Solid cell nests of the thyroid gland. Optic and immunohistochemical study at autopsies.

In order to establish the prevalence of solid cell nests (SCN) in adult thyroids, we studied 100 consecutive glands at necropsy. These were serially sectioned and stained with routine and immunoperoxidase techniques in order to detect calcitonin, carcinoembryonic antigen, thyroglobulin and keratin. SCN may be considered as normal thyroid gland components, and they share with C cells a common origin in the ultimobranchial body.     

Solid cell nests of the human thyroid in early stages of postnatal life. Systematic autopsy study

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.     

Solid cell nests of the thyroid. An anatomical survey and immunohistochemical study for the presence of thyroglobulin

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.     

Mixed follicles of the human thyroid gland

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.     

Expression of 'visceral' cytokeratin and ultrastructural findings in solid cell nests of the thyroid

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.     

C-cell in vestiges of the ultimobranchial body in human thyroid glands.

Calcitonin-containing cells were demonstrated in the so-called solid cell nests of three human thyroid glands, which supports the theory of the ultimobranchial origin of these cell nests.     

Thyroid follicles with acid mucins in man: A second kind of follicles?

Summary 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.     

Expression of the epithelial marker E-cadherin by thyroid C cells and their precursors during murine development.

Studies of chick-quail chimeras have reported that avian ultimobranchial C cells originate from the neural crest. It has consequently been assumed, without much supporting evidence, that mammalian thyroid C cells also originate from the neural crest. To test this notion, we employed both Connexin43-lacZ and Wnt1-Cre/R26R transgenic mice, because their neural crest cells can be marked. We also examined the immunohistochemical expression of a number of markers that identify migratory or postmigratory neural crest cells, namely, TuJ1, neurofilament 160, nestin, P75NTR, and Sox10. Moreover, we examined the expression of E-cadherin, an epithelial cell marker. At embryonic day (E)10.5, the neural crest cells densely populated the pharyngeal arches but were not distributed in the pharyngeal pouches, including the fourth pouch. At E11.5, the ultimobranchial rudiment formed from the fourth pouch and was located close to the fourth arch artery. At E13.0, this organ came into contact with the thyroid lobe, and at E13.5, it fused with this lobe. However, the ultimobranchial body was not colonized by neural crest-derived cells at any of these developmental stages. Instead, all ultimobranchial cells, as well as the epithelium of the fourth pharyngeal pouch, were intensely immunoreactive for E-cadherin. Furthermore, confocal microscopy of newborn mouse thyroid glands revealed colocalization of calcitonin and E-cadherin in the C cells. The cells, however, were not marked in the Wnt-Cre/R26R mice. These results indicated that murine thyroid C cells are derived from the endodermal epithelial cells of the fourth pharyngeal pouch and do not originate from neural crest cells.     

The relation between solid cell nests and C cells of the thyroid gland

Summary Thyroid tissue of 300 routine autopsies was processed in a standardized manner. So-called solid cell nests (SCN) were found in 21 patients (7 %). These cases were investigated carefully by serial step sectioning. In order to explore the correlation of SCN to the C-cell system, the sections were stained by silver impregnation and the immunoperoxidase method. Morphometric analyses revealed a significant increase in the density of C cells in the proximity of the SCN. With progressive distance from the SCN, the C-cell density decreased and reached normal values. In 30 % of the cases argyrophilic and calcitonin-positive cells were found lying within the SCN. Occasionally, mixed follicles could be discerned: These were lined on the one side by a multilayered squamous epithelium, on the other side by normal monolayered cubic follicular epithelium, and contained a peculiar granular material. In one case, SCN were associated with intrathyroid portions of the parathyroids and adult adipose tissue, in a second case with adipose tissue only. Most probably SCN are vestiges of the ultimobranchial body and should be interpreted as such, despite the fact that other authors have expressed different views. The lack of disturbances in the calcium metabolism of the patients and the absence of medullary carcinoma in their family histories led us to interpret locally confined C-cell hyperplasia not as reactive nor premalignant, but rather as normal.     

Position of ultimobranchial body cysts in the human fetal thyroid gland

In a series of 21 human fetal thyroid glands examined histologically in serial sections, seven ultimobranchial body cysts were found. The position of these cysts correlated well with the distribution of calcitonin-containing cells found by previous investigators in the adult thyroid gland. Ultimobranchial body cysts found external to the thyroid lobes may offer a developmental explanation for the paucity of calcitonin found in some adult thyroid glands. The close developmental relationship between the parathyroid gland and the ultimobranchial body could explain the presence of calcitonin found in these glands in some adults.     

