Heterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease.

Rationale: Renal cysts in patients with autosomal dominant polycystic kidney disease (ADPKD) can originate from any nephron segments, including proximal tubules (PT), the loop of Henle (LOH), distal tubules (DT), and collecting ducts (CD). Previous studies mostly used limited cell markers and failed to identify cells negative for these markers. Therefore, the cell composition and origin of ADPKD cyst are still unclear, and mechanisms of cystogenesis of different origins await further exploration. Methods: We performed single-cell RNA sequencing for the normal kidney tissue and seven cysts derived from superficial or deep layers of the polycystic kidney from an ADPKD patient. Results: Twelve cell types were identified and analyzed. We found that a renal cyst could be derived either from CD or both PT and LOH. Gene set variation analysis (GSVA) showed that epithelial mesenchymal transition (EMT), TNFA signaling via the NFKB pathways, and xenobiotic metabolism were significantly activated in PT-derived cyst epithelial cells while robust expression of genes involved in G2M Checkpoint, mTORC1 signaling, E2F Targets, MYC Targets V1, MYC Targets V2 were observed in CD-derived cells. Conclusion: Our results revealed that a single cyst could originate from CD or both PT and LOH, suggesting heterogeneity of polycystic composition and origin. Furthermore, cyst epithelial cells with different origins have different gene set activation.

Imaging Characterization of Renal Masses.

The detection of a renal mass is a relatively frequent occurrence in the daily practice of any Radiology Department. The diagnostic approaches depend on whether the lesion is cystic or solid. Cystic lesions can be managed using the Bosniak classification, while management of solid lesions depends on whether the lesion is well-defined or infiltrative. The approach to well-defined lesions focuses mainly on the differentiation between renal cancer and benign tumors such as angiomyolipoma (AML) and oncocytoma. Differential diagnosis of infiltrative lesions is wider, including primary and secondary malignancies and inflammatory disease, and knowledge of the patient history is essential. Radiologists may establish a possible differential diagnosis based on the imaging features of the renal masses and the clinical history. The aim of this review is to present the contribution of the different imaging techniques and image guided biopsies in the diagnostic management of cystic and solid renal lesions.

Pediatric Cystic Lung Lesions: Where Are We Now?

Pediatric cystic lung lesions have long been a source of confusion for clinicians, radiologists, and pathologists. They encompass a wide spectrum of entities with variable prognostic implications, including congenital lung malformations, pulmonary neoplasms, and hereditary conditions. As our understanding of the developmental and genetic origins of these conditions has evolved, revised nomenclature and classifications have emerged in an attempt to bring clarity to the origin of these lesions and guide clinical management. This review discusses cystic lung lesions and the current understanding of their etiopathogenesis.

CystAnalyser: A new software tool for the automatic detection and quantification of cysts in Polycystic Kidney and Liver Disease, and other cystic disorders.

The Polycystic Kidney Disease (PKD) is characterized by progressive renal cyst development and other extrarenal manifestation including Polycystic Liver Disease (PLD). Phenotypical characterization of animal models mimicking human diseases are commonly used, in order to, study new molecular mechanisms and identify new therapeutic approaches. The main biomarker of disease progression is total volume of kidney and liver in both human and mouse, which correlates with organ function. For this reason, the estimation of the number and area of the tissue occupied by cysts, is critical for the understanding of physiological mechanisms underlying the disease. In this regard, cystic index is a robust parameter commonly used to quantify the severity of the disease. To date, the vast majority of biomedical researchers use ImageJ as a software tool to estimate the cystic index by quantifying the cystic areas of histological images after thresholding. This tool has imitations of being inaccurate, largely due to incorrectly identifying non-cystic regions. We have developed a new software, named CystAnalyser (register by Universidade de Santiago de Compostela-USC, and Fundación Investigación Sanitaria de Santiago-FIDIS), that combines automatic image processing with a graphical user friendly interface that allows investigators to oversee and easily correct the image processing before quantification. CystAnalyser was able to generate a cystic profile including cystic index, number of cysts and cyst size. In order to test the CystAnalyser software, 795 cystic kidney, and liver histological images were analyzed. Using CystAnalyser there were no differences calculating cystic index automatically versus user input, except in specific circumstances where it was necessary for the user to distinguish between mildly cystic from non-cystic regions. The sensitivity and specificity of the number of cysts detected by the automatic quantification depends on the type of organ and cystic severity, with values 76.84-78.59% and 76.96-89.66% for the kidney and 87.29-93.80% and 63.42-86.07% for the liver. CystAnalyser, in addition, provides a new tool for estimating the number of cysts and a more specific measure of the cystic index than ImageJ. This study proposes CystAnalyser is a new robust and freely downloadable software tool for analyzing the severity of disease by quantifying histological images of cystic organs for routine biomedical research. CystAnalyser can be downloaded from https://citius.usc.es/transferencia/software/cystanalyser (for Windows and Linux) for research purposes.

