Thyroid Nodules and Cancer

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Thyroid Nodules and Cancer. Netee Papneja, PGY5. Objectives. Review Epidemiology of thyroid nodules/cancers Approach to thyroid nodules Newer evidence re: indications for biopsy Molecular characterization of FNA results Thyroid cancer guidelines. Epidemiology. - PowerPoint PPT Presentation

Text of Thyroid Nodules and Cancer

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    Conclusion Thyroid cancer incidence rates have been increasing worldwide?due to increased detection rates from US No associated higher mortality ATA guidelines may be modified to decrease frequency of FNA doneNew molecular methods for indeterminate FNA samples seem to be promising, but not available in Canada yet

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    Questions?

    *In the past, ionizing radiation was used to treat a wide variety of benign conditions of the head and neck, although this practice essentially ceased in the late 1950s to early 1960s due to increased appreciation of the carcinogenic effects of radiation on the thyroid******KIM ET AL, THYROID, Diagnostic Accuracy of the Ultrasonographic Features for Subcentimeter Thyroid Nodules Suggested by the Revised American Thyroid Association Guidelines, Volume 23, Number 12, 2013

    *In addition to hypoechogenicity, infiltrative margin, microcalcification, and taller-than-wide shape that were suggested by the ATA guidelines, solid composition and macrocalcification were significantly associated with malignancy on multivariate analysis (p=0.001 and 0.003, respectively).Increased vascularity, however, was not significantly associated with malignant nodules (odds ratio 0.729, p = 0.212). Among the eight guidelines, the ATA guidelines showed the lowest diagnostic performance (Az = 0.616). Excluding increased vascu-arity and including solid composition with or without macrocalcification to the suspicious ultrasonographic features of the ATA guidelines improved sensitivity (96.6% vs. 97.0%), specificity (26.6% vs. 42.9%), PPV (48.3% vs. 54.7%), and NPV (91.7% vs. 95.2%), thereby resulting in the highest Az value (Az = 0.699, p < 0.001).Conclusions: This study suggests that excluding increased vascularity and adding solid composition to the suspicious ultrasonographic features of the ATA guidelines would significantly improve the diagnostic per- formance in subcentimeter nodules for the identification of malignant lesions.

    *Analyzed the medical records of 8,806 patients who underwent 11,618 thyroid ultrasound examinations at a UCSF inpatient or outpatient facility from January 2000 through March 2005.The patients did not have a diagnosis of thyroid cancer at the time of the ultrasound, but were referred to ultrasound for a variety of reasonsThe researchers linked the patients with the California Cancer Registry and identified 105 who were diagnosed with thyroid cancer. The cancer patients were matched with a group of cancer-free control subjects from the same cohort, based on factors such as gender, age and the year of the ultrasound exam.

    *If 1 characteristic is used as an indication for biopsy, most cases of thyroid cancer would be detected (sensitivity, 0.88; 95% CI, 0.80-0.94), with a high false-positive rate (0.44; 95% CI, 0.43-0.45) and a low positive likelihood ratio (2.0; 95% CI, 1.8-2.2), and 56 biopsies will be performed per cancer diagnosed. If 2 characteristics were required for biopsy, the sensitivity and false-positive rates would be lower (sensitivity, 0.52; 95% CI, 0.42-0.62; false-positive rate, 0.07; 95% CI, 0.07-0.08), the positive likelihood ratio would be higher (7.1; 95% CI, 6.2-8.2), and only 16 biopsies will be performed per cancer diagnosed. Compared with performing biopsy of all thyroid nodules larger than 5 mm, adoption of this more stringent rule requiring 2 abnormal nodule characteristics to prompt biopsy would reduce unnecessary biopsies by 90% while maintaining a low risk of cancer (5 per 1000 patients for whom biopsy is deferred).

