Ultimobranchial Research Articles

A pre-vertebrate endodermal origin of calcitonin-producing neuroendocrine cells.

Vertebrate calcitonin-producing cells (C-cells) are neuroendocrine cells that secrete the small peptide hormone calcitonin in response to elevated blood calcium levels. Whereas mouse C-cells reside within the thyroid gland and derive from pharyngeal endoderm, avian C-cells are located within ultimobranchial glands and have been reported to derive from the neural crest. We use a comparative cell lineage tracing approach in a range of vertebrate model systems to resolve the ancestral embryonic origin of vertebrate C-cells. We find, contrary to previous studies, that chick C-cells derive from pharyngeal endoderm, with neural crest-derived cells instead contributing to connective tissue intimately associated with C-cells in the ultimobranchial gland. This endodermal origin of C-cells is conserved in a ray-finned bony fish (zebrafish) and a cartilaginous fish (the little skate, Leucoraja erinacea). Furthermore, we discover putative C-cell homologs within the endodermally-derived pharyngeal epithelium of the ascidian Ciona intestinalis and the amphioxus Branchiostoma lanceolatum, two invertebrate chordates that lack neural crest cells. Our findings point to a conserved endodermal origin of C-cells across vertebrates and to a pre-vertebrate origin of this cell type along the chordate stem.

Ultimobranchial body cyst in an adult horse: clinical, histopathologic, and immunohistochemical features.

A 9-y-old Mangalarga Marchador gelding was referred to a veterinary hospital because of a swelling on the upper right side of the neck. Ultrasound examination revealed a multilocular structure adjacent to the thyroid gland with low echogenic content suggestive of fluid. The mass was removed surgically. Histologically, the cystic cavities in the surgical sample were filled with abundant eosinophilic secreta and lined by cuboidal, segmentally ciliated, columnar epithelium with interspersed goblet cells. Segmental crowding of the multilayered lining of the cyst was noted. Immunohistochemistry suggested the presence of both C cells and follicular cells, given the positivity of the immunomarkers calcitonin and TTF-1, respectively. The histogenesis of ultimobranchial cysts is uncertain. Based on clinical, histopathologic, and immunohistochemical identification, the cystic structure in this case is compatible with an ultimobranchial body cyst.

Cribriform Morular Thyroid Carcinoma - Ultimobranchial Pouch-Related? Deep Molecular Insights of a Unique Case.

A 44-year-old female patient with a familial adenomatous polyposis (FAP) was diagnosed with a cribriform morular thyroid carcinoma (CMTC). We observed within the very necrotic tumor a small but distinct poorly differentiated carcinomatous component. As expected, next generation sequencing of both components revealed a homozygous APC mutation and in addition, a TERT promoter mutation. A TP53 mutation was found exclusively in the CMTC part, while the poorly differentiated component showed a clonal evolution, harboring an activating PIK3CA mutation and copy number gains of BRCA2, FGF23, FGFR1, and PIK3CB-alterations which are typically seen in squamous cell carcinoma. The mutational burden in both components was low, and there was no evidence for microsatellite instability. No mutations involving the mitogen-activated protein kinase (MAPK) pathway, typically seen in papillary thyroid carcinomas, were detected. Immunohistochemically, all tumor parts were negative for thyroglobulin, providing further evidence that this entity does not belong to the follicular epithelial cell-derived thyroid carcinoma group. CD5 was negative in the poorly differentiated component, making a relation to intrathyroidal thymic carcinoma rather unlikely. However, since this marker was seen in the morules, a loss in the poorly differentiated component and a relation to the ultimobranchial body cannot be excluded either. After total thyroidectomy and radioiodine ablation, the patient was disease-free with no residual tumor burden on 2-year follow-up.

C-cell differentiation in the wall of an aberrant ultimobranchial sinus in the thyroid gland of an old rat.

