Erratum to "Gastroenteropancreatic Neuroendocrine Neoplasia Characterization in Portugal: Results from the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism".

[This corrects the article DOI: 10.1155/2019/4518742.].

Gastroenteropancreatic Neuroendocrine Neoplasia Characterization in Portugal: Results from the NETs Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism.

BACKGROUND: The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) has been increasing in the last five decades, but there is no large-scale data regarding these tumours in Portugal. We conducted a cross-sectional, multicentric study in main Portuguese centers to evaluate the clinical, pathological, and therapeutic profile of GEP-NENs. METHODS: From November, 2012, to July, 2014, data from 293 patients diagnosed with GEP-NENs from 15 centers in Portugal was collected and registered in an online electronic platform. RESULTS: Median age at diagnosis was 56.5 (range: 15-87) years with a preponderance of females (54.6%). The most frequent primary sites were the pancreas (31.1%), jejunum-ileum (24.2%), stomach (13.7%), and rectum (8.5%). Data regarding hormonal status was not available in most patients (82.3%). Stratified by the tumour grade (WHO 2010 classification), we observed 64.0% of NET G1, 24.7% of NET G2, and 11.3% of NEC. Poorly differentiated tumours occurred mainly in older patients (p = 0.017), were larger (p < 0.001), and presented more vascular (p = 0.004) and lymphatic (p = 0.001) invasion. At the time of diagnosis, 44.4% of GEP-NENs presented metastatic disease. Surgery (79.6%) and somatostatin analogues (30.7%) were the most frequently used therapies of GEP-NENs with reported grading. CONCLUSION: In general, Portuguese patients with GEP-NENs presented similar characteristics to other populations described in the literature. This cross-sectional study represents the first step to establish a national database of GEP-NENs that may aid in understanding the clinical and epidemiological features of these tumours in Portugal.

Emergence of Thelazia callipaeda Infection in Dogs and Cats from East-Central Portugal.

The eyeworm Thelazia callipaeda (Spirurida, Thelaziidae) infects domestic animals, wildlife and human beings, and is considered an emerging pathogen in Europe. This study aimed at investigating the prevalence and risk factors of T. callipaeda infection in dogs and cats from east-central Portugal, a region where the parasite was previously detected in two red foxes (Vulpes vulpes). Thelazia callipaeda was found in 22 (3.8%) of 586 dogs and in four (23.5%) of 17 cats. A total of 178 adult worms (71.9% of females and 28.1% of males) were collected from the conjunctiva of the infected dogs. The number of worms collected per dog ranged from 1 to 35 (average ± standard deviation: 8.08 ± 9.49), with four dogs (18.2%) harbouring only a single parasite. Worms were gathered from dogs throughout all months of the year. A total of 17 adult worms (64.7% of females and 35.3% of males) were obtained from cats. The number of worms per cat ranged from 1 to 14 (4.3 ± 6.5), with three cats (75.0%) having a single parasite. Eyeworm infection was statistically more prevalent in pastoral and farm dogs, in those dogs with contact with other animals and in dogs with ocular manifestations. T. callipaeda is endemic in the east-central part of Portugal, reportedly infecting domestic (dogs and cats) and wild carnivores (red foxes) and evidencing a southerly dissemination. Future investigations should be focused on determining the local distribution and density of the insect vector (Phortica variegata) in this geographical area. This emergent zoonosis should be included by veterinarians, physicians and ophthalmologists in the differential diagnosis of ocular manifestations in their patients, particularly in areas where T. callipaeda is endemic.

Underexpression of peroxisome proliferator-activated receptor (PPAR)gamma in PAX8/PPARgamma-negative thyroid tumours.

The expression of peroxisome proliferator-activated receptor (PPAR)gamma in thyroid neoplasias and in normal thyroid (NT) tissues has not been fully investigated. The objectives of the present work were: to study and compare the relative expression of PPARgamma in normal, benign and malignant thyroid tissues and to correlate PPARgamma immunostaining with clinical/pathological features of patients with thyroid cancer. We analysed the expression of PPARgamma in several types of thyroid tissues by reverse transcription-polymerase chain reaction (RT-PCR), interphase fluorescent in situ hybridisation, real-time RT-PCR and immunohistochemistry. We have demonstrated that NT tissues express PPARgamma both at mRNA and at protein level. PAX8-PPARgamma fusion gene expression was found in 25% (six of 24) of follicular thyroid carcinomas (FTCs) and in 17% (six of 36) of follicular thyroid adenomas, but in none of the 10 normal tissues, 28 nodular hyperplasias, 38 papillary thyroid carcinomas (PTCs) and 11 poorly differentiated thyroid carcinomas (PDTCs). By real-time RT-PCR, we observed that tumours negative for the PAX8-PPARgamma rearrangement expressed lower levels of PPARgamma mRNA than the NT. Overexpression of PPARgamma transcripts was detected in 80% (four of five) of translocation-positive tumours. Diffuse nuclear staining was significantly (P<0.05) less prevalent in FTCs (53%; 18 of 34), PTCs (49%; 19 of 39) and PDTCs (0%; zero of 13) than in normal tissue (77%; 36 of 47). Peroxisome proliferator-activated receptorgamma-negative FTCs were more likely to be locally invasive, to persist after surgery, to metastasise and to have poorly differentiated areas. Papillary thyroid carcinomas with a predominantly follicular pattern were more often PPARgamma negative than classic PTCs (80% vs 28%; P=0.01). Our results demonstrated that PPARgamma is underexpressed in translocation-negative thyroid tumours of follicular origin and that a further reduction of PPARgamma expression is associated with dedifferentiation at later stages of tumour development and progression.

