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Background: Adenosquamous carcinoma of the lung (ASC) is a rare non-small-cell lung cancer (NSCLC) subtype combining components of squamous cell carcinoma (SCC) and adenocarcinoma (AC). Data on ASC, particularly in Caucasian populations, are limited. Methods: We reviewed clinicopathological and radiological characteristics of ASC patients diagnosed between 1996 and 2023. Patients were classified into AC-predominant ASC (AC-ASC) and SCC-predominant ASC (SCC-ASC) groups for analysis. Results: Among the 66 patients included, the median overall survival was 41.7 (95% CI, 25.0-54.4), while it was 48.1 (95% CI, 27.3-88.0) in patients treated with curative surgery (n = 44) and 15.3 (95% CI, 6.5-42.6) months for palliative patients (n = 22). The five-year survival rates were 39% and 26%, respectively. Recurrence occurred in 43% of stage I patients and was associated with worse survival (HR 3.303 (95% CI, 1.10-9.89) p = 0.033). AC-ASCs (n = 17) more frequently showed air-bronchogram ( p = 0.002) and pleural effusions ( p = 0.054) compared to SCC-ASCs (n = 26). SCC-ASCs exhibited more vascular invasion ( p = 0.006) and PD-L1 values between 1 and 49% (TPS) ( p = 0.032). The subtype did not influence survival. EGFR and ALK alterations were found in 17% and 2% of patients, respectively. Conclusions: Despite early-stage disease, ASC patients had a high recurrence rate, associated with worse survival. Clinicopathologic differences between AC-ASCs and SCC-ASCs did not influence survival.

Background: Definite diagnosis of prion diseases or transmissible spongiform encephalopathies (TSEs) requires neuropathology, usually at autopsy. Epidemiology of human TSEs has relied on definite as well as 'probable' cases in which neuropathological confirmation is lacking, usually because of low autopsy rates in most countries., Methods: In Austria, an active surveillance program for human prion diseases was established in 1996. Since then, more than 900 referrals were analyzed. Postmortem investigation of brain tissue is mandatory in every suspect case of TSE. Thus, epidemiological data on TSEs from Austria may serve as autopsy-controlled reference for countries with lower autopsy rates., Results: The total number of TSE cases in Austria since 1969 is 206. The average yearly mortality for the active surveillance period from 1996 to 30 June 2006 is 1.39 per million, with the highest rates for Vienna (2.37) compared with other provinces. Eighty-five percent of definite TSEs were classified as sporadic Creutzfeldt-Jakob disease (sCJD). We observed a significant linear increase in the mean age at death of 0.6 years per calendar year. Clinical diagnostic surveillance criteria had a sensitivity and specificity of 82.7 and 80.0% for probable CJD, respectively, and a positive predictive value of 80.5% for probable and 38.9% for 'possible' CJD. Alternative neuropathological diagnoses in suspect cases included Alzheimer's disease with or without Lewy body pathology, vascular encephalopathy, metabolic encephalopathies and viral or limbic encephalitis., Conclusion: The steady increase in mortality rates, especially in old age groups, most likely reflects improved case ascertainment due to active surveillance causing higher awareness of the medical community. In comparison with other European countries, it is reassuring to note that the overall death rate of TSEs does not differ from the Austrian autopsy-controlled data, thus confirming the value of clinical surveillance criteria., (Copyright 2008 S. Karger AG, Basel.)