In mammals, the thyroid gland possesses two types of endocrine cells, follicular cells and C cells, which have different functions but share a similar endodermal origin (although from different regions of the primitive pharynx). Specifically, follicular cells derive from the ventral pharyngeal floor, while C cells derive from the fourth pair of pharyngeal pouches through the ultimobranchial bodies (UBBs). Disruptions to human midline thyroid morphogenesis are relatively frequent and known as thyroid dysgenesis, which is the leading cause of congenital hypothyroidism. In contrast, fourth branchial apparatus anomalies are very rare clinical entities. The aim of this study was to analyze the morphological features and the immunohistochemical pattern of an aberrant ultimobranchial remnant, align with its persistent contribution to the formation of new C cells. The thyroid gland of an old rat was serially sectioned and immunostained for the following markers: calcitonin, thyroglobulin, cytokeratins, PCNA, P63, E-cadherin, beta-tubulin and CD3. We detected a spontaneous congenital defect in the organogenesis of the UBB in an old rat, giving rise to an 'ultimobranchial sinus', which was accompanied by thymic tissue and an abscess. The epithelium contained basal/stem cells and contributed to the formation of abundant C cells and scarce follicular cells. The ultimobranchial sinus is an exceptional finding for representing the first spontaneous abnormality in the development of UBB reported in rats, and the opportunity to observe sustained C-cell differentiation from stem cells in an old rat. These findings are consistent with a common origin of both C cells and follicular cells from UBB.

PSAT283 Sclerosing Mucoepidermoid Cancer – A Unique Entity

Abstract Introduction - Sclerosing mucoepidermoid thyroid cancer is a rare entity with approximately 60 cases reported in the literature. Initially described by Chan. Et al in 1991,1 it was included as a separate entity by WHO in 2004.2 Previously considered to have indolent nature, recent evidence has reported aggressive nature ranging from local invasion to metastasis. Case - 66-year-old female with complaints of difficulty in swallowing, breathing, and sensation of a lump in her throat for last 6 months, was noted to have left thyroid mass on ultrasound. Thyroid ultrasound showed solid hypoechoic nodule, 8.2×5.3×5.9 cm replacing left thyroid lobe with solid hypoechoic nodule 2.2×1.1x 1.6 cm at the right end of the isthmus. The neck ultrasound was negative for lymph nodes. Past medical history was significant for long-standing hypothyroidism, and recently diagnosed invasive ductal carcinoma of the breast. CT chest showed an enlarged thyroid gland with substernal extension and mass effect on the trachea. FNA thyroid showed Bethesda category 5, suspicious for papillary thyroid cancer. The patient underwent a total thyroidectomy. Pathology for left nodule showed sclerosing mucoepidermoid carcinoma with eosinophils, 8.6×6.9×5.8 cm, p T4a N×Mx, with positive margins for tumor, no angiolymphatic invasion with co-existing right-sided papillary microcarcinoma (follicular variant) with chronic lymphocytic thyroiditis. Levothyroxine was dosed to aim goal TSH <0.1, considering the high risk of recurrence. Post-op Thyroglobulin was 1 ng/ml (< 2 ng/ml) with elevated Thyroglobulin antibodies 6.4 U/ml (<0.4). The patient further had radioiodine ablation with 150 mCi I-131, 3 months later. Post therapy whole-body scan showed multiple foci of increased uptake in thyroid bed consistent with thyroid tissue/ residual disease. No distant metastasis was noted. Discussion – Sclerosing mucoepidermoid cancer is thought to be derived from the ultimobranchial body.1 It is more common in females in age groups 3rd - 8th decade.3 Most common presentation is unilateral painless thyroid mass. Coexistent chronic lymphocytic thyroiditis and papillary thyroid cancer are usually found. On literature review of 56 cases, the gross extrathyroidal extension was seen in 26% of cases with distant metastasis was most commonly seen in lungs.3 No established treatment strategy exists due to a small number of reported cases, however, treatment ranges from only Thyroid surgery to Thyroid surgery with radiation +/- chemotherapy and radioactive iodine. References Shah AA, La Fortune K et al. Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia: a clinicopathologic and molecular analysis of a distinct entity. Mod Pathol. 2017;30: 329–339. Pantola C, Kala S, Athar M, et al. Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: a cytological dilemma. J Cytol 2016; 33: 37. Chambers M, Nosé V et al. Salivary-Like Tumors of the Thyroid: A Comprehensive Review of Three Rare Carcinomas. Head Neck Pathol. 2021 Mar;15(1): 212-224. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Morphological, histological and ultra-structural studies on the ultimobranchial body of goat (Capra hircus).

