The expression of peroxisome proliferator-activated receptor (PPAR)g 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 PPARg in normal, benign and malignant thyroid tissues and to correlate PPARg immunostaining with clinical/pathological features of patients with thyroid cancer. We analysed the expression of PPARg 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 PPARg both at mRNA and at protein level. PAX8-PPARg 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-PPARg rearrangement expressed lower levels of PPARg mRNA than the NT. Overexpression of PPARg transcripts was detected in 80% (four of five) of translocation-positive tumours. Diffuse nuclear staining was significantly (Po0.05) 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 receptorg-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 PPARg negative than classic PTCs (80% vs 28%; P ¼ 0.01). Our results demonstrated that PPARg is underexpressed in translocation-negative thyroid tumours of follicular origin and that a further reduction of PPARg expression is associated with dedifferentiation at later stages of tumour development and progression.

Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

Recently, a translocation t(2;3)(q13;p25), leading to the formation of a chimeric PAX8-peroxisome proliferator-activated receptor (PPAR)gamma 1 oncogene, was detected in follicular thyroid carcinomas (FTC), but not in follicular thyroid adenomas (FTA), papillary thyroid carcinomas (PTC), or multinodular hyperplasias. However, previous cytogenetic studies have identified the t(2;3)(q13;p25) translocation also in some cases of FTA. In this study, we have combined RT-PCR with primers in exons 4-8 of PAX8 and in exon 1 of PPAR gamma 1 with PPAR gamma immunohistochemistry to study PAX8-PPAR gamma 1 oncogene activation in FTC (n = 9), FTA (n = 16), PTC (n = 9), anaplastic thyroid carcinomas (n = 4), and multinodular hyperplasias (n = 2). PAX8-PPAR gamma 1 rearrangements were detected by RT-PCR in 5 of 9 (56%) FTC and in 2 of 16 (13%) FTA. By contrast, all cases of PTC, anaplastic thyroid carcinomas, and multinodular hyperplasia were RT-PCR-negative. Diffuse nuclear immunoreactivity for PPAR gamma was observed in 7 of 9 (78%) FTC, 5 of 16 FTA (31%), and 1 of 9 PTC (11%). Positivity was focal in 3 cases (1 FTC, 1 PTC, and 1 multinodular hyperplasia). Diffuse nuclear staining for PPAR gamma was present in RT-PCR- negative cases of FTC (n = 3), FTA (n = 3), and PTC (n = 1), suggesting that a different PAX8-PPAR gamma 1 breakpoint, a rearrangement between PPAR gamma 1 and a non-PAX8 partner, or overexpression of the native protein might be present. Our findings that PAX8-PPAR gamma 1 rearrangements are present in both follicular carcinomas and adenomas suggest that this oncogene is not a reliable marker to differentiate between FTC and FTA in fine-needle aspiration biopsies of follicular neoplasms of the thyroid.

Abstract. This report describes a case of sacrococcygeal teratoma with adenocarcinomatous transformation in a 45-year-old woman. This is an infrequent location for teratoma in adults and malignant transformation has rarely been described. Prognosis depends on complete excision. Clinical manifestations, imaging aspects and histological findings of this case are presented. CT and MRI adequately document the mixed cystic and solid nature of the tumour, its extension and relations with adjacent structures, allowing accurate pre-operative planning.Sacrococcygeal teratoma is the most common solid neoplasm in neonates, with an estimated prevalence of 1 in 35 000-40 000 live births. They can be diagnosed prenatally by fetal ultrasound and 50-70% are found during the first few days of life. 80% are diagnosed by the sixth month and fewer than 10% beyond the age of 2 years [1,2]. Reported cases of sacrococcygeal teratomas in adults are rare. Treatment consists of complete surgical resection. Long-term survival is possible for malignant tumours, but incomplete surgical removal carries a poor prognosis. If the tumour invades adjacent structures, neoadjuvant pre-operative combination chemotherapy should be given [7].We report an unusual case of a 45-year-old woman with intestinal and urinary obstructive symptoms due to a large sacrococcygeal teratoma with adenocarcinomatous transformation. CT and MRI appropriately demonstrated the combined cystic and solid nature of the tumour, its extension and relations with adjacent structures, allowing accurate pre-operative planning. Case reportA 45-year-old woman with a 1-year history of gradually increasing lower back and pelvic pain, presented with constipation, dysuria and urinary frequency that had progressively developed over 2 months. There was an obstetrical history of dystocic forceps deliveries at ages 21 and 27. On gynaecological and rectal examination a large palpable mass was found in the right pelvis, posterior to the rectum. Neurological examination was unremarkable. Alpha-fetoprotein, carcinoembryonic antigen and human chorionic gonadotropin levels were normal. On pelvic CT (Figure 1) a regularly marginated thin walled cystic mass measuring 15 cm611.5 cm610.5 cm was identified, anterior to the sacrum and coccyx and extending inferiorly into the left ischiorectal fossa, compressing the urinary bladder and sigmoid colon and anteriorly displacing the rectum and vagina. Its content had homogeneous density near to that of water (10 Hounsfield Units), with a discrete amount of floating fat. At the coccyx bone level, a contrast enhancing 2.5 cm solid nodule was also evident as vegetation from the posterior wall. No evidence of bone destruction or invasion of the adjacent structures was found. Hysterectomy, bilateral adnexectomy and biopsies of the tumour were performed at laparotomy. Histopathological evaluation showed the wall of the cystic portion to be composed of a fibrous capsule with an inner lining of respiratory epithelium and areas of squamous epithelium. The described ...

