Molecular Profiling in Thyroid cancer- Using next generation sequencing to differentiate rare cases of papillary thyroid hyperplasia from papillary thyroid carcinoma

Introduction/Objective Differentiating papillary thyroid hyperplasia from papillary thyroid carcinoma is made primarily on differences in key histologic and cytomorphologic features. These include architectural features such as invasion and nuclear changes such as chromatin pallor, nuclear grooves, and intranuclear pseudoinclusions. Distinguishing between these two diagnoses is not always straightforward in a minority of cases, as papillary thyroid hyperplasia nodules can be misinterpreted as papillary thyroid carcinoma and vice versa. This is because the nuclear changes can be subtle and be induced artificially by poor or inadequate formalin fixation. Immunostains such as cytokeratin 19 (CK19), galectin-3, and HBME1 may be used to distinguish between papillary thyroid hyperplastic nodules and papillary thyroid carcinoma; however, as immunostaining results are not always definitive, other more definitive ancillary tests are sometimes utilized such as molecular testing. Methods/Case Report Thyroid cases with indeterminate diagnoses (n=6) were obtained from the archives. Such cases included papillary thyroid hyperplasia and cases with descriptive diagnoses such as well-differentiated encapsulated and low-grade papillary carcinoma. Five cases of definitive papillary thyroid carcinoma and one case of follicular thyroid carcinoma (n=6) were used as a comparison group. Next generation sequencing (NGS) assays were performed using a custom SLIMamp targeted DNA solid tumor panel (Pillar Biosciences) and a targeted multi gene RNA fusion panel (Invitae). Results (if a Case Study enter NA) All of the definitive cases of papillary thyroid carcinoma showed characteristic mutations such as BRAF V600E as well as RNA fusions such as RET/PTC while all of the indeterminate cases did not show any detectable DNA mutations or RNA fusions, confirming their benign nature. A separate case that was signed out as non-invasive follicular thyroid neoplasm with papillary-like nuclear features showed an NRAS Q61R mutation and a novel ETV1-ERG fusion. Conclusion This study demonstrates the utility of molecular testing as an adjunct to histopathological evaluation in definitive diagnosis and differentiation of papillary thyroid hyperplasia from papillary carcinoma. Next generation sequencing with targeted DNA and RNA panels will be beneficial for both known and novel variant or fusion detection in suspect cases.

Nutrition and Metabolism of Minerals in Fish

Aquatic animals have unique physiological mechanisms to absorb and retain minerals from their diets and water. Research and development in the area of mineral nutrition of farmed fish and crustaceans have been relatively slow and major gaps exist in the knowledge of trace element requirements, physiological functions and bioavailability from feed ingredients. Quantitative dietary requirements have been reported for three macroelements (calcium, phosphorus and magnesium) and six trace minerals (zinc, iron, copper, manganese, iodine and selenium) for selected fish species. Mineral deficiency signs in fish include reduced bone mineralization, anorexia, lens cataracts (zinc), skeletal deformities (phosphorus, magnesium, zinc), fin erosion (copper, zinc), nephrocalcinosis (magnesium deficiency, selenium toxicity), thyroid hyperplasia (iodine), muscular dystrophy (selenium) and hypochromic microcytic anaemia (iron). An excessive intake of minerals from either diet or gill uptake causes toxicity and therefore a fine balance between mineral deficiency and toxicity is vital for aquatic organisms to maintain their homeostasis either through increased absorption or excretion. Release of minerals from uneaten or undigested feed and from urinary excretion can cause eutrophication of natural waters, which requires additional consideration in feed formulation. The current knowledge in mineral nutrition of fish is briefly reviewed.