Ultimobranchial body (UBB) remnant was considered as an enigma till the last few years, then it was recognized as a necessary organ where it is the origin of the parafollicular cells. The samples were fixed and processed for the histological and electron microscopic examination. Macroscopically, the UBB remnant appeared as a white mass at the end of the cranial one-third of the thyroid lobe. It was composed of solid cell nest, cluster of cells and small thyroid follicles. Transmission electron microscope showed some round cells containing euchromatic nuclei, numerous parafollicular cells with darkly stained granules and paler ones. It also showed some mast cells with heterochromatic nuclei and large darkly stained granules. The parafollicular cells were distributed throughout the thyroid gland but concentrated within the UBB remnant. To our knowledge, our findings represent very unique histological manifestations specially the ultra-structural ones which revealed an original finding about the new clear type of cells suggested to be a UBB remnant and ensure those of the light microscope.

Solid Cell Nests Hyperplasia (Ultimobranchial Body Remnants) of the Thyroid: A Pitfall

Abstract Introduction/Objective Solid cell nests (SCN) are small epithelial cell nests interspersed within thyroid parenchyma, resembling squamous/transitional epithelium. SCNs, which are ultimobranchial remnants, are popularly considered pluripotent stem-cells responsible for developing follicular and C-cells. While SCNs are not an uncommon incidental findings in thyroid, solid cell nest hyperplasia is rare. SCNs are often mistaken for benign entities such as C-cell hyperplasia (CCH) or malignant lesions such as papillary thyroid carcinoma (PTC), metastatic squamous cell carcinoma, or medullary thyroid microcarcinoma (MTC). Methods/Case Report To reiterate this diagnostic dilemma, we present a case of a 57-year-old male with a six-year history of Hashimoto thyroiditis and multiple bilateral thyroid nodules. Ultrasonography revealed two nodules, one in each lobe, measuring 2.0x1.9x1.8cm(right) and 1.6x1.5x1.5cm(left). Both were solid, hypoechoic nodules with smooth margins and no echogenic foci. Fine-needle aspiration of right nodule was suspicious for follicular neoplasm, Hürthle- cell type, and the left nodule was atypia of unknown significance. Right-hemithyroidectomy specimen revealed follicular adenoma and oncocytic adenomatous nodules in a background of florid lymphocytic thyroiditis (Hashimoto). In two blocks, small solid nests of cells were identified, largest focus measuring 0.5 cm. The cells were polygonal to epithelioid with moderate amphophilic cytoplasm. Nuclei were centrally located, irregular to oval with occasional grooves. While nests had a squamoid appearance, they did not have intercellular bridges. Although nuclear grooves and evenly dispersed chromatin and chromocenters were noted, they lacked optical clearing or intra-nuclear inclusions characteristic for PTC. Thus, excluding these two possibilities, primary diagnostic considerations were SCN versus CCH. Immunohistochemical analysis showed cells positive for P63 and CK5/6 and negative for PAX-8, TTF-1, thyroglobulin, CEA, and calcitonin. Results (if a Case Study enter NA) NA Conclusion If wrongly diagnosed as CCH, patients may be placed in a high-risk category for possible development of MTC. It is, thus, necessary to be aware of SCN, which can occasionally become hyperplastic, to prevent misdiagnosis.

