Clinically evident metastases of carcinomas to the thyroid gland are rare, particularly from a colorectal primary tumor. We present a case of colonic adenocarcinoma metastatic to the thyroid gland with histopathologic and immunohistochemical findings. A 68-year-old woman with a history of Dukes' stage B colon carcinoma presented a mass in the thyroid gland. The tumor was confirmed to be metastatic adenocarcinoma from the colon. The immunohistochemical findings demonstrated positive staining for cytokeratin 20, low-molecular-weight cytokeratin, villin and carcinoembryonic antigen, but stains were negative for cytokeratin 7 and thyroglobulin.
Adenocarcinoma/secondary* ; Adenocarcinoma/radiography ; Aged ; Carcinoembryonic Antigen/analysis ; Carrier Proteins/analysis ; Case Report ; Colonic Neoplasms/pathology* ; Female ; Human ; Immunoenzyme Techniques ; Intermediate Filament Proteins/analysis ; Keratin/analysis ; Microfilament Proteins/analysis ; Thyroid Neoplasms/secondary* ; Thyroid Neoplasms/radiography ; Thyroid Nodule/radiography ; Thyroid Nodule/chemistry ; Tomography, X-Ray Computed ; Tumor Markers, Biological

OBJECTIVETo study immunohistochemical expression of cytokeratin19 (CK19), galectin-3 (Gal-3) and HBME-1 in thyroid lesions and to assess their usefulness as markers in the differential diagnoses of thyroid nodular lesions.

METHODSImmunohistochemical staining was performed on formalin-fixed paraffin-embedded tissue of 21 cases of nodular goiters, 14 cases of toxic goiters, 15 cases of follicular adenomas (FA), 13 cases of follicular carcinomas (FC), 13 cases of follicular variant papillary carcinomas (FVPC) and 48 cases of classic papillary carcinomas (CPC).

RESULTSAll three markers were expressed in the cytoplasm with no or weak expression in benign lesions and diffuse and strong in malignant cases. Positive expressions of CK19, Gal-3 and HBME-1 were present in 11of 21, two of 21, four of 21 in nodular goiters, seven of 14, one of 14, one of 14 in toxic goiters, nine of 15, two of 15, two of 15 in FA, 10 of 13, eight of 13, seven of 13 in FC, 13 of 13, 11 of 13, 12 of 13 in FVPC, and 48 of 48, 45 of 48, 46 of 48 in CPC. The expression rates of the three markers between benign lesions (nodular goiters, toxic goiters and FA) and malignant lesions (FA, FVPC and CPC) were statistically significant. Among the three follicular lesions (FA, FC and FVPC), the differences were statistically significant as well. Nine, seven and six cases were negative for all three markers in nodular goiters, toxic goiters and FA, respectively. Only one case in FC was negative for all three markers, no case was all negative in FVPC and CPC; the rate of one case with two or more positive marker expression in nodular goiters, toxic goiters, FA, FC, FVPC and PC was 14.2% (3/21), 21.43% (3/14), 20.0% (3/15), 69.2% (9/13), 92.3% (12/13), 100.0% (48/48), the differences between benign lesions and malignant lesions and between FA, FC and FVPC were also statistically significant.

CONCLUSIONSImmunohistochemical stains of CK19, Gal-3 and HBME-1, especially when used in combination, can be an important adjunct to the histopathological diagnoses of thyroid lesions.

