The Importance of Muscle and Nerve Biopsies in the Diagnosis of Neuromuscular Diseases

Although the etiopathogenesis of infections has been largely illuminated by technical and scientific developments in the past century; many issues are still not clear today. The motto 'there is no disease, there is a patient' expressed by our instructors is stil valid today. Because the immune response of the host is as important as the virulence of the pathogen in infections and course of the disease can vary a lot according to the individual Cytokine storm is seen exactly in a group of diseases where the host response is very prominent. For this reason, Cytokine Storm Syndrome (CSS) is mostly mentioned. Cytokine Storm Syndrome (CSS) emerging due to different inflammatory etiologies; is an overwhelming systemic inflammation, hemodynamic imbalance, multiple organ failure, and potentially leading to death. After being first seen in Influenza in 2003 as a viral agent, CSS was seen in the most recent human diseases caused by SARS-Cov, MERS-CoV and SARS-CoV2 belonging to Coronaviridea family.The novel coronavirus SARS-CoV2 causes COVID-19, a pandemic threatening millions. Uncontrolled production of proinflammatory mediators contributes to acute respiratory distress syndrome (ARDS) and cytokine storm syndrome in COVID-19 disease

Is neurogenous hyperplasia a cause of appendiceal obliteration ? (a retrospective study of 1397 cases)

Amaç: Bu çalışmada çoğu akut appendisit ön tanısıyla çıkartılan appendektomi örneklerinde saptanan oblitere appendikslerdeki nöral doku komponentinin varlığı araştırılmış ve akut appendisit, karsinoid tümör gibi diğer appendiks lezyonlarıyla ilişkisi irdelenmiştir. Gereç ve yöntem: Retrospektif olarak taranan 1397 rutin appendektomi materyalinde " " tanısı almış 66 olgu bulundu. Ancak bunlardan uygun nitelikli 38 tanesi çalışma kapsamına alındı. Bu olguların hematoksilen-eosin ve Masson trikrom boyalı preparatları incelendi.Ayrıca materyallerde immünhistokimyasal olarak S-100 protein reaktivitesi araştırıldı. Bulgular: Işık mikroskopik düzeyde appendiks lümenlerinde nodül yapmaksızın gevşek dizilimli iğsi hücrelerin proliferasyonuyla oluşmuş obstrüksiyon izlendi. Miksoid zemin ve arada kısılı yağ dokusu da sıklıkla mevcuttu. 38 olgunun 18'inde(%47,3 ) iğsi hücrelerde S-100 protein immün reaktivitesi gözlendi. Sonuç: Bu çalışmada oblitere appendikslerde nöral hiperplazinin oldukça sık görülen bir antite olduğu ve çoğu kez fibröz obliterasyon olarak nitelenen lezyonun gerçekte nörojenik kökenli bir gelişim olabileceği vurgulanmaya çalışıldı.Aim: In this study the presence of neural tissue components was investigated in appendectomy specimens with an obliterated appendix. Relationship of the neural tissue presence with other appendical lesions such as carcinoid tumors and acute appendicitis was also evaluated. Material and method: Retrospective analysis of 1379 consecutive routine appendectomy specimens revealed 66 cases as "obliterated appendix" (an incidence of 4,2%). Only 38 appropriate cases have been included in this study. Results: By light microscopy, obliteration was located centrally in the appendix without nodule formation. Loose proliferation of spindle cells, usually in a myxoid background, and with entrapped fat tissue was frequently observed. The spindle cells were positive for S-100 protein in 18 of 38 cases (47,3 %). Conclusion: We emphasise that neurogenous hyperplasia in obliterated appendices is a rather common entity, andthatmost cases ofso-calledfibrous obliteration actuallyrepresentneurogenicappendicopathy

Hypoxia-inducible factor 1 alpha expression is an indicator of invasiveness in uterine cervical tumors

