Search

Verruka vulgaris, insan papilloma virüsünün (HPV) neden olduğu benign bir enfeksiyondur. Lezyonlar öncelikle kutanöz yüzeylerde görülür; bununla birlikte, mukozal tutulum daha az sıklıkta görülmektedir. Tipik görünüm, boyut ve sayı olarak değişkenlik gösteren asemptomatik papüllerdir. Ayırıcı tanı, iyi huylu ve kötü huylu çeşitli durumların bir listesini içerir. Bu yazıda, dahiliye fizik muayenesinde tesadüfen dilde karnabahar benzeri asemptomatik kitle saptanan 65 yaşında bir erkek hasta sunulmaktadır. Eksizyonel biyopsi verruka vulgaris olarak sonuçlandı ve takiplerinde yeni lezyon izlenmedi., Verruca vulgaris is a benign infection caused by the human papillomavirus (HPV). The lesions appear primarily on the cutaneous surfaces; however, mucosal involvement is less frequent. The typical presentation is asymptomatic papules varying in size and number. The differential diagnosis includes a diverse list of benign and malignant conditions. Herein, we present a 65-year-old male patient with an asymptomatic cauliflower-like mass on the tongue incidentally observed during internal medicine physical examination. The excisional biopsy revealed verruca vulgaris, and no new lesions were detected in the follow-up.

Supplemental material, sj-docx-1-ijs-10.1177_10668969211022708 for Metastatic Liver Tumors in Surgical Pathology: Impact of Contemporary Diagnostic and Therapeutic Paradigms in a Tertiary Care Center by Ayşe Armutlu, Omer Saeed and Romil Saxena in International Journal of Surgical Pathology

Background: Concern for hepatic cysts being “hepatobiliary cystadenocarcinoma” along with the allegedly high frequency of its occurrence in the literature (up to 30% of the hepatic cysts) remains a major driver for the management of cystic lesions in this organ.

