Mucinous thyroid carcinomas.
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Biomedical subjects
Publications and source records attributed to H R Harach.
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Mixed follicles are structures composed of squamous-like and follicular epithelia. Little attention has been generally paid to these peculiar follicles of the human thyroid; thus the aim of the present study was to investigate their prevalence and biological properties by means of systematic autopsy, histochemical and immunohistochemical surveys. Mixed follicles were found to be present in 54% and 81% of the patients with solid cell nests, as well as in 50% and 77% of the total number of the ultimobranchial nests, when one or two histological samples from each solid cell nest were examined, respectively. The follicular lumen of mixed follicles usually contained an eosinophilic and PAS-positive colloid-like material, although in 22% of the cases acid mucins sometimes intermixed with PAS-positive granular material and cell debris were also present within lumina. Follicular cells lining mixed follicles basically did not stain positively for calcitonin. The results indicate that mixed follicles are not rarely found in the human thyroid. The presence of intraluminal mucins and cell debris and the absence of calcitonin-containing cells in the follicular epithelium lining these peculiar follicles suggest that at least some thyroid follicular cells could originate from ultimobranchial tissue.
Solid cell nests of the thyroid display histological features that resemble squamous epithelium. In the present study we investigated whether these ultimobranchial nests express a renal tubular cell cytokeratin which is found to be widely distributed in epithelia but does not appear in squamous tissue. All 17 solid cell nests studied, in contrast to squamous epithelium lining an intrathyroid thyroglossal cyst, stained positively for this intermediate filament. These findings, together with the gland-like features shown ultrastructurally by these ultimobranchial remnants, further support the view that solid cell nests of the thyroid should not be regarded as a kind of intrathyroid squamous inclusion. In addition, they were electron-microscopically comparable to mammalian ultimobranchial tissue.
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The thyroids from 93 autopsies performed on children and young adults younger than age 40 years, were subserially sectioned at 2- to 3-mm intervals. Thirteen thyroids revealed 17 foci of occult papillary carcinoma (OPC), giving a prevalence rate of 14%. The youngest affected patient was a boy aged 18 years. The prevalence rate of individuals between age 18 and 40 years was 27%. The rate appears to be rather constant in adults, although there may be a slight rise in middle age. The prevalence rate was higher for males, but no statistically significant difference was seen. The arise of OPCs after puberty would favor the view that hormonal factors are related to their appearance.
The anatomical position and prevalence of solid cell nests (SCN) of the thyroid in early stages of postnatal life have not yet been clearly determined. In order to find out about these unsettled questions a systematic search of these ultimobranchial nests from 92 autopsied thyroids from neonates, children and young adults was undertaken. SCN were present in 61% of the patients; they were mainly located in the middle third of the lateral thyroid lobes, and placed along a central to paracentral and slightly dorsal longitudinal axis. These findings, as compared with our previous observations made in older adult thyroids, further demonstrate that there exist a constant anatomical position and prevalence of SCN in postnatal life. The significantly higher frequency of SCN in males (68%) than in females (48%) (p less than 0.01) found in a study that was further extended to 192 thyroids at early and late stages of postnatal life, is a question that requires further investigation.
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The thyroids from 101 consecutive autopsies from Finland were subserially sectioned at 2- to 3-mm intervals. From 36 thyroids, 52 foci of occult papillary carcinoma (OPC) were found, giving a prevalence rate of 35.6%, the highest reported rate in the world. The rate was higher, although not significantly, in males (43.3%) than in females (27.1%), but it did not correlate to the age of the patients. Twenty-six glands contained one tumor focus and ten glands contained two to five tumor foci. Only a minority of the smallest tumors can be detected with the method used. The probable number of OPCs over 0.15 mm in diameter was calculated to be about 300 in this material. The tumor diameter varied from 0.15 mm to 14.0 mm, with 67% of tumors under 1.0 mm. The smallest tumors were usually circumscribed and were composed almost solely of follicles. Larger tumors had more papillary structures and were often invasive. Fibrosis and, in the largest OPCs, lymphocytic reaction were seen around the invasive islands. All tumors were positively stained for thyroglobulin and all but one of the tumors stained positively for epidermal keratin. OPC appears to arise from follicular cells of normal follicles. Apparently the great majority of the tumors remain small and circumscribed and even from those few tumors that grow larger and become invasive OPCs only a minimal proportion will ever become a clinical carcinoma. According to the study, OPC can be regarded as a normal finding which should not be treated when incidentally found. In order to avoid unnecessary operations it is suggested that incidentally found small OPCs (less than 5 mm in diameter) were called occult papillary tumor instead of carcinoma.
