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The rules say that plans must pay for a medical service or item if regular Medicare would pay for it in this case. 
You can find this rule at 42 Code of Federal Regulations (CFR) Section 422.101. 
 
The rules state that there are many different relationships that exist in the provision of pathology services in the 
United States. Some physicians, groups, laboratories and hospitals submit global claims for the services 
described in this policy. In other instances, there are separate individuals or entities providing the professional 
and the technical services. It is the obligation of each party to recognize that they are responsible for the 
medical necessity of the services submitted. For example, when a physician or physician group performs the 
professional component of services described in this policy and another entity performs the technical services, 
it is the obligation of each entity to independently assure the medical necessity of the services rendered by each 
entity.  
 
Special Stains/IHC Medical Necessity 
 
The CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, 80.6.5 ...there 
may be additional tests, such as special stains, that the pathologist may need to perform, even though they have 
not been specifically requested by the treating physician/practitioner. The pathologist may perform such 
additional tests under the following circumstances: 
 
    Services are medically necessary so that a complete and accurate diagnosis can be reported to the treating 
physician/practitioner; 
    Results of the tests are communicated to and are used by the treating physician/practitioner in the treatment 
of the beneficiary; and 
    Pathologist documents in his/her report why additional testing was done. 
 
 
The above citation means that reflex templates or pre-orders for special stains and/or IHC stains prior to review 
of the routine H&E stain by the pathologist are not reasonable and necessary. A pathologist must first review 
the H&E stain prior to ordering special stains or IHC.  
 Exceptions do exist and are recognized standards of care in the practice of pathology. These exceptions include 
but are not limited to renal, liver, and neuromuscular biopsies, and for the suspicion of an infectious disease, 
particularly in an immune compromised patient. In certain clearly defined circumstances, it may be reasonable 
to perform some IHC on sentinel lymph nodes when the frozen sections show they are free of tumor. 
 
The medical necessity for the special stain or IHC studies, and the results of the stain or IHC, must be 
documented in the surgical pathology report.  
 
IHC for Breast Pathology 
 
The clinical care of patients with breast cancer depends upon the accurate diagnosis and the assessment of 
biomarkers. Hormone receptor assays and Her2 testing are recommended on all primary invasive breast 
cancers, and on recurrent or metastatic cancers. At the current time, there is no recommendation for Her2 
testing on in situ breast lesions outside of a clinical trial. While there are a number of promising additional 
biomarkers, such as Ki-67, PI3K and gene expression assays, the College of American Pathologists (CAP), the 
American Society of Clinical Oncologists (ASCO) and the National Comprehensive Cancer Network (NCCN) 
have not recognized these markers in patient treatment pathways.  
 
Estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (Her2) are well-
established prognostic markers in invasive breast cancer management. The triple negative breast carcinoma 
subtype (ER-/PR-/Her2-) has been associated with worse overall prognosis in comparison with other subtypes 
in study populations consisting of ethnic minorities and young women.  
 
The clinical utility of testing for hormone receptors in in-situ breast cancer differs from those of invasive 
disease. Guidelines and the peer reviewed literature support the use of ER testing for in-situ breast neoplasia 
and PR testing only when the ER status is negative (Lester, personal communication). Clinical guidelines have 
not been established for the use of Her2 or other biomarkers in patients with non-invasive breast neoplasia.  
 
In the absence of professional guidelines based on proven scientific literature, standing orders from clinicians 
for such tests as Ki-67 and EGFR on every breast cancer are not reasonable and necessary, and are not a 
covered Medicine service.  
 
In addition, basal phenotype markers (eg, IHC for CK5) are not routinely necessary. Neither are IHC stains 
such as E-cadherin, p27, or high molecular weight cytokeratin to distinguish ductal from lobular differentiation 
necessary on every breast case, nor are myoepithelial cell markers such as p63 or smooth muscle myosin heavy 
chain necessary on every case.  
 
Special Stains and/or IHC for Prostate Pathology 
 
The accuracy of the pathologic diagnosis of prostate cancer is critical for optimal patient care. The diagnosis 
can usually be made on morphologic features such as growth pattern, nuclear atypia and the absence of basal 
cells. However, it may be difficult to reach a firm diagnosis by routine H&E stain for small foci of cancer in 
needle biopsies because many benign conditions can mimic prostate cancer.  
 
