Single-cell RNA sequencing reveals cellular and molecular landscape of fetal cystic hygroma.

BACKGROUND: The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. METHODS: Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. RESULTS: The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. CONCLUSION: Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.

Lethal multiple pterygium syndrome, large cystic hygroma, and cleft palate: Rare and severe fetal presentations of RYR1- and NEB-related congenital myopathies.

Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present broadly. The most severe presentation is neonatal with arthrogryposis and, rarely, fetal akinesia and pterygia, features also seen in lethal multiple pterygium syndrome (LMPS). We describe two fetuses with similar phenotype, including hydrops fetalis, large cystic hygromas, bilateral talipes, and fetal akinesia in the second trimester. Genetic diagnoses were made using exome sequencing. Both fetuses had a severe form of congenital myopathy. In the first fetus, we identified two novel compound heterozygous likely pathogenic variants consistent with autosomal recessive RYR1-related congenital myopathy (congenital myopathy 1B). In the second fetus, we identified two likely pathogenic variants, one of which is novel, likely in trans consistent with a diagnosis of autosomal recessive NEB-related congenital myopathy. Reaching a genetic diagnosis for these fetuses allowed the families to receive accurate genetic counseling for future pregnancies. These fetuses highlight the genetic and phenotypic heterogeneity of LMPS, and support a broad approach to genetic testing.

Severe skeletal dysplasia caused by a novel FLNB gene mutation.

A late adolescent primigravida was found to have a fetus with a cystic hygroma and significant shortening of the limbs on first-trimester ultrasound. She underwent chorionic villus sampling with normal microarray result. In the early second trimester, the fetus was found to have the absence of all four limbs and a thorough skeletal dysplasia workup was pursued, identifying a variant in the FLNB gene (c.62C>G). The patient underwent termination of pregnancy. The care of this patient was expedited by first-trimester sonographic evidence of limb abnormalities enabling timely clinical management.

Early prenatal diagnosis of causative homozygous variants in ASCC1 in a fetus with cystic hygroma and additional homozygous variants of unknown significance associated with a neurological phenotype not visible in early gestation: Dual diagnosis or not?

A consanguineous couple was referred at 10 weeks of gestation (WG) for prenatal genetic investigations due to isolated cystic hygroma. Prenatal trio exome sequencing identified causative homozygous truncating variants in ASCC1 previously implicated in spinal muscular atrophy with congenital bone fractures. Prenatal manifestations in ASCC1 can usually include hydramnios, fetal hypo-/akinesia, arthrogryposis, contractures and limb deformities, hydrops fetalis and cystic hygroma. An additional truncating variant was identified in CSPP1 associated with Joubert syndrome. Presentations in CSPP1 include cerebellar and brainstem malformations with vermis hypoplasia and molar tooth sign, difficult to visualize in early gestation. A second pregnancy was marked by the recurrence of isolated increased nuchal translucency at 10 + 2 WG. Sanger prenatal diagnosis targeted on ASCC1 and CSPP1 variants showed the presence of the homozygous familial ASCC1 variant. In this case, prenatal exome sequencing analysis is subject to a partial ASCC1 phenotype and an undetectable CSPP1 phenotype at 10 weeks of gestation. As CSPP1 contribution is unclear or speculative to a potentially later in pregnancy or postnatal phenotype, it is mentioned as a variant of uncertain significance. The detection of pathogenic or likely pathogenic variants involved in severe disorders but without phenotype-genotype correlation because the pregnancy is in the early stages or due to prenatally undetectable phenotypes, will encourage the clinical community to define future practices in molecular prenatal reporting.

Malformación linfática quística gigante del hígado: dos casos pediátricos con diferente abordaje quirúrgico / Giant cystic lymphatic malformation of the liver: two pediatric cases with different surgical approach

Introducción. Las malformaciones linfáticas quísticas, también llamadas linfangiomas quísticos, aparecen muy raramente de forma aislada en el hígado. Casos clínicos. Se presentan dos pacientes femeninas de edad preescolar con marcada hepatomegalia, dependiente de lesiones quísticas multitabicadas, secundarias a malformación linfática quística gigante del hígado, que fueron tratadas en el Hospital Pediátrico Universitario William Soler, La Habana, Cuba. Resultados. En ambos casos el diagnóstico se apoyó en los estudios de imágenes, la laparoscopia y el análisis histopatológico. En un caso el tratamiento fue la hepatectomía derecha, mientras que en el otro se empleó la escleroterapia, ambas con evolución favorable. Conclusión. A pesar de su rareza, este diagnóstico no debe obviarse ante un paciente pediátrico con lesiones hepáticas quísticas. El tratamiento de elección es la resección quirúrgica, pero su indicación y envergadura debe valorarse de forma individualizada