A 70-year-old man with a long-standing history of increased neck volume was examined in the Ear, Nose, Throat Clinic because he was complaining of dysphagia and dyspnea on exertion. His medical history was irrelevant except for a family history of goiter in several relatives. At clinical examination, an enlarged right thyroid gland lobe with a lobulated surface that was soft was detected. The gland was mobile with deglutition, but the inferior limit of the right lobe could not be palpated.Laboratory findings disclosed normal thyrotropin, triiodothyronine, and thyroxine levels, and no antithyroid antibodies were detected. Fine-needle aspiration biopsy of the right lobe of the thyroid gland was performed without imaging guidance and revealed normal follicular cells and colloid and no neoplastic cells. Scintigraphic findings disclosed absence of activity at the site of the nodule.The patient then underwent neck and mediastinal computed tomography (CT) to evaluate for intrathoracic component and airway patency. Additionally, magnetic resonance (MR) imaging of the neck and ultrasonography (US)-guided fine-needle aspiration biopsy were performed. IMAGING FINDINGSTransverse CT scans (Fig 1) showed a large nonhomogeneous nodule partially replacing the right lobe of the thyroid gland and extending inferiorly into the superior mediastinum along the prevascular space. This nodule had well-defined margins and contained several areas of low attenuation, which suggested fat, and a small calcification. There was slight tracheal displacement to the left side and a slight decrease in the transverse diameter of the tracheal lumen. The lesion was clearly separate from the esophagus. The left lobe of the thyroid gland showed no abnormalities.The possible presence of fat within the nodule put the initial diagnosis of colloid goiter in question, and additional MR imaging and US-guided fine-needle aspiration biopsy were performed to further characterize this lesion. At MR imaging (Fig 2a, 2b), a large heterogeneous nodule was seen replacing the right lobe of the thyroid gland. This nodule contained large irregular areas of T1-weighted hyperintensity that became hypointense on the fat-suppressed transverse spectral presaturation inversion-recovery T1-weighted MR image (Fig 2c), and these findings further indicated the presence of fat. The MR image showed the intrathyroid location of the lesion, its welldefined borders, and clear cleavage planes with adjacent anatomic structures.No cervical, supraclavicular, or superior mediastinal lymphadenopathy was detected. A scan obtained at US-guided fineneedle aspiration biopsy (Fig 3) showed the heterogeneity of the nodule of the right lobe of the thyroid gland and large hyperechoic areas within the nodule, which reflected the fatty component. A reverberation artifact caused by the tip of the needle was seen in the middle of the hyperechoic component of the lesion.

Objective: X-chromosome inactivation analysis was performed in order to assess the clonal origin of non-medullary thyroid tumours and to distinguish between multicentricity and multifocality in multiple papillary thyroid carcinoma (PTC). Methods: One hundred and thirteen tumour samples from 31 patients with isolated PTC, 16 patients with multinodular PTC, 14 patients with follicular thyroid adenoma (FTA) and 15 patients with follicular thyroid carcinoma (FTC) were collected. The corresponding normal thyroid tissues were analysed, and in 14 cases, tumour-surrounding tissue was also studied. Genomic DNA was digested with HpaII and HhaI previous to PCR amplification of the polymorphic CAG repeat, on exon 1 of the human androgen receptor gene (HUMARA). PCR products were analysed by denaturing gel electrophoresis, silver staining and densitometric analysis. PCR products were also used to determine the number of CAG repeats of patients with isolated PTC, FTA, FTC and of 41 healthy volunteers. Results: Heterozygosity for the HUMARA polymorphism was found in 64/76 (84%) cases. Lyonization of the thyroid was observed in 15/76 (20%) cases, which were excluded from clonal analysis. Except for two cases of isolated PTC, all tumour samples studied presented monoclonal X-inactivation patterns, while normal thyroid tissue was polyclonal. Monoclonal patterns were also found in 4/14 tumour-surrounding tissues. No difference was found in the length of CAG alleles between patients and controls. Of eight informative cases of multinodular PTC, three showed evidence of multicentricity and five revealed patterns consistent with multifocality. Conclusions: Both isolated and multinodular PTC as well as FTA and FTC are of monoclonal origin. Our results also suggest that approximately one-third of multiple PTC have an independent origin for the different nodules (multicentricity). Monoclonality was also found in tissues surrounding some PTC nodules. No association was found between the length of CAG alleles and thyroid malignancies.

Different neurological manifestations of COVID-19 in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicenter observational study using the International Severe Acute Respiratory and emerging Infection Consortium cohort across 1507 sites worldwide from January/30th/2020 to May/25th/2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161,239 patients (158,267 adults; 2,972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%), and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%), and central nervous system (CNS) infection (0.2%). Each occurred more frequently in ICU than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU vs. non-ICU (7.1% vs. 2.3%, P &lt; .001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease, and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure, and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.

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