14-3-3 proteins have been reported to be detected specifically in the cerebrospinal fluid (CSF) from patients with Creutzfeldt-Jakob disease (CJD). To elucidate the role of 14-3-3 proteins in patients with CJD, we performed immunohistochemical studies on 14-3-3 proteins in autopsied brains from five patients with sporadic CJD (sCJD), three patients with Alzheimer's disease (AD), and seven normal control subjects. Formalin-fixed, paraffin-embedded sections from all cases were immunostained with several types of specific anti-14-3-3 antibodies. In the normal control brains, 14-3-3 immunoreactivity was localized mainly in the neuronal somata and processes; in contrast, glial cells showed no or faint immunoreactivity. In the brains from the patients with AD, 14-3-3 immunoreactivity was observed in the surviving neurons as well as some neurofibrillary tangles. In the brains from the patients with sCJD, 14-3-3 immunoreactivity was well preserved in the remaining neurons. Furthermore, the glial cells, especially the reactive astrocytes, were intensely immunostained in the brains affected by sCJD. Our findings suggest that 14-3-3 proteins may be up-regulated in the glial cells, particularly in reactive astrocytes, and that the enhanced expression of 14-3-3 proteins in these glial elements may be associated with the pathogenesis of sCJD.

Objectives: Few data are available about myopathy and polyneuropathy as rare side effects of chloroquine treatment. Even more rarely are cerebrospinal fluid (CSF) abnormalities in chloroquine polyneuropathy/myopathy., Case Description: The patient is an 81-year-old woman with a 30-year history of chronic polyarthritis. As a basic therapy, she received chloroquine (250 mg per day) since 1997. Already, 1 year later she developed slowly progressive gait disturbance, which led to recurrent falls, and forced her to use crutches and other orthotic devices. Since March 2001, she was no longer able to climb stairs. Since then she also developed sensory disturbances in both lower limbs. Clinical neurological investigation revealed weakness and wasting of all four limbs and reduced tendon reflexes and stocking-type sensory disturbances. Nerve conduction studies were indicative of an axonal polyneuropathy. Electromyography was non-specifically abnormal. Muscle biopsy of the gastrocnemius muscle disclosed neuropathic and myopathic features and frequent fibers with partially rimmed vacuoles, containing concentrically or parallelly sliced inclusions. CSF investigations disclosed increased protein but otherwise normal findings. Five months after discontinuation of chloroquine and replacement by leflunomid, there was marked clinical improvement., Conclusions: Chloroquine polyneuropathy/myopathy may go along with increased CSF protein. Discontinuation of the causative agent results in prompt recovery of the described abnormalities.

We have compared the immunomorphological spectrum of the deposition of the disease-associated prion protein (PrP(Sc)) in the cerebral and cerebellar cortex of 32 Creutzfeldt-Jakob disease (CJD) patients with the PrP gene (PRNP) E200K mutation to 45 sporadic CJD and 14 other genetic prion disease cases. PrP deposits correlate with the genotype at the methionine/valine (MV) polymorphic codon 129. While the diffuse/synaptic and patchy/perivacuolar PrP deposits and PrP plaques have a similar distribution and correlation with the genotype at codon 129 as in sporadic CJD, an additional peculiar PrP immunostaining pattern occurs in the cerebellum in 81% E200K mutation brains including 93% of M129M, 71% of M129V, but not in the single V129V case. It is localized to the molecular layer and consists of coarse granular PrP deposits arranged in a stripe-like manner predominantly perpendicular to the surface, closely resembling the parasagittal arborization of climbing fibers. Our results suggest that (1) the type of PrP deposits in the cerebellum may suggest genetic disease and the need for genetic testing; and (2) the peculiar stripes of PrP deposits might reflect selective vulnerability of cerebellar structures.

Recently, several studies proposed a physiological role for the cellular prion protein (PrP(c)) in defense against oxidative stress. Since the pathogenesis of prion disease necessarily involves a disturbance of PrP(c) homeostasis, we hypothesized that such diseases would be associated with concomitant disturbances in oxidative balance. In support of such a notion, in this study we show increased oxidative damage to nucleic acids in affected brains of patients with Creutzfeldt-Jakob disease. These data suggest that damage by free radicals is a likely cause for neurodegeneration in human prion disease, and antioxidants are a potential therapy for these disorders. Further, our data support the hypothesis that loss of the anti-oxidant function of PrP(c) plays a key role in the pathogenesis of these disorders., ((c) 2002 Elsevier Science (USA).)

