CD26 Is Differentially Expressed throughout the Life Cycle of Infantile Hemangiomas and Characterizes the Proliferative Phase.

Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5-10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4-7 years). The mechanisms underlying this neoplastic disease still remain uncovered. Twenty-seven IH tissue specimens (15 proliferative and 12 involuting) were subjected to hematoxylin and eosin staining and a panel of diagnostic markers by immunohistochemistry. WT1, nestin, CD133, and CD26 were also analyzed. Moreover, CD31pos/CD26pos proliferative hemangioma-derived endothelial cells (Hem-ECs) were freshly isolated, exposed to vildagliptin (a DPP-IV/CD26 inhibitor), and tested for cell survival and proliferation by MTT assay, FACS analysis, and Western blot assay. All IHs displayed positive CD31, GLUT1, WT1, and nestin immunostaining but were negative for D2-40. Increased endothelial cell proliferation in IH samples was documented by ki67 labeling. All endothelia of proliferative IHs were positive for CD26 (100%), while only 10 expressed CD133 (66.6%). Surprisingly, seven involuting IH samples (58.3%) exhibited coexisting proliferative and involuting aspects in the same hemangiomatous lesion. Importantly, proliferative areas were characterized by CD26 immunolabeling, at variance from involuting sites that were always CD26 negative. Finally, in vitro DPP-IV pharmacological inhibition by vildagliptin significantly reduced Hem-ECs proliferation through the modulation of ki67 and induced cell cycle arrest associated with the upregulation of p21 protein expression. Taken together, our findings suggest that CD26 might represent a reliable biomarker to detect proliferative sites and unveil non-regressive IHs after a 12-month life cycle.

Treatment of left tenth rib haemangioma vascularised by a costal artery giving the artery of Adamkiewicz.

Haemangioma of the ribs is considered an extremely rare benign tumour. Here, we present a case of a young male with left tenth rib haemangioma vascularised by a costal artery giving the artery of Adamkiewicz presented as chronic cough. This was successfully treated through preoperative embolisation and surgical resection. A preoperative angiogram was performed to identify the origin of the artery of Adamkiewicz. The final diagnosis was confirmed histopathologically. There were no complications in the postoperative course and no recurrence during 12 months of follow-up.

Malignant transformation of an intraparenchymal hemangioma in the cervical spinal cord of a German shepherd dog.

An 8-year-old female spayed German shepherd dog was presented for evaluation of a 1-week history of right thoracic limb monoparesis. Magnetic resonance imaging (MRI) identified an intraparenchymal, T2 hypointense and T1 isointense, strongly heterogeneously contrast-enhancing mass with moderate internal susceptibility artifact on T2* images at the level of the cranial extent of the C5 vertebral body. Euthanasia was elected after a rapid neurologic decline in the 24 hours after MRI. Necropsy and histopathology identified an intraparenchymal hemangiosarcoma arising from a hemangioma in the cervical spinal cord, with no evidence of neoplastic disease in any other examined organs. The spectrum of vasoproliferative disorders in the central nervous system in veterinary species has been codified recently, but hemangiosarcoma is considered metastatic to the central nervous system. Herein we describe the clinical, imaging, and histologic findings in a dog with a novel primary location of hemangiosarcoma in the cervical spinal cord.

Anastomosing hemangioma of the ovary - a comprehensive review of this rare ovarian entity.

BACKGROUND: Anastomosing hemangioma of the ovary is a rare vascular tumor that predominantly affects middle-aged women. Despite its benign nature, its histological appearance can mimic aggressive vascular lesions, posing diagnostic challenges. This review aims to provide an overview of this uncommon entity. METHODS: The PubMed and Scopus databases were searched for relevant articles published in English. Information on all retrieved cases was extracted and reviewed in detail. RESULTS: We found 33 cases with relevant details of anastomosing heamangioma of the ovary. Despite the small number of cases we found, our study demonstrated the importance of an accurate hystopathological evaluation. CONCLUSIONS: Although the preliminary imaging and initial microscopic features may appear alarming, careful microscopic examination reveals benign behavior. There is a need to raise awareness of this unusual and rare entity to improve morphologic recognition and avoid misdiagnosis that could lead to unnecessary treatment or patient anxiety.

