Category: Clinical Updates

Per the National Comprehensive Cancer Network (NCCN) Myelodysplastic Syndromes Guidelines [version 1.2023 (09/12/22)]:

Posted on July 12, 2023July 12, 2023

July 2023: Updates to Recommended Myelodysplastic Syndrome Testing

Updates to Recommended Myelodysplastic Syndrome (MDS) Testing

Effective August 17, 2023.

Cleveland Clinic Laboratories’ Molecular Pathology & Cytogenomics section offers several testing options for individuals suspected to have Myelodysplastic Syndrome (MDS):

Chromosome Analysis Only CHRBMH
Chromosome Analysis with reflex to FISH with MDS Panel* (if there are no chromosome results or the chromosome analysis was sub-optimal) CHRMDS
Chromosome Analysis with reflex to Microarray (CMA) BMCHF

FISH Only with MDS Panel*, blood FSHMDS
FISH Only with MDS Panel*, bone marrow FSMDSM

*MDS Panel contains FISH probes specific to chromosomes 5, 7, 8, and 20.

Testing Guidelines

If standard cytogenetics (with ≥20 metaphases) cannot be obtained, a chromosome microarray [(CMA), also known as chromosome genomic array testing (CGAT)] or MDS-related fluorescence in situ hybridization (FISH) panel should be performed. If karyotype is normal, consider CMA. Note that CMA will detect not only somatic but constitutional (germline) changes.

Recommended Testing

In keeping with the NCCN guidelines, Chromosome Analysis with Reflex to FISH (CHRMDS) is Cleveland Clinic Laboratories’ recommended test for individuals suspected to have MDS.

Discontinued Testing

Beginning August 17, 2023, the FISH Only with MDS Panel (FSHMDS & FSMDSM) for blood and bone marrow will be discontinued.
Note: Chromosome Analysis Only (CHRBMH) and Chromosome Analysis with reflex to Microarray (BMCHF) may still be ordered.

Questions?

Please contact your CCL Sales Manager or Client Services at 800.628.6816.

Posted on July 11, 2023

Cleveland Clinic and LabConnect Announce Strategic Alliance

Clinical Update

Cleveland Clinic and LabConnect Announce Strategic Alliance

Collaboration on lab services will accelerate clinical trials to better impact patient care.

Cleveland Clinic Laboratories and LabConnect have announced a strategic alliance to accelerate clinical trials and connect patients to new medicines for improved patient care.

Through this alliance, LabConnect will utilize Cleveland Clinic Laboratories, the reference laboratory within Cleveland Clinic. LabConnect will leverage the health system’s extensive array of testing and assay validation services to support laboratory testing for an increasing number of clinical trials.

CC-SIGN® Targeted Oncology Panel (TOP) by Next-Generation Sequencing

Clinical Updates

New Test: CC-SIGN^® Targeted Oncology Panel (TOP) by Next-Generation Sequencing

Available to order starting on June 20, 2023.

A new, enhanced 59-gene hotspot Next-Generation Sequencing (NGS) panel is available for tumor DNA and RNA evaluation.

The Targeted Oncology Panel (TOP) is a custom 59-gene Next-Generation Sequencing (NGS) panel developed for the identification of single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number gains (CNVs) from DNA specimens, and fusion transcripts and aberrant transcripts from RNA specimens.

The workflow allows for the concurrent testing of DNA and RNA to analyze over 1,000 biomarkers.

Read the Technical Brief

Targeted Oncology Panel by NGS

Order Codes
TOPTO (FFPE Tissue)
TOPCY (Cytology Alcohol or Formalin fixed cell block)
TOPBM (Bone Marrow Aspirate)
TOPPB (Peripheral Blood)

This test requires 5-10% tumor purity and does not evaluate circulating tumor DNA.

CPT Code
81445

Methodology
Next-Generation Sequencing

Specimen Type
FFPE Tissue
• 15 charged, unbaked, and unstained slides sectioned at 7 μm.
• One pre and one post H&E slide with tumor area circled, and percent rumor indicated.

Cytology
• 15 charged, unbaked and unstained slides sectioned at 7 μm.
• One H&E slide with tumor percent indicated.

