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Current CPT Coding and Payment Policy Implications for Immunohistology Services

Myles, Jonathan L., MD*; Synovec, Mark, MD; Klemp, Todd, MA, MBA, MSc; Black-Schaffer, William S., MD§

doi: 10.1097/PAP.0000000000000207
Review Articles

Immunohistology is essential to the practice of modern surgical and cytopathology. There are 3 major types of immunohistologic services provided in clinical practice: traditional immunohistochemistry, morphometric analysis of tumor immunohistochemistry, and immunofluorescence. Proper Current Procedural Terminology coding for these services has been updated to reflect current medical practice. Subsequent to changes in the Current Procedural Terminology coding structure for these services, the valuation of these services have been reviewed by the American Medical Association/Specialty Society Relative Value Update Committee and new valuations instituted by the Centers for Medicare and Medicaid Services. Although valuations for services may be established, the circumstances of payment may be affected by Medicare Contractor’s Local Coverage Determinations or service limits imposed by the National Correct Coding Initiative.

*Department of Pathology, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH

Topeka Pathology Group, LLC, Topeka, KS

College of American Pathologists, Washington, DC

§Massachusetts General Hospital and Harvard Medical School, Boston, MA

The authors have no funding or conflicts of interest to disclose.

Reprints: Jonathan L. Myles MD, Department of Pathology, Cleveland Clinic, 9500 Euclid Ave, L25, Cleveland, OH 44195 (e-mail:

Immunohistology plays an integral role in the evaluation of anatomic pathology specimens. The formal medical description, or coding, of the work for these services has evolved significantly over the past decade. Proper procedural coding is necessary to insure appropriate reimbursement for these services and compliance with applicable regulations and payment policies. In this paper we review the current appropriate procedural coding for immunohistology services [immunohistochemistry (IHC), morphometric tumor IHC, and immunofluorescent procedures] and review other factors following the development of a Current Procedural Terminology (CPT) code which may affect payment for a service.

To understand the nuances of coding and reimbursement for immunohistochemical procedures, it is important to briefly note how CPT codes are valued on Medicare’s physician fee schedule (PFS). The American Medical Association/Specialty Society Relative Value Update Committee (AMA-RUC) is tasked with providing valuation recommendations to the Centers for Medicare and Medicaid Services (CMS) for all codes on the PFS. They do this through a formalized process. The valuation is based upon the individual resources required to perform the procedure in a typical case. This includes both the technical (technologist preparation of the slides, all medical supplies, and equipment used) and professional (physician interpretation and reporting) components of the service. Both the technical and professional components are thoroughly vetted by the AMA-RUC within distinct AMA-RUC committees through separate mechanisms. The AMA-RUC process has been recently reviewed elsewhere.1 The keyword is “typical” for the valuation of a CPT code. The valuation of all CPT codes on the PFS is based on the typical service performed, recognizing that individual cases that use the code may require more or less resources than the typical case used in determining the value for that code.

CPT codes are developed by the AMA’s CPT Editorial Panel, based on input from various stakeholders. Each year the AMA publishes updated CPT codes in a dedicated AMA publication.2 IHC and immunocytochemistry services are currently coded using the CPT codes listed in Table 1. The use of IHC for both tissue (histologic) and cellular (cytologic) specimens is, from a CPT coding standpoint, indistinguishable. Originally, all IHC procedures were coded using code 88342. This code was initially valued before the widespread use of multiplex antibody staining procedures, where binding of multiple antibodies are separately identifiable on a histologic slide from one single IHC procedure. The resources typically used in a multiplex antibody staining procedure are greater than those for a single antibody staining procedure, where the binding of only one antibody is identifiable. The introduction of multiplex antibody staining procedures confounded the appropriate units of service that would be utilized when 88342 was the sole code used for nonmorphometric IHC services. The concern among payers and the CMS in 2014 led to introduction of the short-lived Medicare Level 2 HCPCS G-codes, G0461 and G0462, to code for IHC procedures.3 G-codes are so called because they are government created codes, and not developed by the AMA CPT Editorial Panel. The G-codes caused confusion among stakeholders, as different codes were used by private payers from the G-codes used for Medicare claims. The CMS designated G-codes were discontinued for 2015 after an update and revision was made to the IHC code set to reflect current medical practice.



