bromochloroacetic-acid and Adenocarcinoma--Follicular

The precise diagnosis of follicular thyroid lesions is frequently debated because of the subjective nature of capsular invasion as well as both the histological and cytological characteristics. Furthermore, several different prognostic indices have been devised to examine prognosis associated with thyroid cancer. Herein, we describe how these confounding elements can affect the ability to accurately predict prognosis for patients with follicular thyroid lesions.

Topics: Adenocarcinoma, Follicular; Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Galectin 3; Humans; Keratins; Lymphatic Metastasis; Neoplasm Invasiveness; Prognosis; Thyroid Neoplasms

Although patients with minimally invasive follicular thyroid carcinoma (MIFTC) generally have an excellent prognosis, distant metastasis occurs in some patients. Risk factors for distant metastasis have been reported, none has been found to be conclusive. This study evaluated risk factors for distant metastasis, including protein markers, in patients with MIFTC.. A review of patient records identified 259 patients who underwent surgery at Asan Medical Center from 1996 to 2010 and were subsequently diagnosed with MIFTC. After review of pathological slides, 120 patients with paraffin blocks suited for tissue microarrays (TMA) were included in this study. Immunohistochemical stain of TMA slides was performed by protein markers; β-catenin, C-MET, CK19, estrogen receptor (ER) α, ER β, HBME-1, MMP2, PPAR γ and progesterone receptor.. 120 patients included 28 males (23.3%) and 92 females (76.7%), of mean age 41.5±10.8 years (range, 13-74 years). Eight patients (6.7%) had distant metastases during follow-up. Univariate analysis showed that age (≥45 years), male sex, and extensive vascular invasion (≥4 foci) were associated with distant metastasis. Multivariate regression analysis showed that extensive vascular invasion was the only independent risk factor for distant metastasis (p = 0.012). Although no protein markers on TMA analysis were directly related to distant metastasis of MIFTC, CK19 expression was more frequent in patients with than without extensive vascular invasion (p = 0.036).. Extensive vascular invasion was the only independent risk factor for distant metastasis of MIFTC. No proteins markers were directly related to distant metastasis, but CK19 was associated with extensive vascular invasion.

Topics: Adenocarcinoma, Follicular; Adult; Biomarkers, Tumor; Disease-Free Survival; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Metastasis; Reproducibility of Results; Risk Factors; Thyroid Neoplasms; Tissue Array Analysis

This study describes an encapsulated thyroid tumor having 3 different concentric appearances in a 70-year-old man. The most peripheral neoplasm showed features of a microfollicular adenoma; the intermediate lesion displayed typical features of the follicular variant of papillary thyroid carcinoma (FVPTC); and the main, central neoplasm, showed a basaloid configuration. At variance with the other neoplasms, the latter component exhibited high mitotic activity. Necrosis, angio-invasion, or capsular invasions were not observed. The centrally located neoplasm was immunoreactive for several cytokeratins, p63, carcinoembryonic antigen, and galectin-3, and negative for thyroid transcription factor 1, thyroglobulin, calcitonin, CD5, and CK20, featuring a phenotype similar to that of thyroid solid cell nests. A N-RAS mutation was found both in the basaloid and in the FVPTC components. The clinicopathological and immunohistochemical data ruled out the alternative possibilities of intrathyroidal metastasis and tumor from ectopic (thymic, parathyroid, or salivary gland) tissues.

Topics: Adenocarcinoma, Follicular; Galectin 3; Humans; Keratins; Thyroglobulin

Extracellular matrix proteins, adhesion molecules, and cytoskeletal proteins form a dynamic network interacting with signalling molecules as an adaptive response to altered gravity. An important issue is the exact differentiation between real microgravity responses of the cells or cellular reactions to hypergravity and/or vibrations. To determine the effects of real microgravity on human cells, we used four DLR parabolic flight campaigns and focused on the effects of short-term microgravity (22 s), hypergravity (1.8 g), and vibrations on ML-1 thyroid cancer cells. No signs of apoptosis or necrosis were detectable. Gene array analysis revealed 2,430 significantly changed transcripts. After 22 s microgravity, the F-actin and cytokeratin cytoskeleton was altered, and ACTB and KRT80 mRNAs were significantly upregulated after the first and thirty-first parabolas. The COL4A5 mRNA was downregulated under microgravity, whereas OPN and FN were significantly upregulated. Hypergravity and vibrations did not change ACTB, KRT-80 or COL4A5 mRNA. MTSS1 and LIMA1 mRNAs were downregulated/slightly upregulated under microgravity, upregulated in hypergravity and unchanged by vibrations. These data indicate that the graviresponse of ML-1 cells occurred very early, within the first few seconds. Downregulated MTSS1 and upregulated LIMA1 may be an adaptive mechanism of human cells for stabilizing the cytoskeleton under microgravity conditions.