Primary hyperparathyroidism caused by bilateral parathyroid cystic carcinoma in a cat

Case summary A 16-year-old neutered female Korat cat presented with chronic vomiting, mild azotaemia and mild hypercalcaemia. Physical examination revealed bilateral palpable masses on each side of the trachea. Laboratory results were consistent with primary hyperparathyroidism, diagnostic imaging findings with cystic thyroid or parathyroid masses, and fine-needle aspiration cytology with thyroid hyperplasia or adenoma. In order to confirm whether one or two of the masses were the cause of the hyperparathyroidism, cystic fluid was aspirated from both for parathyroid hormone concentration measurement. The concentration was shown to exceed that of the serum manyfold in both samples, confirming both masses to be functional and of parathyroid origin. A total parathyroidectomy and thyroidectomy were performed on the right side, and a subtotal thyroidectomy and a subtotal to total parathyroidectomy on the left, without any major postoperative complications. Histopathology was consistent with bilateral parathyroid carcinoma. Relevance and novel information To our knowledge, this report is the first to describe a rare case of bilateral parathyroid cystic carcinoma in a cat. It highlights the usefulness of determining parathyroid hormone concentration in the cystic fluid of a suspected neoplastic parathyroid mass preoperatively. It also demonstrates that it may be possible to remove most of the cervical parathyroid and thyroid tissue of a cat without causing any clinically relevant hypocalcaemia or iatrogenic hypothyroidism. However, serum concentrations of ionised calcium, thyroxine and creatinine should be closely monitored in the postoperative period in order to detect and control possible complications.

Functional condition of the thyroid gland of newborns from methers with a diffuse toxic goiter

Objective: to study the functional state of the thyroid gland in newborns from mothers with diffuse toxic goiter, depending on the level of antibodies to thyroid stimulating hormone receptors (AB-rTSH).Materials and methods: 68 newborns from 67 mothers with diffuse toxic goiter were examined. The control group included 49 newborns from 49 mothers without thyroid pathology. To assess the functional state of the thyroid gland of newborns, we determined the levels of thyroid stimulating hormone, free thyroxine (fT4), and AB-rTSH in cord blood and calculated the TSH/fT4 coefficient, which allows us to differentiate congenital hypothyroidism from neonatal thyrotoxicosis. On the 4-7th day of life, all newborns underwent ultrasound examination (ultrasound) of the thyroid gland.Results: newborns from mothers with diffuse toxic goiter had lower growth-weight indices in comparison with the same indices of the control group and they often showed thyroid hyperplasia. It was shown that the increased content of AB-rTSH in the blood serum of pregnant women with diffuse toxic goiter and in the umbilical cord blood of newborns can contribute to the development of neonatal thyrotoxicosis, detected in 16.2 % of newborns.Conclusions: increased levels of AB-rTSH in the blood serum of mothers with DTG, especially in the second half of pregnancy, and in the umbilical cord blood of newborns affect the formation of thyroid hyperplasia in newborns and contribute to the development of neonatal thyrotoxicosis.

Thyroid diseases in the complex treatment of lymphogranulomatosis

A total of 212 patients with Hodgkin ’s disease were examined in different periods after multiple-modality treatment. Hypothyroid status was established in 19.8%) and thyroid hyperplasia in 5.4%o patients. Polychemotherapy did not affect the incidence of complications. The incidence and severity of hypothyrosis after multiple-modality treatment of Hodgkin ’s disease depend on the patient's age by the moment of radiation exposure, administration of iodine-containing x-ray contrast agents, and dose of the thyroid exposure. Indications for substitution therapy with thyroid hormones are defined.

Juvenile hyperthyroidism in a dog

Hyperthyroidism is the most common endocrinopathy in cats, and most cases are caused by multinodular hyperplasia or follicular cell adenoma, although thyroid carcinomas occur infrequently. Hyperthyroidism is rare in dogs, and most cases are caused by functional thyroid carcinomas. There are case reports of canine hyperthyroidism secondary to exogenous sources, and rarely thyrotoxicosis can be seen with therapeutic doses of levothyroxine prescribed for hypothyroidism. A case of juvenile hyperthyroidism has been reported in a cat and a histopathological diagnosis of diffuse thyroid hyperplasia was made. This is the first reported case of functional eutopic thyroid tissue in a young dog. Histopathological examination reported bilateral hyperplastic change in the thyroid glands, similar to the case of feline juvenile hyperthyroidism.