Siroz etyolojisi ve kliniği çeşitlilik gösteren son dönem karaciğer hastalığıdır. Güncel histolojik evreleme sistemleri sirozu tek bir kategoride değerlendirmektedir. Son yıllarda karaciğer yetmezliği ve portal hipertansiyon kliniği gelişen hastalarda, bazı belirleyici histolojik bulgular olduğu ve sirozun etyolojiye yönelik tedavi ile gerileyebildiği vurgulanmış; ve sirozun histolojik alt klasifikasyonuna ihtiyaç duyulmuştur.Bu çalışmada siroz tanısı almış 43 rezeksiyon materyalinde, Laennec fibrozis skorlarının klinik ve radyolojik parametrelerle ilişkisi araştırılmıştır. Ayrıca siroz zemininde gelişen prekanseröz lezyonlarda ve hepatosellüler karsinomda Glutamin sentetaz ve HSP 70 belirteçleri değerlendirilmiştir. Laennec fibrozis skorları ile hastaların asit, varis, kanama durumu ve evre arasında istatistiksel olarak anlamlı farklılık saptanmıştır. Nodül içi nekroinflamatuar aktivite derecesi ile asit, kollateral oluşumu, dalak boyutu ve evre arasında; portal/septal inflamasyon ve interfaz aktivite derecesi ile etyoloji arasında istatistiksel olarak anlamlı farklılık saptanmıştır. Siroz hastalarından 17'sinde saptanan toplam 45 adet nodüler lezyonda GS ve HSP 70 sitoplazmik boyanması ile nodül tipleri arasında anlamlı fark saptanmış, ancak HSP 70 nükleer boyanması ile fark saptanmamıştır. Nodül çapları ile hastaların AFP düzeyinin sirotik nodülden hepatosellüler karsinoma doğru ilerledikçe arttığı dikkati çekmiş olup, nodül çapı ile nodül tipleri arasında anlamlı fark saptanmıştır.Sonuçta, rezeksiyon materyallerinde de iğne biyopsilerinde olduğu gibi Laennec Fibrozis skorlarının, klinik verilerde anlamlı farklılıklar gösteren alt grupları temsil ettiği görülmüştür. Sirozun alt klasifikasyonunun prognozun ve tedaviye cevabın belirlenmesinde yararlı olabileceği düşünülmüştür. Ayrıca 2 cm'in altındaki nodüler lezyonlara tanı verirken literatürde de yer aldığı gibi HSP 70, GS ve Glipican-3'ü içeren immünhistokimyasal panel uygulanması gerektiği sonucuna varılmıştır.Anahtar kelimeler: Siroz, Laennec, Displazi, Hepatosellüler Karsinom, İmmünhistokimya Cirrhosis is the end result of chronic liver disease which has etiologic and clinic diversity. Current histologic staging systems evaluate cirrhosis in a single category. Recently regression in fibrosis has been noticed and some highlighted histologic features has been realized in cirrhotic patients suffering from portal hipertension and liver failure. Therefore a new histologic classification of cirrhosis has been challanged.In this study, 43 resection materials having cirrhosis had been enrolled. The Laennec fibrosis scores were applied and found to be correlated with clinical and radiological parameters. Furthermore, Glutamine synthetase and HSP 70 stainings were evaluated in the materials having precancerous lesions and hepatocellular carcinoma. Laennec fibrosis scores were significantly correlated with the presence of ascites and variceal bleeding. Statistically significant differences were detected in between the degree of intranodular necroinflammatory activity and decompansation parameters. There were also statistically significant differences in between the etiology and degree of portal inflamation and interface activity. A total of 45 nodular lesions were detected in 17 patients. The cytoplasmic staining of GS and HSP70 in these nodules with showed significant differences according to the type of the nodules. However nuclear staining of HSP70 was not significant. The size of the nodule and AFP levels were found to be increased throught to progression of benign nodule to HCC. As a conclusion, Laennec fibrosis scores were found to be correlated significantly with the clinical subgroups of cirrhosis. Subclassification of cirrhosis is thought to be useful in determining the prognosis and evaluating the response to treatment. Furthermore, GS and HSP 70 are found to be useful markers in the diagnosis of nodular lesions smaller than 2 cm.Keywords: Cirrhosis, Laennec, Dysplasia, Hepatocellular carcinoma, Immunohıstochemistry 133

Clear cell Renal Cell Carcinoma (ccRCC) is among the 10 most common cancers in both men and women and causes more than 140,000 deaths worldwide every year. In order to elucidate the underlying molecular mechanisms orchestrated by phosphorylation modifications, we per-formed a comprehensive quantitative phosphoproteomics characterization of ccRCC tumor and normal adjacent tissues. Here, we identified 16,253 phosphopeptides, of which more than 9000 were singly quantified. Our in-depth analysis revealed 600 phosphopeptides to be significantly differentially regulated between tumor and normal tissues. Moreover, our data revealed that significantly up -regu-lated phosphoproteins are associated with protein syn-thesis and cytoskeletal re-organization which suggests proliferative and migratory behavior of renal tumors. This is supported by a mesenchymal profile of ccRCC phos-phorylation events. Our rigorous characterization of the renal phosphoproteome also suggests that both epidermal growth factor receptor and vascular endothelial growth factor receptor are important mediators of phos-pho signaling in RCC pathogenesis. Furthermore, we determined the kinases p21-activated kinase 2, cyclin-dependent kinase 1 and c-Jun N-terminal kinase 1 to be master kinases that are responsible for phosphorylation of many substrates associated with cell proliferation, inflammation and migration. Moreover, high expression of p21-activated kinase 2 is associated with worse survival outcome of ccRCC patients. These master kinases are targetable by inhibitory drugs such as fostamatinib, min-ocycline, tamoxifen and bosutinib which can serve as novel therapeutic agents for ccRCC treatment., NO acknowledges the Royal Society Newton Advanced Fellowship (NA170389) .