Background: Hypoxia is a common feature of cancers. Hypoxia-inducible factor 1A (HIF1A) is a causative agent that changes the transcriptional response of tumors under hypoxia. Some alterations lead to an increase in HIF1A activity and this supports other critical pathways leading to angiogenesis, metabolic adaptation and tumor progression. This retrospective study was designed to evaluate the differences of tissue expressions of HIF1A in a spectrum of cervical neoplasms.Methods: Tissue expression of HIF1A was studied in a total of 107 formalin-fixed, paraffin-embedded uterine cervical tumors specimens and its association with different clinicopathologic parameters was evaluated.Results: In this series, there were 30 low and 29 high grade cervical intraepithelial neoplasms (CINs), 27 squamous cell carcinomas, 15 adenosquamous carcinomas and 6 adenocarcinomas. Strong and diffuse nuclear staining was evaluated as positive HIF1A expression. Positive HIF-1 alpha expression was detected in 7 (25.9%) of squamous cell carcinomas, 1 of adenocarcinomas (16.7%) and only 1 of HGSILs (3.4%). Statistically it was determined that the positivity rate of strong nuclear HIF1A expression was significantly higher in invasive carcinomas when compared with in non-invasive squamous cell carcinomas (p=0.07). Contrary, there was no statistically significant difference according to the subtypes of carcinomas due to scarce number of cases with adenocarcinoma (p=0.188).Conclusions: Our findings were demonstrated to link of nuclear HIF1A expression and the invasive characters of uterine neoplasms. As a result, HIF-1 alpha expression may be important in foreseeing of the invasion and tumor progression

Foreign body aspiration in childhood

Amaç: Solunum sistemine aspire edilen yabancı cisimlerin belirlenip, çıkarılması komplikasyonların önlenmesi açısından önemlidir. Bu nedenle 10 aylık sürede yabancı cisim aspirasyonu süphesi ile klinigimize yatan 22 hasta retrospektif olarak degerlendirildi. Hastalar ve yöntem: Hastaların 16'sı erkek, 6'sı kız ve yasları 11 ay ile 57 ay arasında idi (ortalama 24 ay). En sık basvuru sikayeti; öksürük, hısıltılı solunum ve morarma olup, hastaların sadece 8'i solunum sıkıntısı ile basvurmustu. Olguların 15'inde fizik muayene bulguları, 14' ünde ise akciger grafisi bulguları tanıyı desteklemekteydi. Yabancı cisim öyküsü olan 19 olgunun 14'ünde akciger dinleme bulguları, 11'inde radyoloji pozitif saptandı. Öyküsü olmayan 3 olgunun 1'inde akciger dinleme bulguları varken, hepsinde radyoloji pozitif bulundu. Bulgular: Hastaların 21'inde (%95,5) bronkoskopide yabancı cisim çıkarıldı. Bir olguda yabancı cisim bulunamadı ve bol mukus aspire edildi. Yabancı cisim öyküsü oldugu halde fizik muayenede ve akciger grafisinde herhangi bir bulgusu olmayan 4 olgunun 3'ünde yabancı cisim çıkarılması öykünün öneminin vurgulanması açısından degerli bulundu. Çıkarılan yabancı cisimlerin 15'i organik, 2'si inorganik idi, 2'sinin orijini belirlenemedi. Iki hastada darlık yapan granülasyon dokusu tespit edildi ve bu granülasyon dokuları kürete edildiginde; 1'inde bitkiye benzer materyal saptanırken digerinde granülasyon dokusu içinde yabancı cisime rastlanmadı. Yabancı cisimlerin hastaların 10'unda (%47.6) sol ana bronstan çıkarılması ilginç bulundu. Hastaneye basvuru sürelerine göre olgular klinik, semptomatoloji ve radyolojik bulgulara göre karsılastırıldıgında iki grup arasında sadece radyolojik bulgular açısından anlamlı fark bulundu(p=0.0045). Sonuç: Bu çalısma 6 yas altı çocukluk döneminde yabancı cisim aspirasyonlarının sanılandan daha sık oldugu, yabancı cisimden süphelenmenin ve iyi bir öykünün en önemli tanı kriterleri oldugunun hatırlatılması amacıyla sunuldu.Aim: Determining and removing the aspirated foreign bodies from airways is important in preventing complications. Thus, 22 patients who had admitted to our clinic with the suspicion of airway foreign body within a period of 10 months were retrospectively evaluated. Material and methods: Sixteen patients were boys and six were girls, and their ages differed from 11 to 57 months (median 24 months). The common complaints were cough, wheezing and cyanosis. Only 8 patients were admitted to the hospital with respiratory distress. The physical examination revealed the diagnosis in fifteen of the patiens. On the other hand, the chest roentgenography revealed the diagnosis in thirteen. The foreign bodies were removed by bronchoscopy in 21 patients (95.5%). In spite of positive history, no signs and symptoms were determined by physical examination and chest roentgenography in 3 of 4 patients, the foreign body was removed from airway and it was accepted valuable to stress the importance of history. Results: Fifteen of the removed foreign bodies were organic, 2 were inorganic, and 2 could no be determined. In 2 patients the granulation tissue which had caused obstruction in the airway was curetted and in one patient a plant- like material was obtained. Only in one patient no foreign body was obtained. In 10 patients (47.6%) the foreign body was removed from left main bronchi, in 8 patients (38.1%) from right main bronchi, in 2 patients from trachea and in 1 patient from bilateral bronches. Conclusion: We presented this study to remind that in making the diagnosis of airway foreign body, which is more common in infancy than expected, suspicion and history are the most important diagnostic criteria