Introduction. Cystic lymphatic malformations, also called cystic lymphangiomas, are very rarely found in the liver. Clinical cases. Two pediatric female preschool-age patients. presented with hepatomegaly due to multi-septated cystic lesions of the liver, who received treatment at Hospital Pediátrico Universitario William Soler, La Habana, Cuba. Results. We report two pediatric cases with giant cystic lymphatic malformation of the liver. In both cases, the diagnosis were based on imaging, laparoscopy and pathology. In one case the treatment was right hepatectomy, whereas in the other, sclerotherapy was performed, both with a favorable outcome. Conclusion. Despite its rarity, this diagnosis should be considered in pediatric patients with hepatic cystic lesions. The recommended treatment is surgical resection, but its indication and extent should be assessed individually for each patient.

Postoperative Spinal Subdural Extra-arachnoid Hygroma Because of Trauma: Resolution with Lumbar Puncture: A Case Report.

CASE: A 73-year-old woman, after spinal surgery, presented with symptomatic spinal subdural extra-arachnoid hygroma (SSEH) because of a fall on the third postoperative day. The hygroma was diagnosed by magnetic resonance imaging (MRI). Lumbar puncture was performed under local anesthesia, after which the leg pain disappeared immediately. MRI obtained immediately after puncture and 1 week later confirmed disappearance of the hygroma. CONCLUSION: Although dural transection is mentioned in most of the reports on treatment of symptomatic postoperative SSEH, we were able to treat this entity by epidural puncture. In the absence of paraplegia or cystorectal disturbance, puncture can be an effective and minimally invasive treatment option.

Subdural Hygroma After Management of Ruptured Intracranial Aneurysms: Incidence, Associated Factors, Clinical Course, and Management Options.

OBJECTIVE: To evaluate the incidence, associated factors, clinical course, and management options of subdural hygroma in patients treated for aneurysmal subarachnoid hemorrhage (aSAH). METHODS: From January 2013 until June 2022, 336 consecutive patients with aSAH underwent treatment in our center. No one patient was excluded from the study cohort. Computed tomography (CT) examinations were performed at admission, immediately after surgery and on the first postoperative day, and subsequently in case of any neurologic deterioration or, at least, once per week until discharge from the hospital. Thereafter, CT examinations were at the discretion of specialists in the rehabilitation facility, referring physicians, or neurosurgeons at the outpatient clinic. RESULTS: The length of radiologic follow-up starting from CT at admission ranged from 1 to 3286 days (mean, 673 ± 895 days; median, 150 days). Subdural hygromas developed in 84 patients (25%). An average interval until this imaging finding from the initial CT examination was 25 ± 55 days (median, 8 days; range, 0-362 days). Evaluation in the multivariate model showed that patient age ≥72 years (P < 0.0001), cerebrospinal fluid (CSF) shunting (P < 0.0001), and microsurgical clipping of ruptured intracranial aneurysm (RIA; P < 0.0001) are independently associated with the development of subdural hygroma. In 54 of 84 cases (64%), subdural hygromas required observation only. Increase of the lesion size with (5 cases) or without (10 cases) appearance of midline shift was associated with patient age <72 years (P = 0.0398), decompressive craniotomy (P = 0.0192), and CSF shunting (P = 0.0009), whereas evaluation of these factors in the multivariate model confirmed independent association of only CSF shunting (P = 0.0003). Active management of subdural hygromas included adjustment of the shunt programmable valve opening pressure, cranioplasty, external subdural drainage, or their combination. Overall, during follow-up (mean, 531 ± 824 days; median, 119 days; range, 2-3285 days) after the start of observation or applied treatment, subdural hygromas showed either decrease (50 cases) or stabilization (34 cases) of their sizes, and no one lesion showed progression again. CONCLUSIONS: The clinical course of subdural hygromas in patients treated for aSAH is generally favorable, but occasionally these lesions show progressive enlargement with or without the appearance of midline shift, which requires active management.