Bone Marrow Aspirate
• 2 mL, Lavender K₂EDTA Tube

Peripheral Blood
• 4 mL, Lavender K₂EDTA Tube

Days Performed
2–3 times per week

Turnaround Time
8 days

Overview

Single nucleotide variants (SNVs), small insertions and deletions (indels), copy number gains, select fusions, and aberrant transcripts evaluated by this assay can aid in the diagnostic and therapeutic assessment of a variety of tumor types, including non-small cell lung cancer, melanoma, colorectal cancer, prostate cancer, breast cancer, glioblastoma, thyroid cancer, and others.

This panel can also provide focused tumor profiling for patients with locally advanced/metastatic disease, who are candidates for anti-cancer therapy, to identify uncommon but targetable alterations. In particular, this panel can be utilized for small biopsies and cytology specimens that may not be amenable to more comprehensive genomic sequencing.

Targeted Genes & RNA Fusions

For a full list of targeted genes & RNA fusions, please refer to the Targeted Oncology Panel by Next-Generation Sequencing Technical Brief.

How to Order

Place an order through an electronic interface or complete a Molecular Oncology & Associated Biomarkers Requisition and submit it with the specimen(s).

Hot Spot Panel Discontinuation

The TOP NGS panel will replace solid tumor hotspot mini-panels (Lung, Colorectal, Melanoma, GIST, etc.), as all previously detected biomarkers are included in the new testing.

In situations where the mini-panels were previously used as part of an upfront diagnostic workup, pathologist diagnostic and reflex ordering will utilize TOP testing.

Posted on May 18, 2023May 18, 2023

May 2023: New Test – Clozapine (CLOZA)

Clinical Updates

New Test: Clozapine (CLOZA)

Effective May 23, 2023.

Therapeutic drug monitoring for clozapine will be offered as an in-house test starting Tuesday, May 23, 2023.

The current send-out test, Clozapine and Metabolites, Serum or Plasma, Quantitative (CLOZSP), currently sent out to ARUP Laboratories, will be discontinued on June 20, 2023.

Clozapine (CLOZA)

New Test – CLOZA

Specimen Type
Red Serum Tube (No Additive)

Methodology
Turbidimetric immunoassay

Result Components
Clozapine

Days Performed
Monday – Saturday

Turnaround Time
1-4 days

Clozapine results greater than 1000 ng/mL have been designated as urgent.

Sendout Test – CLOZSP

Specimen Type
Red Serum Tube (No Additive) or Lavender K₂EDTA Tube

Methodology
Liquid chromatography-tandem mass spectrometry

Result Components
Clozapine
Norclozapine
Clozapine-N-Oxide

Days Performed
Sunday – Saturday

Turnaround Time
2-4 days

Posted on May 2, 2023

May 2023: Changes to Legionella Diagnostic Testing (LEGPCR)

Clinical Updates

Changes to Legionella Diagnostic Testing (LEGPCR)

Effective May 2, 2023.

Improvements to Cleveland Clinic Laboratories’ Legionella PCR assay will result in the discontinuation of most Legionella cultures.

Beginning May 2, 2023, Legionella pneumophila PCR (LEGPCR) will include additional DNA targets for Legionella, including species other than Legionella pneumophila, and a target specific for Legionella pneumophila serogroup 1.

This assay design is modeled after the U.S. Centers for Disease Control & Prevention’s assay.¹

Legionella pneumophila PCR (LEGPCR)

Specimen Requirements
Lower respiratory samples, including bronchoalveolar lavage (BAL) and sputa, will continue to be the acceptable specimen types for PCR.

Results
Possible interpretations of test results include:

Legionella pneumophila Serogroup 1 Detected
Legionella pneumophila (not Serogroup 1) Detected
Legionella species (not pneumophila) Detected

Additional Updates
Beginning May 23, 2023, routine culture for Legionella spp. (LEGCUL) will be discontinued, but culture will reflexively be performed on any sample with detectable Legionella DNA by PCR.

Note: There is no change to Legionella urine antigen (LEGUAG) testing.