Relapsing-Remitting Hepatic Pseudo-Cyst: A great simulator of malfunctioning ventriculoperitoneal shunt. Case report and proposal of a new classification.

BACKGROUND: Ventriculoperitoneal shunt is the most common treatment to manage hydrocephalus; it is unfortunately burdened by up to 25% of complications. The peritoneal approach may expose patients to many complications, however the formation of a liver pseudocyst is a rare occurrence, and its mechanisms are still largely unknown. CASE REPORT: We report the case of a 69-year-old woman with ventriculoperitoneal shunt, inserted for the management of post aneurysmal subarachnoid hemorrhage hydrocephalus, presenting to the Accident and Emergency for acute cholecystitis. Besides confirming the diagnosis, an ultrasound investigation revealed the presence of a hepatic cyst. Conservative treatment with antibiotics and non-steroidal anti-inflammatory drugs was performed with favorable outcome and resorption of the cyst. Interestingly the patient kept on presenting several similar episodes managed well by non-steroidal anti-inflammatory drugs alone, each of them associated with transient symptoms and signs of ventriculoperitoneal shunt malfunction. Computerized Tomography brain and lumbar puncture were normal, whereas CT abdomen showed the ventriculoperitoneal shunt distal catheter passing through the hepatic cyst. Given the ventriculoperitoneal shunt malfunction, in the context of an infective/inflammatory process a conversion of the ventriculoperitoneal shunt into a ventriculo-atrial shunt was carried out with successful clinical outcome. CONCLUSION: Based on current literature we propose a clinical and radiological classification of such pseudocysts related to ventriculoperitoneal shunt. Clinical presentation, diagnostic findings and management options are proposed for each type: purely infective, spurious (infective/inflammatory) and purely inflammatory. In the absence of system infection, a simple replacement of the distal catheter seems to be the best solution.

Diagnostic challenges of posterior fossa hemangioblastomas: Refining current radiological classification scheme.

Hemangioblastomas (HBMs) are known to exhibit very typical radiological features and thus classified by well-established radiological classification scheme. We reviewed our series of posterior fossa HBMs in order not only to evaluate the relevance of current classification scheme, but also to possibly refine it. Also, we added descriptions on several cases with unusual radiological magnetic resonance imaging (MRI) findings in which differential diagnosis was challenging. We retrospectively reviewed preoperative MRI of 118 patients with pathologically diagnosed posterior fossa HBMs at our institution between 2002 and 2015. Total 128 tumors were included to this study and classified into four categories based on the presence and nature of cystic components: extratumoral cystic (Type Ce, classical cystic with a mural nodule), intratumoral cystic (Type Ci), mixed cystic (Type Cm), and solid (Type S). The association with von Hippel-Lindau (VHL) disease was also investigated. In 118 patients (65 male and 53 female), 79 (66.9%) had solitary HBMs and 39 (33.1%) were diagnosed with VHL disease. Type Ce with typical radiological findings was the most prevalent type of HBM (63.3%), followed by Type S (21.1%). HBMs with intratumoral cysts were uncommon (Type Ci, 11.7%) and mixed extratumoral and intratumoral cysts (Type Cm) accounted for only 3.9%. No intergroup differences were observed in the proportions of each subtype between the solitary and VHL disease-associated HBMs. The blood loss was much lower in Type Ce than in other subtypes. In Type Cm, radical resection was often challenging as the differentiation between intratumoral and extratumoral cysts was difficult resulting in incomplete resection. Refined radiological classification scheme is more practical because it does not only help surgeons determine whether the cystic wall should be removed or not, but also covers cases with atypical radiological presentations. For solid and extraparenchymal HBMs, differential diagnosis is more difficult as well as very critical as surgical removal is often very challenging.

