bromochloroacetic-acid and Goiter--Nodular

We report 3 cases of primary renal cell tumor simulating atrophic kidney with distinct gross, morphologic, immunohistochemical, and molecular genetic features. The tumors were retrieved out of more than 17 000 renal tumors from the Plzen Tumor Registry. Tissues for light microscopy had been fixed, embedded, and stained with hematoxylin and eosin using routine procedures. The tumors were further analyzed using immunohistochemistry, array comparative genomic hybridization, and human androgen receptor. Analyses of VHL gene and loss of heterozygosity (LOH) 3p were also performed. The patients were 2 women and 1 man, with ages ranging from 29 to 35 years (mean, 31.3 years). Grossly, the neoplasms were encapsulated and round with largest diameter of 3.5 cm (mean, 3.2 cm). Follow-up available for all patients ranged from 2 to 14 years (mean, 8 years). No aggressive behavior was noted. Histologically, akin to atrophic (postpyelonephritic) kidney parenchyma, the tumors were composed of follicles of varying sizes that were filled by eosinophilic secretion. Rare areas contained collapsed follicles. Each follicle was endowed with a small capillary. The stroma was loose, inconspicuous, and focally fibrotic. Two types of calcifications were noted: typical psammoma bodies and amorphous dark-blue stained calcified deposits. Immunohistochemically, tumors were strongly positive for cytokeratins (OSCAR), CD10, and vimentin, with weak immunopositivity for CAM5.2 and AE1-AE3. WT1 and cathepsin K were weakly to moderately focally to diffusely positive. Tumors were negative for cytokeratin 20, carbonic anhydrase IX, parvalbumin, HMB45, TTF1, TFE3, chromogranin A, thyroglobulin, PAX8, and ALK. Only 1 case was suitable for molecular genetic analyses. No mutations were found in the VHL gene; no methylation of VHL promoter was noted. No numerical aberrations were found by array comparative genomic hybridization analysis. LOH for chromosome 3p was not detected. Analysis of clonality (human androgen receptor) revealed the monoclonal nature of the tumor. We describe an unknown tumor of the kidney that (1) resembles renal atrophic kidney or nodular goiter of thyroidal gland; (2) contains a leiomyomatous capsule and 2 types of calcifications; (3) lacks mitoses, atypias, necroses, and hemorrhages and nearly lack Ki-67 positivity; and (4) so far showed benign biological behavior.

Topics: Adult; Atrophy; Biomarkers, Tumor; Calcinosis; Comparative Genomic Hybridization; Diagnosis, Differential; DNA Methylation; Female; Goiter, Nodular; Humans; Keratins; Kidney; Kidney Neoplasms; Leiomyomatosis; Loss of Heterozygosity; Male; Mutation; Receptors, Androgen; Thyroid Gland; Vimentin; Von Hippel-Lindau Tumor Suppressor Protein

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

The specific pathogenesis of nodular goiter and the role of apoptosis in goitrogenesis are not known. We sought to examine the regulation of the TNF-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL)-induced apoptosis pathways in primary thyroid cells from 17 patients with nodular goiter, using 10 normal thyroids as controls. Both goitrous and normal thyroid cells were resistant to recombinant human TRAIL and an agonist anti-Fas antibody under basal conditions. However, all normal thyrocytes could be sensitized by TNFalpha/IL-1beta or interferon gamma/IL-1beta to undergo apoptosis in response to TRAIL or FasL, respectively. In contrast, the majority of goiter-derived cells remained resistant to TRAIL (12 of 17 samples) or FasL (9 of 17 samples) after cytokine pretreatment; 14 of 17 goiter nodules were resistant to at least one death ligand. Goiter size was inversely correlated with the sensitivity to TRAIL-mediated apoptosis. The resistance of goiter cells to TRAIL did not appear to be due to transcriptional regulation or cell surface expression of death and decoy receptors. However, increased proteasome activity was found in a subset of goiter cells resistant to both death ligands, and proteasome inhibitors could sensitize these goiter cells to TRAIL-mediated apoptosis. In conclusion, goiter-derived thyroid cells are resistant to TRAIL and/or Fas-induced apoptosis in vitro, and this may represent a new aspect of aberrant growth regulation in goiter nodules. The increased proteasome activity associated with this resistance suggests that the proteasome may be an important regulator of apoptosis in nodular goiter.