Serum calcitonin-negative medullary thyroid carcinoma: role of CgA and CEA as complementary markers

The biochemical activity of medullary thyroid carcinoma (MTC) includes production of calcitonin (CT), chromogranin A (CgA) and carcinoembryonic antigen (CEA). Routine CT measurement has been proposed as part of the initial evaluation of thyroid nodules and its use could ultimately decrease the morbidity and mortality of MTC. We report on a 43-year-old female patient with a large MTC expressing CT, CgA and CEA on immunostains but with negative preoperative CT and CgA results. Serum CEA was slightly increased and its rapid disappearance predicted radical cure by surgery as confirmed by 2-year follow-up. Our report illustrates that a diagnosis of MTC cannot always be excluded by negative preoperative CT. Fine-needle aspiration with cytomorphological analysis and complementary immunocytochemistry remains an essential diagnostic tool. Finally, serum aliquots must be stored before thyroid surgery in order to measure circulating forms of complementary markers found by tissue immunostaining (CEA and CgA).     

Origin of cholinesterase-containing follicle cells and parafollicular cells of the developing thyroid gland in the rat

Summary The location of cholinesterase-containing cells in the thyroid gland and its precursors (median thyroid primordium and ultimobranchial bodies) has been investigated light-microscopically in rat embryos from the 13 to the 20th day of gestation.From the 13th to the 16th day of gestation the median thyroid primordium and the ultimobranchial bodies are distinct from each other. Cholinesterase-containing cells are found in both. On the 17th–18th day of gestation the reacting ultimobranchial cells spread into the median thyroid primordium where they take up a parafollicular position. At the 19th–20th day of gestation the distribution of cholinesterase-containing cells is as in the adult rat. The results seem to show that cholinesterase-containing follicular cells derive from the median thyroid primordium and cholinesterase-containing parafollicular cells from the ultimobranchial body.     

Roles of circulating carcinoembryonic antigen and calcitonin in diagnosis of medullary thyroid carcinoma: a comparative study.

Carcinoembryonic antigen (CEA) and calcitonin (CT) were simultaneously determined in sera and tumor tissues from 15 patients with medullary carcinoma of the thyroid (MCT). Serum CEA was increased in all but one patient, and CT did in all of them. Both levels were significantly related to the weight of excised tumor, but not to the presence of metastasis. Furthermore, a significant correlation was noted between the basal levels of CT and CEA. Both levels fell to normal after a radical operation had been performed. Tissue concentrations of CEA and CT in the MCT were more than 100 times those in hyperthyroidism, and the ratios of tissue over serum levels averaged 770 in CEA and 1000 in CT. In the calcium infusion test, CEA levels were not significantly changed in contrast with a distinct increase in CT levels. The results indicate that CEA and CT represent separate activities of the tumor cells, and that circulating CEA together with CT is a useful indicator in the diagnosis and follow-up of the disease.     

Intracytoplasmic lumina in medullary carcinoma of the thyroid gland. Report of a case with cytologic and immunocytochemical features

BACKGROUND: Intracytoplasmic lumina (ICL) have been observed frequently in breast carcinoma cells. However, they are extremely rare in thyroid gland tumors. We encountered a medullary carcinoma of the thyroid (MCT) with ICL and present a case with cytologic, immunocytochemical and ultrastructural features. CASE: A 15-year-old female was admitted with a left thyroid mass. Ultrasound examination revealed a well-defined tumor in the left lobe of the thyroid. Fine needle aspiration cytology showed mainly dispersed spindle cells with oval nuclei and some polymorphic or triangular tumor cells. The tumor cells containing ICL were noted at high magnification. The ICL contained sparse microvilli and abundant granular material with dense, round bodies on ultrastructural sections. Immunocytochemically, these tumor cells were positive for calcitonin and carcinoembryonic antigen (CEA). Moreover, CEA was recognized in the ICL with immunocytochemical staining. All tumor cells were negative for thyroglobulin. Pathologic examination confirmed the diagnosis of medullary carcinoma of the thyroid gland. CONCLUSION: MCT can include ICL with granular material containing CEA.     

Evidence of the occurrence of calcitonin cells in the ultimobranchial follicle of the rat postnatal thyroid.

A study on thyroid glands of Wistar rats of ages ranging from 1 to 120 days was carried out. The glands were serially sectioned and stained for calcitonin using the peroxidase antiperoxidase method. All the thyroids contained ultimobranchial follicles (UBF) located partially embedded among the usual follicles but in a 5-day-old rat this structure showed an unusual position in the interstitium of connective tissue between the cartilage of the trachea and the thyroid gland. We have observed in the wall of that UBF the presence not only of resting C cells but also mitotic figures of C cells. Furthermore, on the opposite side of the same UBF an active area of formation of thyroid follicles was found. These observations provided the first evidence of the contribution of the UBF in the formation of C cells during the postnatal life of the rat. Furthermore, it is suggested that some C cells may share a common origin with ultimobranchially derived follicular cells.     