Aggressive metastatic follicular thyroid carcinoma with anaplastic transformation arising from a long-standing goiter in a patient with Pendred's syndrome.

In this article we describe detailed pathological and molecular genetics studies in a consanguineous kindred with Pendred's syndrome. The index patient was a 53-year-old female patient with congenital deafness and goiter. Her parents were first-degree cousins. She had a large goiter (150 g) that had been present since childhood. One of her sisters and a niece are also deaf and have goiter as well. The presence of Pendred's syndrome was confirmed by a positive perchlorate test and the demonstration of a Mondini malformation. Thyroid function tests (under levothyroxine [LT4] therapy) were in the euthyroid range with a thyrotropin [TSH] level of 2.8 microU/mL (0.2-3.2), a serum total thyroxine (T4) of 90 nmol/L (54-142), and a serum total triiodothyronine (T3) of 2.7 nmol/L (0.8-2.4). Total thyroidectomy was performed, and the mass in the right lobe was found to have invaded adjacent tissues. The histopathological findings were consistent with a follicular carcinoma with areas of anaplastic transformation and lung metastasis. The patient was treated twice with 100 mCi 131iodine (3,700 MBq) and received suppressive doses of LT4. Postoperatively, the serum thyroglobulin (Tg) levels remained markedly elevated (2,352 to 41,336 ng/mL). The patient died of a sudden severe episode of hemoptysis. Sequence analysis of the PDS gene performed with DNA from the two relatives with Pendred's syndrome revealed the presence of a deletion of thymidine 279 in exon 3, a point mutation that results in a frameshift and a premature stop codon at codon 96 in the pendrin molecule. We concluded that prolonged TSH stimulation because of iodine deficiency or dyshormonogenesis in combination with mutations of oncogenes and/or tumor suppressor genes, may result in the development of follicular thyroid carcinomas that undergo transformation into anaplastic cancers. It is likely that these pathogenetic mechanisms have been involved in the development of aggressive metastatic thyroid cancer in this unusual patient with Pendred's syndrome.

Detection of thyroglobulin mRNA transcripts in peripheral blood of individuals with and without thyroid glands: evidence for thyroglobulin expression by blood cells.

OBJECTIVE: Recent studies have assigned clinical significance and prognostic value to the detection of thyroglobulin (Tg) mRNA in the blood of patients subjected to total thyroidectomy for a papillary or follicular thyroid carcinoma. In this study, we investigated the diagnostic specificity of Tg mRNA detection, analysing blood samples from healthy volunteers and from patients previously subjected to total thyroidectomy for reasons other than a carcinoma of the follicular epithelium. DESIGN AND METHODS: Total RNA was extracted from whole blood, reverse-transcribed and the cDNA amplified for Tg and glyceraldehyde-3-phosphate dehydrogenase with specific primers. Expression levels were analysed by using a semi-quantitative PCR. In a few cases, Lymphoprep gradients were used to separate the mononuclear and polymorphonuclear cells prior to further analysis by reverse transcription/PCR. RESULTS: Our data suggested that all individuals expressed Tg mRNA. Moreover, no differences in the expression levels between subjects with and without thyroid glands were documented. Documentation of Tg expression by the mononuclear and polymorphonuclear layers in patients without thyroid glands support the hypothesis that both lymphocytes and granulocytes express Tg and may justify a background expression in blood, independently of the presence of follicular cells in circulation. CONCLUSIONS: Tg mRNA expression is not limited to follicular cells of the thyroid gland, and its expression by normal blood cells should be considered in tests performed for diagnostic purposes.

Medullary carcinomas of the thyroid: a monoclonal origin.

We studied the clonality of medullary thyroid carcinomas (MTC) from 16 female patients by determining X chromosome inactivation by polymerase chain reaction (PCR) amplification of a CAG repeat in exon 1 of the human androgen-receptor gene. One patient with sporadic medullary thyroid carcinoma (MTC) was homozygous for this microsatellite and was not considered for the assessment of clonality. Sixteen tumor samples from the informative 15 patients were studied: 11 were from sporadic cases and 5 were from familial cases (3 cases of multiple endocrine neoplasia type 2A [MEN 2A]; 1 case of familial medullary thyroid carcinoma [FMTC]). Fourteen tumor samples (10/11 sporadic, 3/4 MEN 2A and 1/1 FMTC) were clearly monoclonal with allelic cleavage ratios between 2.5 and 49.1. Sixty-four percent of these cases (9/14) had the preferential amplification of the shorter allele while 36 percent (5/14) had the preferential amplification of the longer allele. Two frozen tumor samples (1 sporadic and 1 MEN 2A) were polyclonal. However, the corresponding tumor embedded in paraffin from the sporadic case was monoclonal. The other polyclonal tumor was found in the right thyroid lobe of a patient with MEN 2A who had a monoclonal tumor in the left lobe. Our results clearly demonstrate that MTC have a monoclonal origin in the majority of the cases.