Topics: Acetylcysteine; Apoptosis; Apoptosis Regulatory Proteins; Cell Survival; Cells, Cultured; Cysteine Proteinase Inhibitors; Epithelial Cells; fas Receptor; Goiter, Nodular; Humans; Immunoblotting; Interferon-gamma; Keratins; Membrane Glycoproteins; Recombinant Proteins; Reference Values; Thyroid Gland; Thyroidectomy; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha

The most common benign lesion of thyroid, multinodular goiter, may mimic papillary carcinoma if it contains papillary areas. Although it is usually not very difficult to distinguish between these benign and malignant lesions, some cases may be problematic in differential diagnosis. In these cases, we decided to use cytokeratin 19 (CK19), which is shown to be effective in discriminating papillary carcinoma from follicular carcinoma of thyroid, and we also evaluated the immunoreactivity of CK19 in follicular adenomas. Twenty-five cases of multinodular goiter showing papillary formations, 25 cases of papillary thyroid carcinoma, and 15 cases of follicular adenoma were selected from archives of our institution. Immunohistochemical staining for CK19 was performed on deparaffinized sections. Diffuse and intense CK19 positivity was found in the cells of all papillary carcinomas. In the multinodular goiter group, 20 of 25 cases showed no staining while the remaining 5 were focally reactive with CK19. Three of the five were thought to be false positive owing to hemorrhage. Weak and focal CK19 staining was seen in some follicular adenomas. Our observations suggest that the staining features of CK19 may be helpful in differential diagnosis between papillary carcinoma and multinodular goiter showing papillary areas. Focal and pale staining for CK19 may be seen in multinodular goiter with papillary formations, and this feature should be considered in evaluation.

Topics: Adenocarcinoma, Papillary; Adolescent; Adult; Aged; Biomarkers, Tumor; Diagnosis, Differential; Female; Goiter, Nodular; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Papilloma

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 presence of intermediate filament proteins of cytokeratin/prekeratin type and vimentin type was evaluated in non-neoplastic thyroid glands and in different types of thyroid neoplasms. Follicular epithelium of both normal and goitrous thyroids showed a strong reaction with anticytokeratin antibodies that widely cross-react with various simple epithelia. On the other hand, in normal thyroid, there were only occasionally (in one of 12 cases) solitary cells reacting with antibodies to epidermal prekeratin. In nodular goiters, such cells were often seen (eight of 18), especially among the lining cells of cysts, and in chronic thyroiditis in all (12 of 12) cases. Only the stromal cells and intraluminal macrophages reacted with antibodies to vimentin. Neoplastic cells of papillary carcinomas showed a positive staining reaction both with antibodies to cytokeratins and to epidermal prekeratin. Follicular carcinoma cells, although positive for cytokeratins, could generally not be stained with antibodies to epidermal prekeratin. Medullary carcinoma cells also showed cytokeratin positivity and, only occasionally, positivity for epidermal prekeratin. Anaplastic carcinomas were also reactive with antibodies to cytokeratin but, for the most part, were negative for epidermal prekeratin. Interestingly, some neoplastic cells of all types of thyroid carcinomas also appeared to contain vimentin, as shown with both polyclonal and monoclonal antivimentin antibodies. In contrast to carcinomas, the intermediate filaments of thyroid sarcomas and lymphomas were only of vimentin type. Furthermore, it was found that the papillary structures in benign goiters were only reactive with cytokeratin antibodies and lacked, in contrast to papillary carcinomas, epidermal prekeratin-like immunoreactivity. Hence, the analysis of intermediate filament proteins of thyroid tumors can be utilized to differentiate between papillary and follicular carcinomas and between benign and malignant papillary lesions as well as between anaplastic thyroid carcinomas and sarcomas or lymphomas.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Papillary; Chronic Disease; Epithelium; Fluorescent Antibody Technique; Goiter, Nodular; Humans; Intermediate Filament Proteins; Keratins; Lymphoma; Protein Precursors; Sarcoma; Thyroid Gland; Thyroid Neoplasms; Thyroiditis; Vimentin

56 thyroid gland tumours and non neoplastic alterations were studied for keratin and thyroglobulin staining, using the indirect immunoperoxidase method on serial formalin fixed paraffin embedded sections. Papillary carcinomas showed a strong reaction with anti-keratin serum but a weak reaction with anti-thyroglobulin serum. Follicular adenomas and carcinomas showed virtually no reaction for keratin but a strong reaction for thyroglobulin. Undifferentiated and medullary carcinomas did not react with either antiserum, except for single cells in two undifferentiated carcinomas which reacted with anti-keratin serum. In nodular goiters, hyperplastic follicles showed little or no reaction with anti-keratin serum and strong reaction with anti-thyroglobulin serum. It is suggested that this virtually type-specific staining for keratin or thyroglobulin may be related to different degrees of cellular differentiation and organelle content in the tumour cells.

Topics: Adenocarcinoma; Carcinoma; Carcinoma, Papillary; Diagnosis, Differential; Goiter, Nodular; Graves Disease; Histocytochemistry; Humans; Immune Sera; Immunochemistry; Keratins; Thyroglobulin; Thyroid Diseases; Thyroid Neoplasms; Thyroiditis