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AIMS: The purpose of this study is to report novel and unusual USP6 fusion partners in aneurysmal bone cysts (ABCs). These findings may be useful in routine diagnostics as well as in studying the biology of USP6-related disorders. METHODS: A cohort of seven patients diagnosed with ABC examined between 2014 and 2023 at Motol University Hospital in Prague was included into this retrospective non-randomised study. All cases were analysed using histopathological evaluation, immunohistochemistry and Anchored multiplex RNA methods. Demographic characteristics and clinical data were also analysed. RESULTS: We identified two novel (ZFX and IP6K2), three unusual (MEF2A, EIF1 and COL1A2) and two common (CDH11) fusion partners with USP6 gene among all seven cases of ABC. CONCLUSIONS: Cases in our study were diagnosed as ABCs due to characteristic clinical and morphological presentation. However, not all cases are as self-evident, and molecular testing is necessary. The identification of these gene alterations can be useful in distinction between true ABC and ABC-like changes among many benign and malignant bone tumours.
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OBJECTIVES: The vascular supply to the neck and body of the pancreas is highly variable. The dorsal pancreatic artery is the dominant artery feeding this area. The aim of this study was to describe the vascular supply of postresection pancreatic remnants after pancreaticoduodenectomy. Patients with hazardous anatomical arrangement may be at a higher risk of postresection remnant ischemia and postoperative pancreatic fistula development. METHODS: The modified Whipple procedure was performed on 20 cadaveric donors. The macroscopic anatomical supply of the postresection pancreatic remnant of each donor was evaluated. RESULTS: The arterial supply of the postresection remnant was highly variable. In 30% of cases (6/20), the dorsal pancreatic artery was cut during the pancreatoduodenectomy or it was missing. In these cases, the area of the pancreaticojejunostomy construction was fed only through anastomoses between the transverse pancreatic artery and the pancreatic branches of the splenic artery. CONCLUSIONS: In 30% of cases, the arterial supply of the postresection pancreatic remnant was dependent on inconstant intraparenchymal arterial anastomoses. These patients may be at a higher risk of postoperative pancreatic fistula development.
Subject(s)
Pancreatic Fistula , Pancreaticoduodenectomy , Humans , Pancreaticoduodenectomy/adverse effects , Pancreatic Fistula/etiology , Pancreas/surgery , Arteries/surgery , Postoperative Complications/etiology , CadaverABSTRACT
PURPOSE: Pleomorphic adenoma (PA), the most common benign tumour of the parotid gland, requires accurate preoperative diagnosis owing to its capacity for malignant transformation. The aim of this study was to evaluate our experience with ultrasound-guided fine-needle aspiration biopsy (FNAB) in the diagnostic algorithm for patients with PA and to assess clinical outcomes for those with different surgical approaches. MATERIAL AND METHODS: We carried out a retrospective analysis of patients treated for parotid gland mass between 2010 and 2016. These had had preoperative FNAB and had undergone subsequent surgery. RESULTS: 165 patients had FNAB with the result of PA and the definitive histology confirmed PA in 159 cases (96.4%). On the other hand, in 179 patients, the definitive histology showed PA and the preoperative FNAB result corresponded in 159 cases (88.9%). The measured sensitivity, specificity and accuracy of ultrasound-guided FNAB in the diagnosis of PA were, respectively, 88.83%, 96.23% and 92.31%. Most of the patients underwent superficial or partial superficial parotidectomy, followed by extracapsular dissection which was associated with statistically lower risk of facial nerve injury (P=0.04). CONCLUSION: Ultrasound-guided FNAB is simple, accurate and valuable in the diagnosis of PA and provides results that can lead to the choice of less invasive operative treatment.