IL13RA2 promotes progression of infantile haemangioma by activating glycolysis and the Wnt/ß-catenin signaling pathway.

Background: Interleukin 13 receptor subunit alpha 2 (IL13RA2) plays an essential role in the progression of many cancers. However, the role of IL13RA2 in infantile haemangioma (IH) is still unknown. Materials and Methods: IL13RA2 expression in IH tissues was analyzed using western blot, qRT-PCR, and immunofluorescence. The role of IL13RA2 in haemangioma-derived endothelial cells (HemECs) was determined following knockdown or overexpression of IL13RA2 using CCK-8, colony formation, apoptosis, wound healing, tubule formation, Transwell, and western blot. Results: IL13RA2 expression was upregulated in IH tissues. IL13RA2 overexpression promoted proliferation, migration, and invasion of HemECs and induced glycolysis, which was confirmed with a glycolysis inhibitor. Specifically, IL13RA2 interacted with ß-catenin and activated the Wnt/ß-catenin pathway in HemECs, which were involved in the above-mentioned effects of IL13RA2. Conclusions: These findings revealed that targeting IL13RA2 is a potential therapeutic approach for IH.

Identification of Potential Therapeutics for Infantile Hemangioma via in silico Investigation and in vitro Validation.

Introduction: Infantile Hemangioma (IH) is a prevalent benign vascular tumor affecting approximately 5-10% of infants. Its underlying pathogenesis remains enigmatic, and current therapeutic approaches show limited effectiveness. Our study aimed to discover potential IH-associated therapeutics through a transcriptomic, computational drug repurposing methodology. Methods: Utilizing the IH-specific dataset GSE127487 from the Gene Expression Omnibus, we identified differentially expressed genes (DEGs) and conducted weighted gene coexpression network analysis (WGCNA). Subsequently, a protein-protein interaction (PPI) network was constructed to obtain the top 100 hub genes. Drug candidates were sourced from the Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD). Results: Our analysis revealed 1203 DEGs and a significant module of 1780 mRNAs strongly correlated with IH. These genes were primarily enriched in the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathway. After creating a PPI network of overlapping genes, we filtered out the top 100 hub genes. Ultimately, 44 non-toxic drugs were identified through the CMap and CTD databases. Twelve molecular-targeting agents (belinostat, chir 99021, dasatinib, entinostat, panobinostat, sirolimus, sorafenib, sunitinib, thalidomide, U 0126, vorinostat, and wortmannin) may be potential candidates for IH therapy. Moreover, in vitro experiments demonstrated that entinostat, sorafenib, dasatinib, and sirolimus restricted the proliferation and migration and initiated apoptosis in HemEC cells, thereby underscoring their potential therapeutic value. Conclusion: Our investigation revealed that the pathogenic mechanism underlying IH might be closely associated with the PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling pathways. Furthermore, we identified twelve molecular-targeting agents among the predicted drugs that show promise as therapeutic candidates for IH.

Transcriptomic analysis used to discover potential therapeutics for Infantile Hemangioma (IH). Key IH-related pathways: PI3K/AKT/MTOR, RAS/MAPK, and CGMP/PKG signaling identified. Identified 44 non-toxic drugs as potential IH therapies via CMap and CTD. Twelve molecular agents show potential as IH therapy candidates. In vitro studies confirmed entinostat, sorafenib, dasatinib, and sirolimus inhibit HemEC cell proliferation and induce apoptosis.

[A case of abscessed hepatic hemangioma with Edwardsiella tarda].