Molecular identification of cystic echinococcosis in humans and pigs reveals the presence of both Echinococcus granulosus sensu stricto and Echinococcus canadensis G6/G7 in the hyperendemic focus of the Republic of Moldova.

Cystic echinococcosis is caused by the parasitic species of the complex Echinococcus granulosus sensu lato. This disease is hyperendemic in the Republic of Moldova. Recent molecular analyses have revealed the exclusive presence of E. granulosus sensu stricto in sheep and cattle. Previous reports of prevalence in pigs suggest the potential presence of Echinococcus canadensis G6/G7, as this species is also reported in neighboring countries. The presence of cystic echinococcosis in pigs was specifically monitored at the slaughterhouse. In the meantime, human cases were genotyped for the first time. E. canadensis G6/G7 was identified in all ten pigs infected by E. granulosus s.l. One human case of infection by E. canadensis G6/G7 was also identified, while E. granulosus sensu stricto was found to be the cause for the 13 others. The description of one human case of E. canadensis G6/G7 has confirmed its zoonotic impact in the country. Future studies will be needed to estimate the relative proportion and distribution of both parasitic species in Moldova.

Application of endoscopic ultrasound-guided-fine needle aspiration combined with cyst fluid analysis for the diagnosis of mediastinal cystic lesions.

BACKGROUND: Mediastinal cystic lesions account for approximately 15-20% of all mediastinal masses and are difficult to differentiate because of similar imaging manifestation. The aim of this study was to differentiate mediastinum cystic lesions through endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA) and parameters from cyst-fluid analysis. METHODS: Over a period of eight years, 37 patients suspected with mediastinal cystic lesions were assessed. Cyst fluid was collected via EUS-FNA and further examined using cytological and biochemical techniques. Definitive diagnosis was established based on cytology, surgical pathology, and/or clinical follow-up. RESULTS: Based on the final pathological reports or long-term follow-up, 19 patients were diagnosed with benign cysts, 14 with benign or malignant tumors, 2 with tuberculosis, 1 with an abscess, and 1 with a pancreatic pseudocyst. Computed tomography or magnetic resonance imaging mistakenly distinguished eight cases as solid masses (27.03%), but EUS revealed cystic characteristics. Carcinoembryonic antigen and lactate dehydrogenase (LDH) were evaluated from the cyst fluid obtained by EUS-FNA. There was no statistically significant difference in carcinoembryonic antigen values between benign and malignant cysts; however the average LDH value in the malignancy group was significantly higher than in the benign group. CONCLUSION: EUS-FNA showed great potential for differentiating mediastinal lesions by combining imaging manifestation and cytological examination. The elevated LDH value from cyst fluid chemical analysis could be used as an auxiliary indicator for diagnosing malignancy.

Classification of Lumbar Facet Joint Cysts Using the NeuroSpine Surgery Research Group (NSURG) Grading Score and Correlation with Recurrence and Clinical Outcomes.