Human thyroid follicles containing acid mucins have been regarded as a very rare finding and their significance has not yet been clarified. Therefore, a systematic anatomical, histochemical and immunohistochemical survey for the presence of such follicles in human thyroids was undertaken. Follicles with Alcian blue-positive acid mucins were practically confined to the 18% of sections that also contained ultimobranchial solid cell nests. Immunohistochemistry revealed that these follicles were mostly composed of and/or related to the presence of numerous calcitonin-immunoreactive cells, sometimes intermixed with occasional alcianophilic mucinous cells. These findings, with histometrical studies, demonstrate that there exists a relationship between mucinous C cell complexes and mucin/C cell-containing solid cell nests. The finding of calcitonin immunoreactivity in very occasional groups of cells with mucinous changes further suggests that at least some human follicular cells originate in ultimobranchial tissue.
An apparently new tumor entity of the thyroid is reported. The tumor was histologically characterized by good demarcation, lobular pattern, keratin-positive spindle cells, glandular elements, stromal hyalinization, and calcifications. These findings are suggestive of a tumor related to spindle-cell thymoma and apparently closely related to the recently described entity, ectopic hamartomatous thymoma. The patient, a 23-year-old man is alive and well 10 years after diagnosis. Two histologically similar cases have earlier been reported in the English literature under the heading "malignant teratoma."
Thyroid growth in the rat in response to a sustained elevation of serum thyrotropin (TSH) is limited by a progressive desensitization of the follicular cells to the mitogenic action of TSH which is not reversed by withdrawal of stimulation or by reduction of cell number. This study shows that, in thyroids which have reached a 'plateau' of growth, wounding induces a marked local follicular cell mitotic response which is equal in magnitude to that seen in control glands. This demonstrates that these cells, which are refractory to TSH, have not lost the capacity to divide. It is concluded that limitation of TSH-induced thyroid growth is not due to a non-specific loss of mitotic capacity resulting from severe hypothyroidism or goitrogen toxicity, or to an inherent limitation of the number of divisions which a follicular cell can undergo. The implications of these findings are discussed.
Mucoepidermoid carcinoma of the thyroid (MECT) has been recently recognized as a pathological entity. The origin of MECT is unknown but the morphology of this tumour closely resembles features seen in the ultimobranchial body (UB) vestiges. Recent studies in man have shown strong evidence that the so-called solid cell nests (SCN) of the thyroid may correspond to the human UB vestiges. To investigate whether these vestiges are the site of origin of this tumour a comparative study on SCN and MECT was undertaken. One hundred autopsied thyroids cut at 2-3 mm intervals were studied for the presence of SCN. Histochemical (H & E, Alcian blue-PAS, Mayer mucicarmine) and immunohistochemical studies (calcitonin, epidermal keratin) were performed in SCN and four cases of MECT. Sixty percent of thyroids were found to have SCN. They were mainly composed of epidermoid-like cells arranged in solid structures or lining cystic cavities, tubular and follicular structures. Solid clusters usually showed lumina containing PAS-positive and mucin-positive cell debris. Mucin stains also revealed mucinous cells placed around lumina filled by mucosubstances. Characteristic PAS-positive rounded bodies were found filling lumina as well as within some apical epidermoid-like cells, mucinous cells and cell debris. An obvious transition between these cells, cell debris and mucosubstances filling the lumina was noticed; suggesting degenerative changes undergone by the epidermoid-like cell. MECT basically presented all histological and histochemical features shown by SCN, furthermore, calcitonin containing cells were observed in 54% of SCN, while a metastatic MECT also showed scattered C cells within solid islands. The presence of epidermal keratin in all SCN and MECT, together with the previous findings, are strong evidence that MECT could originate in the SCN or human UB vestiges.