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BACKGROUND: Composite haemangioendothelioma is a rare vascular neoplasm with indolent to intermediate malignant potential. Diagnosis of this disease relays on histopathological identification of at least two different morphologically distinctive vascular components in proper clinical settings. Exceedingly rare cases of this neoplasm can exhibit areas resembling high-grade angiosarcoma, which does not change the biological behaviour. Such lesions tend to occur in the setting of chronic lymphoedema and thus, can mimic Stewart-Treves syndrome, which has a much worse clinical outcome and prognosis. CASE PRESENTATION: We present a case of 49 years old male suffering from chronic lymphoedema of the left lower extremity who had developed a composite haemangioendothelioma with high grade angiosarcoma-like areas mimicking the Stewart-Treves syndrome. Given the multifocality of the disease, the only potentially curable surgical treatment would be hemipelvectomy, which was refused by the patient. The patient has been followed-up, with no signs of local progression of the remaining disease, nor a distant spread outside the involved extremity for two years. CONCLUSIONS: Composite haemangioendothelioma represents a rare malignant vascular tumour, with significantly more favourable biological behaviour than angiosarcoma, even in cases where angiosarcoma-like areas are present. For that reason, composite haemangioendothelioma can be easily misdiagnosed as true angiosarcoma. The rarity of this disease unfortunately hampers the development of clinical practice guidelines and the implementation of treatment recommendations. Most of the patients with localized tumour are treated by wide surgical resection, without neo- or adjuvant radiotherapy or chemotherapy. However, in the case of this diagnosis, the watch-and-wait approach is better than mutilating procedure, highlighting the necessity of establishing of the correct diagnosis.
Subject(s)
Hemangioendothelioma , Hemangiosarcoma , Lymphangiosarcoma , Lymphedema , Humans , Male , Middle Aged , Hemangiosarcoma/pathology , Lymphangiosarcoma/diagnosis , Lymphangiosarcoma/etiology , Lymphangiosarcoma/pathology , Lymphedema/diagnosis , Lymphedema/etiology , Hemangioendothelioma/diagnosisABSTRACT
Mazabraud's syndrome represents rare benign disorder characterized by simultaneous occurrence of fibrous dysplasia of bone and intramuscular myxomas within surrounding soft tissue. Mutations of GNAS1 gene were proven to be causative for this condition. Here, we present a case report of a patient with unusual manifestation of this disease, who developed a pathological fracture of the femur in the setting of monostotic fibrous dysplasia. The intramuscular myxoma of the thigh was discovered during the following orthopedic operation, where the intraoperative diagnosis became a pitfall of the case, as the intramuscular myxoma was initially diagnosed as a low-grade sarcoma from the frozen section. Apart from clinical findings, the diagnosis of Mazabraud's syndrome was further proven by histopathological evaluation and molecular studies of GNAS1 gene. This case raises awareness of such condition as it can easily become a diagnostic pitfall.
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Inflammatory rhabdomyoblastic tumor (IRMT) is a rare, recently described skeletal muscle neoplasm of uncertain malignant potential. We report an unusual tumor in the right arm of a 5-year-old boy, which is the first case of a pediatric IRMT. Immunohistochemically, most cells in the tumor were positive for CD163 and CD68 staining. The neoplastic cells themselves showed a skeletal muscle phenotype with a diffuse expression of desmin and a focal expression of myoD1. Mitotic activity was low (1/10 HPF), and no necrosis was observed.
Subject(s)
Neoplasms , Humans , Biomarkers, Tumor/metabolismABSTRACT
In melanoma and other cancers, invasion, epithelial-to-mesenchymal transition, metastasis and cancer stem cell maintenance are regulated by transcription factors including the Snail family. Slug (Snail2) protein generally supports migration and apoptosis resistance. However, its role in melanoma is not completely understood. The present study investigated the transcriptional regulation of the SLUG gene in melanoma. It demonstrated that SLUG is under the control of the Hedgehog/GLI signaling pathway and is activated predominantly by the transcription factor GLI2. The SLUG gene promoter contains a high number of GLI-binding sites. Slug expression is activated by GLI factors in reporter assays and inhibited by GANT61 (GLI inhibitor) and cyclopamine (SMO inhibitor). SLUG mRNA levels are lowered by GANT61 as assessed by reverse transcription-quantitative PCR. Chromatin immunoprecipitation revealed abundant binding of factors GLI1-3 in the four subregions of the proximal SLUG promoter. Notably, melanoma-associated transcription factor (MITF) is an imperfect activator of the SLUG promoter in reporter assays, and downregulation of MITF had no effect on endogenous Slug protein levels. Immunohistochemical analysis confirmed the above findings and showed MITF-negative regions in metastatic melanoma that were positive for GLI2 and Slug. Taken together, the results demonstrated a previously unrecognized transcriptional activation mechanism of the SLUG gene, which may represent its main regulation of expression in melanoma cells.
