A scanning and transmission electron microscopic study of human nodular goitre.
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Biomedical subjects
Publications and source records attributed to J V Johannessen.
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A significant reduction in nuclear pore density observed in papillary carcinomas compared to normal thyroid, adenomas and follicular carcinomas probably disturbs the nucleo-cytoplasmic transfer of ribonucleoproteins. This may contribute to the slow growth and indolent biological behavior of these tumors where even the presence of regional lymph node metastases does not worsen the prognosis. The signs of nuclear hyperactivity may result from an attempt to compensate for the nuclear membrane defect.
A flow cytometric (FCM) analysis of biopsies from 19 patients with thyroid lesions (Hashimoto's thyroiditis, hyperplastic goiter, colloid and adenomatous nodular goiter, follicular adenoma, follicular carcinoma, anaplastic carcinoma) was performed to evaluate the relevance of such results for the individual diagnosis and prognosis and prognosis of such diseases. All cases of Hashimoto's thyroiditis, the colloid nodular goiters, and the hyperplastic goiter had a unimodal diploid pattern, while the anaplastic carcinomas were aneuploid. These lesions are, however, easily diagnosed on morphological grounds and their FCM classification would only be redundant. Follicular adenomas and follicular carcinomas may be either unimodal diploid or aneuploid, and our single case of adenomatous colloid goiter showed a bimodal DNA distribution. This means that a diploid modal DNA content in a follicular tumor does not rule out malignancy, while aneuploidy is not an unequivocal sign on malignancy. The evaluation of the percentage of cells in S-phase did not seem to contribute valuable information for the individual diagnosis of malignancy within the group of thyroid lesions studied. Our study indicates a rather limited clinical value of FCM measurements of DNA in the individual case of thyroid disease.
Twenty-five adenomas of the thyroid were studied by transmission and scanning electron microscopy: 14 embryonal, fetal, and simple adenomas, 1 colloid adenoma, 2 toxic adenomas, 2 oxyphil adenomas, 2 "atypical adenomas" and 4 adenomas with capsular invasion, formerly designated "malignant adenomas." The only adenomas that presented with special ultrastructural features were the oxyphil and the toxic varieties. The toxic adenomas had organelle-rich cells with numerous and long microvilli on their surfaces. The oxyphil adenomas showed Hürthle cell changes, including abundant mitochondria, and smooth cell surfaces. The subdivision of the other forms of adenomas was impossible at the ultrastructural level; and this study did not reveal ultrastructural features which could distinguish the so-called "atypical" and "malignant" adenomas from ordinary thyroid adenomas. "Malignant" adenomas should preferable be called what they are: adenomas with capsular invasion. Neither does this study support the view that electron microscopy is a useful method to separate an adenoma from a well-differentiated follicular carcinoma in the occasional patient who presents problems.
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NHIK 3025 cells derived from a carcinoma in situ were exposed to hematoporphyrin derivative (Hpd) and light and examined by light microscopy, freeze-etching, scanning, and transmission electron microscopy. The first morphologic changes observed were shrinkage of mitochondria and formation of vesicles on the cell membrane. Furthermore, increased membrane permeability led to accumulation of Hpd and cellular swelling, with a concomitant reduction in the number and size of the microvilli. Some of the vesicles seemed to originate from microvilli. The freeze-etching appearance of the membranes of the majority of the cells was unaltered by treatment with Hpd and light. However, in some cases clustering of membrane particles was observed. At low doses membrane vesiculation and cell swelling were reversed within a few hours after treatment, indicating that repair processes were operative.
The surface features of nodular goitre, follicular adenomas, focal and Hashimoto type thyroiditis, Graves' disease, follicular carcinomas, papillary carcinomas, anaplastic carcinomas, medullary carcinomas and malignant lymphomas are presented in this scanning electron microscopic study of 95 cases. Scanning electron microscopy was found to be an excellent method for studying the surface topography of the diseased cells at high magnification and with a great depth of field. However, scanning electron microscopy does not seem to be a valuable tool for the diagnostic and prognostic routine evaluation of thyroid disorders.
An acinic cell carcinoma (ACC) arising in the nasal cavity, a rare entity, is presented. The tumor involved the left lower turbinate and showed the classic features of ACC on light microscopic examination. On ultrastructural examination, tumor cells contained numerous secretory granules, diagnostic of ACC. Scanning electron microscopy demonstrated the secretory granules as well as numerous apical microvilli where tumor cells surrounded lumens. As far as the authors are aware, the scanning electron microscopic findings in ACC have not been previously reported.
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We present the first comprehensive flow cytometric analysis of papillary carcinoma of the human thyroid. All but one of the 22 papillary carcinomas showed a unimodal distribution of the nuclear DNA content. The mean modal DNA was significantly lower in papillary carcinomas than in normal thyroid tissue, a finding which is contradictory to some earlier reports based on conventional cytophotometry. Tumors predominantly composed of Hürthle cells had a significantly higher mean modal DNA, whereas no significant difference was found between tumors with many ground glass nuclei and those lacking this nuclear feature. A very low percentage of S-phase cells was found both in the primary tumors and their metastases. This percentage was even lower than in normal thyroid tissue. The low proliferative activity may in part explain why most papillary thyroid carcinomas run such a surprisingly indolent course even after the establishment of regional lymph node metastases.
We have studied normal thyroid specimens from 20 euthyroid patients with the scanning electron microscope. A significant negative correlation was found between the diameter of the apical cell surface and the density of microvilli. Large follicles were usually surrounded by smooth-surfaced cells with a large apical diameter, while the smaller follicles were surrounded by smaller cells with numerous and large microvilli. Exceptions to this rule were, however, not uncommon, and the morphological differences between neighbouring cells in one and the same follicle were as great as those between the cells of different follicles. Concurrent transmission electron microscopy showed that the morphology of the apical cell membrane reflects the activity of the follicular cells. The scanning electron microscopical findings thus indicate that the thyroid may have an intrafollicular functional cycle as important or more important than an interfollicular cycle. Our study shows that one to five cilia are regular constituents of the normal follicular cells and that their number is not correlated with the diameter of the apical cell surface nor with the density of microvilli. Although we do not rule out the possibility that they may be fetal rudiments, we suggest that they may play a functional role probably by stirring the colloid.
A human melanoma cell line with unusually high growth potential was established from a xenograft growing in athymic mice. When xenograft fragments were cultured in vitro, melanoma cells grew out rapidly without any contamination of mouse stromal cells. An established cell line, FME, derived from this tumour, grew both in monolayer and in shaker suspension culture with doubling times of about 20 h. The cells grew easily at low serum concentrations and could even be cultured in serum-free medium supplemented with insulin and transferrin. The cultured cells were hyperdiploid, as were the cells of the xenograft. The cells grew easily in soft agar and formed tumours in athymic mice. When growing exponentially, the cells were almost unpigmented, but when grown to high density, their melanin content increased. Upon treatment with dimethyl sulphoxide (DMSO), retinoic acid and theophylline, as well as with the tumour promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), the cells showed growth inhibition and increased melanin synthesis.