Category: Clinical Updates

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.

Read More: Cleveland Clinic Newsroom

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.

Special Communications
Immediate Test Changes
News & Updates

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

Special Communications
Immediate Test Changes
News & Updates

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

Special Communications
Immediate Test Changes
News & Updates

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™.

Register Now!

Symposium Co-Directors

Sanjay Mukhopadhyay, MD

Sean Williamson, MD

Sean Williamson, MD

Faculty Presenters

John Goldblum, MD

John Goldblum, MD

Amy Joehlin-Price, MD

Amy Joehlin-Price, MD

Andrew Sciallis, 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

Special Communications
Immediate Test Changes
News & Updates

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.

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

Download this Overview (PDF)

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

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.

Special Communications
Immediate Test Changes
News & Updates

Pathology Insights: Update on Small Round Cell Tumors with Scott Kilpatrick, MD

Pathology Insights Video Series

Update on Small Round Cell Tumors with Scott Kilpatrick, MD

Presented by Scott Kilpatrick, MD

In this video, Scott Kilpatrick, MD, Director of Orthopedic Pathology at Cleveland Clinic, provides historical context and WHO updates on the evolving classification of undifferentiated round cell sarcomas, including Ewing sarcoma and the so-called Ewing family of sarcomas.

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.

Estimated Glomerular Filtration Rate (eGFR) Updates

Clinical Update

Estimated Glomerular Filtration Rate (eGFR) Updates

The National Kidney Foundation and American Society of Nephrology joint task force recently released recommendations on including a race variable in eGFR reporting (PMID: 34563581).

Based on these recommendations and internal review, the following changes will occur on February 26, 2022:

Adult eGFR Creatinine Calculation

The adult eGFR creatinine equation will be updated from MDRD to the 2021 CKD-EPI creatinine equation in all blood-based creatinine panels (e.g. BMP).

This equation utilizes creatinine, sex, and age, but does not include a race variable.

The new upper reporting limit will increase from 60 to 150 mL/min/1.73m2.

Adult Cystatin C-Based eGFR

eGFR confirmation with a cystatin C-based calculation is recommended near clinical decision-making thresholds.

Two new equations will be available:

2012 eGFR cystatin C (CYSTC)

  • Variables include cystatin C, age, and sex, but not race.

2021 eGFR creatinine-cystatin C (CRECYS)

  • Variables include creatinine, cystatin C, age, and sex, but not race.

Pediatric eGFR Reporting

The task force recommendations focus on the adult population; however, several changes related to EHR transformation will affect the pediatric population:

– The Bedside Schwartz creatinine factor will no longer be reported. The Bedside Schwartz creatinine equation will be provided as a comment: Bedside Schwartz equation = 0.413 x [height (cm) / serum creatinine (mg/dL)].

– The 2012 Schwartz cystatin C equation will be utilized for patients 2-17 years old when cystatin C (CYSTC) is ordered.

– The 2021 eGFR creatinine-cystatin C equation (CRECYS) is valid for adults only and will not be available to order for patients less than 18 years of age.

Special Communications
Immediate Test Changes
News & Updates

September 2021: New Test – Beta(β)-D-Glucan Assay

Clinical Update

New Test: Beta(β)-D-Glucan Assay

In-house Beta(β)-D-Glucan (BDG) testing is now available.

The assay diagnoses certain systemic fungal infections, such as Candidemia, and assists in the prognostication and monitoring response to anti-fungal therapy in hospitalized patients.

This FDA-approved test is a protease zymogen-based colorimetric assay (FUNGITELL® ASSAY) based on a modification of the Limulus Amebocyte Lysate (LAL) pathway in which BDG, where present in the sample, binds Factor G. Activated Factor G turns a proclotting enzyme to clotting enzyme. The latter cleaves an artificial chromogenic substrate (a short peptide) to generate a color. The reaction occurs at 37°C and is kinetically read by a spectrophotometer to generate a standard curve and sample readouts that are subsequently converted to BDG concentrations in pg/ml.

It is important to note that certain fungi, such as the genus Cryptococcus that produces very low levels of BDG, may not result in serum BDG levels sufficiently elevated to be detected by the assay. Infections with fungi of the order Mucorales, such as Absidia, Mucor, and Rhizopus, that are not known to produce BDG can also yield non-detectable serum BDG levels. In addition, the yeast phase of Blastomyces dermatitidis produces little BDG and may not be detected by the assay. Furthermore, positive BDG results have been seen in hemodialysis patients, those who received certain fractionated blood products (such as albumin, IVIg), and those exposed to glucan-containing gauze or surgical sponges.

The sample should be centrifuged within 2 hours of collection to separate the serum from the cells.

Separated samples or serum should be stored refrigerated pending delivery to the testing laboratory.

Heel and fingerprick collections are unacceptable.

Test Name
(1,3) B-D Glucan

Test Code
BDGLUC

CPT Code
87449

Methodology
Protease zymogen-based colorimetric assay (FUNGITELL® ASSAY)

Specimen Requirements
Type: Serum
Volume: 0.5 mL
Container: Gold BD Hemogard™ Serum Separation Tubes (SST)™
Transport Temperature: Refrigerated

Stability
Ambient: Unacceptable
Refrigerated: 7 days
Frozen: 1 year

Reference Range
Negative; <60 pg/mL

Reportable Range
31 to 500 pg/mL

Days Performed
Monday, Wednesday, Friday

Special Communications
Immediate Test Changes
News & Updates