A 55-year-old man with a history of pancreatic cancer surgery and was undergoing chemotherapy presented with high fever. A computed tomography scan revealed a liver abscess at the location of a previously identified hemangioma. PTAD was performed, and contrast imaging revealed a connection with the bile duct. Edwardsiella tarda was detected in the abscess culture. Hemangioma-related abscess formation is extremely rare, with no reported cases of E. tarda detection in such abscesses.

[Surgical treatment of littoral cell angioma of the spleen]. / Opyt khirurgicheskogo lecheniya «pribrezhnokletochnoi¼ (littoral cell) angiomy selezenki.

Littoral cell angioma is a very rare benign splenic neoplasm with typical morphological features. It is difficult to differentiate this angioma from other benign or malignant splenic tumors. It is a unique vascular tumor followed by abdominal pain or detected incidentally during examination. Incidence of this tumor is small, as only few appropriate cases were described in the literature. We present successful surgical treatment of littoral cell angioma of the spleen. The issues of clinical course, diagnosis, therapeutic tactics, morphologic and histochemical features are discussed.

[Genetic analysis of a child with Hereditary hemorrhagic telangiectasia type I in conjunct with Splenic sinus shore cell hemangioma].

OBJECTIVE: To explore the genetic basis and pathogenesis for a child with type I Hereditary hemorrhagic telangiectasia (HHTⅠ) and Splenic sinus shore cell hemangioma (LCA). METHODS: A child with HHT complicated with LCA diagnosed at the First Affiliated Hospital of Dali University in April 2022 was selected as the study subject. Clinical data of the child and her relatives were collected, and pathogenic variants were screened by whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient, a 16-year-old female, had recurrent epitaxis since childhood, which sometimes necessitated hemostasis treatment. She also had splenectomy due to splenic rupture and was diagnosed with LCA. Her father and grandmother also had a history of recurrent epitaxis. Her father had deceased due to cerebral vascular rupture. The child was found to harbor a c.360+1G>A variant in the ENG gene. The same variant was not found in her asymptomatic mother and brother. CONCLUSION: The c.360+1G>A variant of the ENG gene probably underlay the pathogenesis in this child.

Maternal history of angioma is associated with infantile hemangioma and port-wine stain in children: a population-based, cohort study of mother-child pairs from the United Kingdom.

The two most prevalent childhood vascular abnormalities are infantile hemangioma (IH) and port-wine stain (PWS). They become apparent shortly after birth but have distinct pathophysiology and clinical manifestations. The goal of this study was to determine if mother's history of angioma or PWS is associated with these vascular abnormalities. We evaluated an UK anonymized electronic medical records database with medical records that were linked between children and their mothers. Cox proportional hazards models were used to evaluate the association between maternal factors and the time of onset of either IH or PWS in children. Between 2004 and 2021, 639,085 children were linked to their mom's medical data with a total of 4,270,773 person-years of follow up. Children born to mothers with an angioma as compared to a mother without an angioma were more than 60% more likely to have an IH (HR: 1.64 [1.07, 2.52]). Children born to mothers with a PWS as compared to children born to mothers without a PWS were nearly 20 times more likely to have a PWS (18.95 [4.71,76.26]). Mothers with angiomas were not more likely to have children with PWS and mothers with PWS were not more likely to have children with IH. The effect estimates were minimally changed after adjustment. We demonstrated that children born to mothers with angiomas or PWS were at increased risk of IH or PWS, respectively.

Focal liver lesion diagnosis with deep learning and multistage CT imaging.

Diagnosing liver lesions is crucial for treatment choices and patient outcomes. This study develops an automatic diagnosis system for liver lesions using multiphase enhanced computed tomography (CT). A total of 4039 patients from six data centers are enrolled to develop Liver Lesion Network (LiLNet). LiLNet identifies focal liver lesions, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), metastatic tumors (MET), focal nodular hyperplasia (FNH), hemangioma (HEM), and cysts (CYST). Validated in four external centers and clinically verified in two hospitals, LiLNet achieves an accuracy (ACC) of 94.7% and an area under the curve (AUC) of 97.2% for benign and malignant tumors. For HCC, ICC, and MET, the ACC is 88.7% with an AUC of 95.6%. For FNH, HEM, and CYST, the ACC is 88.6% with an AUC of 95.9%. LiLNet can aid in clinical diagnosis, especially in regions with a shortage of radiologists.

