CPT 0566U: Episeek MPE Pleural Fluid Methylation Test

CPT code 0566U is a Proprietary Laboratory Analyses (PLA) code for the Episeek™ MPE (Malignant Pleural Effusion Detection Test) from Precision Epigenomics Inc., a molecular diagnostic test that analyzes pleural fluid using quantitative polymerase chain reaction (qPCR) to assess methylation changes across 13 DNA regions and generates a qualitative algorithm-based result; service type: laboratory molecular diagnostic assay; typical site of service: clinical laboratory or hospital laboratory processing pleural fluid specimens.

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CPT 0566U: Episeek MPE Pleural Fluid Methylation Test

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Get alerted when payer policies referencing 0566U are released or updated.

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Receive email alerts as soon as relevant payer policies are published or updated.

Clinical & Coding Specifications

Clinical Context

A typical patient scenario involves an adult presenting with a pleural effusion of unclear etiology identified on chest radiograph or chest CT. The treating clinician (pulmonologist, thoracic surgeon, or interventional radiologist) performs thoracentesis to obtain pleural fluid for diagnostic testing. When cytology and standard laboratory testing (cell count, chemistry, Gram stain/culture) are inconclusive for malignancy, the clinician sends pleural fluid for the Episeek™ MPE (Malignant Pleural Effusion Detection Test) to evaluate DNA methylation patterns in 13 genomic regions by quantitative PCR. The laboratory performs the proprietary assay and runs an algorithm to provide a qualitative result (e.g., positive/negative for methylation patterns associated with malignant pleural effusion). Typical sites of service include hospital-based laboratories, hospital outpatient departments, and independent clinical reference laboratories that process specimens received from inpatient or outpatient settings. The clinical workflow: patient evaluation → thoracentesis and specimen collection → standard pleural fluid studies and cytology → send additional aliquot to the lab performing the Episeek™ MPE (0566U) → laboratory analytic processing and algorithmic interpretation → result returned to ordering clinician for integration into diagnostic decision-making regarding malignant pleural effusion.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`32421`	Diagnostic thoracentesis, with imaging guidance when performed (needle or catheter), initial or subsequent	Performed to obtain pleural fluid specimen for cytology and molecular testing such as the Episeek™ MPE.
`88112`	Cytopathology, fluid, washings, or brushings, for diagnosis (interpretation)	Standard cytologic evaluation of pleural fluid typically performed alongside molecular testing to detect malignant cells.
`83890`	Molecular pathology procedure, each targeted genomic sequence analysis, direct probe technique (e.g., qPCR)	Represents molecular analytic methods similar in technique (qPCR) though `0566U` is a PLA code specific to the Episeek™ assay; labs may bill `0566U` instead of generic molecular codes.
`36415`	Collection of venous blood by venipuncture	Common specimen collection CPT for required blood tests that may accompany pleural fluid diagnostic workup (pre-procedure labs, biomarkers).

Related Modifiers

5 rows

Modifier	Description	When to Use
22	Modifier –22 (Increased Procedural Services) is used when a reported procedure is substantially more extensive than normally required. The CPT Manual and CMS state it may be appended only when the…	- When to use: Append modifier -22 to a procedural CPT code when the service performed is substantially more extensive than the usual service described by that code — i.e., the procedure required…
52	Modifier ‑52 (Reduced Services) indicates that a service or procedure was partially reduced or omitted at the provider’s discretion, allowing reporting of the basic procedure number with a qualifier…	- Use modifier -52 when a physician or qualified health professional electively reduces or omits part of a procedure or service (for example, performing fewer required views or omitting a portion of…
53	Modifier 53 (Discontinued Procedure) signals that a surgical or diagnostic service was begun by the physician but terminated because of extenuating circumstances that threatened the patient’s…	- Use modifier -53 when a physician/qualified healthcare professional has started a surgical or diagnostic procedure (e.g., anesthesia administered, incision or scope insertion) and then discontinues…
[object Object]
25	CPT modifier 25 indicates that on the same day as another procedure or service, the same physician or other qualified health care professional provided a significant, separately identifiable…	- When to apply: Use modifier 25 only on an E/M code to indicate the same provider delivered a significant, separately identifiable E/M service on the same day as another procedure or service — i.e.,…