Subject(s)
Hedgehog Proteins , Melanoma , Humans , Hedgehog Proteins/genetics , Melanoma/genetics , Transcription Factors/genetics , Apoptosis , Signal TransductionABSTRACT
AIMS: This retrospective non-randomised study aims to identify new and rare fusion partners with USP6 in the setting of nodular fasciitis. It has been proven, that nodular fasciitis can harbour different variants of USP6 fusions, which can be used in routine diagnostics and even determine the biological behaviour of the process. METHODS: A total of 19 cases of nodular fasciitis examined between 2011 and 2022 at Motol University Hospital in Prague were included into this study. Next to the histopathological evaluation, all cases were assessed using immunohistochemistry, RT-PCR and Anchored multiplex RNA methods. Patient's main demographic characteristics and corresponding clinical data were also analysed. RESULTS: This study presents one novel (KIF1A) and five rare examples (TMP4, SPARC, EIF5A, MIR22HG, COL1A2) of fusion partners with USP6 among 19 cases of nodular fasciitis. CONCLUSION: Identification of USP6 fusion partners in nodular fasciitis helps to understand the biology of such lesions. Moreover, it can be useful in routine histopathological practice of soft-tissues diagnostics, especially in preventing possible misdiagnosis of malignancy.
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The new WHO classification of CNS tumors is largely based on molecular diagnostic. Without molecular methods some entities can no longer be diagnosed. We are trying to show a rational approach to the CNS tumors diagnostics, which is based on conventional molecular methods such as RT-PCR, Sanger sequencing, MLPA, extended by the next generation sequencing (NGS) and methylation SNP array.
Subject(s)
Central Nervous System Neoplasms , High-Throughput Nucleotide Sequencing , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/genetics , Humans , MutationABSTRACT
It has been postulated that platelets are produced by fragmentation of the megakaryocytes within the pulmonary circulation rather than budding of their cytoplasm within the bone marrow. Although literature is scarce depicting the levels of the megakaryocytes within the lungs from previously healthy individuals, there are several studies describing the presence of these cells in human necropsy specimens, and it has been hypothesized that their rearrangements could contribute to the pathogenesis of chronic pulmonary vascular disorders. The objective of this study was to describe the characteristics, distribution and total count of megakaryocytes in explants from lung transplant (LTx) recipients based on the final clinicopathological diagnosis, as well as in samples from LTx donors without previously known pulmonary disease. Using the immunohistochemical marker CD61 we quantified and characterized such cells in 20 biopsy samples from LTx donors and in 30 biopsy samples from LTx recipients with different pathologic conditions: vascular disorders of the lungs, obstructive pulmonary disorders and fibrotic lung diseases. Patients suffering from idiopathic pulmonary arterial hypertension (IPAH) showed morphological differences and strikingly higher numbers of the lungs megakaryocytes (264.5 cells/cm2) compared to all the other groups (the average count among donors was 33.55 megakaryocytes/cm2). Such finding could contribute to the understanding of the origin of vasoconstriction, thrombosis and vascular remodeling of the pulmonary circulation - all the basic mechanisms leading to the development of IPAH, as for there is an increasing evidence of several products of platelets and megakaryocytes to be capable of triggering such processes.