The immunohistochemical diagnosis of prostate cancer largely depends on panels of markers because no 
absolutely specific and sensitive marker for prostate cancer has yet been identified. These panels usually 
include at least 1 basal cell marker, such as high-molecular-weight cytokeratin (HMWCK) or p63, and the 
prostate cancer-specific marker, alpha-methyl-CoA-Racemase (AMACR). Although AMACR is considered a 
useful IHC marker for prostate cancer, because of non-standardized immunostaining protocols, interpretation 
criteria and heterogeneous staining pattern, there is wide variation in the sensitivity and specificity of AMACR 
immunoreactivity in prostate biopsies. Furthermore, because AMACR expression has been demonstrated in 
high-grade prostatic intraepithelial neoplasia (PIN), atypical adenomatous hyperplasia/adenosis and nephrogenic adenoma, it is recommended that AMACR is best restricted to the evaluation of morphologically 
highly suspicious foci in which negative immunoreactivity of basal cell markers alone is insufficient to 
establish a diagnosis of cancer.  
 
PTEN and MYC may provide some prognostic information but neither is part of any standard treatment 
protocol and neither should be routinely performed. ERG is another IHC that is more likely to be positive in 
cancer than in benign tissue, but it does not add information to conventional PIN4 testing. Similarly, 
neuroendocrine markers, such as IHC for synaptophysin, may be indicated in cases of recurrent/metastatic 
prostate carcinoma that have undergone small cell transformation after hormone therapy. The latter marker is 
only necessary for high grade, undifferentiated tumors and should not be used routinely.  
 
It is not reasonable and necessary to perform for IHC testing (either single antibody or antibody cocktails) on 
cases with morphologically negative cores. It is not reasonable and necessary to perform for IHC testing in a 
negative or a suspicious core biopsy when obvious prostate cancer is present in other cores. While the 
pathologist may choose to confirm a suspicious focus in one or more cores in a case where the diagnosis of 
cancer has already been made, it is not a Medicare covered service because it provides no additional actionable 
information to the treating physician.  
 
Prostate cases that may require reasonable and necessary IHC staining include but are not limited to the 
following: 
 
    Indeterminate/suspicious focus and no other cores are positive for cancer 
    Single worrisome core with minimal % tumor (roughly less than 5%) 
    Worrisome core(s) contralateral to a positive core(s): 
        In a multi-part biopsy with Gleason 3+3=6 cancer in 1 part, and atypical small acinar proliferation (ASAP) 
suspicious for Gleason 3+3=6 cancer in other part(s); the number of positive biopsy sites and % core 
involvement of these sites can affect therapeutic choices for active surveillance (AS), focal therapy or surgery 
        In a multi-part biopsy with 4+3=7 or 4+4=8 cancer in 1 part, and ASAP suspicious for the same grade 
cancer in other part(s); workup is justified since the extent of high-grade cancer affects treatments 
    Identify tumor invasion of adjacent structures 
    Determine origin of undifferentiated/poorly differentiated neoplasm, such as bladder vs. prostate 
    Other unexpected results when specific cell stains would be necessary 
 
Prostate cases when IHC workup is Not Reasonable and Necessary include the following: 
 
    In a multi-part biopsy with greater than or equal to 3+4=7 cancer in 1 part, and ASAP suspicious for 3+3=6 
cancer in other part(s), because stains are unlikely to change treatment; or 
    In a multi-part biopsy with greater than or equal to 4+3=7 cancer in 1 part, and "atypical cribriform lesson" 
(ACL) suspicious for intra-ductal carcinoma versus invasive, Gleason pattern 4 cancer in other part(s), because 
intra-ductal carcinoma is almost always closely associated with invasive high-grade cancer. 
 
The International Society of Pathology (ISUP) recommendations state that at the current time, there are no 
prognostic IHC or molecular studies that are recommended to be routinely performed on biopsy or resection 
specimens.  
 
The surgical pathology report is expected to designate the specific block(s) upon which IHC testing is 
performed, the reason for IHC testing, the specific markers, and whether single antibody(ies) or a cocktail of 
antibodies is utilized. A statement alone in the pathology report that states IHC confirms the diagnosis will 
not be covered as reasonable and necessary.  
 
IHC for Chemosensitivity and Resistance Tumor Profiling 
 ER, PR, and Her2 hormonal receptor status have demonstrated clinical utility in invasive breast cancer, as well 
as ER, and PR when appropriate, for in-situ breast cancer. ER and PR are performed by IHC specifically for 
tamoxifen therapy. Her2 testing has proven clinical utility in esophago-gastric and gastric cancers to determine 
response to trastuzumab. ER, PR and Her2 testing for the purpose of identifying patients likely to respond to 
hormonal therapy, biologics or chemotherapy is a covered Medicare service when medically necessary for 
breast and gastric adenocarcinoma. 
 