Related Provider Taxonomies

8 rows

Taxonomy Code	Specialty	Notes
2084P0800X	Psychiatry Physician	A Psychiatrist specializes in the prevention, diagnosis, and treatment of mental disorders, emotional disorders, psychotic disorders, mood disorders, …
363L00000X	Nurse Practitioner	(1) A registered nurse provider with a graduate degree in nursing prepared for advanced practice involving independent and interdependent decision mak…
207K00000X	Allergy & Immunology Physician	An allergist-immunologist is trained in evaluation, physical and laboratory diagnosis, and management of disorders involving the immune system. Select…
208000000X	Pediatrics Physician	A pediatrician is concerned with the physical, emotional and social health of children from birth to young adulthood. Care encompasses a broad spectru…
175M00000X	Lay Midwife	A person qualified by experience and limited specialized training to provide obstetric and neo-natal care in the management of women having normal pre…
156FC0801X	Contact Lens Fitter	An optician or other ancillary support staff person who, where authorized by state law and trained or certified to do so, may fit or dispense contact …
237600000X	Audiologist-Hearing Aid Fitter	An audiologist/hearing aid fitter is the professional who specializes in evaluating and treating people with hearing loss, conducts a wide variety of …
2083P0011X	Undersea and Hyperbaric Medicine (Preventive Medicine) Physician	A specialist who treats decompression illness and diving accident cases and uses hyperbaric oxygen therapy to treat such conditions as carbon monoxide…

Related ICD-10-CM Codes

24 rows

ICD-10-CM Code	Description
B90.9	Sequelae of respiratory and unspecified tuberculosis
C34.11	Malignant neoplasm of upper lobe, right bronchus or lung
C34.12	Malignant neoplasm of upper lobe, left bronchus or lung
C34.31	Malignant neoplasm of lower lobe, right bronchus or lung
C34.32	Malignant neoplasm of lower lobe, left bronchus or lung
C34.90	Malignant neoplasm of unspecified part of unspecified bronchus or lung
C38.4	Malignant neoplasm of pleura
C78.7	Secondary malignant neoplasm of liver and intrahepatic bile duct
D04.9	Carcinoma in situ of skin, unspecified
D49.9	Neoplasm of unspecified behavior of unspecified site

Showing 1–10 of 24

CPT 0001U: PreciseType HEA Erythrocyte Antigen Genotyping

CPT-0002U-POLYPDX-URINE-METABOLOMIC-ASSAY-ADENOMATOUS-POLYP-RISK

CPT 0002U: PolypDX™ Urine Metabolomic Risk Assay

CPT-0003U-OVAR-A-NEXT-GENERATION-OVARIAN-CANCER-RISK-ASSAY

CPT 0003U: Overa (MIA2G) Ovarian Cancer Risk Assay

CPT-0005U-PROSTATE-EXOSOMEDX-INTELLISCORE-GENE-EXPRESSION-URINE-TEST

CPT 0005U: ExosomeDx Prostate (IntelliScore) urine gene expression test

CPT-0007U-TOXPROTECT-URINE-DRUG-SCREEN-WITH-DNA-AUTHENTICATION

CPT 0007U: ToxProtect Urine Drug Screen With DNA Authentication

CPT-0008U-H-PYLORI-ANTIBIOTIC-RESISTANCE-SEQUENCING-PANEL

CPT 0008U: H. pylori Antibiotic Resistance Gene Panel

CPT-0009U-DEPARRAY-HER2-FISH-TUMOR-CELL-ISOLATION

CPT 0009U: DEPArray HER2 Tumor‑Cell Isolation with FISH Analysis

CPT-0010U-BACTERIAL-TYPING-WHOLE-GENOME-SEQUENCING-MAYO-CLINIC

CPT 0010U: Bacterial Typing by Whole Genome Sequencing, Mayo Clinic

CPT-0011U-CORDANT-CORE-ALGORITHMIC-ORAL-FLUID-DRUG-TEST

CPT 0011U: Oral Fluid Drug Test with Algorithmic Steady‑State Comparison

CPT-0016U-BCR-ABL1-MAJOR-MINOR-FUSION-TRANSCRIPT-TESTING

CPT 0016U: BCR–ABL1 Major and Minor Breakpoint Fusion Transcripts

Showing 1–10 of 536

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.

