Biomedical subjects
Publications and source records attributed to H R Harach.
Rat thyroid follicular cells desensitized to the mitogenic action of TSH by prolonged stimulation retain the capacity to respond to the mitogenic stimulus of wounding. The implications for thyroid growth control and neoplasia are discussed.
The original descriptions of medullary carcinoma stressed the lack of papillary and follicular differentiation and the presence of amyloid. During the last few years, the spectrum of histological features seen in tumours of C cell origin has broadened, and papillary and anaplastic forms have been reported. We have recently studied three cases of medullary carcinoma with a major 'tubular' or 'follicular' component, giving a microscopic picture suggestive of follicular carcinoma of the thyroid. These cases were studied with routine techniques, electron microscopy, and immunohistological methods using antibodies to calcitonin and thyroglobulin. In all three cases the calcitonin localization was positive, and apart from included peripheral thyroid follicles, the thyroglobulin was negative--even in the tumour with large follicles containing PAS positive colloid. In the cases with tubular lumina, electron microscopy showed a concentration of granules in the apical portion of the cells, with corresponding immunolocalization of calcitonin in a ring about the lumen. We conclude that medullary carcinoma should be considered in the differential diagnosis of every unusual thyroid carcinoma, even those showing glandular differentiation and containing apparent follicles, and that immunolocalization techniques using calcitonin and thyroglobulin are essential for accurate diagnosis of thyroid carcinomas.
Riedel's thyroiditis is a rare disease which has in the past been confused with the much commoner fibrous variant of Hashimoto's thyroiditis. We have compared the histological and immunohistochemical characteristics of three cases diagnosed as Riedel's thyroiditis with five cases of the fibrous variant of Hashimoto's thyroiditis. The major distinguishing features on light microscopic study were that Riedel's thyroiditis showed (a) extra-thyroid extension of the fibrous tissue, (b) a phlebitis with distension of the vein lumen by lymphoid or fibrous tissue, and (c) relatively normal surviving thyroid tissue, while in Hashimoto's thyroiditis the fibrous tissue did not extend outside the thyroid, the veins were surrounded by fibrous tissue, but did not show a phlebitis, and all thyroid tissue was affected by the process. These findings confirm those of other workers in suggesting that there is a clear histological distinction between these two processes. The quantitative immunohistochemical studies showed that in the fibrous variant of Hashimoto's thyroiditis, cells containing kappa chains outnumbered lambda chain cells in all cases, the mean ratio of kappa to lambda being very close to that found generally in the circulation, with lambda chain cells forming 36% of all light chain containing cells. In contrast, the mean proportion of lambda chain cells in Riedel's thyroiditis was 71%. In Hashimoto's thyroiditis the dominant plasma cell was, as expected, the IgG containing cell, with IgA cells forming only 15% of all heavy chain cells. In Riedel's thyroiditis IgA containing plasma cells were unusually prominent, forming 47% of all plasma cells present. These findings confirm the separation of the two entities, and demonstrate an unusual pattern of restriction of antibody forming cells in Riedel's thyroiditis. It is possible that IgA plays a role in the pathogenesis of Riedel's thyroiditis.
Factor VIII-related antigen is a recognised marker of endothelial cells. A brief immunocytochemical study of its distribution in follicular carcinoma of the thyroid and its value in the recognition of vascular invasion by this tumour has been carried out. Ten cases of follicular carcinoma of the thyroid were studied. In each strong endothelial staining was found in the majority of vessels in the adjacent normal thyroid. Lymphatic endothelium was negative. In eight of the 10 cases the staining of vessels within the tumour was absent or very weak. Staining was also absent in the majority of vessels completely occluded by tumour, but was present in the endothelium of vessels only partly occluded by tumour. It is concluded that factor VIII-related antigen staining has only limited value in the recognition of vascular invasion in follicular carcinoma. The absence of vascular staining in the tumour leads us to suggest that inhibition of factor VIII production by the tumour could be a possible mechanism which facilitates vascular invasion and metastasis.
Immunohistological methods were used to investigate the presence of calcitonin, thyrotrophin, carcinoembryonic antigen, beta pregnancy specific glycoprotein, human placental lactogen, and the beta subunit of human chorionic gonadotrophin in formalin fixed lung tumour tissue sections. Carcinoembryonic antigen was observed in 71% of 101 tumours studied (70%), beta 1 pregnancy specific glycoprotein in 66 of 97 tumours (68%), beta subunit of human chorionic gonadotrophin in 35 of 97 (36%), human placental lactogen in 19 of 97 (20%), calcitonin in 10 of 71 (14%), and thyrotrophin in one of 27 lung tumours studied. There appeared to be no direct association between the presence of any given marker and the presence of any other. Similarly, the association between the presence of a tumour marker and histological type was poor. This study shows that the presence of tumour markers is relatively common in human lung tumours.
This study was designed to investigate the mitotic response to wounding in the rat thyroid. The spatial distribution of mitotic activity 48 hr after incision of the thyroid isthmus, or mere exposure of the gland (sham-operation), was assessed using a stathmokinetic technique. Incision resulted in a 66-fold increase over normal in metaphase index adjacent to the wound, falling over 2 mm to a stable 13-fold elevation. Sham-operation produced a smaller response with a complete return to normal levels over 1-1 X 5 mm. The results demonstrate that there is a dramatic localized mitotic response to wounding in the thyroid together with a smaller generalized response. Further, the response to sham-operation indicates that thyroid follicular cells respond to a diffusible 'wound hormone'. We suggest that this may be a major mechanism mediating reparative growth in this gland.