Under the current CPT coding system, the initial antibody staining procedure by IHC per specimen is coded as one unit of 88342. Each additional single antibody staining procedure performed on that same specimen is coded as 88341. Each multiplex antibody staining procedure performed on a specimen is coded as 88344. CPT coding language and the National Correct Coding Initiative (NCCI) Policy Manual4 are very specific in terms of the appropriate use of these codes. The key to coding surgical pathology cases in most instances is the specimen, not the case. If a case is comprised of multiple specimens or parts (A, B, C, etc.), the initial single antibody staining procedure (88342) applies for each specimen (eg, part A), not each case. Multiple specimens may be present in a given case. Thus, if multiple IHC procedures are needed to be performed on a case, it would be appropriate to use the 88342 code for each initial single antibody IHC stain procedure performed on each part. For example, if it were medically necessary to perform an AE1/AE3 IHC stain on part A and part B, and those would be the only IHC stains performed on the case, the appropriate coding for those services would be one unit of 88342 for part A and one unit of 88342 for part B. Each additional single antibody stain procedure performed on a specimen subsequent to the initial one is coded as 88341. Code 88341 is therefore used in conjunction with code 88342. For example, in part A in the case, if AE1/AE3 IHC stain was performed on one slide, and a CD45 IHC stain was performed on another slide, the IHC stains for part A would be coded as 88342×1 and 88341×1. If the same specimen (part) had an AE1/AE3, CD45, and S100 IHC stains performed using 3 separate procedures, the case would be coded as 88342×1 and 88341×2.

Each multiplex antibody staining procedure is coded as one unit of 88344. This code was developed upon the introduction of single antibody staining procedures on the condition for identification of the binding of multiple separately identifiable antibodies. These types of stains may be utilized in prostate biopsy evaluations for suspected prostatic neoplasia or in a skin biopsy evaluation of melanocytic lesions.5 The correct use of this code is to limit its use to when the binding of multiple separately identifiable antibodies is provided by a single IHC procedure in a given specimen. The key words are “separately identifiable.” The binding of different antibodies may be separately identifiable by use of different chromogens used in the same procedure. An example would be the use of an IHC staining procedure in a prostate biopsy specimen, where different chromogens are used for the different antibodies. Cytokeratin cocktails such as AE1/AE3, does not contain separately identifiable antibodies and as such are appropriately coded using 88342 or 88341. The AMA CPT Coding Manual also indicates that the same separately identifiable antibodies may not be coded more than once using 88341, 88342, or 88344 per specimen. What this means in practice is that if you have a specimen (part of a case) that contains multiple blocks and the same antibody is used on >1 block, that stain may only be billed once per part (specimen).

Codes 88341, 88342, and 88344 are used to code nonmorphometric (qualitative) immunohistochemical procedures. This is contrast to the quantitative IHC codes 88360 and 88361. These codes are described in CPT as illustrated in Table 2. There are 2 central points for the use of codes 88360 and 88361. First is that these codes are used for tumor IHC only, and are not applicable to non-tumor specimens. Second, the codes must involve some form of morphometric analysis of the IHC stain procedure. Codes 88360 and 88361 may not be interpreted simply as positive or negative, but must produce a quantitative result (eg, a specific percentage of cells staining) in order to be properly utilized. Simply denoting an arbitrary intensity of staining, such as 1+ to 4+, does not qualify a procedure for the use of the 88360 or 88361 codes. This does not however exclude the use of 88360 for specific uses where a numerical “+” scoring system is utilized, such as for Her-2 analysis, where the score incorporates a percentage of positive tumor cells. Code 88360 involves using a manual analysis. Code 88361 is used when computer technology assists the pathologist’s interpretation in formulating a clinically meaningful result. CPT specifically states that morphometric analysis of a multiplex antibody stain should be reported with only one unit of 88360 or 88361 per specimen when a multiplex assay is performed. In situ hybridization codes are coded with 88365-88377, and those procedures are not reported with the 88360 and 88361 codes. A final caveat on the use of 88360 and 88361 is that the quantitative result must be medically necessary. An example of where morphometric analysis of an immunohistochemical stain is useful is Ki-67 staining in the evaluation of certain lymphomas.6 Key to reporting IHC services (like any other billable services) is to document the medical reason for the use of the study, the result of the study, and methodology of the study.



Following the revision of coding for the immunohistochemical procedures, CPT changes also occurred in the evaluation of immunofluorescent procedures as is illustrated in Table 3. Code 88346 is used for the initial single antibody stain procedure per specimen. Each additional single antibody staining procedure on a given specimen is coded as 88350. Multiplex immunofluorescent studies are coded using 88399 (unlisted surgical pathology procedure), however, multiplex immunofluorescent procedures are not in wide clinical use at present.



When there is a need for the modification, deletion, or creation of a CPT code or set of codes, the process entails submitting a Code Change Application (CCA) to the AMA CPT Editorial Panel for evaluation. The entities submitting the CCA typically address the potential favorable and unfavorable reimbursement and payment policy ramifications of the proposed changes. Following action by the CPT Editorial Panel, new and revised codes are then forwarded to the AMA-RUC, whence a recommendation is made to CMS for the valuation of a service. This process has been recently reviewed in detail elsewhere.1 There are several issues related to the valuation process that are of special interest to the immunohistology codes.

