[428] Is Follicular Adenoma with Equivocal Nuclear Atypia the Precursor Lesion of Encapsulated Follicular Variant of Papillary Thyroid Carcinoma? Fine Needle Aspiration, Histology and Molecular Study
T Yakoushina, T Scognamiglio, GCH Yang. Weill Medical College of Cornell University, New York, NY
Background: It has been shown that 2% of thyroid malignancies arise within a preexisting benign thyroid nodule and 10% of surgically excised follicular tumors have equivocal nuclear atypia, which may be biologically borderline between follicular adenoma (FA) and encapsulated (E) follicular variant (FV) of papillary carcinoma (PC). In addition, molecular tumor markers have been identified in some histologically classified FA. In this study we compare those tumors with EFVPC and analyzed their cytological and molecular characteristics.
Design: Fine needle aspiration (FNA) of 27 cases of EFVPC (category 1) and 14 cases of FA with equivocal nuclear features of PC (category 2) were reviewed for the nuclear features. 3 cases from each category were analyzed for BRAF V600E, NRAS 12/13, NRAS 61, KRAS 61, HRAS 12/13, HRAS 61 mutations by DNA sequencing following microdissection.
Results: In category 1, 22 patients were female and 5 were male, age ranged from 24 to 70 years (mean 42), nodule size ranged from 0.7 cm to 4.6 cm (mean 2.3). The PC nuclei were focal in 17 (63%) cases and diffuse in 10 (37%) cases. A case with mixed normal and atypical nuclei is illustrated in Figure 1.
The result of molecular study is shown in Table 1.
| BRAF V600E | N-RAS 12/13 | N-RAS 61 | K-RAS 61 | H-RAS 12/13 | H-RAS 61 | |
| Case 1 | (-) | (-) | (-) | (-) | (-) | (-) |
| Case 2 | (-) | (-) | (-) | (-) | (-) | (-) |
| Case 3 | (-) | 1265G>C | (-) | (-) | (-) | (-) |
In category 2, 13 patients were female and 1 male, age ranged from 21 to 82 years (mean 45), nodule size ranged from 0.8 cm to 4 cm. The PC nuclei were focal in 10 (71%) cases and diffuse in 4 (29%) cases. The result of molecular study is shown in Table 2.
| BRAF V600E | N-RAS 12/13 | N-RAS 61 | K-RAS 61 | H-RAS 12/13 | H-RAS 61 | |
| Case 1 | (-) | (-) | (-) | (-) | Poor amp. | Poor amp. |
| Case 2 | (-) | (-) | (-) | (-) | (-) | (-) |
| Case 3 | (-) | (-) | (-) | (-) | 1266G>GC | (-) |
Conclusions: More PC nuclei were present in FNA of EFVPC than FA with equivocal nuclei, but it is a continuum. EFVPC were similar to FA with equivocal nuclei in that they showed occasional RAS mutation and no BRAF mutation. Our findings supports the proposal of FA with equivocal nuclei possibly could be the precursor to EFVPTC, a biological continuum from FA to EFVPTC may exist. Molecular analysis of additional cases for each category are necessary to verify this pilot study.
Category: Cytopathology
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 37, Wednesday Afternoon