A Review of the Significance in Measuring Preoperative and Postoperative Carcinoembryonic Antigen (CEA) Values in Patients with Medullary Thyroid Carcinoma (MTC).

Background and Objectives: Medullary thyroid carcinoma (MTC) accounts for 1–2% of all thyroid malignancies, and it originates from parafollicular “C” cells. Carcinoembryonic antigen (CEA) is a tumor marker, mainly for gastrointestinal malignancies. There are references in literature where elevated CEA levels may be the first finding in MTC. The aim of this study is to determine the importance of measuring preoperative and postoperative CEA values in patients with MTC and to define the clinical significance of the correlation between CEA and the origin of C cells. Materials and Methods: The existing and relevant literature was reviewed by searching for articles and specific keywords in the scientific databases of PubMedCentraland Google Scholar (till December 2020). Results: CEA has found its place, especially at the preoperative level, in the diagnostic approach of MTC. Preoperative CEA values >30 ng/mL indicate extra-thyroid disease, while CEA values >100 ng/mL are associated with lymph node involvement and distant metastases. The increase in CEA values preoperatively is associated with larger size of primary tumor, presence of lymph nodes, distant metastases and a poorer prognosis. The clinical significance of CEA values for the surgeon is the optimal planning of surgical treatment. In the recent literature, C cells seem to originate from the endoderm of the primitive anterior gut at the ultimobranchial bodies’ level. Conclusions: Although CEA is not a specific biomarker of the disease in MTC, itsmeasurement is useful in assessing the progression of the disease. The embryonic origin of C cells could explain the increased CEA values in MTC.

Intrathyroidal Branchial Cleft Cysts Presenting as Bilateral Thyroid Nodules

Introduction: Intrathyroidal brachial cleft cysts are a rare entity and are usually associated with Hashimoto’s thyroiditis. Etiology is not very clear at this point, but they are thought to arise from the ultimobranchial body remnant during embryogenesis of the gland versus originating secondary to chronic inflammation as a form of squamous metaplasia. They are a common finding in the lateral neck but not with the thyroid. We present a case of a suspicious appearing bilateral thyroid nodules which were found to branchial cleft cysts on biopsy. Clinical Case: A 56-year-old woman presented to us for evaluation of thyroid nodules. Her past medical history was pertinent for endometrial cancer status post surgery and radiation, obesity, sleep apnea, hyperlipidemia and hypothyroidism. She was diagnosed with hypothyroidism around 30 years ago and had been on Levothyroxine since then. She was recently noted to have a low TSH level on routine labs done by her primary care provider and therefore her Levothyroxine dose was adjusted. She also underwent a thyroid ultrasound due to exam findings of a palpable thyroid nodule. The ultrasound revealed a suspicious 2.2 cm hypoechoic solid nodule with irregular margins and micro-calcifications in the left mid thyroid lobe. Additionally, she was also noted to have a 0.8 cm hypoechoic nodule with irregular margins in the right mid thyroid lobe. No concerning cervical lymphadenopathy was identified. She was hence referred to us for further evaluation. She denied having compressive symptoms and did not have history of head/neck radiation or family history of thyroid cancer. Both nodules were biopsied but were interpreted as non-diagnostic with insufficient follicular cells and colloid. She underwent repeat biopsy of both nodules which again was interpreted as non-diagnostic. After discussion with patient, given her suspicious ultrasound findings and inconclusive biopsy results she was referred to endocrine surgery for surgical evaluation. Shortly after she underwent total thyroidectomy with pathology consistent with bilateral benign branchial cleft like cysts associated with adjacent thyroid follicles undergoing squamous metaplasia admixed with chronic inflammation. Conclusion: Pathogenesis of these intrathyroidal branchial cleft cysts is still unclear and not many similar cases have been reported in the literature so far. These commonly present as a painless mass but sometimes can also be an incidental finding. There are not a lot of specific details in the literature regarding imaging or pathology characteristics of these lesions therefore resulting in surgical intervention to reach a definitive diagnosis.