Clear cell renal cell carcinoma (ccRCC) is the third most common and most malignant urological cancer, with a 5-year survival rate of 10% for patients with advanced tumors. Here, we identified 10,160 unique proteins by in-depth quantitative proteomics, of which 955 proteins were significantly regulated between tumor and normal adjacent tissues. We verified four putatively secreted biomarker candidates, namely, PLOD2, FERMT3, SPARC, and SIRPa, as highly expressed proteins that are not affected by intratumor and intertumor heterogeneity. Moreover, SPARC displayed a significant increase in urine samples of patients with ccRCC, making it a promising marker for the detection of the disease in body fluids. Furthermore, based on molecular expression profiles, we propose a biomarker panel for the robust classification of ccRCC tumors into two main clusters, which significantly differed in patient outcome with an almost three times higher risk of death for cluster 1 tumors compared with cluster 2 tumors. Moreover, among the most significant dustering proteins, 13 were targets of repurposed inhibitory FDA-approved drugs. Our rigorous proteomics approach identified promising diagnostic and tumor-discriminative biomarker candidates which can serve as therapeutic targets for the treatment of ccRCC. Implications: Our in-depth quantitative proteomics analysis of ccRCC tissues identifies the putatively secreted protein SPARC as a promising urine biomarker and reveals two molecular tumor phenotypes., NA

We analyzed metastatic liver tumors received in the department of pathology in a tertiary care center over a 3-year period. There were 509 metastatic liver tumors; counterintuitively, there were as many resections (235 cases) as biopsies (274 cases). This unexpected finding reflects contemporaneous organ-specific paradigms for diagnosis and management of metastatic liver disease in oncologic practice, and the association of our practice with a National Cancer Institute-designated comprehensive cancer center with expertise and specialization in liver surgery. We receive a large number of resections for metastatic liver tumors because metastasectomy from a variety of primary tumors is associated with improved overall, and in many instances, disease-free, long-term survival. Metastatic colorectal carcinomas, metastatic neuroendocrine tumors, and metastatic gastrointestinal stromal tumors constituted 78% of resections because the largest body of literature and cumulative experience exists for these lesions. In contrast, breast carcinomas and pancreatic carcinomas, which are the next common metastatic liver tumors were biopsied but rarely resected, because metastasectomy is not the standard of care for these tumors. Immunohistochemistry was performed in less than a quarter of the total number of cases (23%), because the primary tumor site was known in the vast majority of cases. Of the 42 cases with unknown primary tumor, it was elucidated in 50% of the cases by immunohistochemical and clinical work-up. Of the cases with known primary tumor, immunohistochemistry was performed mostly in metastatic breast, colon, and lung carcinomas. In these cases, biomarker analyses provided additional information relevant to clinical management., NA

Background: to investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. Methods: four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. Results: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). Conclusion: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels., University of Gottingen Open Access Publication Funds

Autoimmune hepatitis (AIH) is a chronic progressive autoimmune liver disease characterized by hypergammaglobulinemia, interface hepatitis, a female preponderance, and the presence of autoantibodies in most patients. The presence of HLA-DR3/DR4 and functional impairment in regulatory T cells are associated with AIH. However, AIH is a multifactorial complex disease. This report is a description of a case of seronegative AIH in a girl with chronic hepatitis, a high immunoglobulin E (IgE) level, perforating nodular dermatitis, and sheer eosinophilia. To re-evaluate the diagnosis, whole exon sequencing was performed. It was determined that the patient had ancestral haplotype A1-B8-DR3, which is associated with autoimmunity. Importantly, it was also noted that an undocumented point mutation (Ala627Thr) of the FMS-like tyrosine 3 kinase (FLT3) receptor was present. This FLT3 receptor gain-of-function mutation is associated with the activation of the mechanistic target of rapamycin (mTOR), and dendritic cell activation. In addition, a loss-of-function mutation in the melanocortin-3 receptor gene, which inhibits interleukin 4, was detected. The constellation of these immune deregulatory factors may have propagated auto-aggression of the liver, causing chronic hepatitis with AIH features. The findings of seronegativity with eosinophilia and a high IgE level led us to hypothesize that the pathognomonic mechanism in this case was unlike that of classic AIH pathophysiology. Since mTOR is constitutively activated, mTOR inhibitors may be a useful option to treat AIH and dermatitis., NA

