs), 127, 136 Pulmonary fibrosis, 435
Pleuritic chest pain, 217 Pulmonary salivary gland-type carcinomas, 151
Plexiform vasculature and signet-type lipoblasts, 220 Pyrosequencing, 122, 194
448 Index

Q BRAF mutations, 193, 194

Qualitative reverse transcriptase PCR (RT-PCR), 306 BRAF mutations, limitations, 194, 195
Quality assurance, 81 BRAF mutations, testing for, 195
Quantitative polymerase chain (qPCR), 306, 424 targetable mutations, 195
components and conditions, 31 dermatofibrosarcoma protuberans, unequivocal diagnosis of, 197, 198
delta Ct value, 32 malignant melanoma
detection methods, 32 molecular studies, 193
Quickscore, 96 proliferative nodules and molecular findings, 193
melanoma, prognosis for, 195, 196
molecular testing, 190, 191
R muir-torre syndrome, 196, 197
RAD51 foci assays, 103 mycosis fungoides
Radiation-associated angiosarcoma, molecular testing in, 211 diagnosis of, 197
RB gene, 7 nevoid malignant melanoma and benign melanocytic nevi, 191, 192
Reactive large granular lymphocytosis, 381 sebaceous neoplasm, 201, 203
Real-time PCR (qPCR), 27, 30 spitz tumors, 192, 193
Receptors tyrosine kinase (RTK) gene, 150 targeted therapy, 199, 200
Recurrent clear cell sarcoma, 224 Small cell carcinoma of the lung (SCLC), 150
Red cell phenotyping (RCP), 424 Small round cell tumors, differential of, 208
Reed-Sternberg cells, 353 SNP microarray, 334
RefSeq accession number, 64, 67 SNP-aCGH, 198, 199
Regulator proteins, 8 Soft tissue angiofibroma, 213
Regulatory DNA sequences, 6 Soft tissue tumors
Renal cell carcinoma, VHL mutations or 3p deletions, 233, 234 adipocytic tumors, molecular testing in, 209
RET rearrangement, 149 ALT/WDL, MDM2 FISH for diagnosis of, 209, 210
Retinoblastoma, 250 alveolar rhabdomyosarcoma, 211
Reverse transcription, 35 benign vascular tumor, 211
RNA analysis, molecular applications, 35 dedifferentiated liposarcoma, MDM2 FISH testing, 210
RNA-based analyses fibroblastic/myofibroblastic tumors, 213–215
translocations, 35 intermediate/low-grade vascular neoplasms, 211
Rosai-Dorfman disease (RDD), 417 myxoid liposarcoma, 210
Round cell sarcoma, 208 radiation-associated angiosarcoma, molecular testing in, 211
RUNX1 mutations, 290–292 skeletal muscle tumors, molecular testing in, 211
acute myeloid leukemia, 285 umbrella term spindle cell/sclerosing rhabdomyosarcoma, 212
uncertain differentiation, molecular testing, 212, 213
undifferentiated round cell sarcomas
S classification, 207–209
Sanger sequencing, 33 ewing sarcoma and, 209
Sarcoma/bone cancer predisposition syndromes, 247 NGS, limitations for, 209
Sclerosing epithelioid fibrosarcoma, 215 undifferentiated round cell sarcomas, molecular testing in, 207
Sclerosing extramedullary hematopoietic tumor, 220 vascular tumors, molecular testing in, 210, 211
Sclerosing rhabdomyosarcoma, 212 Solitary fibrous tumors (SFTs), 133, 214
Sebaceous neoplasm, 201, 203 Spindle cell rhabdomyosarcoma, 212
Secondary primary malignancies (SPMs), 365 Spitz tumors, 192, 193
Sequencing depth, 41, 42 Splice site mutation, 164
Sex cord-stromal tumors Sporadic cancer
molecular testing in, 111, 112 cellular pathways, molecular events of, 250, 251
Short tandem repeats (STRs), 425, 426 Squamous cell carcinoma (SCC)
biological and testing artifacts, 432, 433 mutation landscape of, 149, 150
genotyping, 112 mutation testing for, 150
interpretation and donor and recipient DNA quantification, Standard operation procedure (SOP), 81
428–431 STR electropherograms, 434
multiplex STR STR electropherograms of recipient, 435, 436
advantages and disadvantages, 431, 432 Stutter peaks, 432
Single gene sequencing, 122 Subcutaneous clear cell neoplasm, 226
Single nucleotide polymorphism (SNP) arrays, 122 Subcutaneous panniculitis-like T-cell lymphoma (SPTCL), 387, 388
Single-probe assay, 97 Sufficient T-cells, 197
Skeletal muscle tumors, molecular testing in, 211 Supratentorial ependymoma, 135
Skin tumors Symptomatic myeloma
BRAF mutations, 199, 201 work up and diagnostic criteria for, 367, 368
clonal T-cell receptor gene rearrangement, 203, 204 Synchronous multifocal lung cancers, 160
copy number variants, 191 Synovial sarcoma (SS), 212
cutaneous malignancies, gene expression profiling, 196 Systemic anaplastic large cell lymphoma (s-ALCL), 385
cutaneous melanoma, 189, 190 Systemic mastocytosis, diagnostic criteria for, 316, 317
Index 449