Iodine prophylaxis was introduced to the moderately severe goitre endemic area in Salta, Argentina, in 1963. All thyroidectomies from a 20 year period were reviewed, and 148 thyroid malignancies carefully studied. The period from 5 to 15 years after iodization was associated with a lower frequency of follicular carcinomas and a higher frequency of papillary carcinomas than the period before and up to 5 years after prophylaxis. Lymphoid infiltration in the non-tumorous thyroid was relatively infrequent before iodine prophylaxis: it was much higher in each of the post-prophylaxis periods. These results, in agreement with other studies, support the view that an increased iodine intake is associated with an increased incidence of papillary carcinoma of the thyroid and thyroiditis.
It was recently demonstrated that C cells, mucosubstances, and the intermediate filament epidermal keratin are present in solid cell nests (SCN) of the thyroid. The reliability and usefulness of these markers in detecting these ultimobranchial nests have, so far, not been comparatively investigated. In the light of this, a study for the presence of these tracers in SCN at different stages of postnatal life was undertaken. The existence of carcinoembryonic antigen (CEA) in this gut-derived tissue was also searched for. Epidermal keratin was present in the epidermoid-like cells from all SCN studied; calcitonin-immunoreactive C cells and mucosubstances did not always occur. These findings reveal that this cytokeratin would remain as a potential marker to detect and trace back the ultimobranchial tissue component of the thyroid in earlier stages of development. The presence of CEA in practically all SCN surveyed would further support the view that they originate in the gut. This antigen would also be of great value for histological identification of these nests. The usefulness of these markers for the interpretation of the histogenesis of some ultimobranchial-related thyroid neoplastic growths, specifically the medullary and mucoepidermoid carcinomas, is briefly discussed.
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A systematic anatomical study of 100 adult human thyroids from autopsies was undertaken for the presence of solid cell nests (SCN). SCN were mainly located in the middle third, with a slight tendency to the upper third, of the lateral thyroid lobes, and placed along a central to paracentral and slightly dorsal longitudinal axis. Immunohistochemical studies for thyroglobulin revealed positive staining in follicular cells connected to SCN and, occasionally, in isolated cells lying within solid clusters from SCN. The anatomical position SCN showed in the present survey is comparable to that shown by the ultimobranchial body (UB) vestiges of human fetuses. The presence of thyroglobulin-positive cells within solid clusters, together with the existence of follicular cells connected to SCN, suggest that SCN may also be a probable source of follicular epithelium as occurs with the UB of some mammals.
Clinical and morphological features of three cases of primary mucoepidermoid carcinoma of the thyroid are described. The tumours were composed of two cell types. One of these resembled squamous epithelium and ultrastructurally showed tonofilaments and numerous desmosomes. The other cell type contained Alcian blue and mucicarmine positive mucin and, on electron microscopy, showed mucigen granules. Marked stromal fibrosis and psammoma bodies were seen in all tumours. Immunohistochemical studies showed that the tumour cells were negative for thyroglobulin. A few calcitonin-containing cells were seen in one metastatic tumour. One tumour showed, in addition to the histological features of mucoepidermoid carcinoma, anaplastic areas with obvious transition between the two histological patterns. The same thyroid also had a small thyroglobulin-positive papillary carcinoma in the opposite lobe. All tumours presented lymph node metastases. In two cases the primary tumour was confined within the thyroid capsule but that with anaplastic areas invaded surrounding structures. This patient died 13 months after diagnosis; the other patients are alive and symptomless one and 10 years since diagnosis. Mucoepidermoid carcinoma of the thyroid appears to be a clinicopathological entity that resembles papillary carcinoma in its natural history. The origin of the tumour is unclear. There is, however, some histological and immunohistological data suggesting that the tumour might be related to the ultimobranchial system although some histological features also appear to favour a common origin with papillary carcinoma.
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