Demonstration of the abnormal form of the prion protein (PrP) in the brain confirms the diagnosis of human prion disease (PrD). Using immunohistochemistry, we have compared ten monoclonal antibodies in PrD subtypes including sporadic and variant Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Alzheimer's disease (AD), and control brains. CJD subgroups were determined using Western blot analysis for the protease-resistant PrP type in combination with sequencing to determine the genotype at the methionine/valine polymorphism at codon 129 of the prion protein gene. None of the antibodies labeled given subgroups exclusively, but the intensity of immunoreactivity varied among morphologically distinct types of deposit. Fine granular or synaptic PrP deposits stained weakly or not at all with antibodies against the N-terminus of PrP, and were visible in one case only with 12F10 and SAF54. Coarser and plaque type deposits were immunolabeled with all antibodies. The immunostaining patterns appear characteristic for the disease subgroups. Labeling of certain neurons in all cases irrespective of disease, and staining at the periphery and/or throughout the senile plaques of AD patients were also noted. Antibodies such as 6H4 and 12F10 failed to give this type of labeling and are therefore less likely to recognise non-pathological PrP material in immunohistochemistry.

Background: Left ventricular hypertrabeculation (LVHT) has not been described in myotonic dystrophy Type I (MD1) before., Case Report: A 42-year-old man developed typical features of MD1 since 1992. Creatinekinase was slightly, but recurrently elevated. Needle electromyograms were myogenic and showed extensive spontaneous activity. Muscle biopsy was compatible with MDI. DNA analysis revealed a heterozygous 300 CTG-repeat expansion in the myotonic-dystrophy proteinkinase gene on chromosome 19q13.3. Cardiac history and clinical cardiologic examination were normal. On ECG, ST elevation and atrial flutter were found. The AECG was normal except for atrial flutter. Surprisingly, transthoracic echocardiography revealed LVHT, previously described only in Becker's muscular dystrophy, mitochondriopathies, and Barth syndrome., Conclusion: A rare cardiac manifestation of MD1 may be LVHT which alone has no therapeutic implication.

Fatal familial insomnia (FFI) is a unique hereditary prion disease with characteristic disturbances of sleep. We studied the serotonergic system in 8 FFI-affected subjects by immunohistochemistry for the serotonin-synthesizing enzyme, tryptophan hydroxylase (TH). Quantification of neurons in median raphe nuclei showed no total neuronal loss in FFI but a substantial increase of TH+ neurons (approximately 62%) in FFI subjects compared with controls. Our data indicate an alteration of the serotonergic system that might represent the functional substrate of some typical symptoms of FFI.

A novel phenotype of familial Creutzfeldt-Jakob disease (CJD) with mutated codon 200 of the prion protein gene (PRNP) coupled with the valine codon 129 (E200K-129V haplotype) has two features never observed in subjects carrying the pathogenic mutation coupled with the methionine codon 129 (E200K-129M haplotype): (1) plaque-like prion protein (PrP) deposits in the cerebellum and (2) type 2 protease-resistant prion protein (PrP(res)). This observation further underlines the role of codon 129 on the mutated PRNP allele in modulating the phenotype of familial prion diseases.

Case Report: A 42-year-old man with a history of Billroth II-gastrectomy, chronic alcoholism, and malnutrition developed acute tetraparesis, two days before admission. He presented with bilateral, proximal upper and lower limb weakness, limb girdle wasting, bilaterally reduced Achilles tendon reflexes, and bilateral stocking-type sensory disturbances. Laboratory data revealed hypokalemia (2.2 mmol/L), elevated creatine kinase (7282 U/L), metabolic alkalosis and reduced urine potassium, albumin, and total protein. Muscle biopsy showed atrophic, necrotic, and regenerating fibers, endomysial macrophages, and vacuolar degeneration, interpreted as hypokalemic myopathy. With the correction of the serum potassium, tetraparesis rapidly resolved. With other causes excluded, malnutrition and gastrectomy were considered responsible for hypokalemia in this patient with acute tetraparesis and chronic alcoholism.