Immunohistochemistry Cocktails Are Here to Stay

Center for Medicare and Medicaid Services Should Revise Its New Reimbursement Policy

On January 1st, 2012, the Center for Medicare and Medicaid Services (CMS) implemented a policy in conjunction with the National Correct Coding Initiative (NCCI) to pay pathologists and laboratories for immunohistochemistry (IHC) cocktail stains as a single unit of Current Procedural Terminology (CPT) code 88342, regardless of how many individually interpretable antibodies are included in the cocktail. Medicare has, in the past, paid for IHC cocktail stains based on the American Medical Association’s prescription: 1 unit of CPT code 88342 was payable for each separately interpreted and reported antibody (eg, via unique color expression compared with other markers in the cocktail).

Knowledgeable sources indicate that this new policy is a reaction by CMS to a dramatic increase in the number of IHC charges on physician and laboratory claims during the past 2 or 3 years. This period roughly corresponds to the observed proliferation of in-office and other histology laboratory arrangements entered into, particularly but not exclusively, by urologists and gastrointestinal practitioners. Overutilization of IHC stains—the application of diagnostic markers in medically suspect situations (eg, staining all of a patient’s biopsy specimens instead of just 1 or 2 tumor-rich samples, applying a stain to rule out a condition not suggested by the H&E slides)—by these physicians, and perhaps by a minority of overly aggressive pathologists as well, is a natural cause for alarm among government payers and private medical insurers alike.

As taxpayers and as ethical practitioners of the medical arts, we are highly sympathetic to the goal of CMS and other parties to eliminate waste and abuse in the laboratory industry. Notwithstanding, it is the strong opinion of leaders in the field of IHC testing that the aforementioned sledgehammer approach to cost reduction in the cocktail stain arena will inevitably result in reduced quality of care for patients, and will add greatly to the risks of mistreatment or maltreatment of many patients with cancer. In this context, it may be useful to discuss specific examples to support this contention.

One widely used antibody cocktail is commonly referred to as “PIN4”; it consists of a combination of 1 or 2 antibodies against high-molecular-weight (HMW) keratin plus antibodies to p63 and p504s (also known as AMACR enzyme). The usefulness of this cocktail has been proven beyond doubt in the literature. When many years ago urologists began using the smallest possible needle gauge to perform prostate needle biopsies, pathologists encountered great difficulty in reliably diagnosing (or ruling out) small foci of cancer; examination of multiple minute tissue fragments was time-consuming, and reproducibility of diagnosis was poor. The introduction of IHC staining with HMW keratin antibodies demonstrated absence of basal cell layer, a finding suggestive, but of itself not diagnostic, of invasive carcinoma. Subsequently, the use of antibodies to p63 in the nuclei of basal cells and the “malignancy”-associated protein p504 that was detectable in almost all invasive carcinomas provided additional assistance in diagnosis. However, pathologists encountered great difficulty in colocalizing the 3 antibody signals on 3 different slides. In many cases this proved impossible because the “suspicious areas” were small and often were not found in deeper cuts of the tissue block. However, when these antibodies are used in a multiplex, multicolor, cocktail format on the exact same tissue section, pathologists can evaluate each of these critical markers in exactly the same focus or foci of interest, thereby greatly improving reproducibility among pathologists. This method improves the accuracy of diagnosis of invasive cancer to near certainty.

More recently, similar multiplex, multicolor methods have also been shown to provide new diagnostic criteria and increased accuracy in other areas of pathology. For example, in breast pathology, the application of 2 different antibodies (eg, p63 and myosin-heavy chain cocktail) against the myoepithelial cell layer has been shown to increase the reproducibility and sensitivity of detection of invasive vs noninvasive breast lesions. In hematopathology, the ability to demonstrate whether a group of atypical lymphocytes coexpress CD20 and CD5, CD20 and κ, CD20 and λ, and CD20 and Ki-67 has also increased the accuracy of diagnosis of subtypes of lymphoma. This has allowed the application of principles long accepted as valuable in flow cytometry (and reimbursed for multiple marker testing). With the use of additional detection technologies, such as spectral imaging, there is little doubt that new and important diagnostic criteria will develop that cannot be applied by single stains on separate multiple sections.1

It is the conviction of the leaders in the field that the current IHC technology cannot now, in the year 2012, return to the old 1 antibody, 1 slide approach. Diagnoses would revert to earlier less accurate, less reproducible standards; patients would suffer; and in the final analysis costs would soar because of inappropriate therapies given in the context of inadequate diagnoses. One other vital issue must be considered, namely, the conservation and efficient use of the minute amounts of tissue collected with modern endoscopic biopsy and needle aspiration methods. Multiplex, multicolor cocktails are crucial to maximize the number of diagnostic antibody studies that can be applied to these tiny tissue biopsy specimens. Every pathologist is faced on a daily basis with the nightmare scenario of inadequate diagnostic tissue that precludes the performance of all stains essential to the diagnosis. Reversal of the multiplex cocktail approach (because of lack of reimbursement) will invariably lead to an increase in the number of nondefinitive and nondiagnostic IHC workups, with the result that clinicians will be increasingly forced to repeat biopsy procedures on their patients, increasing costs and, equally importantly, risk to the patients.

There are, in our opinion, other reasonable means to limit unnecessary use of IHC studies, without compromising diagnostic workup, repeating biopsies, and incurring the attendant risks and costs. Several suggestions are offered as a starting point for CMS and NCCI to reevaluate their approach toward IHC:

  1. Convene an IHC utilization advisory group of “thought leaders” in the field, including clinicians in key areas, to provide utilization guidelines. Then enforce the guidelines. Ban the clearly abusive practices and blatant overuse of IHC. For example, no one argues with the fact that it is exceedingly rare to require PIN4 studies on every biopsy core in 12-pack prostate biopsies. A letter of medical necessity should be required to justify performing more staining procedures than the recommended minimum.

  2. Create a separate CPT code or unique Healthcare Common Procedure Coding System (HCPCS) level II modifier for IHC screening studies that are important in certain clinical situations but not necessary for the population at large. Screening for Helicobacter pylori in the absence of any evidence of gastritis is an example of when stains are often performed as “defensive practice,” in the absence of community standard guidelines. Similar “screening” CPT codes or unique HCPCS level II modifiers could be created in other settings, such as keratin studies on multiple sentinel node levels.

  3. Mandate that all pathology laboratories, regardless of ownership, affiliation, or location, be subjected to the same licensing and inspection process as hospital-based pathology laboratories. Most “in-office laboratories” today are never inspected by the College of American Pathologists, which means they do not participate in IHC proficiency testing for the effectiveness and use of multiplex stains. Such a requirement would make it difficult for these laboratories to operate completely independent of any regulatory body that knows anything about IHC.

  4. Investigate laboratories and pathologists who violate these guidelines and impose administrative sanctions, or refer such cases to the US Department of Justice for criminal prosecution.

In summary, cost-containment in the field of IHC is possible and necessary. But it needs to be done right. Depriving pathologists of the compensation for cocktail studies places conscientious pathologists and institutions in an impossible situation, by either providing care that is substandard or performing the right test for no cost. This approach is not the right way to do it, but we understand the motive behind it. As a group of thought leaders representing many of the IHC pathologist experts in the United States, authors of leading texts, and members of the Society for Applied Immunohistochemistry, we urge CMS and NCCI to overturn this unwarranted policy. We welcome the idea of evaluating cost containment in a collaborative and comprehensive fashion that brings the best diagnostic practice to bear on our patients in the most cost-effective manner.

Acknowledgments

The authors wish to thank Dennis Padget for his insightful review of the manuscript.

Reference

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