T Tumorigenesis, principles of, 9, 10

T lymphoblastic leukemia (T-ALL) Tyrosine kinase inhibitors (TKIs) therapy, 198
molecular genetic changes in, 332 chronic myeloid leukemia
T lymphoblastic leukemia/lymphoma (T-ALL) cause of, 307, 308
molecular genetic workup of, 326, 336 complete response, 307
Target-based amplification method, 36 tests recommended monitoring response, 307, 308
T-cell gene rearrangements
skin tumors, 197
T-cell large granular lymphocytic leukemia (T-LGLL), 381, 382 U
T-cell leukemia/lymphoma U.S. Food & Drug Administration, 77
among mature T-cell neoplasms, 379, 380 Ultinucleotide variants (MNV), 19, 20
T-cell prolymphocytic leukemia(T-PLL), 392 Umbrella term spindle cell/sclerosing rhabdomyosarcoma, 212
characteristic genetic alterations, 378, 379 Undifferentiated round cell sarcomas, 208
diagnosis of, 379 classification, 207–209
T-cell receptor (TCR) gene rearrangement, 377, 378 ewing sarcoma and, 209
T-cells, 423 NGS, limitations for, 209
Telomere, 5 Undifferentiated round cell sarcomas, molecular testing in, 207
Ten-eleven translocation proteins (TETs), 7 Urothelial carcinoma (UC) screening, 235, 236
Therapy-related malignancies, 365 molecular assays and indications, 236
Therapy-related myeloid neoplasms, molecular testing of, 370, 371 UroVysion assay, 236
TP53 mutations, 16, 152, 262 Uterine serous carcinoma, HER2 testing in, 110
acute myeloid leukemia, 284, 285 UV spectrophotometry, 26, 27
myeloid neoplasm, 17, 18
TP53 p.R342* mutation, 357
Transcriptomics, 123 V
Transfusion associated graft versus host disease (TA-GVHD), 422 Variant allele frequency (VAF), 254
Transient abnormal myelopoiesis (TAM), 285, 286 Variant filtering, bioinformatics, 74, 75
Translocation, 5 Vascular tumors, molecular testing in, 210, 211
Tri-alleleic bands, 433 VCF file, 61, 64
Trilineage hematopoiesis, 347 Vertigo, 215
Triple negative breast cancers (TNBC), 93 VNTR, 424
Trisomy 7, 240
Tumor mutational burden (TMB), 156, 157
Tumor suppressor genes, 6, 7, 250 W
features of, 251 Well-circumscribed submucosal mass, 223
Tumorigenesis, mismatch repair protein deficiency in, 174, 175 Wilms tumor, genetic alterations in, 235