Microcystin-LR Affects Ultimobranchial Gland of Catfish Heteropneustes fossilis

Microcystin-LR (2.5 µg/25 g) was injected intraperitoneally to the fish Heteropneustes fossilis on day 1, 10 and 20 kept in either freshwater or freshwater containing ZnCl2. The fishes were killed on day 5, 10, 20 and 30 day. The serum calcium levels was estimated and ultimobranchial glands were processed for routine histology. Microcystin-LR administration to fish Heteropneustes fossilis induced hypocalcemia and ultimobranchial gland exhibit decreased nuclear volume of the ultimobranchial cells. Degenerative ultimobranchial gland cells were obtained after day 20. While the fish injected with MC-LR kept in ZnCl2 has shown no change in serum calcium levels as well as in histology of ultimobranchial gland cells.

KISSING SUPERIOR PARATHYROID GLANDS: A CASE REPORT

Parathyroid glands are responsible for maintaining the calcium level in blood and usually a pair of superior and inferior parathyroid glands are located in the thyroid gland. Parathyroid glands are smaller and have variations in their size, shape, number and location. Thus, it is difficult to identify the parathyroid gland and leads to its accidental removal during thyroidectomy. This case report is an incidental finding of two superior parathyroid glands in the left lobe of thyroid gland in 68-year female cadaver. Both superior parathyroid glands were located at the first tracheal ring, 2 mm in size, circular in shape, tan yellow in colour, covered by a thin capsule and separated from each other in a distance less than 1 mm. They appear similar as a twin pair and seems to kiss each other. Both were confirmed by the histological method as parathyroid tissues. Superior parathyroid gland developed from the dorsal wing of fourth pharyngeal pouch, get detached from its origin and assumed a relatively constant final location either at the cricothyroid junction or at first tracheal ring. In this present case, the dorsal wing of the fourth pharyngeal pouch have undergone earlier embryological division into two separate superior glands during its descent to the cervical region in the left side. Embryological development of thyroid gland is linked with the development of parathyroid, thymus and ultimobranchial body. Thyroid gland developed from two sources. The median one contributes to thyroid isthmus and parts of the lateral lobe of thyroid. Lateral thyroid lobes derived its contributions from the caudal pharyngeal endoderm of the 4th and 5th pharyngeal pouches. The fusion of median and lateral thyroid forms the Zuckerkandl’s tubercle. Superior parathyroid gland might have travelled along the superior border of isthmus and any changes in the development of thyroid might have influence in the development of parathyroid glands. Up to now a very few cases of kissing parathyroid glands are reported in the literature and this will provide an additional anatomical information of kissing superior parathyroid glands. KEY WORDS: Kissing superior parathyroid glands, Complications of thyroidectomy, Parathyroidectomy, Cricothyroid junction, Twin parathyroid.

Thyroid Tubercle of Zuckerkandl May Not Arise from the Ultimobranchial Body: Results from Histological Analysis

Thyroid tubercle of Zuckerkandl (TZ) is a nodule arising from the posterolateral thyroid, considered to be a remnant of the ultimobranchial body (UB). Considering that C cells and solid cell nests also arise from the UB, we hypothesized that these would be present in the TZ. We examined the presence of C cells and solid cell nests in the TZ using the histological analyses of 21 patients with grade 2 or 3 TZs following Pelizzo’s grading system. Out of 21 TZs, 19 (90.5%) were located in the right lobe of the thyroid. Microscopically, solid cell nests were found within the TZ in 1 case (4.8%), and within the main thyroid tissues in 3 cases (14.3%). Calcitonin-positive C cells were scattered within the TZ in 1 case (4.8%), and within the main thyroid tissue in 15 cases (71.4%). The distribution of C cells within the main thyroid tissue was denser than that within the TZ. The above-mentioned results indicated the lack of C cells and solid cell nests in the TZ. Although the TZ may have an embryological origin different from that of ordinary thyroid tissue, it is unlikely that the remnants of the UB are involved in the formation of the TZ.