Subject(s)
Lung Diseases , Megakaryocytes , Humans , Megakaryocytes/pathology , Familial Primary Pulmonary Hypertension/pathology , Pulmonary Artery/pathology , Lung/pathology , Blood Platelets/pathology , Lung Diseases/pathologyABSTRACT
Uterus transplantation is a new experimental treatment method of absolute uterine factor infertility which affects 3-5% of infertile women. Absolute uterine factor infertility includes infertile women with agenesis or severe malformation of the uterus, several acquired uterine diseases causing infertility, and patients of fertile age after hysterectomy because of various causes. Uterus transplantation is considered a new method of assisted reproduction which allows women with absolute uterine factor infertility to have own biological offspring. However, uterus transplantation is considered a radical method of reproduction by some ethicists. Nevertheless, recent analysis of newborns from transplanted uterus has shown high level of childbirths of mature and near-to-term newborns and did not confirm increased risk for both babies and mothers. Therefore, together with gestational surrogacy and adoption, uterus transplantation is nowadays considered promising and unique solution for women with absolute uterine factor infertility. Similarly to other solid organ transplants, the pathologist should be an integral part of the multidisciplinary uterus transplantation research teams. The primary role of the pathologist is histopathological evaluation of rejection changes in the biopsy samples from the ectocervix of the uterine allografts that is based on the provisional scoring system suggested by Swedish pioneers in uterus transplantation research. As the word provisional suggests, this scoring system is continuously studied and the principles of the evaluation of rejection after uterus transplantation could be adjusted in the future.
Subject(s)
Infertility, Female , Organ Transplantation , Female , Humans , Infant, Newborn , Infertility, Female/etiology , Infertility, Female/surgery , Organ Transplantation/adverse effects , Organ Transplantation/methods , Pathologists , Uterus/abnormalities , Uterus/transplantationABSTRACT
BACKGROUND/OBJECTIVES: The dorsal pancreatic artery is the main artery of the body and tail of the pancreas. Its origin and branching is highly variable. The aim of this study was to perform a meta-analysis to generate pooled prevalence data on the presence and origin of the dorsal pancreatic artery. Clinically important aspects of the dorsal pancreatic artery were summarised during the literature review. METHODS: Major medical databases were searched. Data on the presence and point of origin of the dorsal pancreatic artery were extracted and quantitatively synthesised. The obtained data of anatomical based studies and computed tomography based studies were statistically analysed. RESULTS: In total, 30 studies, comprising 2322 anatomical and computed tomography based cases were included. The dorsal pancreatic artery was present in 95.8% of cases. It originated from the splenic artery in 37.6% of cases, common hepatic artery in 18.3% of cases, coeliac trunk in 11.9% of cases and the superior mesenteric artery in 23.9% of cases. Other rare origins were present in 2.77% of cases. Multiple dorsal pancreatic arteries were found in 1,7% of cases. There was no significant difference in the presence or origin of the dorsal pancreatic artery between anatomical and computed tomography based studies. CONCLUSION: The dorsal pancreatic artery is present in the vast majority of cases. Its origin and branching are highly variable. Multiplicity of the dorsal pancreatic artery is infrequent.
Subject(s)
Celiac Artery , Splenic Artery , Humans , Mesenteric Artery, Superior , Pancreas/blood supply , Pancreas/diagnostic imaging , Splenic Artery/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
INTRODUCTION: Uterus transplantation is a causal treatment for absolute uterine factor infertility. Assessing rejection signs using a histopathological examination of the ectocervical biopsy from the transplanted uterus is common practice in all human uterus transplants worldwide to date. A provisional scoring system was used for the histopathological assessment of subclinical rejection signs in uterus recipients. Here we hypothesized that histopathological and immunohistochemical findings in the normal uteri would differ from the borderline category of subclinical rejection in uterine transplants. MATERIAL AND METHODS: This prospective observational study included ectocervical biopsies of 54 women who underwent hysterectomy for benign reasons. All biopsy samples were assessed histopathologically and immunohistochemically. RESULTS: Most of the ectocervical biopsies showed clustering lymphocytic infiltrates affecting the stromal-epithelial interface with the epithelial influx of lymphocytes, primarily CD45RO-positive activated T-cells with CD8 T-lymphocyte predominance. CD4-positive T-lymphocytes and B-cells were rarely detected in the ectocervix. These morphological findings and immunoprofiles of lymphocytic populations overlapped with the so-called borderline changes defined in the provisional scoring system for rejection in the transplanted uteri. The immunoprofiles of ectocervical and endocervical lymphocytic populations differed, with strikingly prominent B-cell participation in the endocervix vs the rare detection of B-cells in the ectocervix. CONCLUSIONS: The histopathological and immunohistochemical findings in the uteri of premenopausal women were similar to the borderline category of the currently used provisional scoring system of subclinical uterine rejection utilized in all uterine transplant studies. However, future similar studies are required to validate our findings.