Reference

¹ Benitez AJ, Winchell JM. Clinical application of a multiplex real-time PCR assay for simultaneous detection of Legionella species, Legionella pneumophila, and Legionella pneumophila serogroup 1. J Clin Microbiol. 2013 Jan;51(1):348-51. doi: 10.1128/JCM.02510-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536254/pdf/zjm348.pdf

Posted on March 30, 2023April 3, 2023

2024 Cleveland Clinic Multispecialty Pathology Symposium – Register Now!

Clinical Updates

2024 Cleveland Clinic Multispecialty Pathology Symposium

January 26-28, 2024 | Wynn Las Vegas

Overview

This pathology symposium will focus on practical discussions of commonly encountered problems in surgical pathology. The goal is to provide useful tips that the speakers utilize in their own practice at the microscope. We aim to address and discuss common problems and avoid an undue focus on esoterica.

In this course, renowned subspecialists who are highly sought-after for their teaching skills will cover a broad spectrum of cases, including genitourinary pathology, thoracic pathology, gastrointestinal and soft tissue pathology, gynecologic cancer, and breast pathology.

Practicing pathologists, fellows, and residents who attend will maintain, develop, and increase their knowledge, competence, and professional performance, with the intent to improve diagnosis and positively impact patient care.

Target Audience: Pathologists, Pathology Residents & Fellows

This activity has been approved for AMA PRA Category 1 credit™.

Symposium Co-Directors

Sanjay Mukhopadhyay, MD
Director, Pulmonary Pathology

Sean Williamson, MD
Director, Genitourinary Pathology

Faculty Presenters

John Goldblum, MD

Amy Joehlin-Price, MD

Andrew Sciallis, MD

Agenda

Friday

Friday, January 26, 2024

7:00 am Registration, Continental Breakfast, and Exhibits

8:00 am Welcoming Remarks – Sean Williamson, MD, and Sanjay Mukhopadhyay, MD

Genitourinary Pathology

8:10 am Pattern Based Approach to Renal Cell Tumors – Sean Williamson, MD

9:00 am What’s New in Prostate Cancer Pathology? – Sean Williamson, MD

9:45 am Question & Answer Period

10:00 am Refreshment Break and Exhibits

GI and Soft Tissue Pathology

10:30 am Barrett’s Esophagus and BE-related Dysplasia: A Practical Approach to the Most Common Problems – John Goldblum, MD

11:15 am IBD and IBD-related Dysplasia with a Focus on Unusual Variants of Ulcerative Colitis – John Goldblum, MD

12:00 pm Question & Answer Period

12:15 pm Lunch served at Wynn Las Vegas

Pulmonary Pathology

1:15 pm The New, the Exciting, and the Annoying. Updates in Lung Cancer in 2023 – Sanjay Mukhopadhyay, MD

2:00 pm What I Learned from Mistakes in Thoracic Pathology – Sanjay Mukhopadhyay, MD

2:45 pm Questions & Answer Period

3:00 pm Refreshment Break and Exhibits

Gynecologic Pathology

3:30 pm Practical Staging in Endometrial Cancer: Important Details Made Easier – Amy Joehlin-Price, MD

4:15 pm Classifying High Grade Endometrial Cancer: When Histotype Matters and Why – Amy Joehlin-Price, MD

5:00 pm Question & Answer Period

5:15 pm Adjourn

Saturday

Saturday, January 27, 2024

7:15 am Continental Breakfast and Exhibits

Breast Pathology

8:00 am Problematic Intraductal Breast Lesions – Andrew Sciallis, MD

8:45 am Papillary Neoplasms of the Breast – Andrew Sciallis, MD

9:30 am Question & Answer Period

9:45 am Refreshment Break and Exhibits

Pulmonary Pathology

10:15 am 10 Lung Tumors You Must Have in Your Toolbox – Sanjay Mukhopadhyay, MD

11:00 am Mesothelioma and Thymoma: Tips and Tricks to Simplify Your Life – Sanjay Mukhopadhyay, MD

11:45 am Question & Answer Period

12:00 pm Lunch – On Your Own

GI and Soft Tissue Pathology

1:30 pm Common Problems in Diagnosis and Terminology in Colorectal Polyps – John Goldblum, MD