Adenocarcinoma, Follicular ; chemistry ; diagnosis ; pathology ; Adenoma ; chemistry ; diagnosis ; pathology ; Biomarkers, Tumor ; biosynthesis ; genetics ; Carcinoma, Papillary, Follicular ; pathology ; Diagnosis, Differential ; Galectin 3 ; biosynthesis ; genetics ; Goiter, Nodular ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Keratins ; biosynthesis ; genetics ; Thyroid Neoplasms ; chemistry ; diagnosis ; pathology ; Thyroid Nodule ; chemistry ; diagnosis ; pathology

The distinction between benign and malignant thyroid tumors is critical for the management of patients with thyroid nodules. We applied immunohistochemical staining for galectin-3, HBME-1, cytokeratin 19 (CK19), high molecular weight cytokeratin (HMWCK), cyclin D1 and p27(kip1) in 295 thyroid lesions to determine their diagnostic accuracy. The expression of all markers was significantly associated with differentiated thyroid carcinoma (DTC).The sensitivity for the diagnosis of DTC was 94.7% with galectin-3, 91.3% with HBME-1, and 90.3% with CK19. The specificities of these markers were 95.5%, 69.7%, and 83.1%, respectively. Combining these markers, co-expression of galectin-3 and CK19 or galectin-3 and HBME-1 was seen in 93.2% of carcinomas but in none of the benign nodules. Comparing follicular variant of papillary carcinoma (FVPC) with follicular carcinoma (FC), the expression of galectin-3, CK19, and HMWCK was significantly higher in FVPC. When comparing FC with FA, the expression of galectin-3 and HBME-1 was significantly higher in FC. These results suggest that 1) galectin-3 is a useful marker in the distinction between benign and malignant thyroid tumors, 2) the combined use of HBME-1 and CK19 can increase the diagnostic accuracy, and 3) the use of CK19 and HMWCK can aid in the differential diagnosis between PC and FC.
Adenocarcinoma, Follicular/diagnosis/metabolism ; Carcinoma, Papillary, Follicular/diagnosis/metabolism ; Cyclin D1/analysis ; Cyclin-Dependent Kinase Inhibitor p27/analysis ; Diagnosis, Differential ; Galectin 3/analysis ; Humans ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins/analysis ; Keratin-19/analysis ; Keratins/analysis ; Sensitivity and Specificity ; Thyroid Gland/chemistry/*pathology ; Thyroid Nodule/*diagnosis/metabolism ; Tumor Markers, Biological/*analysis

BACKGROUND: Several molecular assays have been developed to detect the BRAF V600E mutation in fine needle aspirates (FNAs) for the diagnosis of papillary thyroid cancer. Using a multiplex PCR technique, we evaluated the Anyplex BRAF V600E Real-time Detection (Anyplex) assay and compared its efficacy with that of the Seeplex BRAF V600E ACE Detection (Seeplex) method. METHODS: We tested 258 consecutive FNA specimens using the Seeplex and Anyplex assays. Any conflicting results between the two assays were confirmed by using mutant enrichment with 3'-modified oligonucleotide (MEMO) sequencing. The limits of detection (LODs) and reproducibility for each assay were evaluated with serially diluted DNA from a BRAF V600E-positive cell line. RESULTS: The BRAF V600E mutation was detected in 36.4% (94/258) FNA specimens by either the Seeplex or Anyplex assay. Results for the two assays showed 93.4% (241/258) agreement, with a kappa value of 0.861 (95% confidence interval, 0.798-0.923). Of the eight specimens that were BRAF V600E-positive by the Anyplex assay but not by the Seeplex assay, five were found to be BRAF V600E-positive by MEMO sequencing. The mutation detection rate of the Seeplex and Anyplex assays was 79.0% and 84.0%, respectively, in the FNA specimens diagnosed as malignant (n=81). The LOD as determined by probit analysis was 0.046% (95% confidence interval, 0.019-0.532%). CONCLUSIONS: The Anyplex assay performed better than the Seeplex assay with respect to the detection of the BRAF V600E mutation.
Adult ; Aged ; Asian Continental Ancestry Group/genetics ; Biopsy, Fine-Needle ; DNA/chemistry/metabolism ; DNA Mutational Analysis/*methods ; DNA Primers/*metabolism ; Female ; Humans ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction ; Oligonucleotides/metabolism ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins B-raf/*genetics ; Republic of Korea ; Thyroid Nodule/*metabolism/pathology