Differentiation of human pluripotent stem cells toward pharyngeal endoderm derivatives: Current status and potential.

The pharyngeal apparatus, a transient embryological structure, includes diverse cells from all three germ layers that ultimately contribute to a variety of adult tissues. In particular, pharyngeal endoderm produces cells of the inner ear, palatine tonsils, the thymus, parathyroid and thyroid glands, and ultimobranchial bodies. Each of these structures and organs contribute to vital human physiological processes, including central immune tolerance (thymus) and metabolic homeostasis (parathyroid and thyroid glands, and ultimobranchial bodies). Thus, improper development or damage to pharyngeal endoderm derivatives leads to complicated and severe human maladies, such as autoimmunity, immunodeficiency, hypothyroidism, and/or hypoparathyroidism. To study and treat such diseases, we can utilize human pluripotent stem cells (hPSCs), which differentiate into functionally mature cells in vitro given the proper developmental signals. Here, we discuss current efforts regarding the directed differentiation of hPSCs toward pharyngeal endoderm derivatives. We further discuss model system and therapeutic applications of pharyngeal endoderm cell types produced from hPSCs. Finally, we provide suggestions for improving hPSC differentiation approaches to pharyngeal endoderm derivatives with emphasis on current single cell-omics and 3D culture system technologies.

Prolactin Induced Alterations in Plasma Minerals (Calcium and Phosphate) and Ultimobranchial Gland of Stinging Catfish, Heteropneustes fossilis Maintained in Different Calcium Media

Prolactin Induced Alterations in Plasma Minerals (Calcium and Phosphate) and Ultimobranchial Gland of Stinging Catfish, Heteropneustes fossilis Maintained in Different Calcium Media

Slc:Wistar/ST rats develop unilateral thyroid dysgenesis: A novel animal model of thyroid hemiagenesis

Developmental anomalies of the thyroid gland lead to congenital malformations such as thyroglossal duct cysts and thyroid dysgenesis. However, the pathogenesis of thyroid dysgenesis remains unclear due to the lack of suitable animal models. This study demonstrated that Slc:Wistar/ST rats frequently developed unilateral thyroid dysgenesis, including hemiagenesis, characterized by the absence of one lobe. In Wistar/ST rats, each thyroid lobe was frequently different in size, and approximately 27% and 20% of the rats presented with hemihypoplasia and hemiagenesis of the thyroid gland, respectively. Dysgenesis was predominant on the left side in both sexes, without sex differences. At a young age, thyroid hemiagenesis did not alter body weight. In rats of both sexes with thyroid hemiagenesis, plasma total triiodothyronine and total triiodothyronine levels remained unchanged while plasma thyroid-stimulating hormone levels were significantly elevated in young rats. The remaining thyroid lobes increased in weight, but the follicular epithelial cells appeared normal in terms of their height and proliferating activities. On the side of thyroid dysgenesis, the parathyroid glands were normally localized and were situated at the same location as the contralateral glands. The ultimobranchial body remnants were localized at the level of the thyroid gland along with the cranial thyroid artery and vein, forming cell clusters or cystic structures and containing calcitonin-positive C-cells. In conclusion, Wistar/ST rats developed unilateral thyroid dysgenesis and may be novel and useful animal models for thyroid hemiagenesis in humans and for morphogenesis of pharyngeal pouch-derived organs.