2:15 pm The Trouble with Fat: How to Handle the Most Common Lipomatous Tumors – John Goldblum, MD

3:00 pm Question & Answer Period

3:15 pm Refreshment Break and Exhibits

Genitourinary Pathology

3:45 pm What’s New in Bladder Cancer Pathology? – Sean Williamson, MD

4:30 pm Common Challenges in Testicular Tumors – Sean Williamson, MD

5:15 pm Question & Answer Period

5:30 pm Adjourn

Sunday

Sunday, January 28, 2024

7:15 am Continental Breakfast and Exhibits

Gynecologic Pathology

8:00 am Ovarian Frozen Section Pathology: How What You Say Affects What They Do – Amy Joehlin-Price, MD

8:45 am Vulvar Squamous Cell Carcinoma: Why We’re Making It More Complicated and How to Think about It Simply – Amy Joehlin-Price, MD

9:30 am Question & Answer Period

9:45 am Refreshment Break and Exhibits

Breast Pathology

10:15 am Challenging Spindle Cell Lesions of the Breast – Andrew Sciallis, MD

11:00 am Fibroepithelial Lesions of the Breast: An Overview – Andrew Sciallis, MD

11:45 am Question & Answer Period

12:00 pm Closing Remarks – Sean Williamson, MD, and Sanjay Mukhopadhyay, MD

12:15 pm Adjourn

Download this Overview (PDF)

Posted on December 1, 2022December 1, 2022

Pathology Insights: Tumors of the Lung with Sanjay Mukhopadhyay, MD

Pathology Insights Video Series

Tumors of the Lung

Presented by Sanjay Mukhopadhyay, MD

In this video, an expert pulmonary pathologist and director of Cleveland Clinic’s Pulmonary Pathology service briefly covers all lung tumor types – including all the subtypes of lung cancer – listed in the new (2021) World Health Organization classification. Dr. Mukhopadhyay then describes the primary pathologic features of these tumors with high-quality pathology images provided in most cases.

This video should be helpful for patients, surgeons, pulmonologists, oncologists, pathologists, residents, and medical students.

**As part of our educational mission for our clients and communities, Cleveland Clinic Laboratories presents the Pathology Insights video series.**

These short videos break down information about interesting pathology cases to better inform doctors, laboratory staff, patients, or anyone interested in the field of pathology. Each episode features important cases, methods, and practices that are personally presented by our staff pathologists.

Posted on August 29, 2022August 29, 2022

September 2022: Best Practice for Detecting Hyperhomocysteinemia – Homocysteine Testing—Not MTHFR Genotyping

Best Practice for Detecting Hyperhomocysteinemia: Homocysteine Testing—Not MTHFR Genotyping

There is no conclusive evidence supporting the clinical value of MTHFR polymorphism genotyping.

Practice guidelines from multiple professional societies agree that MTHFR polymorphism genotyping should not be ordered as part of clinical evaluation.

If there is a clinical concern regarding hyperhomocysteinemia, Cleveland Clinic Laboratories recommends Homocysteine testing (HOMCYS) in place of MTHFR genotyping. Homocysteine testing is less expensive, generates a result more quickly, and provides additional actionable information for patient management.

Best Practice

If there is a clinical concern regarding hyperhomocysteinemia (HCC), Cleveland Clinic Laboratories recommends Homocysteine testing (HOMCYS) in place of MTHFR genotyping

Homocysteine (HOMCYS)

Upcoming Changes

November 15, 2022: MTHFR genotyping (MTHFRM) will no longer be available as a send-out test, even if ordered as a miscellaneous test.

March 16, 2021: Homocysteine testing (HOMCYS) will replace MTHFR genotyping at Cleveland Clinic.

HOMCYS Test Overview

Homocysteine (HOMCYS) Test Details

Test Name

Homocysteine

Test Code

HOMCYS

CPT Code

83090

Performing Laboratory

Cleveland Clinic Laboratories

FDA Compliance

In Vitro Diagnostic (IVD)

Methodology

Enzymatic

Days Performed

Sun – Sat

Turnaround Time

8 hours

Specimen Requirements

Type:
Plasma

Volume:
1 mL

Specimen Container:
Light Green Lithium Heparin Plasma Separator Tube (PST)

Transport Temperature:
Refrigerated

Place specimen on ice after draw.