Topics: Actin Cytoskeleton; Adenocarcinoma, Follicular; Cell Line; Collagen Type IV; Cytoskeleton; Down-Regulation; Extracellular Matrix; Fibronectins; Gene Expression Regulation, Neoplastic; Gravity, Altered; Humans; Keratins; LIM Domain Proteins; Microfilament Proteins; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Osteopontin; RNA, Messenger; Thyroid Neoplasms; Up-Regulation; Vibration

Topics: Adenocarcinoma, Follicular; Adenoma; Aged; Carcinoma, Renal Cell; Chromogranin A; Diagnosis, Differential; DNA-Binding Proteins; Female; Humans; Keratins; Kidney Neoplasms; Neprilysin; Thyroglobulin; Thyroid Neoplasms; Transcription Factors; Vimentin

To study Twist expression in thyroid papillary carcinoma (PTC) by immunohistochemistry and to assess its usefulness as marker in the differential diagnosis of PTC, follicular adenomas (FA) and benign papillary lesions (BPL).. Fifty cases of PTC, 48 cases of FA and 47 cases of BPL were evaluated using manual tissue chip and SP immunohistochemical stain to detect the expression of Twist and HBME-1, and comparing the staining to that of cytokeratin 19 (CK19).. In PTC, positive rates of Twist, HBME-1 and CK19 were 100% (48/48), 94.0% (47/50) and 78.0% (39/ 50) respectively; in FA, positive rates were 0, 6.7% (3/45) and 0 respectively; in BPL, positive rates were 7.0% (3/34), 2.1% (1/47) and 0, respectively. The differences between PTC and FA and between PTC and BPL were both statistically significant (P = 0. 000). The sensitivity of Twist, HBME-1 and CK19 was 100%, 94.0% and 78.0%; the specifity was 96.4%, 95.7% and 100%; overall accurary was 97.7%, 95.1% and 91.9%, respectively.. Positive rates of Twist is higher than the other markers in PTC. Immunohistochemical staining of Twist has important significance in the differential diagnosis of thyroid lesions. Twist immunohistochemistry maybe helpful in diagnosis and differential diagnosis of PTC.

Topics: Adenocarcinoma, Follicular; Adenocarcinoma, Papillary; Adenoma; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Galectin 3; Immunohistochemistry; Keratin-19; Keratins; Nuclear Proteins; Thyroid Neoplasms; Thyroid Nodule; Twist-Related Protein 1

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.

Topics: Adenocarcinoma, Follicular; Biomarkers, Tumor; Carcinoma, Papillary, Follicular; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p27; Diagnosis, Differential; Galectin 3; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Keratin-19; Keratins; Sensitivity and Specificity; Thyroid Gland; Thyroid Nodule

Supposedly, thyrocyte-specific transcripts such as thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R) were proposed to be useful for the diagnosis of circulating tumour cells in patients suffering from differentiated thyroid carcinoma (DTC). However, several research groups reported blood-borne Tg transcripts in healthy individuals. This study determines in particular the origin of Tg mRNA in nucleated blood cells and analyses whether other tumour-associated sequences are absent in leukocytes, but widely expressed in DTC. Therefore, expression analyses for Tg, TSH-R, cytokeratin 19 (CK 19), human telomerase reverse transcriptase (hTERT) and oncofoetal fibronectin (onfFN) were carried out using cDNAs derived from (1) leukocyte fractions, (2) 18 follicular thyroid carcinomas (FTCs) and 48 papillary thyroid carcinomas (PTCs), and (3) leukocytes of two thyrocyte-depleted individuals treated for C-cell carcinoma of the thyroid. Expression of onfFN was additionally analysed by semiquantitative RT-PCR and by quantitative fluorescence-based real-time PCR. Tg and TSH-R expression was demonstrated not only in both athyroid individuals, but in all leukocyte subgroups tested, while hTERT was absent in resting CD4+ cells and only weakly expressed in the CD8+ group. CK 19 was notable in each leukocyte population except for resting CD14(+), as well as for activated and resting CD19+ cells. All blood cell fractions proved negative for onfFN mRNA, whereas its presence in thyroid carcinoma was 78/98% (FTC/PTC). Threshold cycle values were calculated at: porphobilinogen deaminase (PBGD) = 25.95+/-0.73 (FTC)/24.55+/-5.43 (PTC) (P = 0.2878); onfFN = 25.48+/-3.15 (FTC)/21.44+/-3.44 (PTC) (*P = 0.0001). Finally, onfFN transcripts were detected in blood samples of six out of nine patients with known DTC metastases, demonstrating a reliable assay functionality. We propose that real-time RT-PCR of onfFN mRNA is superior to other markers in monitoring minimal residual disease in DTC with regard to both assay sensitivity and specificity.