    *UpTODATE

    Molecular markers When cytologic results show follicular lesion/atypia of undetermined significance or follicular neoplasm, the results are often called indeterminate. The risk of malignancy with these cytologic classifications ranges from 5 to 32 percent, and the majority of these patients undergo thyroid surgery. However, most patients (75 to 95 percent) undergo surgery for what is ultimately confirmed to be benign disease (see 'Follicular lesion or atypia of undetermined significance' below and 'Follicular neoplasm' below). Improvement in the assessment of indeterminate FNA results may allow better risk stratification. There are two approaches to the molecular characterization of FNA aspirates that are commercially available in the United States: identification of particular molecular markers of malignancy, such as BRAF and RAS mutational status, and use of high density genomic data for molecular classification (an FNA-trained mRNA classifier) [38]. The mRNA classifier measures the activity level of 167 genes within the nodule (using the FNA aspirate). We favor using an mRNA classifier system (gene expresser classifier), when available, based upon the following findings: In a study of 513 indeterminate samples from 479 patients tested for BRAF, RAS, RET/PTC, and PAX8/PPARgamma mutations prior to surgery, the detection of any mutation conferred a risk of histologic malignancy of 88 and 87 percent for samples showing follicular lesion/atypia of undetermined significance and follicular neoplasm, respectively [39]. However, 6 and 14 percent of nodules with FNA showing follicular lesion/atypia of undetermined significance and follicular neoplasm, respectively, were negative for these mutations and proved to be cancer on surgical histology. Thus, this approach misses a significant proportion of malignant samples that do not contain one of the mutations being tested. In a study of 265 indeterminate nodules (85 of which were malignant), using mRNA expression analysis and a gene expression classifier trained on FNA samples to detect benign thyroid nodules, the classifier had a negative predictive value for malignancy of 95 and 94 percent for samples showing follicular lesion/atypia of undetermined significance and follicular neoplasm, respectively [40,41]. It is suggested that application of this classifier would save over 60 percent of patients from diagnostic thyroid surgery, which would result in overall lower costs [42]. Where available, we suggest using this classifier for evaluating patients with FNA cytology showing follicular lesion/atypia of undetermined significance or follicular neoplasm. The decision to observe a patient with a benign molecular profile using this classifier should be reassessed as more data become available. (See 'Follicular neoplasm' below.)

    *sample undergoes RNA extraction and nucleic acid amplification. Processed Afirma GEC samples are hybridized to a custom Afirma Thyroid microarray and analyzed with a classification algorithm using linear support vector machine logic to produce either a Benign or Suspicious test result. *A benign Afirma GEC result, when applied to nodules with FNA cytology of AUS/FLUS or follicular neoplasm (FN), proved benign in 95% and 94% cases, respectively

    Nodules with indeterminate cytopathology and a benign GEC result have less than 6% likelihood of being malignant (greater than 94% Negative Predictive Value).

    the risk of malignancy of a GEC benign result is comparable to that of nodule diagnosed as benign by cytopathology*

    Of the 17 patients with non-diagnostic Afirma GEC results, 6 were lost to further followup. 3 underwent surgical resection, while 2 had repeat Afirma testing at a later date. 2 others had repeat FNA cytology which was benign, while 2 underwent ultrasound followup showing no change. Finally, 1 nodule was deemed a pseudonodule on repeat imaging and no further intervention recommended, while 1 patients refused further testing.

    *pe- cifics of the 20 patients who did not complete surgery are as follows: 7 patients declined the recommendation, 5 sep- arate patients were lost to follow-up, and 7 have commit- ted to future surgery which has not yet been performed; 1 additional patient died of a separate cause.

    11 of these patients (inclusive of the 4 immediately recommended for surgery above) underwent thyroid surgery, most because of per- sonal preference or compressive symptoms in the neck. 10 of these 11 cases proved benign histologically, while 1 was confirmed malignant (1.0cm sonographic nodules which proved a 0.6cm papillary carcinoma histologically)

    *Of the remainder, 71 (41%) had docu- mented followup at a mean of 8.5 months (median 8 months; range 124 months) following GEC testing. In ten of these 71 patients, a followup clinical examination was performed, while the remaining 61 underwent repeat sonographic assessment. Ultimately, 11 of these patients (inclusive of the 4 immediately recommended for surgery above) underwent thyroid surgery, most because of per- sonal preference or compressive symptoms in the neck. 10 of these 11 cases proved benign histologically, while 1 was confirmed malignant (1.0cm sonographic nodules which proved a 0.6cm papillary carcinoma histologically)*Our data demonstrate a substantial change in practice patterns following the availability of the Afirma GEC (13). Among five major medical centers, clinical recommenda- tions for surgery dropped 93% among patients with cy- tologically indeterminate thyroid nodules. We note some patients (n 11) nonetheless pursued surgery even if Afirma GEC was benign, while others (n 20) did not comply with surgical recommendations. Nonetheless, in an academic clinical setting, a 76% reduction in surgery was observed when the Afirma GEC was applied to pa- tients in whom surgery would otherwise have been typi- cally performed. Follow up assessment of those with Afirma GEC benign results confirms a very low rate of false negative results, and provides support for the clinical utility of this test.

    *Clin Thyroidol 2013;25:288289Next-Generation Sequencing Has Identified New Oncogenic Mutations in Thyroid Nodules*

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