Dihydropyridine Receptor Congenital Myopathy In A Consangineous Turkish Family.

Dihydropyridine receptor congenital myopathy is a recently described congenital myopathy caused by dominant or recessive mutations in the CACNA1S gene. To date, only 11 cases from 7 families were described in a single report. Here, we describe a consanguineous family with three affected children, presenting congenital hypotonia, contractures, ophthalmoplegia and respiratory insufficiency, with a novel homozygous mutation in the CACNA1S gene. They also showed cognitive delay, pes equinovarus deformity and neurogenic changes that have not been associated with this myopathy in the previous reports. This report expands the phenotypic spectrum of dihydropyridine receptor congenital myopathy and underscores the importance of whole exome sequencing in early onset neuromuscular disorders

Evaluation of microsatellite instability and tissue expression levels of MLH1, PMS2, MSH2, MSH6 proteins in wilms tumor

Amaç: Lynch sendromuyla ilişkili kolorektal kanserlerin patogenezindeki rolü ayrıntılı olarak bilinen mikrosatellit instabilite (MSİ) ve yanlış eşleşme tamir (YET) genlerinin Wilms tümöründeki (WT) etkisi kapsamlı olarak araştırılmamıştır. Çalışmamızın amacı MSİ ve YET proteinlerinin WT'ündeki prognostik önemini belirlemektir. Yöntem: Nefroblastomlu 45 olgu çalışma kapsamına alındı. YET protein ekspresyonları arşiv bloklarından yapılan kesitlerde immünhistokimyasal yöntemle incelendi. Tüm olguların parafin bloklarından çıkartılan tümör ve normal böbrek dokularından ekstrakte edilen DNA'ların; BAT25, BAT26, NR21, NR24, mono27, penta D ve PentaC belirleyici genlerinde; real time PCR melting analiz ve floresan kapiller elektroforez (FKE) yöntemleriyle mikrosatellit instabilite varlığı irdelendi. Tüm sonuçlar istatistiksel olarak değerlendirildi. Bulgular: Düşük derecede MSİ 6 olguda (%13,3) gözlendi. MSİ ile evre ve sağkalım gibi bazı prognostik faktörler arasında istatistiksel korelasyon saptanmadı. On dokuz tümörde (%42,2) MLH1, PMS2, MSH2 veya MSH6 protein ekspresyonlarından bazılarında kayıp vardı. YET protein defektiyle; tümör boyutu (p=0,021), evre (p=0,017) ve sağkalım (p<0.01) arasında korelasyon gözlendi. Benzer şekilde MSİ ile tümör boyutu araşında ilişki saptandı (p=0,046). Fakat MSİ ve YET proteinleri arasında ilişki yoktu (p=0,198). Sonuç: Bu çalışma; YET gen defektine bağlı MSİ'nin, Wilms tümörlerinin küçük bir kısmının patogenezinde etkisi olabileceğini göstermiştir. Fakat MSİ ile YET proteinlerinin doku ekspresyonları arasında uyum olmaması; YET genlerinin WT gelişiminde farklı bir mekanizma ile etkili olabileceğini düşündürmektedir. Objective: The importance of microsatellite instability (MSI) and mismatch repair genes (MMR) has not been fully elucidated in Wilms tumor (WT) although it was well defined in colorectal cancer in concept of Lynch syndrome. The aim of this study was to determine the prognostic value of MSI and MMR proteins in WT. Method: This study included 45 nephroblastoma cases of childhood. The expressions of MMR proteins were determined using an immunohistochemical method on archival tissue sections. Real Time PCR melting analysis and