Topics: Adenocarcinoma, Follicular; Antigens, CD; Biomarkers, Tumor; Carcinoma, Papillary; Cell Differentiation; DNA-Binding Proteins; Fibronectins; Humans; Keratins; Neoplasm, Residual; Receptors, Thyrotropin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sensitivity and Specificity; Telomerase; Thyroglobulin; Thyroid Neoplasms

To 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.. Immunohistochemical 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).. All 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.. Immunohistochemical 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.

Topics: Adenocarcinoma, Follicular; Adenoma; Biomarkers, Tumor; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Galectin 3; Goiter, Nodular; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms; Thyroid Nodule

Topics: Adenocarcinoma, Follicular; Biomarkers, Tumor; Drosophila Proteins; Humans; Keratins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Thyroid Neoplasms

We applied monoclonal antibodies against RET and cytokeratin 19 (CK19) to the following tumor sections: classic papillary carcinoma (PC), 16; Hürthle-type PC (HPC), 1; sclerosing PC with nodular fasciitis-like stroma (SPC), 1; PC, follicular variant (FVPC), 12; follicular adenoma (FA), 9; Hürthle cell adenoma (HA), 4; Hürthle cell carcinoma (HC), 3; and follicular carcinoma (FC), 7. CK19+ tumors included 16 PCs, 1HPC, 1SPC, 11 FVPCs, 7 FAs, 4 FCs, and 1HC. RET+ tumors included 4 HAs, 3 HCs, 1HPC, 12 PCs, 7 FVPCs, and 2 FAs. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a RET transcript in 6 Hürthle cell lesions. RET immunoreactivity is less sensitive and specific for PC than CK19. CK19 is useful for identifying PC, although only lesions with diffuse, intense staining should be considered positive. The detection of RET protein by immunohistochemical analysis was corroborated by the presence of the RET transcript by RT-PCR. Further study is warranted to determine whether this represents activation by gene fusion or some other mechanism in this subset of thyroid neoplasms.

Topics: Adenocarcinoma, Follicular; Adenoma; Adenoma, Oxyphilic; Antibodies, Monoclonal; Artificial Gene Fusion; Carcinoma, Papillary; Drosophila Proteins; Humans; Keratins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Thyroid Neoplasms; Transcription, Genetic

Hybrid follicular carcinoma (FC) and papillary thyroid carcinoma (PTC) have not been previously well described. Consecutive cases of 29 FC, 12 Hurthle cell carcinomas (HC), 247 PTC and 13 Hurthle cell PTC (HPTC) were reviewed with special attention to the coarse (CC) and fine chromatin patterns (FIC), as well as to the presence of nuclear grooves, pseudoinclusions or optically clear appearance. Limited nuclear features of PTC (LNF-PTC) are defined as areas of tumor with FIC in addition to some other nuclear features, but insufficient for the diagnosis of PTC. Tumors with nuclei showing an admixture of CC and PTC or LNFPTC were submitted for immunostaining for cytokeratin 19, HBME and Ret/PTC. FC and HC contained areas of LNFPTC in 25 tumors and focal PTC in 3 tumors. None of these cases was associated with lymph node metastasis. Areas with CC were found in 54 PTC and 3 HPTC. The rates of vascular invasion and distant metastasis tended to be higher for PTC with areas of coarse chromatin pattern than for PTC without such areas; however, the difference was not statistically significant. Immunoreactivity for cytokeratin 19 and HBME was moderate to strong for PTC and focal areas of PTC or LNFPTC in FC without Hurthle cell changes. Ret/PTC immunostaining was positive in areas of LNFPTC or focal PTC in three FC. Focal PTC or areas of LNFPTC are frequently seen in FC. Likewise, areas of CC are often present in PTC. The presence of these focal areas does not appear to change the clinical behavior of the tumor and therefore does not warrant a change of nomenclature.