OBJECTIVE: To assess the validity of the proposed NeuroSpine Surgery Research Group Classification System through a retrospective analysis of patients treated surgically for lumbar facet joint cysts at a single institution. METHODS: In a cohort of 166 patients, sagittal T2-weighted magnetic resonance images were used to measure degree of spondylolisthesis, whereas axial T2-weighted magnetic resonance images were used to determine the percentage of vertebral canal occupied by the cyst. Grading was performed by 2 observers. Statistical analysis was conducted to correlate the given grades of each cyst with the treatment performed and the long-term outcomes of cyst and pain recurrence. RESULTS: In total, 158 were treated by decompression, whereas 8 underwent decompression with fusion; 25% of patients presented with a grade 1 cyst, 45% with a grade 2, 13% with a grade 3, 13% with a grade 4, and 4% with a grade 5 cyst. Of patients treated by decompression alone, a greater rate of recurrence was seen in grades 4 and 5 (29.4% and 33.3%) when compared with grades 1-3 (8.8%, 8.5%, and 0%, respectively, P < 0.05). There were no cases of a cyst recurrence after a fusion. CONCLUSIONS: The proposed NeuroSpine Surgery Research Group Classification System for lumbar facet joint cysts is effective in identifying patients most likely to endure a recurrent cyst after decompressive surgery. Patients with grades 4 and 5 cysts should be considered for decompressive surgery with concomitant stabilization of the involved segments on initial presentation.

Contemporary assessment of the correlation between Bosniak classification and histological characteristics of surgically removed atypical renal cysts (UroCCR-12 study).

PURPOSE: To evaluate and compare pathological characteristics of renal cysts Bosniak IIF, III and IV in light of recent histological classification. PATIENTS AND METHODS: The French research network for kidney cancer UroCCR conducted a multicentre study on patients treated surgically for a renal cyst between 2007 and 2016. Independent radiological and centralized pathological reviews were performed for every patient. Pathological characteristics were compared to the Bosniak classification. RESULTS: Of a total 216 patients included, 175 (81.0%) tumours (90.9% of Bosniak IV, 69.8% of Bosniak III) were malignant or had a low malignant potential, with 60% of clear cell renal cell carcinoma (CCRCC), 24% of papillary RCC (PRCC) and 6.9% of multilocular cystic renal tumour of low malignant potential (MCRTLMP). Malignancies were mostly of low pT stage (86.4% of pT1-2), and low ISUP grade (68.0% of 1-2). Bosniak III cysts had a lower rate of CCRCC (46.7 vs. 67.3%), higher rate of PRCC (30 vs. 20.9%) and MCRTLMP (18.3 vs. 0.9%) compared to Bosniak IV (p < 0.001). Low-malignant potential lesions were less likely Bosniak IV and pT3-4 stage was more frequent in Bosniak IV vs. III (15.7 vs. 3.5%; p = 0.04). There were two recurrences (1.1%) and no cancer-related death occurred during follow-up. CONCLUSION: These results confirmed that cystic renal malignancies have excellent prognosis. Bosniak III cysts had a low malignant potential, which suggests surveillance could be an option for these lesions.

Clinical approach to vulvovaginal cysts and abscesses, a review.

Vulvovaginal cysts are a common problem for women, causing significant pain, discomfort and impact on quality of life. For clinicians, classifying and differentiating these cysts from each other and selecting appropriate management can be challenging, yet there is no integrated classification system and little literature that broadly summarises a clinical approach. We aimed to create a useful tool for clinicians by providing a detailed summary of various vulvovaginal cysts and abscesses with a clear novel classification system and hierarchy for diagnosis and management, to aid clinicians in this process.

Iris cysts: A comprehensive review on diagnosis and treatment.

Iris cysts, both primary and secondary, are a diagnostic and treatment challenge. Primary cysts arise either from the iris pigment epithelium or the iris stroma. Posterior pigment epithelial cysts are subdivided according to their location as central, midzonal, and peripheral. Iris stromal cysts are classified either as congenital or acquired. Free-floating cysts are usually dislodged pigment epithelial cysts. Secondary cysts are classified according to the underlying cause as implantation cysts, drug-induced, uveitic, tumor-induced, parasitic, or as cysts associated with systemic disorders. Differential diagnosis is based on the clinical presentation and imaging. Ultrasound biomicroscopy is the gold standard for the imaging of iris cysts, combining excellent resolution with sufficient tissue penetration. Treatment of iris cysts depends largely on whether they become symptomatic or not. Symptoms include obstruction of the visual axis, corneal decompensation, secondary uveitis, and secondary glaucoma. Treatment options cover a range from simple observation to fine-needle aspiration (with or without intracystic injection of absolute alcohol or antimitotic agents), laser (argon, Nd:YAG), or surgical excision. In the past, the prevailing notion was that of a radical surgical intervention in the form of iridectomy or iridocyclectomy. Given the high rate of recurrence, a stepwise conservative approach is currently favored by most clinicians.

