Inherited thyroid tumours.

Inherited thyroid tumours are an important group which need clarification. This is partly because of the common use of the term Familial Non-Medullary Thyroid Cancer when some of the specific entities included under this heading really represent inherited benign tumours with a risk of progression to malignancy. The subject is briefly reviewed, and one syndromic and one non-syndromic type of inherited thyroid tumours of follicular cell origin discussed in more detail to emphasise the point that each of these groups need to be treated as separate entities.

Homozygous loss-of-function mutations in SLC26A7 cause goitrous congenital hypothyroidism.

Defects in genes mediating thyroid hormone biosynthesis result in dyshormonogenic congenital hypothyroidism (CH). Here, we report homozygous truncating mutations in SLC26A7 in 6 unrelated families with goitrous CH and show that goitrous hypothyroidism also occurs in Slc26a7-null mice. In both species, the gene is expressed predominantly in the thyroid gland, and loss of function is associated with impaired availability of iodine for thyroid hormone synthesis, partially corrected in mice by iodine supplementation.

An InDel in Phospholipase-C-B-1 Is Linked with Euthyroid Multinodular Goiter.

Background: Euthyroid multinodular goiter (MNG) is common, but little is known about the genetic variations conferring predisposition. Previously, a family with MNG of adolescent onset was reported in which some family members developed papillary thyroid carcinomas (PTC).

Methods: Genome-wide linkage analysis and next-generation sequencing were conducted to identify genetic variants that may confer disease predisposition.

On the Origin of Cells and Derivation of Thyroid Cancer: C Cell Story Revisited.

We will highlight and put into perspective new lineage tracing data from genetic studies in mice indicating that the genuine progenitors to C cells arise in the endoderm germ layer. This overturns the current concept of a neural crest origin of thyroid C cells referred to in every textbook and dedicated paper to this very day. As will become apparent, except for a single experiment, the neural crest theory has little or no support when the evolution and development of calcitonin-producing cells in the entire chordate family are considered.

Thyroid Growth and Cancer.

It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential.

Dental x-rays and the risk of thyroid cancer: a case-control study.

Unlabelled: The thyroid gland is highly susceptible to radiation carcinogenesis and exposure to high-dose ionising radiation is the only established cause of thyroid cancer. Dental radiography, a common source of low-dose diagnostic radiation exposure in the general population, is often overlooked as a radiation hazard to the gland and may be associated with the risk of thyroid cancer. An increased risk of thyroid cancer has been reported in dentists, dental assistants, and x-ray workers; and exposure to dental x-rays has been associated with an increased risk of meningiomas and salivary tumours.

Twenty years' experience with post-Chernobyl thyroid cancer.

Chernobyl, the largest ever nuclear accident, caused a huge release of radioactive isotopes, including nearly 2x10(18) Bq of iodine-131. Four years later an increase in thyroid cancer incidence, virtually all papillary carcinomas in children, occurred in the highly exposed areas. The increase has continued, and with increasing latency the tumour molecular and morphological pathology has changed; further changes may occur in the future.

Morphologic characteristics of Chernobyl-related childhood papillary thyroid carcinomas are independent of radiation exposure but vary with iodine intake.

Background: The Chernobyl accident caused an unprecedented increase in papillary thyroid carcinoma (PTC) incidence with a surprisingly short latency and unusual morphology. We have investigated whether unexpected features of the PTC incidence after Chernobyl were radiation specific or influenced by iodine deficiency.

Methods: PTCs from children from Belarus, Ukraine, and the Russian Federation exposed to fallout from Chernobyl were compared with PTCs from children not exposed to radiation from the same countries, from England and Wales (E&W) and from Japan.

The Chernobyl accident 20 years on: an assessment of the health consequences and the international response.

Twenty years after the Chernobyl accident the WHO and the International Atomic Energy Authority issued a reassuring statement about the consequences. Our objectives in this study were to evaluate the health impact of the Chernobyl accident, assess the international response to the accident, and consider how to improve responses to future accidents. So far, radiation to the thyroid from radioisotopes of iodine has caused several thousand cases of thyroid cancer but very few deaths; exposed children were most susceptible.

