Mixed medullary-follicular carcinoma of the thyroid: diagnostic dilemmas in fine-needle aspiration cytology.

Mixed medullary-follicular carcinoma (MMFC) of thyroid is an extremely rare tumor, characterized by coexistence of morphological and immunohistochemical features of both medullary carcinoma and follicular (or papillary) carcinoma. We herein present fine needle aspiration (FNA) findings of a histology-confirmed MMFC along with a review of literature. The patient was a 64-year-old woman who had a history of Hashimoto's thyroiditis and presented with enlargement of preexisting right thyroid nodule. An US-guided FNA of the thyroid nodule was performed and conventional smears were prepared. A cytologic diagnosis of "positive for malignancy, consistent with medullary thyroid carcinoma (MTC)" was rendered based on the presence of features characteristic for MTC, and the absence of components of follicular neoplasm (adenoma and carcinoma) or papillary carcinoma. However, microscopic examination of the follow-up total thyroidectomy specimen with the aid of immunocytochemical study detected minor portion of follicular carcinoma in addition to MTC. A histologic diagnosis of MMFC was then established. While specific identification of MMFC by FNA may be difficult, it should be emphasized that adequate sampling in conjunction with the proper immunostaining panel could have highlighted the different aspects of the mixed tumor.

Measurement of inaccuracy and imprecision of HCG methods using dilutions of the WHO 4th IS-HCG standard and a pregnant patient's serum.

INTRODUCTION: Differences in human chorionic gonadotropin (hCG) results obtained by seven different methods were documented by analyzing dilutions of the WHO 4th International Standard (IS) and a pregnant patient's serum. MATERIALS AND METHODS: Biases of +30.9 to -37.5% and +36.8 to -36.1% from the target concentration were found for the WHO 4th IS and patient sample dilutions, respectively. RESULTS: Imprecision was calculated from replicate measurements of hCG on the different sample dilutions. Imprecision ranged from 1.0% to 18.9% and 1.1% to 5.3% for the WHO 4th IS and patient sample dilutions, respectively. Using a maximum allowable error of 12.5% for hCG measurements, we found that two instruments were so biased that their hCG measurements could not be interchanged with hCG values produced by any of the other systems. DISCUSSION: It is ideal to use only one hCG methodology for the serial monitoring of hCG; otherwise, hCG methods should be carefully chosen to minimize inter-method bias.

GADD45 regulates G2/M arrest, DNA repair, and cell death in keratinocytes following ultraviolet exposure.

GADD45 is a multifunctional protein that is regulated by p53. p53 plays an important role in regulating DNA repair and in the response to ultraviolet light in keratinocytes. This study investigates the role of GADD45 in the response to ultraviolet B. Cell cycle analysis demonstrated that wild-type and Gadd45-deficient cells have transient G2/M arrest, but only in the wild-type cells was arrest sustained. Cdc2 kinase activity in immunoprecipitates from normal and Gadd45-deficient cells decreases after irradiation in normal cells but not in Gadd45-deficient cells. An immunofluorescent study with Cdc2 antibody demonstrated diffuse cellular fluorescence before ultraviolet irradiation in both Gadd45-deficient and wild-type cells, but upon ultraviolet irradiation only Gadd45-proficient cells showed Cdc2 sequestration in the cytoplasm. Gadd45-deficient cells also have a slower rate of nucleotide excision repair. The lack of G2/M arrest coupled with reduced DNA repair leads to a higher ultraviolet sensitivity of Gadd45-deficient cells. These results reveal that GADD45 promotes G2/M arrest via nuclear export and kinase activity of Cdc2, increases global genomic DNA repair, and inhibits cell death in keratinocytes. Thus, GADD45 plays an important role in maintaining genomic integrity in ultraviolet-exposed skin.