To determine the extent of neocortical involvement in multiple system atrophy (MSA), we used design-based stereological methods to estimate the total numbers of neurons, oligodendrocytes, astrocytes, ...and microglia in the frontal, parietal, temporal, and occipital cortex of brains from 11 patients with MSA and 11 age- and gender-matched control subjects. The stereological data were supported by cell marker expression analyses in tissue samples from the prefrontal cortex. We found significantly fewer neurons in the frontal and parietal cortex of MSA brains compared with control brains. Significantly more astrocytes and microglia were observed in the frontal, parietal, and temporal cortex of MSA brains, whereas no change in the total number of oligodendrocytes was seen in any of the neocortical regions. There were significantly fewer neurons in the frontal cortex of MSA patients with impaired executive function than in patients with normal executive function. Our results indicate that the involvement of the neocortex in MSA is far more widespread and substantial than previously thought. In addition, our results suggest that the increasingly recognized cognitive impairment in MSA may be related to neuronal loss in the frontal cortex.
Human papillomavirus (HPV) is an established prognostic marker in oropharyngeal squamous cell carcinoma. Currently, the role of HPV in sinonasal carcinoma is being explored.
This systematic review ...addresses the role of HPV in sinonasal cancer, establishing the occurrence of HPV-positive cancers and the influence of HPV-positivity on prognosis in sinonasal cancer as well as the utility of the putative surrogate marker of HPV (p16) in sinonasal cancer.
Studies were identified with searches of Medline via PubMed and Embase via OVID (4 May 2020). Articles on original research concerning sinonasal cancer and HPV in humans written in English were included. Case reports with less than five cases were excluded.
Initially, 545 articles were identified; 190 duplicate articles were removed leaving 355 articles for title/abstract screening. Title/abstract screening excluded 243 articles, leaving 112 studies assessed for eligibility. After full-text screening, 57 studies were included. All articles investigated the significance of HPV in sinonasal carcinomas. HPV was reported in approximately 30% of sinonasal squamous cell carcinoma (SNSCC), where it was associated with a better prognosis. In sinonasal cancer, p16 is associated with diagnostic pitfalls and a putative utility of p16 in SNSCC has yet to be established. HPV was not frequently reported in other types of sinonasal carcinomas, besides the recently described subtype, HPV-dependent Multiphenotypic Sinonasal Carcinoma. In other types of sinonasal carcinoma, HPV is not frequently found.
Approximately 30% of SNSCC are HPV-positive. HPV-positivity in SNSCC is associated with improved survival. HPV occurs only rarely in other sinonasal cancers. There is currently not sufficient evidence for p16 as a surrogate marker of HPV in SNSCC.
The purpose of the study was to determine trends in age-adjusted incidence rates (AAIR) and survival probability in head and neck cancers (HNCs) in the Danish population from 1980 to 2014.
All ...patients registered with HNC in the nationwide Danish Cancer Registry from 1980 to 2014 were included. We evaluated the AAIR per 100,000 and the average annual percent change (AAPC). The relative survival probability at 5 years was calculated in relation to gender, anatomical location and histology, and we constructed age-period-cohort models of incidence.
About 34,606 patients were included (64.7% men). The AAIR increased from 9.1 per 100,000 in 1980 to 17.4 per 100,000 in 2014 with an AAPC of 2.1%. The greatest incidence increase was observed in oropharyngeal cancer (AAPC: 5.4%) followed by hypopharyngeal cancer (AAPC: 4.2%). Adenocarcinomas had the highest AAPC (5.0%) followed by squamous cell carcinomas (AAPC: 2.0%). The AAPC was significantly higher in women (2.4%) compared with men (1.6%). For all HNC patients, the relative survival at 5 years rose significantly from 49.0% in 1980-1984 to 62.4% in 2010-2014. Women had a significantly higher survival than men with a relative survival of 61.7% compared to 50.0% in men. Laryngeal cancer had the best survival probability of cancers in the upper aerodigestive tract with hypopharyngeal cancer having the poorest survival.
This nation-wide study showed a significant rise in incidence of HNC for men and women along with a significant increase in relative survival. Oropharyngeal cancer had the highest increase in incidence followed by hypopharyngeal cancer which showed the poorest survival of HNCs.
