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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 say that the use of molecular testing (MT)* to assess thyroid nodules may be considered medically 
necessary ONCE per nodule workup when ALL of the following criteria are met: 
 
    Thyroid fine-needle aspiration (s) (FNA) performed secondary to established indications based on ultrasound 
characteristics, size and clinical findings 
    Presence of indeterminate thyroid FNA cytopathology described as 
        Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) (i.e., 
Bethesda category III), or 
        Follicular neoplasm (FN) or suspicious for a follicular neoplasm (SFN) (i.e., Bethesda category IV) 
    The need for thyroidectomy is unclear after consideration of clinical, imaging, and cytologic features 
    Local institutional malignancy rates are known and used for optimal extrapolation of results to thyroid 
cancer risk 
    Informed patient willing to potentially undertake surveillance 
 
Summary of Evidence 
 
Thyroid cancer is the most common endocrine malignancy, with over fifty thousand new United States 
diagnoses in 2020. Thyroid nodules are exceedingly common with prevalence rates of up to 68%, with higher 
frequencies in the elderly. While the majority (85-93%) of thyroid nodules are benign, diagnostic testing 
(history and physical, laryngoscopy, hormone and chemistry analysis, ultrasound, CT, FNA, and surgical 
excision) is required to confirm. Over 600,000 thyroid FNAs are performed every year in the United States, 
and the number has been increasing annually by 16%. Despite this diagnostic gauntlet, approximately 20% of 
FNA results are classified indeterminate (Bethesda III/IV) with a 10-40% risk of malignancy. Cancer rates vary 
widely by institution, ranging from 6-48% for Bethesda III and 14-34% for Bethesda IV. Repeat FNA of 
Bethesda III nodules should be strongly considered as it leads to a more definitive reclassification in 60-65%. 
Previously, the majority of patients with an indeterminate FNA, confirmed on repeat aspiration, had diagnostic 
thyroid surgery (usually lobectomy), with most (75-95%) ultimately confirmed to be benign. Rates of thyroid 
surgery-specific postoperative complications (recurrent laryngeal nerve injury, permanent hypoparathyroidism, 
and postoperative hematoma) in high-volume institution studies range between 0.4-7.4%, but a population-
based study found it as high as 12.3%. 
 
 
 In 2012, molecular marker testing (MT) became widely available as a potential method to augment risk 
stratification of indeterminate FNA results, ideally reducing the need for diagnostic thyroid surgery or 
completion thyroidectomy, with their attendant risks and costs. A patient with a low MT malignancy risk is 
potentially recommended for surveillance with serial ultrasounds to ensure nodule stability. Conversely, a high 
malignancy MT result could strengthen a recommendation to move forward with surgical removal (lobectomy 
or total thyroidectomy). Molecular profiling includes genomic alterations (such as point mutations, insertions, 
and deletions), gene fusions resulting in rearrangements or translocations, copy number variations, RNA-based 
gene expression, and/or micro-RNA (miRNA) expression. 
 
In 2016, the nomenclature of encapsulated follicular variant of papillary thyroid cancer was changed to 
noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in recognition of its 
highly indolent nature. Thus, the value of MT may arise both from the avoidance of surgery and the fact that 
surveillance is now a safer and more informed option. Conversely, given clinical guideline recognition that 
more limited cancer operation can lead to equivalent outcomes, the impact of molecular testing in directing the 
extent of surgical resection is diminished. 
 
Thyroseqv3 (CBLPath, Inc.; Rye Brook, NY) 
 
Thyroseqv3 is a targeted next-generation sequencing test that interrogates selected regions of 112 thyroid 
cancer-related genes for point mutations, insertions/deletions, gene fusions, copy number alterations, or gene 
expression alterations. A genomic classifier assigns a value to each detected genetic alteration based on the 
strength of association with malignancy: 0 (no association with cancer), 1 (low cancer probability), or 2 (high 
cancer probability). A score calculated for each sample is a sum of individual values of all detected alterations, 
with scores 0 and 1 accepted as test negative (score 1 commercially reported as currently negative) and scores 2 
and above as positive. 
 
This evidence summary is limited to the current version of Thyroseq (version 3). Also excluded are 
publications combining results from multiple Thyroseq versions in which version 3 results could not be 
specifically isolated. 
 
In a multicenter prospective, blinded, clinical validation study of ThyroSeqv3, including 247 Bethesda III and 
Bethesda IV nodules in which both pathologist and clinicians were blinded to MT results, sensitivity was 94% 
(95% CI, 86%-98%) and specificity 82% (95% CI, 75%-87%). With a cancer/NIFTP prevalence of 28%, the 
negative predictive value (NPV) was 97% (95% CI, 93%-99%), the positive predictive value (PPV) was 66% 
(95% CI, 56%-75%), with a benign call rate (BCR) of 61%. The observed 3% false-negative rate was similar to 
that of benign cytology, and the missed cancers were all low-risk tumors. Results of 10 Bethesda V nodules are 
not separately reported. 
 
In an independent, single-center, non-blinded observational study, a total of 50 Bethesda III/IV cytologically 
indeterminate nodules underwent ThyroSeqv3 testing. Molecular analysis yielded 20 (40%) "positive" results 
and 24 (48%) "negative" results. Six (12%) results were classified as "currently negative" or "negative but 
limited." All 20 positive patients underwent surgery, as well as both currently negative patients (n=2) and 
one patient with a negative but limited result (n=1). All 26 negative patients and one patient with a 
negative but limited result (n=1) continued with surveillance. In total, 23 (46%) patients underwent surgery, 
and 27 (54%) patients were followed with conservative management. BCR was calculated as ("negative" and 
"currently negative")/total, resulting in a BCR of 58%. Ninety-one percent (20 of 22) of the resected target 
nodules were malignant on final pathology. Since surgery was not performed on test-negative patients, test 
specificity, sensitivity, and NPV were not available. You can find these rules in the Local Coverage 
Determination (LCD) Thyroid Nodule Molecular Testing L38968. 
 
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.