Clinicopathological and immunohistochemical analysis of epithelial-lined (true) cysts of the adrenal gland with proposal of a new histogenetic categorization.

Epithelial- lined (true) cysts are rare lesions and until now the only information we had about their histogenesis was based on the analysis of a few cases. We retrospectively reviewed 8 cases of cysts with a true epithelial lining (confirmed immunohistochemically). The pathological findings and immunohistochemical analysis of the epithelial linings allowed for categorization of the cysts into 3 groups. Five cysts had pure mesothelial lining, which was flattened to cuboidal, and demonstrated a positive reaction for mesothelial markers (eg. calretinin, WT1), and a negative reaction for EpCAM, EMA, PAX8 and ER. Two cysts had cuboidal to flattened lining, the cells of which were diffusely or focally positive for mesothelial markers, for some epithelial markers (eg. EpCAM and EMA) and despite a lack of müllerian-type epithelium demonstrated a positive reaction for PAX8 and focally for ER. A cyst derived from adreno-hepatic fusion (AHF)-related intra-adrenal bile ductules was diagnosed in a right adrenal gland which was directly adherent to the liver, microscopically features of AHF were visible with intermingling of adrenal and liver parenchymal cells. The immunoreactivity pattern was similar among the preserved cells of the cyst-lining, the intra-adrenal bile ductules and the normal bile ductules in the adjoining liver parenchyma. On the basis of this case series from a single institution (8 presented now and 1 reported before) we propose a new histogenetic categorization of adrenal epithelial cysts into: 1. pure mesothelial cysts (the most common type), 2. mesothelial cysts with incomplete or complete müllerian metaplasia 3. AHF-related cysts.

Laryngeal Cysts in Adults: Simplifying Classification and Management.

Objective Laryngeal cysts may occur at any mucosa-lined location within the larynx and account for 5% to 10% of nonmalignant laryngeal lesions. A number of proposed classifications for laryngeal cysts exist; however, no previously published classification aims to guide management. This review analyzes contemporary laryngeal cyst management and proposes a framework for the terminology and management of cystic lesions in the larynx. Data Sources PubMed/Medline. Review Methods A primary literature search of the entire Medline database was performed for all titles of publications pertaining to laryngeal cysts and reviewed for relevance. Full manuscripts were reviewed per the relevance of their titles and abstracts, and selection into this review was according to their clinical and scientific relevance. Conclusion Laryngeal cysts have been associated with rapid-onset epiglottitis, dyspnea, stridor, and death; therefore, they should not be considered of little significance. Symptoms are varied and nonspecific. Laryngoscopy is the primary initial diagnostic tool. Cross-sectional imaging may be required, and future use of endolaryngeal ultrasound and optical coherence tomography may revolutionize practice. Where possible, cysts should be completely excised, and there is growing evidence that a transoral approach is superior to transcervical excision for nearly all cysts. Histology provides definitive diagnosis, and oncocytic cysts require close follow-up. Implications for Practice A new classification system is proposed that increases clarity in terminology, with the aim of better preparing surgeons and authors for future advances in the understanding and management of laryngeal cysts.

Algorithm for Bosniak 2F Cyst in Kidney Donation.