For payment purposes, the value of a code is based on the typical resources used in performing the service or procedure. This applies both to the professional work involved as well as the technical component resources required. Direct resources utilized in assessment of the technical component include items such as the amounts of reagents used, the technician time involved in performing the various steps of the service, and the equipment time. The professional work involved in performing a service is predominantly determined by the time it takes to perform the service and the intensity/complexity of the service. This process is distinctly different from laboratory codes that have no physician work directly associated with them. Those code values are mostly nonresource based and have their value determined through the Clinical Laboratory Fee schedule process, as recently modified by PAMA (The Protecting Access to Medicare Act of 2014).7 Much of that process presently involves analysis of private payer payment rates reported to CMS.

As noted earlier, the payment determination for any pathology service on the PFS is based upon the typical service. It is recognized that outliers exist for each CPT code, but payment for each service is based on the typical case. Factors such as batch size, prepping and programing of instruments, and technician time performing the service are all taken into consideration. Even though there are two separate slides in the case of an 88341 and 88342, there is some efficiency involved in performing a second antibody procedure compared with the first antibody procedure. This accounts for the slight decrease in technical component for the 88341 as compared with the 88342. The same analogy can be applied to the professional work involved with 88341 to 88342 and 88350 to 88346. Although each of these separate codes involves different antibodies on different slides, and each slide needs to be interpreted individually, there is presently a 20% diminution in value (denominated in relative value units or “RVUs”) associated with the second antibody procedure. This is to account for efficiencies involved in performing multiple units of service on a given specimen. Although there is some efficiency associated with a second antibody stain on a second slide compared with the first stain on the first slide, the current valuations for immunohistochemical and immunofluorescent services exaggerate this efficiency.

Following the recommendation of a valuation for the service by the AMA-RUC, this recommendation is forwarded to the CMS for their determination of payment. Most often, CMS will accept the AMA-RUC recommended value for the service for the professional work, however, they may adjust, decrease, or reject it altogether. In the last case, they may opt to create a HCPCS level 2 G-Code (government created code) for the service. In the case of the 88341 and 88342, CMS believed that the difference in efficiency between the first and second antibody procedure was underestimated by the AMA-RUC valuation. The CMS evaluation includes a review of each individual resource used in determining the technical component evaluation for a service (eg, amount of antibody used, equipment time, etc.) and each item may be individually adjusted by CMS to determine the reimbursement for the technical component. CMS releases its proposed valuations for a code in the Federal Register in its Proposed Rule on or about July 1st of every year. Stakeholders are given a 60-day period thereafter to comment on its contents, and CMS issues a Final Rule on or about November 1st on the payment for the following year for the code. No formal comment period is available for stakeholders following CMS’s final PFS rulings.

Following the code assignment and description of the service by CPT, the recommendation for the value of the service by the AMA-RUC, and the determination of the payment amount by CMS, additional payment policy considerations may determine the circumstances in which a particular service is payable. Two common policy considerations are manifested in guidance by the NCCI Policy Manual for Medicare Services, and in each Medicare Administrative Contractor (MAC)’s Local Coverage Determinations (LCD).

The NCCI was developed by CMS to promote correct coding methodology and to give guidance as to the appropriate use of CPT codes. This manual is updated annually and is available on the CMS website.4 The NCCI manual provides extensive guidance on pathology services, with pathology and laboratory medicine covered in chapter 10. There are several areas of the NCCI manual relevant to immunohistology services. The manual states that Medicare does not pay for duplicate testing. According to the NCCI, IHC and flow cytometry should not in general be reported for the same or similar specimens. It is possible to use CPT codes for both types of procedures if both techniques are needed to explain all the light microscopic findings. Specifically, the manual states that if the abnormal cells in ≥2 specimens are morphologically similar and testing on one specimen by one method establishes the diagnosis, the same or other methods should not be reported on the same or similar specimens. The NCCI manual defines similar specimens as including but not limited to the following:

  • Bone and bone marrow;
  • bone marrow aspiration and bone marrow biopsy;
  • two separate lymph nodes; or
  • lymph node and other tissue with lymphoid infiltrate.