Oxidized cellulose microneedle patch combined with vascular embolization and local delivery of timolol maleate for hemangiomas.

Hemangiomas are superficial tumors characterized by dense vascular structures that often affect the patient's aesthetic appearance due to the obvious red appearance on the skin. Current treatments, especially timolol maleate in the form of eye drops and hydrogels, suffer from low transdermal drug delivery rates, resulting in prolonged treatment time. To address this challenge, our study introduced a soluble microneedle patch with dextran as the main material to form microcatheters for sustained delivery of timolol maleate. In addition, we proposed a vascular embolization strategy to disrupt the blood supply in hemangiomas. Oxidized cellulose (C-cellulose) was selected for its excellent hemostatic properties. We incorporated C-cellulose into dextran microneedles to facilitate thrombosis in the vascular-rich areas of hemangiomas. The innovative microneedle patch we developed can penetrate the skin to a depth of 430 µm and dissolve rapidly within 3 minutes, ensuring direct drug delivery to the subcutaneous layer. Notably, the treated skin area regained its original appearance within two hours after treatment. In addition to excellent skin permeability and rapid dissolution, these patches significantly promoted apoptosis and inhibited cell migration in mouse hemangioendothelioma EOMA cells. Our results demonstrate that this approach not only achieves significant tumor inhibition in a mouse hemangioma model, but also represents a more effective, convenient, and non-invasive treatment option. Therefore, dextran/C-cellulose/timolol maleate microneedle patch (MNs/Timolol) has broad clinical application prospects in the treatment of hemangiomas, minimizing the risk of additional damage and improving treatment efficacy.

[Sinonasal hemangiomas: principles of diagnosis and treatment. Literature review]. / Sinonazal'nye gemangiomy: printsipy diagnostiki i lecheniya (obzor literatury).

Hemangiomas of the nasal cavity are extremely rare in the practice of an otorhinolaryngologist and can be presented in various histopathological variants. Scientific data on hemangiomas of the sinonasal region are analyzed and systematized. The article describes the principles of diagnosis and choice of the method of surgical treatment of hemangiomas. An analysis of the literature data shows that with hemangiomas of the nasal cavity, a comprehensive examination of the patient is required, including collection of complaints and anamnesis, endoscopy of the nasal cavity and computed tomography of the paranasal sinuses, and with significant hemangiomas spreading to neighboring anatomical areas, magnetic resonance imaging with intravenous contrast.

Case series multilocular cystic hemangioma of the liver: Three cases and literature review.

RATIONALE: Multilocular cystic hemangioma is a rare benign tumor classified as an atypical hemangioma. Currently, there are limited imaging reports available, and the imaging characteristics can be challenging to distinguish from other malignant multilocular cystic liver diseases such as cystadenocarcinoma, necessitating confirmation through pathological diagnosis. Here, we discuss the imaging features of 3 cases of multilocular cystic hemangiomas. PATIENT CONCERNS AND DIAGNOSES: Case 1 was a 24-year-old young female, and Case 2 involved a 60-year-old elderly male. Both patients were asymptomatic and physical examination revealed hepatic space-occupying lesions. Imaging findings revealed multilocular cystic lesions in the left liver with septa, calcification, a high diffusion-weighted magnetic resonance imaging (DWI) signal at the edge of the lesion, and progressive enhancement of the cyst wall and septa. Case 3 involved a 50-year-old male patient with epigastric distending pain for 1 month and sudden severe abdominal pain for 14 hours. Imaging results revealed a multilocular cystic lesion in the left liver with septa and tumor bleeding, a high DWI signal, and an enhanced cyst wall and septa. The pathological diagnosis confirmed a hepatic hemangioma. INTERVENTIONS: All 3 patients underwent liver tumor resection. OUTCOMES: All 3 patients recovered successfully without any intraoperative or postoperative complications during the follow-up periods of 5 years, 6 months, and 5 months. There were no signs of recurrence. LESSONS: Liver imaging revealed multilocular cystic lesions with features, such as compartmentalization, calcification, or bleeding. Multilocular cystic hemangiomas should be considered in imaging diagnosis. Enhancing our understanding of multilocular cystic hemangiomas can aid in improving the differential diagnosis of other malignant multilocular cystic liver diseases, ultimately reducing unnecessary liver resection.