Similarly, the efficacy of imatinib, a CD117 inhibitor, is determined by the mutation status of CD117 
expression (c-KIT mutation). CD117 by IHC has a proven clinical benefit in gastrointestinal stromal tumors 
(GIST), some advanced dermatofibrosarcoma protuberans (DFSP), some lymphoblastic and myeloid 
leukemias, and mast cell tumors, and is a covered Medicare service when medically necessary.  
 
However, IHC testing as above is distinctly different from chemotherapy sensitivity and/or resistance testing 
profiles offered by some labs to assist physicians in their selection of specific chemotherapeutic agents based 
on IHC antigen or protein expression in individual tumors. The goal stated by these profiles is to select a drug 
or combination of drugs from a panel of drugs to which a tumor has greater expression, and to avoid drugs to 
which the tumor has less expression.  
 
Neither the ASCO nor the NCCN has endorsed chemosensitivity tumor profile testing by IHC. ASCO has 
stated, "the use of CSRA's (chemosensitivity and resistance assays) to select chemotherapeutic agents for 
individual patients is not recommended outside of the clinical trial setting." While the NCCN's Guidelines for 
Ovarian Cancer (V3.2014) states "chemosensitivity/resistance and/or other biomarker assays are being used in 
some NCCN member institutions for decisions related to future chemotherapy in situations where there are 
multiple equivalent chemotherapy options available. The current level of evidence is not sufficient (Category 3) 
to supplant standard of care chemotherapy." The NCCN panel also stated that in vitro chemosensitivity testing 
is choose a chemotherapy regimen for recurrent disease should not be recommended due to lack of 
demonstrated efficacy. Such IHC panels include but are not limited to the following biomarkers for specific 
drugs: 
 
    ALK for crixotinib, penetrexed 
    Androgen receptor (AR) for goserelin, leuprolide, gonadorelin, flutamide, bicalutamide, abiraterone; 
    Androgen receptor for bicalutamide, flutamide, abiraterone and enzalutamide; 
    AREG for cetuximab, panitumumab 
    BRAF for venurafenib and dabrafenib 
    BRCA1 for cisplatin, carboplatin 
    cKIT for sorafenib, sunitinib, imatinib 
    cMET for erlotinib, gefitinib 
    EGFR for gefitinib, panitumumab, erlotinib, cetuximab, FOLFIRIEGFRVIII 
    EGFRvIII, GNA11, GNAQ, IDH2  for clinical trials 
    ER and PR for tamoxifen, gefitinib, toremifene, fulvestrant, letrozole, anastrozole, exemestrane, megestrol 
acetate, erlotinib, panitumumab, medroxyprogesterone; 
    ERCC1 for oxaliplatin, cisplatin, carboplatin, CAPOX, FOLFOX 
    EREG for cetuximab, panitumumab 
    Her2 (ErbB2), PGP and TOP2A (topoisomerase IIA) for doxorubincin, liposomal-doxorubicin, epirubicin; 
    Her2 or labatinib; epirubicin, pertuzumab, trastuzumab, liposomal doxorubicin, doxorubicin, 
    KRAS for panitumumab, cetruximab, gefitinib, erlotinib, sorafenib 
    MGMT for temozolomide and dacarbazine 
    MRP1 for vinorelbine, vincrisxtine, doxorfubicin, epirubicin, vinblastine, methotrexate 
    NRAS for cetuximab, panitumumab 
    PDGFRA for imatinib 
    PGP (aka MDR1 and ABCB1) for doxorubicin, vincristine, vinblastine, eptoposide, liposomal doxorubicin, 
paclitaxel , docetaxel, vinorelbine, epirubicin;     PIK3CA for lapatinib, panitumumab, trastuzumab, cetuximab, temsirolimus 
    PTEN for getitinib, cetuximab, erlotinib, trastuszumab, panitumumab, everolimus, temsirolimus 
    RET for vandetanib 
    ROS1 for crizotinib 
    RRM1 for gemcitabine; 
    SPARC (monoclonal and polyclonal) for nab-paclitaxel; 
    TLE3, TUBB3 for docetaxel, paclitaxel; 
    TOPO1 for irinotecan, topotecan, FOLFIRI; 
    TS (thymidylate synthase or TYMS) for fluorouracil, capecitabine and pemetrexed 
 
Chemosensitivity profile tumor panels, regardless of whether it is performed by IHC or chromogenic in-situ 
hybridization (CISH), is not reasonable and necessary for the reasons cited above, and is not a Medicare 
covered service.  
 
You can find these rules in the Local Coverage Determination (LCD) for Lab: Special Histochemical Stains 
and Immunohistochemical Stains, L36353. 
 
If you want to read these Medicare rules, you can go to this website www.medicareappeal.com. 
 
The Plan contract says that the Plan covers items and services in accordance with Medicare rules.