Subject(s)
Cervix Uteri/pathology , Graft Rejection/pathology , Infertility, Female/surgery , Uterus/transplantation , Adult , Biopsy , Female , Humans , Hysterectomy , Middle Aged , Prospective Studies , Research DesignABSTRACT
PURPOSE: Warthin tumour (WT) management options comprise surgery or follow-up. The purpose of this study was to asses our experience with the follow-up strategy in selected patients with an ultrasound-guided fine-needle aspiration biopsy (FNAB) showing WT. METHODS: We performed a retrospective analysis of patients diagnosed with WT using FNAB between 1.1.2006 and 31.12.2019. Patients were divided into three groups according to the therapeutic approach-immediate surgery, follow-up or surgery and follow-up. RESULTS: 323 patients were diagnosed with WT and met the study's inclusion criteria (154 women, 47.7% and 169 men, 52.3%). 192 patients were operated right after the diagnosis, 109 patients were observed with their first detected tumour and 22 patients had parotid WT surgery and were in the wait-and-scan protocol with a contralateral tumour, recurrence or both. The growth rate (GR) of observed WT was highly variable (mean GR 1.0 mm/year (5%), median GR 0.8 mm (9%), range - 19.7 to +20.0 mm/year). From 131 patients in the follow-up group, 19 patients underwent surgery and definitive histology revealed 17 WTs and 2 adenocarcinomas. However, these 2 patients had changes in sonographic findings at their next control. The mean observation time was 44.7 months (range 12-138 months) in patients followed exclusively at our institution and 50.9 months (range 12-110 months) in patients observed in cooperation with an otorhinolaryngologist at the patients' place of residence. CONCLUSION: Ultrasound-guided FNAB is an accurate and simple method in WT diagnosis and based on its result a follow-up strategy can be chosen for selected patients with WT.
Subject(s)
Adenolymphoma , Adenolymphoma/diagnostic imaging , Adenolymphoma/pathology , Adenolymphoma/surgery , Biopsy, Fine-Needle/methods , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Sensitivity and Specificity , Ultrasonography, InterventionalABSTRACT
Molecular assays for translocation detection in different tumors have gradually been incorporated into routine diagnostics. However, conventional methods such as fluorescence in situ hybridization (FISH) and reverse transcriptase-PCR come with several drawbacks. Next-generation sequencing (NGS) can provide in-depth detection of numerous gene alterations. The anchored multiplex PCR assay proved to be a fast and easy-to-analyze approach for routine diagnostics laboratories. Next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Panels) is beneficial in both diagnosis for patient care and in identification of a novel fusion breakpoint in tumors. NGS is useful in identifying targetable molecular changes (point mutations, fusion genes, etc.) in tumors that can serve as a rationale for inclusion of patients with advanced disease in ongoing clinical trials and allow for better risk stratification.