The family of Toll-like receptors (TLRs) plays a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules. It was recently suggested that TLRs have an ...important role in the crosstalk between neurons and glial cells in the central nervous system, thus their deregulation may play a role in neurodegeneration. Multiple system atrophy (MSA) together with Parkinson’s disease belongs to a diverse group of neurodegenerative conditions termed α-synucleinopathies. MSA is a fatal late onset disease characterized by the presence of α-synuclein positive glial cytoplasmic inclusions in oligodendrocytes. α-Synuclein can act as a danger-associated molecular pattern and alter TLR expression thereby activating inflammatory responses in the brain. In this study, using real-time PCR, we assessed the expression of TLRs (TLR1-10) in selected areas of MSA brains (substantia nigra, striatum, cerebral cortex, and nucleus dentatus) in comparison with normal controls. We show evidence for increased levels of mRNA-encoding
hTLR
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3
,
hTLR
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4
, and
hTLR
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5
in substantia nigra, striatum, cerebral cortex, and nucleus dentatus from MSA brains versus normal controls. The levels of expression of
hTLR
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1
mRNA were elevated in substantia nigra and striatum whereas levels of
hTLR
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8
and
hTLR
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9
mRNAs were significantly higher in cerebella from MSA patients. The concerted alteration of expression of multiple TLRs in MSA brains can be of relevance for understanding the pathogenesis of the disease.
The spectrum of tumors arising in the salivary glands is wide and has recently been shown to harbor a network of tumor-specific fusion genes. Acinic cell carcinoma (AciCC) is one of the more ...frequently encountered types of salivary gland carcinoma, but it has remained a genetic orphan until recently when a fusion between the HTN3 and MSANTD3 genes was described in one case. Neither of these 2 genes is known to be implicated in any other malignancy. This study was undertaken to investigate whether the HTN3-MSANTD3 fusion is a recurrent genetic event in AciCC and whether it is a characteristic of one of its histological variants. Of the 273 AciCCs screened, 9 cases showed rearrangement of MSANTD3 by break-apart fluorescence in situ hybridization, 2 had 1 to 2 extra signals, and 1 had gain, giving a total of 4.4% with MSANTD3 aberrations. In 6 of 7 available cases with MSANTD3 rearrangement, the HTN3-MSANTD3 fusion transcript was demonstrated with real-time polymerase chain reaction. Histologically, all fusion-positive cases were predominantly composed of serous tumor cells growing in solid sheets, with serous tumor cells expressing DOG-1 and the intercalated duct-like cell component being CK7 positive and S-100 positive in 6/9 cases. All but one case arose in the parotid gland, and none of the patients experienced a recurrence during follow-up. In contrast, the case with MSANTD3 gain metastasized to the cervical lymph nodes and lungs. In conclusion, we find the HTN3-MSANTD3 gene fusion to be a recurrent event in AciCC with prominent serous differentiation and an indolent clinical course.
Background: The purpose of this registry study was to evaluate trends in incidence and survival of laryngeal cancer in the Danish population from 1980 to 2014.
Methods: This study includes all ...patients with laryngeal cancer registered in the Danish Cancer Registry (DCR) in the period 1980-2014. The age-adjusted incidence rate (AAIR) per 100,000 and average annual percent change (AAPC) were calculated. We evaluated the relative survival at five years in relation to gender, anatomical location, year at diagnosis, and histological type. Further, an age-period-cohort (APC) model of incidence was constructed.
Results: A total of 8748 patients (82% males) were included. The median age at diagnosis was 60 years, range 18-101 years. The AAIR decreased from 3.6 per 100,000 in 1980 to 2.3 per 100,000 in 2014 with an AAPC of -0.8% (p < .008). Considering the anatomic location, we found that glottic cancer had a significantly better survival at five years compared to the other locations. We observed no significant difference in survival for supraglottic, subglottic and larynx unspecified cancer during the observation period. During the period 1980-2014, we found no improvement in five year relative survival.
Conclusions: This nation-wide study reports a significant decrease in the incidence of laryngeal cancer. Glottic cancer had a significantly better survival at five years compared to other locations.
Abstract Total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the basal ganglia and red nucleus were estimated in brains from 11 patients with multiple system atrophy (MSA) and 11 ...age- and gender-matched control subjects with unbiased stereological methods. Compared to the control subjects, the MSA patients had a substantially lower number of neurons in the substantia nigra (p = 0.001), putamen (p = 0.001), and globus pallidus (p < 0.001), and, to a lesser extent in the caudate nucleus (p = 0.03). A significantly lower number of oligodendrocytes were only observed in the putamen (p = 0.04) and globus pallidus (p = 0.01). In the MSA brains the total number of astrocytes was significantly higher in the putamen (p = 0.04) and caudate nucleus (p = 0.01). In all examined regions a higher number of microglia were found in the MSA brains with the greatest difference observed in the otherwise unaffected red nucleus (p = 0.001). The results from the stereological study were supported by cell marker expression analyses showing increased markers for activated microglia. Our results suggest that microgliosis is a consistent and severe neuropathological feature of MSA, whereas no widespread and substantial loss of oligodendrocytes was observed. We have demonstrated significant neuronal loss in the substantia nigra, striatum, and globus pallidus of patients with MSA, while neurons in other basal ganglia nuclei were spared, supporting the region-specific patterns of neuropathological changes in MSA.