Effectiveness of Robot-assisted Adrenalectomy for a Giant Adrenal Hemangioma: A Case Report.

BACKGROUND: Adrenal hemangiomas are extremely rare benign tumors that often need to be distinguished from malignancies. Adrenal tumors >4 cm in size are treated surgically because the possibility of malignancy cannot be ruled out. Traditionally, open surgery has been the mainstay of treatment; however, in recent years, robot-assisted surgery has been increasingly used for tumors of larger size and suspected malignancy. Here, we report a case of robot-assisted adrenalectomy for an 11 cm adrenal hemangioma. CASE REPORT: A 62-year-old male with lateral abdominal pain was referred to our hospital for further examination and treatment. His medical history was significant for hypertension, diabetes, and dyslipidemia. Computed tomography revealed an 11 cm left adrenal tumor, and all endocrinological screening tests were negative. Because the possibility of malignancy could not be ruled out, a robot-assisted adrenalectomy was performed. The operation time was 129 min, and the estimated blood loss was 7 ml. Pathological findings revealed an adrenal hemangioma. The postoperative course was uneventful, and patient's condition subsequently improved postoperatively. CONCLUSION: Robot-assisted adrenalectomy was performed for a giant adrenal hemangioma without any complications. Robotic surgery is useful for resecting adrenal hemangiomas even exceeding 11 cm in diameter.

MR Imaging of Typical Ovarian Hemangioma: A Case Report.

BACKGROUND: Ovarian hemangioma is an extremely rare tumor with atypical clinical manifestations, often discovered incidentally during autopsy or surgery. Approximately 60 cases have been reported in the past, but no more than 10 cases have been investigated by MRI and ultrasound (US). CASE PRESENTATION: ln this paper, we reported a 51-year-old female patient with Ovarian Hemangioma who had no symptoms of abdominal pain, abnormal vaginal bleeding or discharge, or any other discomfort. Laboratory tests revealed an elevated serum carbohydrate antigen (CA125) of 48.99U/ml (reference range: 0-35U/ml). Multiparametric 3.0T magnetic resonance imaging (MRI) showed a cystic solid mass with a clear boundary and regular shape in the left ovarian area and minimal ascites in the abdominal cavity. The histological examination of the mass confirmed an ovarian hemangioma. CONCLUSION: The MRI findings of ovarian hemangiomas are highly similar to those observed in hepatic hemangiomas, emphasizing the distinctive radiological characteristics specific to this condition in the ovary. This paper presents an overview of the typical MRI findings associated with ovarian hemangioma, which holds great importance for accurate diagnosis and effective treatment.

Large placental chorioangioma with maternal and perinatal morbidity.