Topics: Adenocarcinoma; Adenocarcinoma, Follicular; Adenoma, Oxyphilic; Adult; Biomarkers, Tumor; Carcinoma, Papillary; Chromatin; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Oncogene Proteins, Fusion; Protein-Tyrosine Kinases; Retrospective Studies; Thyroid Neoplasms

To assess the potential value of cytokeratins (CK) 8,18,19 as tumor markers for thyroid diseases, a study was performed comparing serum CK 8,18,19 levels in patients affected from thyroid carcinoma, adenoma, other benign thyroid diseases and healthy volunteers as controls. One hundred cases (65 patients and 35 controls) were examined. Thirty patients had thyroid carcinoma (18 papillary--PTC, 8 follicular--FTC, 4 medullary--MTC), 19 non-toxic goiter, 10 thyroid adenoma, 6 chronic thyroiditis and 35 healthy volunteers as controls. These controls were matched by age and sex. The mean value of CK in benign thyroid diseases (46.1 U/L) was significantly higher (p<0.02) than that in healthy controls (29.6 U/L). The mean value of CK in carcinomas (68.1 U/L) was significantly higher than that in healthy controls (p<0.01) and benign thyroid diseases patients (p<0.05). The positive rate of CK in thyroid carcinomas was 28.1%, while in benign thyroid diseases was 17.8%. The CK sensitivity for thyroid carcinomas was 28.1%, with a specificity of 80% and accuracy of 70.4%. In PTC patients the mean CK value was not significantly higher than in the benign diseases' group and in healthy subjects. No evident correlation between CK levels and tumor mass was found. In FTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects. Large tumors showed the highest levels, while small tumor values were similar to the control ones. In MTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects, with the highest peaks in large tumors and metastatic tumors. The detection of increased values in thyroid carcinomas with high metastatic potential (FTC and MTC) seems to confirm the role of these antigens in predicting the malignancy's degree of the neoplasm. These findings, if confirmed in larger series, could play an important role in assessing the CK 8,18,19 serum level as a real prognostic factor. Further repeated serum determinations after total thyroidectomy might indicate the role of CK 8,18,19 as serum markers predicting the risk of metastases.

Topics: Adenocarcinoma, Follicular; Adenoma; Biomarkers, Tumor; Carcinoma, Medullary; Carcinoma, Papillary; Cell Differentiation; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Thyroid Neoplasms

Topics: Adenocarcinoma, Follicular; Adenoma; Carcinoma, Papillary; Diagnosis, Differential; Fluorescent Antibody Technique, Direct; Goiter; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

The morphologic distinction between papillary and follicular neoplasms of the thyroid gland can be difficult, especially on small biopsy specimens or in fine-needle aspirations. To determine whether immunohistochemistry could help in achieving the correct diagnosis, we characterized the staining pattern for a series of papillary and follicular neoplasms of the thyroid gland. A pilot study was performed using a panel of antibodies, including high-molecular-weight keratin (HMWK, 34 beta E12), cytokeratin (CK) 5/6, CK7, CK13, CK14, CK20, AE1/AE3, CAM5.2, involucrin, and villin. Of these antibodies, involucrin and HMWK showed strong differential staining between follicular and papillary neoplasms. HMWK stained 91% of papillary carcinomas, including follicular variants, with a median of 53% positive cells, and involucrin stained 72.5% of papillary neoplasms with a median of 45% positive cells. HMWK stained only 20% of follicular neoplasms, whereas involucrin stained 29% of cases. Papillary neoplasms showed strong, although patchy, staining with HMWK and involucrin, whereas those follicular neoplasms that did have staining showed a weak, diffuse pattern of staining. We believe that HMWK, and involucrin to a lesser degree, could be useful in differentiating papillary from follicular neoplasms, especially for cytologic cell block material or for cases in which the architectural pattern is follicular.