If IHC and flow cytometry are performed on the same or similar type specimens, the pathologist needs to document the reason why this was medically necessary sufficiently to withstand scrutiny over whether both procedures were needed to be performed. The NCCI manual reiterates that a unit of service for IHC is each single staining procedure per specimen (whether one or multiple individual antibodies are used in a single procedure). Each antibody may be reported only once per specimen, regardless of the CPT code used to identify the service. This is distinct from the guidance provided for the use of special stains (CPT codes 88312-88313). For special stain codes, it may be medically reasonable to perform the same stain on >1 block of tissue from a single specimen. If >1 unit of service is performed on a given specimen for the same stain, the reason for doing so for each stain needs to be documented in the report. The same stain performed on multiple levels of one block is not separately reportable and only one unit of service may be billed for that stain per block. For cytology specimens from a single anatomic site only one unit of service may be reported for each special stain regardless of the number of slides stained from that site. This is consistent with CPT’s characterization of these codes, as the associated parenthetical notes states, “Report one unit of (service) for each special stain, on each surgical block, cytology specimen, or hematologic smear.”2

Medically Unlikely Edits (MUEs) are also developed by CMS. The stated purpose of MUEs is to reduce the paid claims error rate from Medicare part B claims. The MUEs describe a maximum unit of service for a particular code. Some MUE values are updated regularly on the CMS website and other MUE values are confidential (not published). All of the immunohistology codes have published MUEs on the CMS website.8

Having a CPT code to describe a professional service and having CMS determine a payment amount for the service does not guarantee that payment will be made for a given service, even when NCCI guidance is followed. Each Medicare Administrative Contractor may determine whether it will cover payment for the test in their jurisdiction. Traditionally, CMS-valued CPT-coded services are covered for the indications upon which the CPT code was based, but a MAC may engage in Local Coverage Determination process if the Contractor Medical Director (CMD) perceives that services are being billed which are not medically reasonable and necessary. In this case, the Medicare contractor will typically propose a draft LCD, put it out for public comment, and then discuss it at its Carrier Advisory Committee (CAC) meeting. The CACs are composed of various stakeholders, primarily physicians of the various specialties practicing in the MAC jurisdiction, who provide recommendations on the draft LCD to the Contractor Medical Director. After input from the CAC and consideration of public comments, the draft LCD may be edited, and a final LCD adopted. These LCDs are publically available. The LCD process in outlined in chapter 13 of the Medicare Program Integrity Manual.9

Twenty-nine of the United States are covered by variations of a LCD that addresses special stains and IHC.10 Although the specifications of this particular LCD are controversial among stakeholders, in jurisdictions in which it is in force, a LCD needs to be followed to be compliant with Medicare guidelines. This LCD highlights some of the established Medicare requirements with regard to coding and billing for IHC services:

Pathologists may perform additional tests (such as IHC) under the following circumstances:

  • The services are medically necessary.
  • The results must be communicated and used by the treating physician in the treatment of the beneficiary.
  • The pathologist documents in the report why additional testing was performed.

The appropriate rate of use of special stains and immunohistology within any individual practice is difficult to assess. Evidence-based practice guidelines are useful in determining which type of testing is needed in the evaluation of a particular type of disease process.11 Such guidelines require extensive resources and time to develop. Although useful if available, there are many practice situations for which practice guidelines do not exist. Individual utilization studies, in particular, practice settings, which are difficult to extrapolate to other practice communities. Pathology practices in different settings with different patient populations with different risk profiles may require different utilization of certain stains. Such considerations illuminate the importance of documenting the necessity of special stains and IHC stains in the pathologist’s report.

In this paper we have reviewed the current CPT coding for immunohistology services and described additional factors beyond CPT which are important in determining payment for a given service. In the future, as payment for pathology services shifts from fee-for-service to value-based care, the work we do as physicians will still need to be described, and it is unlikely that the CPT process will be supplanted by any comparably well-articulated system for representing medical services in the foreseeable future.

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4. Centers for Medicare and Medicaid Services. 2018 National Correct Coding Initiative Policy Manual for Medicare Services. January 1, 2018. Available at: Accessed May 10, 2018.
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7. United States of America 113’Th Congress H.R. 4302 Protecting Access to Medicare Act of 2014.
8. CMS Website. Medically Unlikely Edits. 2018. Available at: Accessed May 11, 2018.
9. CMS Website. Medicare Program Integrity Manual, Chapter 13. Available at: Accessed May 11, 2018.
10. CMS Website. Local coverage determination (LCD): special histochemical stains and immunohistochemical stains (L35922). February 26, 2018. Available at:*1&Cntrctr=379&name=&DocType=Active&s=53&bc=AAAAAAQAAAAA&. Accessed May 11, 2018.
11. Arber DA, Borowitz MJ, Cessna M, et al. Initial diagnostic workup of acute leukemia: guideline from the college of american pathologists and the american society of hematology. Arch Pathol Lab Med. 2017;141:1342–1393.

immunohistochemistry; immunofluorescence; CPT coding; payment policy

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