Laryngeal embryonal rhabdomyosarcoma in an adult - A case presentation in the eyes of geneticists and clinicians

<p>1. Abstract</p> <p>Background</p> <p>Rhabdomyosarcoma is a solid tumor, resulting from dysregulation of the skeletal myogenesis program. For rhabdomyosarcomas (RMS) with a predilection for the head and neck, genitourinary tract, extremities, trunk, retroperitoneum, the larynx is still an unusual site. Till now only several cases of this laryngeal tumor have been described in world literature in the adult population. The entire spectrum of genetic factors underlying RMS development and progression is unclear until today. Multiple signaling pathways seem to be involved in ERMS development and progression.</p> <p>Case presentation</p> <p>In this paper we report an interesting RMS case in which the disease was located within the glottic region. We report an embryonal rhabdomyosarcoma of the larynx in 33 year-old man. After unsuccessful chemotherapy hemilaryngectomy was performed. In follow up CT no signs of recurrence were found. Recently patient is recurrence free for 62 months.</p> <p>Conclusions</p> <p>Considering the histological diagnosis and the highly aggressive nature of the lesion for optimal diagnosis positron electron tomography (PET) and computerized tomography (CT) of the neck and thorax should be performed. At this time surgical treatment with adjuvant radiotherapy seems to be the treatment of choice for this disease. Rhabdomyosarcoma of the larynx has a better prognosis than elsewhere in the body, probably because of its earlier recognition and accessibility to radical surgery.</p

Unusual association of alveolar rhabdomyosarcoma with pancreatic metastasis: emerging role of PET-CT in tumor staging

Pancreatic metastases in childhood cancer have been rarely reported in the radiology literature although ample evidence exists in pathology reports for its occurrence in patients with alveolar rhabdomyosarcomas (RMS). Assess the occurrence of pancreatic metastases in alveolar rhabdomyosarcomas, increase awareness of this association and reassess current staging protocols. Three major oncology centers reviewed their records and imaging examinations. Patients’ history and demographics, primary tumor site and histology, presence of tumor recurrence, and presence and location of other metastases were reviewed. Pancreatic metastases occurred in eight patients with alveolar RMS. Four of these presented at diagnosis and four with disease recurrence. In recurrent disease, the duration between the diagnosis of the primary tumor and pancreatic metastases varied from 8 months to 6 years (mean ± SD: 2.38 ± 2.49 years). In all patients who received PET scans, pancreatic metastases showed a marked FDG-uptake, but had variable detectability with CT. Pancreatic metastases were not associated with certain primary tumor locations or presence of other metastases, mandating an evaluation of the pancreas in all cases of alveolar rhabdomyosarcomas. Radiologists should be sensitized and actively evaluate the pancreas in patients with alveolar RMS. Optimizing CT and PET-CT protocols may increase the diagnostic yield

SUMO-1 possesses DNA binding activity

<p>Abstract</p> <p>Background</p> <p>Conjugation of small ubiquitin-related modifiers (SUMOs) is a frequent post-translational modification of proteins. SUMOs can also temporally associate with protein-targets via SUMO binding motifs (SBMs). Protein sumoylation has been identified as an important regulatory mechanism especially in the regulation of transcription and the maintenance of genome stability. The precise molecular mechanisms by which SUMO conjugation and association act are, however, not understood.</p> <p>Findings</p> <p>Using NMR spectroscopy and protein-DNA cross-linking experiments, we demonstrate here that SUMO-1 can specifically interact with dsDNA in a sequence-independent fashion. We also show that SUMO-1 binding to DNA can compete with other protein-DNA interactions at the example of the regulatory domain of Thymine-DNA Glycosylase and, based on these competition studies, estimate the DNA binding constant of SUMO1 in the range 1 mM.</p> <p>Conclusion</p> <p>This finding provides an important insight into how SUMO-1 might exert its activity. SUMO-1 might play a general role in destabilizing DNA bound protein complexes thereby operating in a bottle-opener way of fashion, explaining its pivotal role in regulating the activity of many central transcription and DNA repair complexes.</p