Topics: Adenocarcinoma, Follicular; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Papillary, Follicular; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Protein Precursors; Thyroid Neoplasms

Thyroid anaplastic (undifferentiated) carcinomas (TACs) comprise a morphologically heterogeneous group of tumors, which can arise in the background of differentiated papillary or follicular carcinoma. The thyroid epithelial differentiation varies in these tumors and has not been completely characterized. In this study, we immunohistochemically analyzed different variants TACs from 35 patients by using antibodies specific to 9 different keratin polypeptides, epithelial membrane antigen, thyroid transcription factor I (TTF-1), and thyroglobulin. These tumors were histologically divided into 3 categories: squamoid-cohesive (SC, 13 tumors), spindle cell sarcomatous (SS, 8 cases) and intermediate group, including tumors with giant cells and solid epithelioid components (GC, 18 tumors); 4 tumors had 2 components. The patients ages ranged from 40 to 89 years, with a mean age in all groups of 70 years. TTF-1 was present in only 2 of 9 of the SC tumors, and absent in all other TACs, but was present in entrapped differentiated components. Thyroglobulin was absent in all but 1 case. A complex keratin (K) pattern of stratified epithelia was typically seen in the SC tumors with extensive K7, K8, K17, K18, and K19, and variable K13 and K14 expression; EMA was also present. K16 was limited to squamous pearls in 1 tumor, and K10 was absent. The GC carcinomas typically had K8 and K18, whereas the expression of K7 was variable and that of K14, K17, and K19 sporadic; EMA was variably present in half of the cases. The keratins in spindle cell sarcomatous tumors were usually limited to K7, K8, and K18, often in limited numbers of cells. EMA was present in 1 case only. These results indicate a complex pattern of keratins in squamoid and giant cell TACs, similar to papillary carcinoma and suggesting the possibility of relationship. There was a progressive loss of epithelial differentiation and keratins in sarcomatoid TACs. Loss of TTF-1 is a nearly uniform feature of TAC and disallows the use of this marker to pinpoint a thyroid origin of these tumors.

Topics: Adenocarcinoma, Follicular; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Female; Fluorescent Antibody Technique, Direct; Humans; Keratins; Male; Middle Aged; Nuclear Proteins; Thyroglobulin; Thyroid Neoplasms; Thyroid Nuclear Factor 1; Transcription Factors

The literature describes a number of vascular alterations in the thyroid gland and its tumors, the majority of which are related to fine-needle aspiration (FNA). These alterations include pseudoangiosarcomatous changes (Masson's lesion), pseudoinvasion in capsular veins, and endothelial proliferations in the needle tract. We present three cases of a unique intravascular endothelial proliferation in the capsular vessels of follicular and/or Hürthle cell thyroid neoplasms (two angioinvasive Hürthle cell carcinomas and one angioinvasive follicular carcinoma), which we think is unrelated to FNA. The lesion consists of spindle cells with plump nuclei, with focal nesting imparting an epithelioid pattern to the lesion. Focally red blood cells percolate between and mix with the spindle cells, recapitulating superficially a Kaposi's like appearance, but we identified no mitotic figures. Only one patient had a preoperative FNA; in that case, the lesions were spatially separate from the needle tract and the usual post-FNA reactive changes. The lesional cells were positive for Factor VIII and CD 31 and negative for cytokeratins and thyroglobulin immunostains. This immunopanel was helpful in distinguishing these lesions from true angioinvasion by thyroid tumor. To date, the etiology of these vascular lesions is unknown, but we postulate that certain follicular-derived thyroid tumors might elaborate angiogenic mediators, which in a cell culture system of follicular thyroid carcinoma can trigger endothelial proliferations.

Topics: Adenocarcinoma, Follicular; Adult; Biomarkers, Tumor; Biopsy, Needle; Endothelium, Vascular; Factor VIII; Female; Hemangioma, Capillary; Humans; Immunoenzyme Techniques; Keratins; Male; Platelet Endothelial Cell Adhesion Molecule-1; Thyroglobulin; Thyroid Neoplasms