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Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

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Clinical & Coding Specifications

Clinical Context

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`32421`	Diagnostic thoracentesis, with imaging guidance when performed (needle or catheter), initial or subsequent	Performed to obtain pleural fluid specimen for cytology and molecular testing such as the Episeek™ MPE.
`88112`	Cytopathology, fluid, washings, or brushings, for diagnosis (interpretation)	Standard cytologic evaluation of pleural fluid typically performed alongside molecular testing to detect malignant cells.
`83890`	Molecular pathology procedure, each targeted genomic sequence analysis, direct probe technique (e.g., qPCR)	Represents molecular analytic methods similar in technique (qPCR) though `0566U` is a PLA code specific to the Episeek™ assay; labs may bill `0566U` instead of generic molecular codes.
`36415`	Collection of venous blood by venipuncture	Common specimen collection CPT for required blood tests that may accompany pleural fluid diagnostic workup (pre-procedure labs, biomarkers).

Related Modifiers

5 rows

Modifier	Description	When to Use
22	Modifier –22 (Increased Procedural Services) is used when a reported procedure is substantially more extensive than normally required. The CPT Manual and CMS state it may be appended only when the…	- When to use: Append modifier -22 to a procedural CPT code when the service performed is substantially more extensive than the usual service described by that code — i.e., the procedure required…
52	Modifier ‑52 (Reduced Services) indicates that a service or procedure was partially reduced or omitted at the provider’s discretion, allowing reporting of the basic procedure number with a qualifier…	- Use modifier -52 when a physician or qualified health professional electively reduces or omits part of a procedure or service (for example, performing fewer required views or omitting a portion of…
53	Modifier 53 (Discontinued Procedure) signals that a surgical or diagnostic service was begun by the physician but terminated because of extenuating circumstances that threatened the patient’s…	- Use modifier -53 when a physician/qualified healthcare professional has started a surgical or diagnostic procedure (e.g., anesthesia administered, incision or scope insertion) and then discontinues…
[object Object]
25	CPT modifier 25 indicates that on the same day as another procedure or service, the same physician or other qualified health care professional provided a significant, separately identifiable…	- When to apply: Use modifier 25 only on an E/M code to indicate the same provider delivered a significant, separately identifiable E/M service on the same day as another procedure or service — i.e.,…

Related Provider Taxonomies

8 rows

Taxonomy Code	Specialty	Notes
2084P0800X	Psychiatry Physician	A Psychiatrist specializes in the prevention, diagnosis, and treatment of mental disorders, emotional disorders, psychotic disorders, mood disorders, …
363L00000X	Nurse Practitioner	(1) A registered nurse provider with a graduate degree in nursing prepared for advanced practice involving independent and interdependent decision mak…
207K00000X	Allergy & Immunology Physician	An allergist-immunologist is trained in evaluation, physical and laboratory diagnosis, and management of disorders involving the immune system. Select…
208000000X	Pediatrics Physician	A pediatrician is concerned with the physical, emotional and social health of children from birth to young adulthood. Care encompasses a broad spectru…
175M00000X	Lay Midwife	A person qualified by experience and limited specialized training to provide obstetric and neo-natal care in the management of women having normal pre…
156FC0801X	Contact Lens Fitter	An optician or other ancillary support staff person who, where authorized by state law and trained or certified to do so, may fit or dispense contact …
237600000X	Audiologist-Hearing Aid Fitter	An audiologist/hearing aid fitter is the professional who specializes in evaluating and treating people with hearing loss, conducts a wide variety of …
2083P0011X	Undersea and Hyperbaric Medicine (Preventive Medicine) Physician	A specialist who treats decompression illness and diving accident cases and uses hyperbaric oxygen therapy to treat such conditions as carbon monoxide…

Related ICD-10-CM Codes

24 rows

ICD-10-CM Code	Description
B90.9	Sequelae of respiratory and unspecified tuberculosis
C34.11	Malignant neoplasm of upper lobe, right bronchus or lung
C34.12	Malignant neoplasm of upper lobe, left bronchus or lung
C34.31	Malignant neoplasm of lower lobe, right bronchus or lung
C34.32	Malignant neoplasm of lower lobe, left bronchus or lung
C34.90	Malignant neoplasm of unspecified part of unspecified bronchus or lung
C38.4	Malignant neoplasm of pleura
C78.7	Secondary malignant neoplasm of liver and intrahepatic bile duct
D04.9	Carcinoma in situ of skin, unspecified
D49.9	Neoplasm of unspecified behavior of unspecified site