Immunohistochemical profiling of the ultimobranchial remnants in the rat postnatal thyroid gland

Ultimobranchial (UB) remnants are a constant presence in the thyroid throughout rat postnatal life; however, the difficulty in identifying the most immature forms from the surrounding thyroid tissue prompted us to search for a specific marker. With that objective, we applied a panel of antibodies reported to be specific for their human counterpart, solid cell nests (SCNs), using double immunohistochemistry and immunofluorescence. Our results demonstrated that cytokeratin 34βE12 and p63 are highly sensitive markers for the immunohistologic screening of UB‐remnants, independently of their maturity or size. Furthermore, rat UB‐follicles (UBFs) coincided with human SCNs in the immunohistochemical pattern exhibited by both antigens. In contrast, the pattern displayed for calcitonin and thyroglobulin differs considerably but confirm the hypothesis that rat UB‐cells can differentiate into both types of thyroid endocrine cells. This hypothesis agrees with recent findings that thyroid C‐cells share an endodermic origin with follicular cells in rodents. We suggest that the persistence of p63‐positive undifferentiated cells in UB‐remnants may constitute a reservoir of basal/stem cells that persist beyond embryogenesis from which, in certain unknown conditions, differentiated thyroid cells or even unusual tumors may arise.     

Morphological and histochemical changes of ultimobranchial follicles of the rat thyroid in the course of postnatal life.

Morphological and histochemical changes of ultimobranchial follicles of thyroid have been investigated in rats from newborn to 18 months of age. The first well-delimited ultimobranchial follicles, though with no lumen, were detected in the thyroid gland of 10-day-old rats. At 30 days of age, follicles possessing regular lumina were present in the thyroid. With age, the follicles gradually increased in volume assuming extreme dimensions in adult age. The follicles displayed varying shapes from simple cysts to bizarre forms. From the age of 50 days the cells of the follicular wall are separated from the cell debris contained in the lumen. The latter gave a PAS positive reaction. The cells of the ultimobranchial follicles did not exhibit argyrophilia and metachromasia showing that they differ considerably from the C-cells likewise of ultimobranchial origin, which are known to give marked argyrophilic and metachromatic reactions.     

Difference between the thyroid gland of normal and hypomyelinated jimpy mice--a light microscopic study

A light microscopic quantitative analysis was performed on normal and jimpy male mice for studying the difference between the structures of the thyroid glands of the two animals. The results of this analysis showed that the thyroid gland of the normal mice consisted of numerous homogenous round follicles with cuboidal follicular cells, separated by thin interlobular and interfollicular connective tissue and a few adipose tissue. The thyroid gland of jimpy mice consisted of a few, small follicles surrounded by columnar follicular cells and intraepithelial capillaries, separated by thick connective tissue and abundant adipose tissue. The number of thyroid follicles are significantly less in the jimpy mice than in the normal mice. Another striking difference is that almost every follicular cell surrounding the follicular lumen of jimpy mice is accompanied by an intraepithelial capillary. In addition, the ratio of the number of intraepithelial capillaries to the number of the thyroid follicular cells are significantly higher in the jimpy mice than in the normal mice. The S-follicles or ultimobranchial cysts of the thyroid gland are well developed in the jimpy mice. The parafollicular cells are normal in appearance. Morphological evidence suggested that the thyroid follicular cells of the jimpy mice are very active in the transport, synthesis and release of thyroglobulin, and secretion of thyroid hormones. But owing to the significantly decreased number of thyroid follicles, the inadequate secretion of the thyroid hormones result in the hypothyroidism and the hypomyelination of the jimpy mice.     

Immunohistochemical differentiation of malignant mesothelioma, mesothelial hyperplasia and metastatic adenocarcinoma in serous effusions, utilizing staining for carcinoembryonic antigen, keratin and vimentin

The cytologic diagnosis of malignant mesothelioma and its distinction from mesothelial hyperplasia and metastatic adenocarcinoma is consistently difficult; tissue studies utilizing the immunohistochemical profiles of carcinoembryonic antigen (CEA) and keratin have demonstrated a reproducible distinction between these tumors. Mesothelium contains vimentin in addition to keratin, but its characterization is hindered by its poor preservation in formalin fixatives; alcohol fixation is far superior. Alcohol-fixed, Papanicolaou-stained smears of serous fluids from five cases of reactive mesothelium, five metastatic adenocarcinomas and five malignant mesotheliomas were stained with polyclonal CEA, antikeratin monoclonals AE1 and AE3 (combined) and monoclonal vimentin utilizing the peroxidase-antiperoxidase method. The study revealed the excellent preservation of mesothelial vimentin staining in all three groups. The reactive mesothelium and mesothelioma groups were strongly positive for vimentin and keratin whereas the metastatic adenocarcinoma group was only positive for keratin and CEA (except one case). These findings support the results of previous tissue studies, disclosing CEA staining in the metastatic adenocarcinomas, but not in the mesotheliomas, and the inability of keratin staining to distinguish between the two. The findings also emphasize that positive vimentin staining will usually exclude a metastatic adenocarcinoma, but will not distinguish between neoplastic and reactive mesothelial states.     

Uptake and storage of indolamines in the ultimobranchial body of the fetal murine thyroid. 1-Autoradiographic histological study]

Incorporation of 3H-5 HTP is studied in ultimobranchial cells and thyroid cells of the mouse foetus from the 13th day to the 18th day of gestation. The APUD characteristics of these cells are first observed on the 14th day when the U.B. bodies are included in the thyroid anlage. The silver granules are then localized on the parafollicular cell cords from which C cells of the adult thyroid arize.