The diagnosis of oncocytic salivary gland tumors can be challenging, especially on core needle biopsies.
Dr. Mobeen Rahman, staff Head & Neck pathologist, discusses an interesting case that explores this issue.
The CC-SIGN® Head & Neck Gene Fusion NGS Panel is available as part of a comprehensive, diagnostic consultation or as a stand-alone test. This laboratory-developed test interrogates gene targets associated with known translocations in salivary gland and other solid tumors. Additionally, this panel identifies the corresponding fusion partner which may be helpful in the selection of treatment targets in some cases.
Results are delivered within 14 days of specimen receipt, allowing for a timely, definitive diagnosis in difficult salivary gland tumors and other head and neck lesions in a stand-alone fashion or with the support of our expert pathologists.
Head and Neck Next Generation Sequencing (HDNK)
81445
88381
14 days (upon specimen receipt)
Formalin-fixed, paraffin-embedded (FFPE) tissue
• Ten (10) unstained, 4 μM sections of FFPE on charged, unbaked slides
• One (1) H&E stained slide with best tumor area* circled by a pathologist
*minimum of 20% tumor content for best results
Room (ambient) temperature
Cleveland Clinic Laboratories
2119 E. 93rd Street, L15
Cleveland, OH 44106
Specimens must be sent via UPS, FedEx, or DHL – review our Shipping Information for more details.
This test is intended for the diagnosis of benign or malignant mesenchymal tumors (sarcomas & their mimics) as well as other solid tumors.
Genes interrogated, including relevant transcripts and exons, are listed in alphabetical order.
Gene, Transcript, Exons
ALK
NM_004304
2, 4, 6, 10, 16-23, 25, 26
Gene, Transcript, Exons
BRAF
NM_004333
Exons 1-5, 7-16, 18
Gene, Transcript, Exons
CAMTA1
NM_015215
Exons 3, 8-10
CRTC1
NM_015321
Exons 1-4
Gene, Transcript, Exons
ETV6
NM_001987
Exons 1-7
EWSR1
NM_005243
Exons 4-14
Gene, Transcript, Exons
FOS
NM_005252
Exon 4
FOSB
NM_006732
Exons 1, 2
FOXO1
NM_002015
Exons 1-3
FUS
NM_004960
Exons 3-11, 13, 14
Gene, Transcript, Exons
GLI1
NM_005269
Exons 4-7
Gene, Transcript, Exons
HMGA2
NM_003483
Exons 1-5
Gene, Transcript, Exons
MAML2
NM_032427
Exons 2, 3
MKL2
NM_014048
Exons 11-13
MYB
NM_001130173
Exons 7-9, 11-16
Gene, Transcript, Exons
NCOA1
NM_147223
Exons 12-15
NR4A3
NM_006981
Exon 2
NR4A3
NM_173200
Exons 3, 4
NTRK1*
NM_002529
Exons 2, 4, 6, 8, 10-14
NTRK2*
NM_006180
Exons 5, 7, 9, 11-18
NTRK3*
NM_001007156
Exon 15
NTRK3*
NM_002530
Exons 4, 7, 10, 12-16
NUTM1
NM_175741
Exons 2-4, 6
*A specimen positive for a fusion in one of these genes makes the patient a candidate for larotrectinib treatment.
Standalone NTRK testing is also available via the CC-SIGN® NTRK Gene Fusion NGS Panel.
Gene, Transcript, Exons
PAX3
NM_181459
Exons 6-8
PAX7
NM_002584
Exons 6-8
PLAG1
NM_002655
Exons 1-4
PRKD1
NM_002742
Exons 10-13
Gene, Transcript, Exons
RET
NM_020630
Exons 2, 4, 6, 11, 15, 16
RET
NM_020975
Exons 8-14
Gene, Transcript, Exons
SS18
NM_001007559
Exons 2-6, 8-11
SS18
NM_005637
Exons 2, 3
STAT6
NM_001178078
Exons 1-7, 15-20
Gene, Transcript, Exons
TFE3
NM_006521
Exons 2-8
Gene, Transcript, Exons
YAP1
NM_001130145
Exons 1-9
In this video, Sanjay Mukhopadhyay, MD, Director of Pulmonary Pathology at Cleveland Clinic, highlights a rare, aggressive, malignant tumor and draws attention to a distinctive immunohistochemical profile that can serve as a tip-off to the correct diagnosis.
The diagnosis of CD30+ T-cell lymphoproliferative disorders, including ALK+ and ALK-negative forms of anaplastic large cell lymphoma, can present challenges. These entities show overlapping morphologic and immunohistochemical features but can vary widely in terms of clinical aggression.
Dr. Genevieve Crane, Staff Hematopathologist at Cleveland Clinic, discusses clinical presentation, morphologic features, and emerging prognostic markers that may aid in diagnosis and clinical management.