Development of a system for measuring calcitonin in the stingray Dasyatis akajei (a cartilaginous fish): the possible involvement of stingray calcitonin in gonadal development

To elucidate the physiological role of calcitonin (CT) in stingrays (cartilaginous fish), an enzyme-linked immunosorbent assay (ELISA) system using a specific antibody against stingray CT has been developed. Synthetic stingray CT was subcutaneously injected into mice four times—once every 2 weeks—together with an adjuvant. We purified the IgG antibody fraction using the protein A affinity chromatography from collected antiserum. Evaluating the antibody titer, we found the antibody’s optimum dilution ratio to be 600 times. Competitive ELISA has been developed using the antibody diluted 600 times. Our antibody did not cross-react with teleost CTs and muscle extraction, but cross-reacted with stingray plasma and the extract of the ultimobranchial gland, the secretary organ of stingray CT. Using this ELISA, we measured the plasma CT level in stingrays and examined its correlation with several mineral concentrations. Plasma CT did not show significant correlation to calcium, magnesium, inorganic phosphorus, sodium, chlorine, or urea, although there was a correlation among the factors involved in osmoregulation, such as sodium, chlorine, and urea. On the other hand, plasma CT was significantly correlated to body weight and length. Furthermore, there was a significant correlation between plasma CT and gonad weight. Since plasma CT was correlated with the weight of liver, which is involved in the synthesis of egg yolk protein, we examined the influence of 17β-estradiol (E2) on CT secretion. After E2 injection, the plasma CT level increased significantly. This is the first study to demonstrate that E2 induced plasma CT secretion in cartilaginous fish.

Response of Ultimobranchial and Parathyroid Glands of the Indian Skipper Frog, Euphlyctis cyanophlyctis to Cadmium Toxicity

Background: Cadmium toxicity has been shown in aquatic animals but the effect on frog’s endocrine glands is not known. We investigated the effects of cadmium on ultimobranchial and parathyroid glands of Indian skipper frog, Euphlyctis cyanophlyctis. Methods: Frogs were exposed to cadmium chloride for short and long terms and sacrificed after 24, 48, 72 or 96 h (short-term) and after 5, 10, 15 and 30 days (long-term). Results: After 48h of cadmium exposure, serum calcium levels decreased and persisted for 96h. After 96h of exposure, weak staining of the ultimobranchial cells was noted, and the nuclear volumes decreased. The histological structures of parathyroid cells remained unchanged. Frogs exposed to cadmium exhibited decreased serum calcium levels from day 10 to day 30. After 15 days of cadmium exposure, ultimobranchial cells exhibited a decline in staining response and the nuclear volume also decreased. The follicular epithelia of the ultimobranchial glands appeared to be reduced at certain areas. After 30 days of cadmium exposure, the nuclear volume was further decreased and the follicular epithelia shrunk and appeared as a single layer. Cellular degeneration and vacuolization were also noticed in the gland. After day 15 of cadmium exposure, the nuclear volume of the parathyroid cells increased with elongated and hyperchromatic appearance. These changes were exaggerated on day 30 of cadmium exposure and few cell lyses appeared among parathyroid cells. Conclusions: Cadmium adversely affected the calcium regulating glands, ultimobranchial and parathyroid glands of the Indian frogs, Euphlyctis cyanophlyctis.

Revisiting the Significance of Prominent C Cells in the Thyroid.

C cell hyperplasia is considered a precursor lesion for hereditary forms of medullary thyroid carcinoma. It has therefore been suggested as a morphological marker to distinguish hereditary from sporadic medullary thyroid carcinoma and to triage genetic testing in resource poor settings. However, numerous definitions for C cell hyperplasia have been suggested, and there is surprisingly little data regarding the number of C cells present in thyroid glands removed for conditions other than medullary carcinoma. We therefore sought to investigate the specificity of different criteria for C cell hyperplasia. We examined the number of C cells and solid cell nests (ultimobranchial body remnants) present in 118 completion thyroidectomy specimens from patients without medullary carcinoma and with no risk factors for MEN2. Morphological review was performed on all H&E-stained slides, and immunohistochemistry for calcitonin was performed on one block from each case. Solid cell nests were found in 4 (3.3%) of thyroids. Increased numbers of C cells sufficient to fulfil criteria for C cell hyperplasia were found in 5 (4.2%) to 36 (30.5%) cases depending on the criteria used. We conclude that large numbers of C cells are commonly found in thyroids not associated with medullary carcinoma. Therefore, regardless of which criteria are used, the presence of C cell hyperplasia is not a specific marker for hereditary medullary thyroid carcinoma.