The expression of simple and stratified epithelial-type cytokeratin (CK) intermediate filaments was evaluated by immunohistochemistry in a series of 41 papillary carcinomas, 10 follicular carcinomas, 2 poorly differentiated carcinomas and 34 specimens of normal thyroid parenchyma and lymphocytic thyroiditis. The aim of the study was to establish the CK profile of normal thyroid and thyroid carcinomas in order to clarify the putative application of CK immunostaining in diagnostic surgical pathology, and to evaluate whether the process of neoplastic transformation and tumour progression in the thyroid may be associated with any particular change in CK expression. Normal thyroid strongly expressed simple epithelial-type CKs 7 and 18 and, to a lesser degree, CKs 8 and 19, but did not express stratified epithelial-type CKs. The same pattern was found in lymphocytic thyroiditis, though the CK 19 immunoreactivity was stronger in these lesions than in the normal thyroid. Papillary and follicular thyroid carcinomas shared the expression of simple epithelial-type CKs 7, 8, 18 and 19. Immunoreactivity for CK 19 was frequently stronger and more widely distributed within each particular tumour in papillary than in follicular carcinomas, but it could also be detected, at least focally, in every follicular carcinoma. Strong expression of CK 19 highlighted small foci of papillary carcinoma not easily identifiable by conventional histological examination. Stratified epithelial-type CKs 5/6 and 13 were detected in a high percentage of papillary carcinomas, in contrast to their absence in follicular carcinomas and normal thyroid. The CK pattern was similar in primary and metastatic papillary carcinomas. We conclude that papillary carcinoma of the thyroid presents a distinct CK profile that may be used for diagnostic purposes.

Topics: Adenocarcinoma, Follicular; Carcinoma, Papillary; Epithelium; Humans; Immunohistochemistry; Intermediate Filaments; Keratins; Reference Values; Thyroid Gland; Thyroid Neoplasms; Thyroiditis

Previous studies indicate that keratins 7, 8 and 18 are present in all thyroid papillary and follicular lesions, but the distribution of other keratins has been incompletely characterized. The profile of individual keratin (K) polypeptides was evaluated immunohistochemically in over 200 non-neoplastic and neoplastic thyroid papillary and follicular lesions. Monoclonal antibodies to K19, K17, K16, K5/6 and K10 were applied in paraffin sections of formaldehyde-fixed tissue. K19 was present variably, often only focally in goitres, and was present only sporadically in papillary hyperplasia. However, K19 was strongly and uniformly expressed in virtually all papillary carcinomas, indicating differential diagnostic usefulness in differentiating papillary hyperplasia and papillary carcinoma. About half of the follicular carcinomas (defined as tumours strictly excluding the follicular variant of papillary carcinoma) were also strongly K19-positive, suggesting that K19 patterns are not reliable in differentiating papillary and follicular carcinoma. K17 and K5/6 were present in cysts and squamous metaplasia of goitres, and focally in papillary but only exceptionally in follicular carcinoma in areas of squamous differentiation and tumour cells in desmoplastic stroma. K16 in turn was present only focally in well-developed squamous metaplasia in goitres but was not found in differentiated thyroid carcinomas. K10, a high-molecular-weight keratin typical of epidermal differentiation, was identified neither in non-neoplastic nor in neoplastic differentiated thyroid lesions, including squamous metaplasia. These results indicate that papillary carcinomas differ from other differentiated thyroid tumours in their varying, usually focal, expression of stratified epithelial keratins that are partly but not exclusively related to squamous differentiation in such lesions. However, papillary carcinomas do not express truly epidermally restricted keratins; their previously described reactivity with polyclonal "epidermal keratin" antibodies most probably results from the reactivity of such antibodies with K19.

Topics: Adenocarcinoma, Follicular; Adenoma; Carcinoma, Papillary; Diagnosis, Differential; Goiter; Humans; Immunohistochemistry; Keratins; Thyroid Neoplasms