Analysis of a bone marrow requires both careful morphologic examination as well as appropriate ancillary studies.
Dr. Megan Nakashima, Staff Hematopathologist at Cleveland Clinic, discusses a complicated bone marrow case involving a patient with thrombocytopenia, monocytosis, and diarrhea. After requiring the incorporation of molecular and immunophenotypic information, two diagnoses are reached.
In addition to this case, Dr. Nakashima reviews relevant changes in the WHO 2016 classification of myeloid and associated neoplasms.
In the breast, the pathologic diagnosis of a small focus of invasion can be quite challenging.
Dr. Miglena Komforti discusses the histopathologic findings, ancillary immunohistochemical stains, and clinical significance of microinvasive cancer of the breast.
Pathologic diagnosis can be challenging in the setting of poorly-differentiated and metastatic renal cancer.
Dr. Sean Williamson, Director of Genitourinary Pathology at Cleveland Clinic, discusses immunohistochemical and molecular testing used to help confirm the diagnosis.
Sanjay Mukhopadhyay, MD, discusses the findings of a study on the lung pathology of vaping.
Featured in an article co-authored by Dr. Mukhopadhyay and published in the American Journal of Clinical Pathology, the study focuses on the results of microscopic examination of biopsied lung tissue from individuals who developed severe lung illness associated with vaping.
This is one of the first case series in the world to examine lung biopsies from patients with vaping-associated lung illness and is the first-ever study on vaping published in a pathology journal. These findings have important public health implications and are detailed in the video.
The US Food and Drug Administration (FDA) has approved the use of first-generation TRK tyrosine kinase inhibitors—including larotrectinib (Vitrakvi®) and entrectinib (Rozlytrek®)—to treat patients whose tumors harbor NTRK1, NTRK2, or NTRK3 fusions.
TRK tyrosine kinase inhibitors, such as larotrectinib and entrectinib, are drugs utilized to treat solid tumors with a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation. These drugs provide a treatment option to patients with no satisfactory alternative therapies or whose cancer has progressed following treatment, specifically in cases that are either metastatic or where surgical resection is likely to result in severe morbidity.1,2 This treatment targets cancers with NTRK fusions and is not limited by tissue or tumor type.
1. U.S. Food & Drug Administration. FDA approves larotrectinib for solid tumors with NTRK gene fusions. Available at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm626720.htm. [Online] Updated Dec 17, 2018.
2. U.S. Food & Drug Administration. FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-entrectinibntrk-solid-tumors-and-ros-1-nsclc [Online] Updated Aug 16, 2019.
NTRK Gene Fusion NGS Panel (NTRK)
81445, 88381
14 days (upon specimen receipt)
Please include the original pathology report with any submitted specimens.
Ten (10) unstained, 4 µM sections of formalin-fixed, paraffin-embedded (FFPE) on charged, unbaked slides
One H&E stained slide with best tumor area circled by a pathologist (minimum of 20% tumor content for best results)
Room (ambient) temperature
Cleveland Clinic Laboratories
2119 E. 93rd Street, L15
Cleveland, OH 44106
Specimens must be sent via UPS, FedEx, or DHL – review our Shipping Information for more details.
This test is intended for determining NTRK gene fusion status to identify candidates for larotrectinib treatment.
This test does not detect single nucleotide variants; some data show acquired kinase domain resistance mutations that are not interrogated by this test.
NTRK1
NM_002529
Exons 2, 4, 6, 8, 10-14
NTRK2
NM_006180
Exons 5, 7, 9, 11-18
NTRK3
NM_001007156
Exon 15
NTRK3
NM_002530
Exons 4, 7, 10, 12-16
The CC-SIGN® Solid Tumor Gene Fusion NGS Panel is available as part of a comprehensive, diagnostic consultation or as a stand-alone test. This laboratory-developed test interrogates gene targets associated with known translocations in mesenchymal and other solid tumors. Additionally, this panel identifies the corresponding fusion partner and predicted exon breakpoints, which can be of diagnostic and prognostic significance. Fluorescence in situ hybridization-based testing is available for specific fusion questions.
Results are delivered within 14 days of specimen receipt, allowing for a timely, definitive diagnosis in difficult sarcoma and solid tumor cases in a stand-alone fashion or with the support of our expert pathologists.
Solid Tumor Gene Fusion NGS Panel (SRCNGS)
81445
88381
14 days (upon specimen receipt)
Formalin-fixed, paraffin-embedded (FFPE) tissue
• Ten (10) unstained, 4 μM sections of FFPE on charged, unbaked slides
• One (1) H&E stained slide with best tumor area* circled by a pathologist
*minimum of 20% tumor content for best results
Room (ambient) temperature
Cleveland Clinic Laboratories
2119 E. 93rd Street, L15
Cleveland, OH 44106
Specimens must be sent via UPS, FedEx, or DHL – review our Shipping Information for more details.