•The age-adjusted incidence rate (AAIR) of thyroid cancer nearly tripled between 1980 and 2014.•The AAIR increased for papillary carcinomas (quintupled) and follicular carcinomas (tripled).•Papillary ...carcinomas had the best overall survival and anaplastic carcinomas had the worst.•There was identified an age-effect on the incidence of thyroid cancer but not a period or cohort effectt.
Thyroid cancer incidence has been reported to be increasing since the 1970 s. The aim of this study was to investigate the change in incidence and survival from 1980 to 2014 in Denmark.
We identified patients registered with thyroid cancer in the period 1980–2014. We evaluated the age-adjusted incidence rate (AAIR) and the average annual percentage change (AAPC), constructed age–period–cohort models (APCs), and evaluated relative survival (RS).
We included 5139 patients. The AAIR was 1.6 cases per 100,000 in 1980 and 4.5 cases in 2014 with an AAPC of 3.4%. The AAIR for papillary carcinomas (n = 2864) quintupled in the study period, and accounts for most of the observed increase in incidence with an AAPC of 4.9%. Follicular carcinomas (n = 920) nearly tripled in AAIR and had the second greatest increase in AAPC. Papillary carcinomas had the best prognosis with 1-year and 5-year RSs of 95% and 91%, followed by the follicular carcinomas with 1-year and 5-year RSs of 90% and 80%, respectively. Anaplastic carcinomas (n = 320) had the worst prognosis with 1-year and 5-year RSs of 18% and 12%. We found a significant age effect in the APC model for the incidence of thyroid cancer but no significant cohort or period effects.
The incidence of thyroid cancer is rising. This is primarily attributable to an increase in papillary carcinomas. The relative survival has improved significantly in Denmark since 1980. The cause of the increasing incidence remains to be established, but enhanced diagnostic scrutiny and increased iodine intake may be influential.
Magnetic resonance imaging (MRI) is the preferred imaging modality for oropharyngeal cancers (OPCs), but it has difficulties distinguishing between small OPCs and unilateral tonsil hypertrophy. We ...hypothesized that surgeon-performed transoral ultrasound (US) could be used to accurately detect T-stage OPCs. We performed a single-center prospective diagnostic accuracy study including patients with suspected or biopsy-verified OPCs during outpatient appointments. All patients were offered transoral US and MRI. If transoral US could not be tolerated by the patient, transcervical US was performed. The primary outcome was the diagnostic accuracy of detecting OPCs with US compared to MRI, using histopathology as the reference standard. The secondary outcome was comparing the primary tumor diameters between US and MRI blinded to each other. Out of the 26 patients included in the study, 21 (81%) had OPCs. Transoral US could be performed in 21/21 and 1/5 patients with suspected palatine and lingual tonsil OPCs, respectively. Overall, US diagnostic accuracy was 92%, compared to 81% with MRI (p = 0.37). US and MRI had a high correlation between tumor diameters in the anteroposterior diameter (R = 0.80, p < 0.001), corresponding to the depth axis on US. In conclusion, this small study showed the promise and feasibility of transoral US to improve the initial clinical evaluations of patients with suspected OPCs.
Thyroid cancer constitutes a major and increasing proportion of head and neck cancers in children and adolescents. The purpose of this study was to determine the incidence and survival of thyroid ...cancer in Danish patients aged 0-24 years from 1980 to 2014.
Patients aged 0-24 years registered with primary thyroid cancer in the Danish Cancer Registry or the Danish Pathology Data Bank during 1980-2014 were included. Crude incidence rates and age-adjusted incidence rates (AAIR) per 100,000, average annual percent change (AAPC), and overall survival (OS) were evaluated in relation to sex, histopathological tumor type, age at diagnosis, and year of diagnosis.
A total of 297 thyroid cancer patients (72% female, 72% papillary carcinoma) were identified. The AAIR per 100,000 increased significantly from 0.36 in 1980 to 0.97 in 2014, with an AAPC of 2.9%. There was no significant increase in incidence among children and adolescents (0-17 years). However, among young adults (18-24 years), a significant increase in incidence was observed (AAPC 3.7%). The incidence of thyroid cancer increased with age from 0.05 among infants aged 0 years to 1.73 among young adults aged 24 years. Female patients and papillary carcinoma showed significant increase in incidence (AAPC 3.3% and 3.2%), whereas male patients and other histopathological tumor types showed no change. The 15-year OS was 99%. The lowest 15-year OS was observed among patients with medullary carcinomas at 96%. There was no significant difference in OS between groups based on histopathological tumor type, and there was no significant change in OS over time.
In this nationwide study, no change in OS was observed, but a significant increase was seen in the incidence of thyroid cancer among young adults (aged 18-24 years), mainly attributed to an increase among females and patients with papillary carcinoma. No increase in incidence was seen among children and adolescents. These findings demonstrate the excellent prognosis for children and adolescents diagnosed with thyroid cancer.
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