BACKGROUND The Bosniak system for radiological classification of renal cysts offers a tool for surgical decision-making in clinical practice. Although 95% of Bosniak 2F cysts remain benign, a consensus on the management of Bosniak 2F cysts in kidney donation has not been developed. CASE REPORT We present a donor with a Bosniak 2F cyst, who successfully donated her kidney after partial resection of the Bosniak 2F cyst. Postoperative pathology examination of the partially resected cystic wall revealed a multilocular cystic renal cell carcinoma. Postoperative pathology examination revealed a multilocular cystic renal cell carcinoma. Resection of the Bosniak 2F cyst provides 2 advantages: the recipient receives a new donor kidney and will be free of dialysis, and the donor will be free of surveillance. CONCLUSIONS We present a practical guideline for kidney donors with Bosniak 2F cysts, balancing the risk of tumor transmission or recurrence with the benefit associated with organ transplantation, without compromising the risk of the donor and recipient. Further evaluation of this algorithm by longer follow-up and more studies is needed to prove its safety.

Do the clinicoradiological outcomes of endoscopic fenestration for intracranial cysts count on age? An institutional experience.

BACKGROUND: The clinicoradiological outcome of endoscopic fenestration of intracranial cysts and predictors of an unfavorable outcome, including age, are under reported in the neurosurgical literature. In this cohort, our experience in the endoscopic fenestration of intracranial cysts is reviewed. MATERIALS AND METHODS: Thirty consecutive patients treated with endoscopic fenestration for intracranial cysts were identified and analyzed. The study population in our series was followed clinically and radiographically. RESULTS: In this series, the overall resolution of clinical symptoms such as headache, seizures, and neurological deficits was 83%, P= 0.0001. The percentage of clinical resolution after endoscopic intervention was significantly higher (85% vs. 76%, P= 0.001) in arachnoid cysts compared to other cyst types. The reduction of arachnoid cyst size was significantly higher in adults with obstructive hydrocephalus compared to the children group (P = 0.037). In addition, requirement of a cystoperitoneal shunt placement (P = 0.0001) and its subsequent revision (P = 0.0001) was significantly lower in adults compared to children. Adults (P = 0.041), presence of an arachnoid cyst (P = 0.026), female gender (P = 0.016), and presence of communicative hydrocephalus (P = 0.015) were significant predictors for improvement in the symptoms of intracranial pressure. Lastly, adults (P = 0.028), presence of arachnoid cyst (P = 0.046), and presence of communicative hydrocephalus (P = 0.012) were significant positive predictors for shunt revision. CONCLUSIONS: This study revealed that endoscopic fenestration is an effective neurosurgical procedure for the management of intracranial cysts both in adults and children. Moreover, endoscopic fenestration is more beneficial in adults and patients with an arachnoid cyst compared to that in children and other cyst types, respectively.

A New Classification for Pathologies of Spinal Meninges, Part 1: Dural Cysts, Dissections, and Ectasias.

BACKGROUND: The clinical significance of pathologies of the spinal dura is often unclear and their management controversial. OBJECTIVE: To classify spinal dural pathologies analogous to vascular aneurysms, present their symptoms and surgical results. METHODS: Among 1519 patients with spinal space-occupying lesions, 66 patients demonstrated dural pathologies. Neuroradiological and surgical features were reviewed and clinical data analyzed. RESULTS: Saccular dural diverticula (type I, n = 28) caused by defects of both dural layers, dissections between dural layers (type II, n = 29) due to defects of the inner layer, and dural ectasias (type III, n = 9) related to structural changes of the dura were distinguished. For all types, symptoms consisted of local pain followed by signs of radiculopathy or myelopathy, while one patient with dural ectasia presented a low-pressure syndrome and 10 patients with dural dissections additional spinal cord herniation. Type I and type II pathologies required occlusion of their dural defects via extradural (type I) or intradural (type II) approaches. For type III pathologies of the dural sac no surgery was recommended. Favorable results were obtained in all 14 patients with type I and 13 of 15 patients with type II pathologies undergoing surgery. CONCLUSION: The majority of dural pathologies involving root sleeves remain asymptomatic, while those of the dural sac commonly lead to pain and neurological symptoms. Type I and type II pathologies were treated with good long-term results occluding their dural defects, while ectasias of the dural sac (type III) were managed conservatively.