We have previously shown that the growth response of the rat thyroid to a sustained elevation of the serum level of TSH, induced by goitrogen administration, is self-limiting. This study investigated the possibility that this limitation of growth is due to the inhibitory action of a chalone secreted by the thyroid follicular cells, the serum concentration of which increases as the gland grows. Twenty-seven adult rats were treated with the goitrogen aminotriazole for 5 months to reach a 'plateau of growth'. One group of 9 rats was then subjected to hemithyroidectomy, another to a sham operation, while a third acted as unoperated controls. Four weeks later there was no significant difference between the groups in thyroid weight, follicular cell number or serum TSH. The absence of regeneration following hemithyroidectomy indicates that a systemically-circulating chalone does not play a role in the regulation of growth in the goitrous thyroid. Other mechanisms including the possible role of a 'local' chalone are briefly discussed.
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Fifty-eight human fetal thyroid glands obtained at autopsy were systematically studied for the presence of intrathyroidal parathyroid tissue. The latter was found in 13 thyroid lobes from 12 fetuses. It was located in a subcapsular position in 9 of 58 cases and lying deep in thyroid tissue in 4 of 58. Our findings suggest that intrathyroidal parathyroid tissue is not such a rare finding and should always be considered especially for the clinical and surgical management of patients with primary hyperparathyroidism due to parathyroid hyperplasia.
Fifty-eight human thyroid glands obtained at autopsy from fetuses with proven retrosternal thymus were systematically studied for the presence of intrathyroidal thymic tissue. The latter was found in one thyroid lobe in each of three fetuses (5.1%). It was located in a subcapsular position in two cases (3.4%) and lying deep in thyroid tissue in one (1.7%). Our findings would support a IV-V pharyngeal pouch origin for some accessory thymic tissue and would provide an explanation of the histogenesis of intrathyroid thymomas.
Pathological and immunohistochemical findings for specific thyroid epithelial cell markers in thyroid/cervical teratomas from four children are reported. All tumors showed components from the three germinal cell layers. Neoplastic thyroglobulin-immunoreactive thyroid follicles occurred in three intrathyroid teratomas, but the findings were negative in a cervical teratoma in which evidence of its thyroid origin could not be ascertained. As previously suggested on histological grounds, thyroid tissue, other than normal trapped thyroid follicles, is not an infrequent component of cervical teratomas. We found no evidence to support an ultimobranchial origin for these tumors, as previously suggested by Roediger et al. (19), because no calcitonin immunoreaction was observed.
The tall cell variant of thyroid papillary carcinoma differs from classic papillary carcinoma in its more aggressive clinical behavior, cell type (columnar amphophilic to oxyphilic) and higher frequency of stromal lymphoid infiltrate. A retrospective study of three such cases was made, with an emphasis given to the utility of fine needle aspiration cytology in their identification. Aspirates revealed papillary fronds and cyanophilic and oxyphilic neoplastic cells with a high proportion of nuclear grooves and cytoplasmic inclusions. These nuclear details allowed a specific diagnosis of papillary carcinoma with oxyphil cells as compared to oxyphilic cell follicular tumors. Smears from two cases showed, in addition, lymphoid cells and multinucleate giant cells. In them a diagnosis of coexisting Hashimoto's disease, granulomatous thyroiditis or inflammatory tumor stroma could not be excluded cytologically.
Fine needle aspirates from 8 thyroid papillary carcinomas, follicular variant, were studied. Histologically the tumors were composed exclusively of follicles (four cases) or an admixture of follicular and trabecular structures (four cases). Follicles were identified in smears from seven cases (87.5%) and sheets reminiscent of a trabecular pattern in one (12.5%). Colloid material presented as intraluminal (one case) or extraluminal, dense, round masses (six cases). Nuclear cytoplasmic inclusions occurred in seven (87.5%) of the cases. All these features have been described for follicular lesions or neoplasia together with occasional nuclear grooves, as occurred in two (25%) of the studied cases. In the other six (75%) cases, a moderate to high proportion of neoplastic cells with nuclear grooves facilitated the diagnosis of papillary carcinoma. Our findings suggest that a careful microscopic search for nuclear grooves should be attempted in aspirates yielding a diagnosis of follicular neoplasia that could otherwise be indistinguishable from the follicular variant of papillary carcinoma of the thyroid.
The accuracy of fine needle aspiration (FNA) cytology of the thyroid was addressed in 142 nodular goiters from an endemic goiter region. The aspirations and their interpretation were based on the methodology of the Karolinska Hospital. For practical purposes, the follicular lesions were divided into type I (benign), type II (atypical benign) and type III (suspicious). Excluding the follicular lesions, the cytohistologic agreement for the whole series was 87%, with a correlation of 81.5% for carcinomas. The type I and type II follicular lesions were benign on histologic grounds; 39% of the carcinomas were detected in the type III follicular lesions. The 0.7% false-positive diagnoses increased to 15% when type III follicular lesions were included. No false negatives were recorded. These observations, together with the increase of surgically resected thyroid carcinomas after FNA was accepted as a diagnostic modality, indicate that FNA biopsy of the thyroid is an accurate diagnostic method and is useful in selecting patients for subsequent surgery in areas of endemic goiter.
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