This test is intended for the diagnosis of benign or malignant mesenchymal tumors (sarcomas & their mimics) as well as other solid tumors.
Genes interrogated, including relevant transcripts and exons, are listed in alphabetical order.
Gene, Transcript, Exons
ABL1
NM_004304
2, 4, 6, 10, 16-23, 25, 26
Gene, Transcript, Exons
BCOR
NM_001123385
Exons 3-8, 12, 14, 15
BCOR
NM_017745
Exon 8
BRAF
NM_004333
Exons 1-5, 7-16, 18
Gene, Transcript, Exons
CAMTA1
NM_015215
Exons 3, 8-10
CCNB3
NM_033031
Exons 2-6
CIC
NM_015125
Exons 12, 17-20
CRTC1
NM_015321
Exons 1-4
CSF1
NM_000757
Exons 5-8
CSF1
NM_172212
Exon 9
Gene, Transcript, Exons
EPC1
NM_025209
Exons 9-11
ETV6
NM_001987
Exons 1-7
EWSR1
NM_005243
Exons 4-14
Gene, Transcript, Exons
FOS
NM_005252
Exon 4
FOSB
NM_006732
Exons 1, 2
FOXO1
NM_002015
Exons 1-3
FUS
NM_004960
Exons 3-11, 13, 14
Gene, Transcript, Exons
GLI1
NM_005269
Exons 4-7
Gene, Transcript, Exons
HMGA2
NM_003483
Exons 1-5
Gene, Transcript, Exons
JAZF1
NM_175061
Exons 2-4
Gene, Transcript, Exons
MAML2
NM_032427
Exons 2, 3
MEAF6
NM_001270875
Exons 4, 5
MKL2
NM_014048
Exons 11-13
MYB
NM_001130173
Exons 7-9, 11-16
Gene, Transcript, Exons
NCOA1
NM_147223
Exons 12-15
NCOA2
NM_006540
Exons 11-16
NCOA3
NM_006534
Exons 2, 13-16
NCOA3
NM_181659
Exon 20
NOTCH1
NM_017617
Exons 2, 4, 24-31
NOTCH2
NM_024408
Exons 5-7, 24-29
NOTCH3
NM_000435
Exons 25-30
NR4A3
NM_006981
Exon 2
NR4A3
NM_173200
Exons 3, 4
NTRK1*
NM_002529
Exons 2, 4, 6, 8, 10-14
NTRK2*
NM_006180
Exons 5, 7, 9, 11-18
NTRK3*
NM_001007156
Exon 15
NTRK3*
NM_002530
Exons 4, 7, 10, 12-16
NUTM1
NM_175741
Exons 2-4, 6
*A specimen positive for a fusion in one of these genes makes the patient a candidate for larotrectinib treatment.
Standalone NTRK testing is also available via the CC-SIGN® NTRK Gene Fusion NGS Panel.
Gene, Transcript, Exons
PAX3
NM_181459
Exons 6-8
PAX7
NM_002584
Exons 6-8
PDGFB
NM_002608
Exons 2, 3
PDGFD
NM_025208
Exons 5-7
PGR
NM_000926
Exons 1-3
PHF1
NM_024165
Exons 1, 2, 10-12
PLAG1
NM_002655
Exons 1-4
PRDM10
NM_199437
Exons 12, 13
PRKD1
NM_002742
Exons 10-13
Gene, Transcript, Exons
RAF1
NM_002880
Exons 4-12
RELA
NM_021975
Exons 3 , 4, 11
RET
NM_020630
Exons 2, 4, 6, 11, 15, 16
RET
NM_020975
Exons 8-14
ROS1
NM_002944
2, 4, 7, 31-38
Gene, Transcript, Exons
SRF
NM_003131
Exons 2-4
SS18
NM_001007559
Exons 2-6, 8-11
SS18
NM_005637
Exons 2, 3
STAT6
NM_001178078
Exons 1-7, 15-20
Gene, Transcript, Exons
TAF15
NM_139215
Exons 5-7
TCF12
NM_207036
Exons 4-6
TFE3
NM_006521
Exons 2-8
TFEB
NM_007162
Exons 1-4, 9
TFG
NM_006070
Exons 3-7
TRIM11
NM_145214
Exons 2, 3
Gene, Transcript, Exons
USP6
NM_004505
Exons 1-3
Gene, Transcript, Exons
WWTR1
NM_015472
Exons 3, 4
Gene, Transcript, Exons
YAP1
NM_001130145
Exons 1-9
YWHAE
NM_006761
Exon 5