Alternative Specimen Requirements

Type:
Serum

Volume:
1 mL

Specimen Container:
Gold Serum Separation Tube (SST)

Transport Temperature:
Refrigerated

Place specimen on ice after draw.

Special Instructions

• Centrifuge and separate plasma/serum from cells less than one hour after collection.

• If collected in a non-gel separator tube, centrifuge and transfer plasma/serum to a CCL tube and refrigerate.

Stability

Ambient:
4 days

Refrigerated:
4 weeks

Frozen:
10 months

Reference Interval

18-99 Years – Normal:
<15.1 umol/L

MTHFR: Lack of Evidence

Lack of Evidence for MTHFR Polymorphism Genotyping

Recommendation: Test Plasma Homocysteine Levels

There is no conclusive evidence supporting the clinical value of MTHFR polymorphism genotyping.

If there is a clinical concern regarding hyperhomocysteinemia, Cleveland Clinic Laboratories recommends Homocysteine (HOMCYS) testing.

• Multiple practice guidelines agree that MTHFR polymorphism genotyping should not be ordered as part of a clinical evaluation.

• A cheaper, faster, and more accurate way to test for hyperhomocysteinemia is to measure plasma homocysteine levels.

• If plasma homocysteine levels are high, patients can supplement with vitamins such as B6, B12, folate, and folic acid.

• If plasma homocysteine levels are normal, no treatment is indicated—even if there is an MTHFR variant.

Plasma homocysteine levels determine clinical management, regardless of the MTHFR genotype result.

Professional Societies with MTHFR Polymorphism Testing Guidelines:

After reviewing these guidelines,
Cleveland Clinic’s RT-PLMI Section of Molecular Pathology, Genomic Medicine Institute, and Laboratory Stewardship Committee agreed to discontinue MTHFR polymorphism genotyping.

Background

The MTHFR gene (OMIM: 607093) on 1p36.22 encodes the 5,10-methylenetetrahydrofolate reductase enzyme, which converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the primary circulatory form of folate. This enzyme is also involved in the metabolism of the amino acid, homocysteine. A deficiency of the enzyme can lead to HHC.

Polymorphisms are common variants within a gene that do not necessarily affect its function, unlike pathogenic or disease-causing variants. Two commonly tested polymorphic variants in MTHFR are:

c.665C>T* (p.Ala222Val)
*Historically referred to as C677T, the ‘thermolabile’ variant

c.1286A>C (p.Glu429Ala)

These variants are so common that approximately 25% of individuals with Hispanic ancestry and 15% of North Americans with European ancestry have two copies of c.665C>T.

The presence of two copies of c.665C>T (homozygosity) may result in decreased MTHFR enzyme activity and mild HHC. Neither of these MTHFR polymorphisms causes severe MTHFR deficiency (<20% enzyme activity).

References

1. Lack of Evidence for MTHFR Polymorphism Testing. ACMG Practice Guideline. Genet Med. 2013;15(2):153-6.
2. Inherited Thrombophilias in Pregnancy. ACOG Practice Bulletin. No. 197. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2018;132:e18–34.
3. Levin BL, Varga E. MTHFR: Addressing Genetic Counseling Dilemmas Using Evidence-Based Literature. J Genet Counsel. 2016;25:901-11.
4. Choosing Wisely® Initiative https://www.choosingwisely.org/
5. Eng, C. A Genetic Test You Don’t Need: Testing MTHFR is usually unnecessary. Cleveland Clinic Health Essentials. https://health.clevelandclinic.org/a-genetic-test-you-dont-need/. Accessed November 19, 2020.

Updating Best Practices

Cleveland Clinic Laboratories encourages providers to incorporate Homocysteine testing (HOMCYS) into their practice in place of MTHFR genotyping.

November 15, 2022: MTHFR genotyping will no longer be available as a send-out test, even if ordered as a miscellaneous test.

March 16, 2021: MTHFR genotyping will no longer be performed in-house at Cleveland Clinic.