Follicular cell lineage in persistent ultimobranchial remnants of mammals.

It has been a subject of much debate whether thyroid follicular cells originate from the ultimobranchial body, in addition to median thyroid primordium. Ultimobranchial remnants are detected in normal dogs, rats, mice, cattle, bison and humans and also in mutant mice such as Eya1 homozygotes, Hox3 paralogs homozygotes, Nkx2.1 heterozygotes and FRS2α2F/2F. Besides C cells, follicular cell lineages immunoreactive for thyroglobulin are located within these ultimobranchial remnants. In dogs, the C cell complexes, i.e., large cell clusters consisting of C cells and undifferentiated cells, are present together with parathyroid IV and thymus IV in or close to the thyroid lobe. In addition, follicular cells in various stages of differentiation, including follicular cell groups and primitive and minute follicles storing colloid, are intermingled with C cells in some complexes. This review elaborates the transcription factors and signaling molecules involved in folliculogenesis and it is supposed why the follicular cells in the ultimobranchial remnants are sustained in immature stages. Pax8, a transcription factor crucial for the development of follicular cells, is expressed in the fourth pharyngeal pouch and the ultimobranchial body in human embryos. Pax8 expression is also detected in the ultimobranchial remnants of Eya1 and Hes1 null mutant mice. To determine whether the C cells and follicular cells in the ultimobranchial remnants consist of dual lineage cells or are derived from the common precursor, the changes of undifferentiated cells in dog C cell complexes are examined after chronically induced hypercalcemia or antithyroid drug treatment.

Anatomy and histomorphology of thyroid, parathyroid and ultimobranchial glands in Guinea fowl (Numida meleagris)

The thyroid, parathyroid, and ultimobranchial glands are of great importance to birds due to the secretion of various hormones including T3, T4, PTH, and calcitonin, as well as species differences. Since no study was conducted on some birds of the pheasant family such as Guinea fowl, the anatomy, histomorphology, and histochemistry of these glands in Guinea fowl were studied. For this purpose, six adult Guinea fowls (three males and three females) were selected. The anatomical results showed that in Guinea fowl, the thyroid gland was symmetrical in the chest near the cephalic artery, common carotid artery, and the artery under the collarbone. The mean length and width of the thyroid gland in male Guinea fowl was greater than that of the female. In addition, it had a pair of parathyroid glands, so that the right parathyroid gland was adjacent to the right thyroid gland and between the common carotid arteries and jugular vein while the left parathyroid gland was adjacent to the left thyroid gland. Ultimobranchial gland was also a pair with an irregular shape and pinkish color. The left ultimobranchial gland, contrary to the right ultimobranchial gland, was adjacent to the posterior parathyroid gland. Histological and histochemical results were similar to other birds except that in the thyroid gland, the colloid substance in the follicle was not seen as a homogeneous material, but it was seen as isolated fibers both in dark and light colors in the follicle. The dark colloid was seen in the active follicle and the light colloid was seen in the low active follicles. The active follicle wall had a simple cuboidal epithelium and low active follicles had a simple squamous epithelium. Large and active follicles were located around the gland and inactive or low active follicles were in the center of the gland. Under the capsule of the thyroid gland, there were many sections of the blood vessels showing its high blood circulation. The parathyroid gland had a dense connective tissue capsule and composed of chief cells located as cord and cluster in dark and bright colors located in the parenchyma of the sinusoid gland. There was no significant difference between the gland in both males and females. The average length and width of the parathyroid gland in female Guinea fowl were greater than that of the male. Ultimobranchial gland had no capsule. Its main cells were parafollicular or C_cells. Collagen fibers were in the form of a thin capsule around it. In terms of morphology, there was no significant difference between these glands in both males and females. The mean length and width of the ultimobranchial gland are equal in the male and female Guinea fowl.