INTRODUCTION: Placental chorioangioma is a benign placenta tumour. Majority of cases, the placental chorioangioma are small and no maternal and fetal complications. We highlight a case diagnosed with large placental chorioangioma with an intrapartum event associated with significant maternal and perinatal morbidity. METHOD: A 38-year-old woman, Gravida 3 Para 1, with one previous miscarriage, presented with preterm labour at 33 weeks gestation. Antenatally, she was referred to a feto-maternal specialist for finding a placental tumour size 12 × 10 cm. Features are consistent with placental chorioangioma with polyhydramnios. The anomaly scan was normal. Antenatal fetal surveillance with Doppler studies were normal. RESULTS: During this admission, corticosteroid was given together with a tocolytic agent and opioid analgesia. Unfortunately, the labour progressed, and the patient felt reduced in fetal movement. The cardiotograph showed suspicious tracing. We proceed with emergency caesarean delivery. The placenta was sent for histopathology assessment which confirmed a large placental chorioangioma. The baby was born with Apgar's score of 9 at 1 min, pH of 7.28 and lactate of 7.28 with anaemia and thrombocytopenia. The uterus developed intermittent uterine atony, and the uterotonic agent was given. She recovered well post-delivery. The baby was admitted to the neonatal intensive care unit (NICU) and received a blood product transfusion and discharged from NICU on day 15 of life. DISCUSSION: Large placental chorioangioma is associated with polyhydramnios, preterm labour, postpartum haemorrhage, fetal anaemia, fetal distress, fetal hydrops and possible perinatal death. Multidisciplinary team involvement with feto-maternal specialists, anaesthetic and neonatologists would improve the outcome of both mother and fetus.

In vivo angle dysgenesis in PHACE syndrome with developmental glaucoma.

A girl in middle childhood presented with glaucoma in her right eye along with segmental haemangiomas on the right side of the face and neck. Magnetic resonance angiography of the brain showed hypoplasia of the right internal carotid artery, leading to the diagnosis of posterior fossa malformations, haemangioma, arterial anomalies, cardiac defects and eye abnormalities (PHACE) syndrome. High-definition anterior segment ocular coherence tomography (AS-OCT) of the right eye showed an absence of Schlemm's canal and a hyperreflective membrane over the trabecular meshwork. The presence of this angle dysgenesis on AS-OCT, a novel finding in this disease, explained the elevated intraocular pressure in the right eye. The embryological basis for the development of angle dysgenesis might help better understand the pathogenesis of PHACE syndrome.

Pediatric intramuscular hemangioma in the submandibular triangle and other musculoskeletal presentations: A pediatric case series.

BACKGROUND: Intramuscular hemangiomas (IMH) account for 0.8 % or less of all benign soft tissue tumors in the general population. Due to their uncommon nature, especially in the head and neck, they are often misdiagnosed and not included in the differential diagnosis. METHODS: This study describes a case series of eleven pediatric patients with a diagnosis of IMH through a retrospective review of the electronic health records and archival records in the Department of Pathology at Children's Hospital of Colorado (CHCO). RESULTS: The index case had a unique presentation in the submandibular triangle, while the remaining ten cases are appendicular and thoracolumbar in nature. CONCLUSIONS: This case series contributes to the sparse scientific literature available regarding IMH, particularly in its head and neck presentation as relevant to otolaryngologists.

Insights into the mechanisms of angiogenesis in infantile hemangioma.

Infantile hemangioma (IH) is the most common benign tumor in infants and usually resolves on its own. However, a small portion of IH cases are accompanied by serious complications and other problems, impacting the physical and psychological health of the children affected. The pathogenesis of IH is highly controversial. Studies have shown that abnormal blood vessel formation is an important pathological basis for the development of IH. Compared with that in normal tissues, the equilibrium of blood vessel growth at the tumor site is disrupted, and interactions among other types of cells, such as immune cells, promote the rapid proliferation and migration of vascular tissue cells and the construction of vascular networks. Currently, propranolol is the most common systemic drug used to inhibit the growth of IHs and accelerate their regression. The purpose of this review is to provide the latest research on the mechanisms of angiogenesis in IH. We discuss the possible roles of three major factors, namely, estrogen, hypoxia, and inflammation, in the development of IH. Additionally, we summarize the key roles of tumor cell subpopulations, such as pericytes, in the proliferation and regression of IH considering evidence from the past few years, with an emphasis on the possible mechanisms of propranolol in the treatment of IH. Angiogenesis is an important event during the development of IH, and an in-depth understanding of the molecular mechanisms of angiogenesis will provide new insights into the biology and clinical treatment of IH.