The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature

C-erbB-2 prognostic value for survival in patients with lung cancer remains controversial. We performed a systematic review of the literature to clarify its impact. Studies were identified by an electronic search in order to aggregate the survival results, after a methodological assessment using the scale of the European Lung Cancer Working Party. To be eligible, a study had to deal with c-erbB-2 assessment in lung cancer patients and to analyse survival according to c-erbB-2 expression. In total, 30 studies were eligible: 24 studies dealt with non-small-cell lung carcinoma (NSCLC), five with adenocarcinoma and one study dealt with small-cell carcinoma. In all, 31% of the patients were positive for c-erbB-2. According to c-erbB-2 expression, 13 studies were 'negative' (significant detrimental effect on survival), one 'positive' (significant survival improvement) and 16 not significant. Significant studies had a better subscore relative to analysis and results report than nonsignificant studies. In total, 86% of the significant studies and only 56% of the nonsignificant studies were evaluable for the meta-analysis. This suggests a possible bias in our aggregated results. For NSCLC, the hazard ratio was 1.55 (95% CI: 1.29-1.86) in favour of tumours that do not express c-erbB-2. In conclusion, the overexpression of c-erbB-2 might be a factor of poor prognosis for survival in NSCLC, but there is a potential bias in favour of the significant studies with an overestimation risk of the magnitude of the true effect of c-erbB-2 overexpression.Journal ArticleResearch Support, Non-U.S. Gov'tReviewinfo:eu-repo/semantics/publishe

Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes

<p>Abstract</p> <p>Background</p> <p>The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto's thyroiditis (HT), although fourteen EAATD patients with Graves' disease (GD) have been also reported.</p> <p>Methods</p> <p>We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term.</p> <p>Results</p> <p>Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management.</p> <p>Conclusions</p> <p>GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.</p

Increased risk of malignancies in a population-based study of 818 soft-tissue sarcoma patients

Soft-tissue sarcomas (STS) have been associated with various rare cancer syndromes and occur at increased frequencies in survivors of childhood cancer. Also adult patients with STS have been suggested to be at an increased risk of additional malignancies. After exclusion of syndrome-associated and radiation-induced sarcomas, we studied multiple primary malignancies in a population-based cohort of 818 patients with primary STS of the extremities and the trunk wall. In total, 203 other malignancies developed in 164 (20%) patients median 10 (0–32) years before and median 4 (0–35) years after the sarcoma diagnosis. Standardised morbidity ratios (SMRs) were determined for primary malignancies following a STS. Hereby individuals who had developed a STS were identified to be at increased risk of second primary malignancies (SMR for all malignant tumours=1.3; 95% CI=1.0–1.5; P=0.02) with STS being the only specific tumour type that occurred at an increased risk (SMR=17.6; 95% CI=8.1–33.5; P<0.001). Hence, this population-based series demonstrates a high frequency of second primary tumours among STS patients and indicates a particularly increased risk of developing a new STS

Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP

Stop codon mutations in the gene encoding the prion protein (PRNP) are very rare and have thus far only been described in two patients with prion protein cerebral amyloid angiopathy (PrP-CAA). In this report, we describe the clinical, histopathological and pathological prion protein (PrPSc) characteristics of two Dutch patients carrying novel adjacent stop codon mutations in the C-terminal part of PRNP, resulting in either case in hereditary prion protein amyloidoses, but with strikingly different clinicopathological phenotypes. The patient with the shortest disease duration (27 months) carried a Y226X mutation and showed PrP-CAA without any neurofibrillary lesions, whereas the patient with the longest disease duration (72 months) had a Q227X mutation and showed an unusual Gerstmann-Sträussler-Scheinker disease phenotype with numerous cerebral multicentric amyloid plaques and severe neurofibrillary lesions without PrP-CAA. Western blot analysis in the patient with the Q227X mutation demonstrated the presence of a 7 kDa unglycosylated PrPSc fragment truncated at both the N- and C-terminal ends. Our observations expand the spectrum of clinicopathological phenotypes associated with PRNP mutations and show that a single tyrosine residue difference in the PrP C-terminus may significantly affect the site of amyloid deposition and the overall phenotypic expression of the prion disease. Furthermore, it confirms that the absence of the glycosylphosphatidylinositol anchor in PrP predisposes to amyloid plaque formation

Assessment of disease progression in dysferlinopathy: A 1-year cohort study

ObjectiveTo assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.MethodsOne hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.ResultsThe functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.ConclusionCertain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.ClinicalTrials.gov identifier:NCT01676077