Objective: to determine the frequency of granulomatous inflammation within hepatocellular carcinoma (HCC) and its clinicopathologic associations. Material and method: fifty-eight HCCs (51 explants, 3 lobectomies, and 4 segmentectomies) were reviewed. Results: five (8.6%) cases (F/M=1/4, mean age: 63.6) were identified with granulomas.1/5 had history of neoadjuvant therapy. 4/5 patients presented with early stage (pT1/2). All were well-differentiated (Grade1-2/4). The mean number of tumor foci was 3.6, with a median size of 2.2 cm. All of them had advanced fibrosis. No difference was identified from cases without granulomas (n=53) in terms of prognosis and aforementioned parameters (p> 0.05). Granulomas were mainly concentrated in peripheral parts of the tumors. One case with nodule-in-nodule formation had granulomas lined along the border of the inner nodule. In 2 cases, granulomas were identified in steatohepatitic areas, while another had clear cell change. Only 1 had necrotizing granulomas, none with acid resistant bacilli. Two cases revealed concomitant granulomas in the adjacent liver parenchyma in addition to the tumor stroma. Except for one with a history of tuberculosis, none of the cases had a granulomatous disease.Conclusion: this is the largest case series of HCCs with granulomas by far. Our data revealed neither clinicopathologic and prognostic difference nor definite etiology related to granulomas. Yet, association with steatotic and clear tumor cells suggests the role of cytoplasmic content, while distribution of granulomas points to host immune response., NA

Background: desmoplastic small round cell tumor (DSRCT) is a rare, aggressive neoplasm seen in children and young adults, usually manifested by involvement of abdominal serosa. Here, we present an unusual case of primary DSRCT of kidney. Case presentation: the patient was an 8-year-old girl with a large renal mass which was confused with primitive neuroectodermal tumor (PNET) in the needle biopsy. The tumor had a variegated histology revealing frequent pseudo-rosette formations, pseudopapillary architecture, rhabdoid, clear or pleomorphic cells in addition to typical small round cell morphology and desmoplasia. It showed immunohistochemical features of DSRCT, and EWSR1 re-arrangement. Conclusions: proffering this diagnosis is particularly difficult for tumors of viscera because of the incognizance of the entity in these locations. Moreover, DSRCT is a great mimicker and may get easily confused with more common kidney malignancies of childhood such as Wilms tumor, PNET/EWS, rhabdoid tumor, clear cell sarcoma, and other small round cell tumors as well as renal cell carcinomas. The distinction is critical as the accurate therapeutic approach will require correct diagnosis., NA

Background: this study aims to investigate the role of endobronchial ultrasonography elastography in predicting malignancy. Methods: between January 2016 and December 2016, a total of 221 lymph nodes were biopsied using the endobronchial ultrasonography-guided transbronchial needle aspiration from 119 consecutive patients (69 males, 50 females; mean age 63.2±12.4 years; range, 16 to 86 years) were included. Lymph nodes were scored by elastography according to their colors in four categories before the procedure. The strain ratio was calculated based on the region of interest after three measurements. Results: of the patients, 93 were diagnosed with a malignancy through endobronchial ultrasonography-guided transbronchial needle aspiration biopsy. The mean lymph node score of benign versus malignant lesions was 2.2±1.0 and 3.2±1, respectively (p, NA

The effect of COVID-19 on the transplant recipients is not well-established. Many reports underestimate the effect of COVID-19 on the immunosuppressed population. Herein, we report on 3 pediatric liver transplant recipients who were transplanted at our center between February 11 and March 10, 2020-during the COVID-19 pandemic era. The 3 patients aged between 5 and 10 months, had a rapid and aggressive respiratory deterioration that necessitated mechanical ventilation and extracorporeal life support; and eventually died. The clinical and pathological pictures likely represent COVID-19 pneumonia. Chest x-rays showed progressive infiltrates. Lung autopsies showed diffuse alveolar damage in two cases. We concluded that COVID-19 is very likely to have catastrophic effects on transplant recipients., NA