Subject(s)
High-Throughput Nucleotide Sequencing , Neoplasms , Humans , In Situ Hybridization, Fluorescence , Multiplex Polymerase Chain Reaction , Neoplasms/diagnosis , Neoplasms/genetics , Translocation, GeneticABSTRACT
Congenital mesoblastic nephroma (CMN), the most common renal tumor of infancy, is a mesenchymal neoplasm histologically classified into classic, cellular, or mixed types. Most cellular CMNs harbor a characteristic ETV6-NTRK3 fusion. Here, we report an unusual congenital mesoblastic nephroma presenting in a newborn boy with a novel EML4-ALK gene fusion revealed by Anchored Multiplex RNA Sequencing Assay. The EML4-ALK gene fusion expands the genetic spectrum implicated in the pathogenesis of congenital mesoblastic nephroma, with yet another example of kinase oncogenic activation through chromosomal rearrangement. The methylation profile of the tumor corresponds with infantile fibrosarcoma showing the biological similarity of these two entities.
Subject(s)
Fibrosarcoma/genetics , Nephroma, Mesoblastic/genetics , Oncogene Proteins, Fusion/genetics , Proto-Oncogene Proteins c-ets/genetics , Receptor, trkC/genetics , Repressor Proteins/genetics , Fibrosarcoma/diagnosis , Fibrosarcoma/pathology , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Male , Nephroma, Mesoblastic/diagnosis , Nephroma, Mesoblastic/pathology , RNA-Seq , ETS Translocation Variant 6 ProteinABSTRACT
Malignant Triton tumour (MTT) is a rare variant of malignant peripheral nerve sheath tumour with partial rhabdomyosarcomatous differentiation. To the best of our knowledge, the importance of the surgical resection margins on the outcome of patients with MTT is unknown. The present study is a retrospective review of 24 patients treated for MTT of the trunk and the extremities between 1997 and 2015 in two institutions. The association of surgical margins with overall and tumour recurrence-free survival was analysed. Furthermore, the typical morphological and immunohistochemical characteristics of the tumour were described. In patients treated with curative intent (17/24), a surgical margin exceeding 1 mm was significantly associated with better overall survival and local recurrence-free survival. The oncological outcome was however poor, with only 28% of patients surviving at 5 years. Histopathologically, necrosis was a common feature, and most tumours displayed focal positivity for S100 protein and focal or strong positivity for desmin. The present results highlight the aggressive behaviour of MTTs and underline the importance of adequate surgical treatment.
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This study aimed to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients that are associated with mild, moderate, severe, and fatal courses of the disease, and through a longitudinal follow-up, to understand the dynamics of the COVID-19 pathophysiology. All severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. A severe course of COVID-19 was associated with an elevation of proinflammatory markers; an efflux of immature granulocytes into peripheral blood; the activation of CD8 T cells, which infiltrated the lungs; transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with a severe form of the disease. In contrast, patients with a fatal course of COVID-19 failed to upregulate markers of inflammation, showed discoordination of the immune response, and progressed toward acute kidney failure. COVID-19 is a disease with a multi-organ affinity that is characterized by the activation of innate and cellular adaptive immunity. Biliary lesions with an elevation of GGT and the organ infiltration of interleukin 6 (IL-6)-producing cells are the defining characteristics for patients with the fulminant disease.
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Graphene nanoplatelets (GNPs) have emerged as one of the most promising filler materials for improving the tribological performance of ceramic composites due to their outstanding solid lubricant properties as well as mechanical and thermal stability. Yet, the addition of GNPs has so far enabled only a very limited improvement in the tribological properties of ceramics, particularly concerning the reduction of their friction coefficient. This is most likely due to the challenges of achieving a continuous lubricating and protecting tribo-film through a high GNP coverage of the exposed surfaces. Here we demonstrate that this can be achieved by efficiently increasing the exfoliation degree of GNPs down to the few-layer (FL) range. By employing FL-GNPs as filler material, the wear resistance of Si3N4 composites can be increased by more than twenty times, the friction coefficient reduced to nearly its half, while the other mechanical properties are also preserved or improved. Confocal Raman spectroscopy measurements revealed that at the origin of the spectacular improvement of the tribological properties is the formation of a continuous FL- GNP tribo-film, already at 5 wt% FL-GNP content.