fluorescence capillary electrophoresis (FCE) were performed for MSI representing BAT25, BAT26, NR21, NR24, mono27, penta D and PentaC genes on the extracted DNA comparing tumor and normal tissues for each case. All results were evaluated statistically. Results: Low MSI was observed in 6 cases (13.3%). There were no statistical correlations between with MSI and some clinical prognosis factors such as stage and survive. Nineteen tumors (42.2%) showed loss of protein expressions of MLH1, PMS2, MSH2 or MSH6. MMR protein defects were correlated with size of tumor (p=0.020), stage (0.019) and survival (p<0.01). Similarly MSI was correlated with the size of the tumor (p=0.046). But there was no relationship between MSI and MMR protein defects (p= 0.198). Conclusion: This study showed that a small proportion of WT might be associated with MSI as defects of DNA mismatch repair genes in pathogenesis. But there was no concordance with the tissue expression of MMR proteins and MSI. These findings suggest that the MMR genes may play an important role in WT evolution with different pathway

Clues for Differential Diagnosis of Neuromuscular Disorders

Congenital myopathies form a clinically, genetically, and morphologically heterogeneous group of neuromuscular disorders. They generally present with hypotonia (±muscle weakness) in the neonatal/infantile period, in some cases, the first symptoms occur in the juvenile or adult period. They occur due to structural defects within muscle fibers, affecting the contractile matrix, excitation-contraction coupling, T-tubules, and sarcoplasmic reticulum while muscle membrane stability is spared. They are also a type of neuromuscular disorder, pathologically characterized by myopathic changes, such as differences in myofiber sizes, internalized nuclei, and the presence of degenerating fibers. Structural abnormalities in a muscle biopsy are classified according to abnormally located organelles and intracellular bodies. These classifications include nemaline myopathy, central core disease, multi-mini core myopathy, centronuclear myopathy, congenital fiber-type disproportion and others. With developments in the field of molecular genetics, these diseases have been associated with more and more genes. Thus, pathological classification and a classification based on molecular genetics are used together. This chapter addresses the congenital myopathies and its subgroups through an overview of the disorder and their pathological and genotype features.</p

Alternative factors in differential diagnosis of infantile fibrosarcoma

The aim of this study was to determine the role of nm23 expression, percentage of Ki-67 labelling, vascularisation, mitosis and histologic features such as pattern, cellularity and density of inflammatory cell infiltrate in differential diagnosis of fibrous tumors. Specimens of 16 fibrous tumor cases were studied: 6 infantile fibrosarcoma (IFS), 3 adult fibrosarcoma (AFS) and 7 benign fibrous proliferations. All findings were examined and correlated statistically. In conclusion, number of inflammatory cells, histologic pattern and age of the patient are helpful in differential diagnosis of IFS and AFS