Applicable Federal Regulations

N/A

Guidelines are lacking regarding the selection and number of antibodies that should be used for most immunohistochemistry evaluations.

Guidelines and Recommendations

CAP has published several reviews in Archives of Pathology & Laboratory Medicine in which detail the quality control measures for IHC as well as published more than 100 small IHC panels to address the frequently asked questions in diagnosis and differential diagnosis of specific entities. These diagnostic panels are based on literature, IHC data, and personal experience. A single IHC marker approach (other than for pathogens such as cytomegalovirus or BK virus) is strongly discouraged since aberrant expression of a highly specific IHC marker can rarely occur. However, aberrant expression of the entire panel of highly specific IHC markers is nearly statistically impossible (Lin & Chen, 2014; Lin & Liu, 2014).

The American Society of Clinical Oncology and the College of American Pathologists currently recommend that “all newly diagnosed patients with breast cancer must have a HER2 test performed.” Also, for those who develop metastatic disease, a HER2 test must be done on tissue from the metastatic site, if available. The HER2 test can be either IHC or FISH.

The National Cancer Coalition Network (NCCN) recommends determination of estrogen receptor, progesterone receptor, and HER2 status for breast cancer, all of which may be done using IHC.

The NCCN also recommends Lynch Syndrome screening (which can be performed by IHC) on the tumors of all individuals with colon cancer who are 70 years old or younger, and for those over 70 years old who meet the Bethesda criteria.

The European Society of Medical Oncology recommends that for cancers of unknown primary, “immunohistochemistry should be applied meticulously in order to identify the tissue of origin and to exclude chemosensitive and potentially curable tumors.” 

Billing/Coding/Physician Documentation Information

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable service codes: 88341, 88342, 88344, 88360, 88361

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Scientific Background and Reference Sources

CF Garcia and SH Swerdlow. “Best Practices in Contemporary Diagnostic Immunohistochemistry Panel Approach to Hematolymphoid Proliferations,” Arch Pathol Lab Med Vol 133, May 2009 756-765.

Comparing the Diagnostic Accuracy of Gene Expression Profiling and Immunohistochemistry for Primary Site Identification in Metastatic Tumors,” Am J Surg Pathol. Volume 37, Number 7, July 2013; 1067-1075.

CR Handorf, A Kulkarni, JP Grenert, LM Weiss, WM Rogers, OS Kim, FA Monzon, M HalksMiller, GG Anderson, MG Walker, R Pillai, and WD Henner. “A Multicenter Study Directly Fitzgibbons, P. L., Bradley, L. A., Fatheree, L. A., Alsabeh, R., Fulton, R. S., Goldsmith, J. D., Swanson, P. E. (2014). Principles of analytic validation of immunohistochemical assays: Guideline from the College of American Pathologists Pathology and Laboratory Quality Center. Arch Pathol Lab Med, 138(11), 1432-1443. doi:10.5858/arpa.2013-0610-CP

G Kristiansen and JI Epstein. “Immunohistochemistry in Prostate Pathology, IHC Prostate Pathology,” Dako, Agilent Technologies, January 2014.

K Fizazi, FA Greco, N Pavlidis and G Pentheroudakis, on behalf of the ESMO Guidelines Working Group. “Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up,” Annals of Oncology 22 (Supplement 6): vi64–vi68, 2011 doi:10.1093/annonc/mdr389.

KA Naert and MJ Trotter. “Utilization and Utility of Immunohistochemistry in Dermatopathology,” Am J Dermatopathol Volume 35, Number 1, February 2013; 74-77.

KA Oien and JL Dennis. “Diagnostic work-up of carcinoma of unknown primary: from immunohistochemistry to molecular profiling,” Annals of Oncology 23 (Supplement 10): x271– x277, 2012 doi:10.1093/annonc/mds357.

Lin, F., & Chen, Z. (2014). Standardization of diagnostic immunohistochemistry: literature review and geisinger experience. Arch Pathol Lab Med, 138(12), 1564-1577. doi:10.5858/arpa.2014-0074-RA

Lin, F., & Liu, H. (2014). Immunohistochemistry in undifferentiated neoplasm/tumor of uncertain origin. Arch Pathol Lab Med, 138(12), 1583-1610. doi:10.5858/arpa.2014-0061-RA Lizotte, P. H., Ivanova, E. V., Awad, M. M., Jones, R. E., Keogh, L., Liu, H., Wong, K. K. (2016). Multiparametric profiling of non-small-cell lung cancers reveals distinct immunophenotypes. JCI Insight, 1(14), e89014. doi:10.1172/jci.insight.89014

Shah, A. A., Frierson, H. F., & Cathro, H. P. (2012). Analysis of Immunohistochemical Stain Usage in Different Pathology Practice Settings. doi:10.1309/AJCPAGVTCKDXKK0X

Policy Implementation/Update Information

1/1/19 New policy developed. BCBSNC will provide coverage for immunohistochemistry when it is determined to be medically necessary because the medical criteria and guidelines are met. Medical Director review 1/1/2019. Policy noticed 1/1/2019 for effective date 4/1/2019. (an)