Multiple brown tumors in primary hyperparathyroidism caused by an adenoma mimicking metastatic bone disease with false positive results on computed tomography and Tc-99m sestamibi imaging: MR findings.

We encountered an unusual case of hyperparathyroidism with both hemosiderin deposits on the ribs and low intensity on T2-weighted magnetic resonance imaging (MRI) caused by a parathyroid adenoma with multiple brown tumors that mimicked metastatic bone tumor due to false positive results on computed tomography (CT) and Tc-99m sestamibi (MIBI) imaging. The patient, a middle-aged woman, had very high serum levels of calcium (14.1 mg/dl), alkaline phosphatase (9,369 IU/l) and intact-PTH (12,400 pg/ml), and a large tumor (2.

The chernobyl accident 20 years on: an assessment of the health consequences and the international response.

Background: The Chernobyl accident in 1986 caused widespread radioactive contamination and enormous concern. Twenty years later, the World Health Organization and the International Atomic Energy Authority issued a generally reassuring statement about the consequences. Accurate assessment of the consequences is important to the current debate on nuclear power.

Risk of thyroid cancer after exposure to 131I in childhood.

Background: After the Chernobyl nuclear power plant accident in April 1986, a large increase in the incidence of childhood thyroid cancer was reported in contaminated areas. Most of the radiation exposure to the thyroid was from iodine isotopes, especially 131I. We carried out a population-based case-control study of thyroid cancer in Belarus and the Russian Federation to evaluate the risk of thyroid cancer after exposure to radioactive iodine in childhood and to investigate environmental and host factors that may modify this risk.

BRAF mutations are not a major event in post-Chernobyl childhood thyroid carcinomas.

The BRAF gene has been shown to be a major target for mutations in papillary thyroid carcinoma (PTC) (36-69%), which forms almost all of the over 2000 cases of thyroid carcinoma that have occurred in Chernobyl. BRAF is activated by point mutation, and were it to occur at a high frequency in Chernobyl-related tumors, it would challenge the dominant role of double-strand breaks in radiation-induced PTC. In a previous study, we detected the BRAF V600E mutation in 46% (23 of 50) of sporadic adult PTC.

Thyroid implants after surgery and blunt trauma.

The differential diagnosis of thyroid tissue found laterally in the neck includes several conditions: lymph node deposits of thyroid carcinoma, "benign metastatic thyroidosis," detached thyroid nodules, and true ectopic thyroid tissue. We have studied nine cases with thyroid deposits in the soft tissues of the neck that do not conform to these diagnoses. We present evidence that they represent surgical or traumatic implantation of thyroid neoplasms.

Modulation of N-methyl-N-nitrosourea-induced crypt restricted metallothionein immunopositivity in mouse colon by a non-genotoxic diet-related chemical.

Red meat consumption is associated with endogenous metabolic generation of mutagenic N-nitroso compounds (NOC) and may be implicated in causation of colorectal cancer. Assessment of a biologically relevant dose of NOCs is hampered by imperfect understanding of NOC interactions with other dietary components. This study tests the hypothesis that NOC effects upon mutational biomarkers in mouse colon may be modulated by a non-genotoxic diet-related compound.

Germline succinate dehydrogenase subunit D mutation segregating with familial non-RET C cell hyperplasia.

C cell hyperplasia is associated with medullary carcinoma of the thyroid in the inherited MEN2 syndromes, in which the great majority of cases have been shown to be due to a mutation in the RET oncogene. We report a study of a family with C cell hyperplasia and hypercalcitoninemia in which no cases of medullary carcinoma have yet occurred and which lacked an identifiable causative RET mutation. Four of the family members showed hypercalcitoninemia, and marked C cell hyperplasia was present in each of the three in whom thyroidectomy has been performed.

Pathology of the autonomously functioning (hot) thyroid nodule.

We describe the pathologic findings of 73 clinically and scintigraphically confirmed hot nodules. In general, hot nodules from an unselected group primarily treated by surgery were smaller and the sex ratio was closer to equality compared with the ample female predominance in the referral, pre-, and post-prophylaxis groups. Malignancy was observed in six cases (8.