[Complicated course of the postoperative period with the development of epidural hygroma and intracranial hypotension after removal of cranio-orbital meningioma. Clinical case and literature review]. / Oslozhnennoe techenie posleoperatsionnogo perioda s razvitiem epidural'noi gigromy i vnutricherepnoi gipotenzii posle udaleniya kranioorbital'noi meningiomy. Klinicheskii primer i obzor literatury.

Surgical removal of cranio-orbital meningiomas is an effective method of treating this pathology. Modern surgical techniques and technologies make it possible to perform operations with a low risk of complications. Lumbar drainage or repeated lumbar punctures are often used intraoperatively or in the early postoperative period to prevent nasal CSF leak; this rarely leads to the development of significant neurological symptoms. We present a case of the development of severe intracranial hypotension with the formation of a subdural hygroma in the early postoperative period after removal of a cranio-orbital meningioma in a 41-year-old patient. The operation was performed using an individual model and molds for simultaneous reconstruction of the bone defect with an implant made of polymethyl methacrylate. On the 1st and 2nd days after surgery, lumbar punctures were performed. From the 2nd day there was a progressive deterioration with the development of symptoms characteristic of intracranial hypotension. Computed tomography revealed an increasing displacement of the midline structures of the brain and an increasing volume of epidural fluid accumulation in the area of surgical intervention. Magnetic resonance imaging revealed characteristic signs of intracranial hypotension. Conservative treatment (bed rest, active hydration) had no effect. On the 6th day after surgery, an epidural blood patch procedure was performed and closed external drainage of the epidural hygroma was performed, and a rapid regression of neurological symptoms was noted. Our experience and literature data indicate that it is necessary to remember the possibility of developing clinically significant intracranial hypotension even after a single lumbar puncture. The formation of hygromas in the surgical area is characteristic of intracranial hypotension, but in most cases does not require additional surgical intervention and does not have a negative impact on the outcome of treatment. Conservative treatment of intracranial hypotension is the first choice and often sufficient. If there is no effect and the patient's condition worsens, it is necessary to perform an epidural blood patch procedure.

Anomalía linfática generalizada en un paciente adulto, un diagnóstico eminentemente radiológico / Generalized lymphatic anomaly in adult patients: an eminently radiological diagnosis

La anomalía linfática generalizada (ALG) es una enfermedad congénita poco frecuente, secundaria a la proliferación de vasos linfáticos en cualquier órgano a excepción del sistema nervioso central, mostrando un amplio abanico de formas de presentación clínicas y radiológicas. Las lesiones osteolíticas son una constante, y las costillas, el hueso más frecuentemente afectado. Se diagnostica principalmente en niños y adultos jóvenes; no obstante, en raras ocasiones la enfermedad puede ser asintomática y detectarse de forma incidental en pacientes de mayor edad. Presentamos un caso inusual de ALG en un paciente de 54 años, asintomático y con presencia de lesiones óseas de distribución atípica en la tomografía computarizada (TC). La naturaleza puramente quística de las lesiones, evidenciada mediante la medición de las unidades Hounsfield, permitió establecer el diagnóstico de sospecha de ALG, que posteriormente se confirmó con resonancia magnética, tomografía por emisión de positrones/TC, punción aspiración con aguja fina guiada por TC y biopsia vertebral percutánea con guía fluoroscópica. Finalmente, se obtuvo el diagnóstico anatomopatológico definitivo tras la resección quirúrgica de una de las lesiones.(AU)

Generalized lymphatic anomaly (GLA) is an uncommon congenital disease secondary to the proliferation of lymphatic vessels in any organ except the central nervous system. GLA has a wide spectrum of clinical and radiological presentations, among which osteolytic lesions are the most widespread, being the ribs the most commonly affected bone. GLA is diagnosed mainly in children and young adults; nevertheless, on rare occasions it can remain asymptomatic and be detected incidentally in older patients. We present an unusual case of GLA in an asymptomatic 54-year-old man who had atypically distributed, purely cystic bone lesions on CT; measuring the Hounsfield (HU) of these lesions enabled us to suspect GLA. This suspicion was confirmed with MRI, PET/CT, CT-guided fine-needle aspiration biopsy, and fluoroscopy-guided percutaneous vertebral biopsy. After surgical resection of one of the lesions, histologic study provided the definitive diagnosis.(AU)

Cystic Lymphangioma of Rectum-A Case Report and Review of Literature.