Using 8 different monoclonal antibodies, immunohistology was performed on 36 follicular adenomas and on 28 follicular, 34 papillary, 27 medullary and 29 anaplastic carcinomas of the thyroid. The panel of antibodies was directed against broad-spectrum cytokeratins (pan-CK, antibody lu-5), against basic and acid high-molecular-weight CK of types #1, 5, 10 and 14, against basic (#5 and 6) and acid high-molecular-weight CK (#13) and against basic (#7 and #8) and acid low-molecular-weight CK (#19 and #20). With the exception of a large number of anaplastic carcinomas, nearly all other tumours exhibited strong immunoreactivity with antibodies against pan-CK, CK 8 and CK 19. CK 20 expression was exclusively shown for 2 medullary carcinomas. Reactivity for high-molecular-weight CK could only, each time focally, be demonstrated for 14 papillary and 2 follicular carcinomas and for 2 anaplastic carcinomas with partial squamous differentiation. Thirteen anaplastic carcinomas were not decorated by any of the CK antibodies applied. CK 7 staining exceeding the staining of individual cells was observed in 26 papillary cancers. In contrast, such a finding could only be obtained with each one follicular adenoma, medullary carcinoma and anaplastic carcinoma and with 5 follicular carcinomas. These results confirm earlier studies in that CK 20 expression among thyroid tumours is restricted to the neuroendocrine medullary carcinomas and that in a larger percentage of anaplastic thyroid carcinomas an epithelial phenotype can not be demonstrated even upon using broad-spectrum CK antibodies. New is the finding that there exist considerable differences between papillary carcinomas and all other non-papillary thyroid tumours regarding CK 7 expression. This result might be of differential diagnostic value for the distinction of follicular and papillary thyroid neoplasias which sometimes have an overlapping histological pattern.

Topics: Adenocarcinoma, Follicular; Adenoma; Antibodies, Monoclonal; Biomarkers, Tumor; Carcinoma; Carcinoma, Medullary; Carcinoma, Papillary; Diagnosis, Differential; Humans; Keratins; Thyroid Gland; Thyroid Neoplasms

The morphological, histochemical, and immunohistochemical findings of seven cases of solid cell nests (SCNs) of the thyroid are described. Light microscopy showed two cell types forming the SCNs, which we refer to as "main cells" and "C cells." In all cases "mixed thyroid follicles" (a unique structure lined by follicular epithelium and epidermoidlike cells) were observed in which the histochemical study confirmed the presence of intraluminal acid mucins. Adult adipose tissue and cartilage were found in one case and foci of cartilage were observed in another case in association with the SCN. Immunohistochemical studies showed positivity of "main cells" for carcinoembryonic antigen (CEA), high- and low-molecular weight keratins, neurotensin, and somatostatin. "C cells" were positive for calcitonin, calcitonin gene-related peptide (CGRP), and chromogranin. The two cell types in SCNs were consistently negative for thyroglobulin. Neuron-specific enolase (NSE)-positive cells were found in the vicinity of the SCN. The unusual association of adipose tissue and cartilage as well as the results of the extended immunohistochemical study in this series provides further support to the belief that SCNs and "mixed thyroid follicles" represent remnants of the ultimobranchial body and should be considered normal components of the thyroid gland.

Topics: Adenocarcinoma, Follicular; Adult; Animals; Carcinoma, Papillary; Female; Goiter, Nodular; Humans; Keratins; Male; Middle Aged; Neuropeptides; Thyroid Neoplasms; Ultimobranchial Body

The pathologic diagnosis of thyroid tumors is often difficult and subjective. Immunohistochemical markers including high molecular weight cytokeratin (HMW-CK), cytokeratin-19 (CK-19) and epithelial membrane antigen have been suggested to be helpful in the distinction of various types of thyroid neoplasia. We collected frozen and/or paraffin-embedded tissues from a total of 116 surgically resected thyroids including 31 nodular hyperplasias, 18 follicular adenomas, 48 papillary carcinomas and 19 follicular carcinomas, stained them for HMW-CK, CK-19 and epithelial membrane antigen, and graded the results on a scale from 0 to 3+. Although little staining for HMW-CK was seen in paraffin-embedded tissues, different results were obtained when both HMW-CK and CK-19 were tested on frozen tissues. In papillary carcinomas, including the follicular variant of papillary carcinoma, diffuse positivity for these antigens was seen immunohistochemically, and these antigens significantly distinguished papillary carcinomas from follicular neoplasms and nodular hyperplasias. Focal staining for epithelial membrane antigen was found in all pathological processes; thus this marker was not useful. We conclude that HMW-CK and CK-19 are useful in the distinction of papillary carcinomas from follicular adenomas, follicular carcinomas, and nodular hyperplasias when applied to frozen tissues. We recommend that samples of thyroid follicular nodules be frozen, and retrieved if necessary to aid in the differential diagnosis of these tumors.

Topics: Adenocarcinoma, Follicular; Adenoma; Antigens, Neoplasm; Biomarkers, Tumor; Carcinoma, Papillary; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Membrane Glycoproteins; Molecular Weight; Mucin-1; Thyroid Neoplasms