Showing 1–10 of 24

CPT 0001U: PreciseType HEA Erythrocyte Antigen Genotyping

CPT-0002U-POLYPDX-URINE-METABOLOMIC-ASSAY-ADENOMATOUS-POLYP-RISK

CPT 0002U: PolypDX™ Urine Metabolomic Risk Assay

CPT-0003U-OVAR-A-NEXT-GENERATION-OVARIAN-CANCER-RISK-ASSAY

CPT 0003U: Overa (MIA2G) Ovarian Cancer Risk Assay

CPT-0005U-PROSTATE-EXOSOMEDX-INTELLISCORE-GENE-EXPRESSION-URINE-TEST

CPT 0005U: ExosomeDx Prostate (IntelliScore) urine gene expression test

CPT-0007U-TOXPROTECT-URINE-DRUG-SCREEN-WITH-DNA-AUTHENTICATION

CPT 0007U: ToxProtect Urine Drug Screen With DNA Authentication

CPT-0008U-H-PYLORI-ANTIBIOTIC-RESISTANCE-SEQUENCING-PANEL

CPT 0008U: H. pylori Antibiotic Resistance Gene Panel

CPT-0009U-DEPARRAY-HER2-FISH-TUMOR-CELL-ISOLATION

CPT 0009U: DEPArray HER2 Tumor‑Cell Isolation with FISH Analysis

CPT-0010U-BACTERIAL-TYPING-WHOLE-GENOME-SEQUENCING-MAYO-CLINIC

CPT 0010U: Bacterial Typing by Whole Genome Sequencing, Mayo Clinic

CPT-0011U-CORDANT-CORE-ALGORITHMIC-ORAL-FLUID-DRUG-TEST

CPT 0011U: Oral Fluid Drug Test with Algorithmic Steady‑State Comparison

CPT-0016U-BCR-ABL1-MAJOR-MINOR-FUSION-TRANSCRIPT-TESTING

CPT 0016U: BCR–ABL1 Major and Minor Breakpoint Fusion Transcripts

Showing 1–10 of 536

Frequently Asked Questions

References

1.CPT® Codes and Descriptions. AAPC. Retrieved Aug 11, 2026.Maintains the CPT code set's official descriptions and guidelines, licensed from the American Medical Association, used as the definitional source for CPT codes on this page.
2.HCPCS Quarterly Update. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's quarterly release of HCPCS Level II codes and short/long descriptors, the source for HCPCS code definitions and update history.
3.ICD-10-CM Full Code List. Centers for Medicare & Medicaid Services (CMS). Retrieved Aug 11, 2026.CMS's complete ICD-10-CM diagnosis code list, used to cross-reference diagnosis codes associated with this procedure or service.

Published by

Trek Health powers OpenPayer with a leading commercial payer intelligence platform, seamlessly converting fragmented payer data into actionable insights for provider organizations.

OpenPayer

CPT 0566U: Episeek MPE Pleural Fluid Methylation Test

Sign up for cpt 0566U policy alerts

OpenPayer

CPT 0566U: Episeek MPE Pleural Fluid Methylation Test

Sign up for cpt 0566U policy alerts

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related ICD-10-CM Codes

Related Codes

References

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related ICD-10-CM Codes

Related Codes

References

CPT 0566U: Episeek MPE Pleural Fluid Methylation Test

Sign up for cpt 0566U policy alerts

CPT 0566U: Episeek MPE Pleural Fluid Methylation Test

Sign up for cpt 0566U policy alerts

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related ICD-10-CM Codes

Related Codes

What does CPT code 0566U represent?

In what clinical scenario is the Episeek™ MPE (0566U) typically ordered?

How does 0566U relate to other CPT codes like 32421, 88112, or 83890?

Where is the Episeek™ MPE (0566U) performed?

Which diagnoses are relevant when billing or considering Episeek™ MPE (0566U)?

References

Clinical & Coding Specifications

Clinical Context

Related CPT Codes

Related Modifiers

Related Provider Taxonomies

Related ICD-10-CM Codes

Related Codes

What does CPT code 0566U represent?

In what clinical scenario is the Episeek™ MPE (0566U) typically ordered?

How does 0566U relate to other CPT codes like 32421, 88112, or 83890?

Where is the Episeek™ MPE (0566U) performed?

Which diagnoses are relevant when billing or considering Episeek™ MPE (0566U)?

References