Colorectal cystic lymphangiomas are rare benign lesions. They are characterized by the presence of either single or multi-cystic spaces lined by endothelium. Though there are multiple case reports of right and transverse colonic lymphangioma; only around 10 cases of lymphangioma of the rectum have been reported. We present a case report of rectal lymphangioma with the relevant literature review.

Retroperitoneal cystic lymphangioma in a cirrhotic patient: A case report and review of the literature.

Retroperitoneal cystic lymphangiomas (RCL) are rare benign tumors of the lymphatic system. They account for less than 1% of all lymphangiomas. Surgical resection is the recommended treatment option; however, obtaining a pre-operative diagnosis is often difficult and, in most cases, the final diagnosis is only possible following histological assessment of the surgical specimen. This report describes a case of RCL in a 58-year-old female cirrhotic patient who presented to our center with dull aching abdominal pain and distension. To our knowledge, this is the first case of a RCL in a cirrhotic patient reported in the literature.

Novel approach for the treatment of canine elbow hygroma with extracorporeal shockwaves.

A hygroma is a fluid filled cavity, which appears due to repetitive traumata over bony prominences. For canine elbow hygroma there is no satisfactory treatment option available. Small hygromas should not be treated at all. Larger hygromas that restrict the dog in daily life, are infected, painful, or ulcerated should be treated surgically with drainage or total excision. Surgical treatment of hygromas results in long rehabilitation times and is associated with a high complication rate. Extracorporeal shockwave therapy (ESWT) is widely used in human and veterinary rehabilitation medicine since several years. Even the mechanisms of action are not fully understood it has a wide range of indications. ESWT provides anti-inflammatory effects, promotes microcirculation, and is used for pain relief. In this case series of 4 consecutive cases in 3 dogs we treated hygromas with extracorporeal shockwaves each for 3 to 6 times usually on a weekly basis. All hygromas regressed completely and no complications were noted. Overall ESWT seems to provide a safe, easy-to-use, as well as cost-effective alternative treatment option for canine elbow hygroma.

Peri-Hilar Cystic Lymphangioma Mimicking a Biliary Cystic Lesion Causing Biliary Obstruction: A Case Report and Literature Review.

BACKGROUND Lymphangiomas are rare and benign malformations of the lymphatic system. The presentation of intra-abdominal lymphangiomas, especially from within the hepatoduodenal ligament, is rare in the adult population. In this report, we examine a lymphangioma within the hepatoduodenal ligament resulting in biliary obstruction. CASE REPORT A 62-year-old man with surgical history of cholecystectomy presented to the hepatobiliary clinic for a peri-hilar cystic lesion identified on surveillance magnetic resonance imaging (MRI). The patient's MRI revealed a 5.5-cm cystic lesion at the peri-hilar region, likely arising from the biliary tree, which had been increasing in size and causing biliary dilatation. The patient underwent an endoscopic ultrasound, showing a 4.3×2.2 cm cystic structure likley arising from the cystic duct stump with internal septation. An endoscopic retrograde cholangiopancreatography (ERCP) was performed and demonstrated no communication between the biliary tree and the cystic lesion. Given the uncertain etiology of the lesion and its obstructive nature, the patient was moved to the operating room for a complete excision. A well-encapsulated cystic lesion was identified between the cystic duct and the common hepatic duct, which did not communicate with the biliary tree. Pathology confirmed the diagnosis of lymphangioma with features of vascular channel proliferation in the background of fibrotic stroma and lymphoid aggregates. The vascular channel proliferation demonstrated positive immunohistochemical staining for D2-40. At 3-year follow-up, there was no evidence of post-resection recurrence. CONCLUSIONS This case represents an acquired lymphangioma occurring as a sequela of cholecystectomy, likely caused by interruption of the lymphatic drainage system secondary to surgical manipulation.

First-trimester septated cystic hygroma, marked non-immune fetal hydrops, 45,X and coarctation of the aorta with neonatal survival.

Marked first-trimester nonimmue hydrops fetalis and 45,X with neonatal survival.