Composite haemangioendothelioma with neuroendocrine marker differentiation presenting as a pink-brown nodule.

We report a case of a 55-year-old female with an asymptomatic pink-brown nodule. Histological examination demonstrated a composite haemangioendothelioma with positive synaptophysin staining.

Effective low-dose sirolimus regimen for kaposiform haemangioendothelioma with Kasabach-Merritt phenomenon in young infants.

AIMS: Management of kaposiform haemangioendotheliomas (KHE) with Kasabach-Merritt phenomenon is challenging in young infants who are subjected to developmental pharmacokinetic changes. Sirolimus, sometimes combined with corticosteroids, can be used as an effective treatment of KHE. Simultaneously, toxicities such as interstitial pneumonitis related to the use of sirolimus may be fatal. As infants have a very low CYP3-enzyme expression at birth, which rises during ageing, we hypothesize that a reduced metabolization of sirolimus might lead to high sirolimus serum levels and low dose may be sufficient without the side effects. METHODS: A case series of 5 infants with kaposiform haemangioendothelioma with Kasabach-Merritt phenomenon was analysed retrospectively. All infants were treated with sirolimus 0.2 mg/m2 every 24 or 48 hours according to their age. Prednisone was added to the therapy for additional effect in 4 patients. RESULTS: In all patients, low dose of sirolimus led to therapeutic sirolimus levels (4-6 ng/mL). All infants (aged 4 days-7 months) had a complete haematological response, without serious adverse events. In all patients, the Kasabach-Merritt phenomenon resolved, the coagulation profile normalized and tumour size reduction was seen. CONCLUSION: Low-dose sirolimus treatment is safe for infants with kaposiform haemangioendothelioma and Kasabach-Merritt phenomenon. It is essential to realize that during the first months of life, metabolism is still developing and enzymes necessary to metabolise drugs like sirolimus still have to mature. To avoid toxic levels, the sirolimus dosage should be based on age and the associated pharmacological developments.

The use of rapamycin to treat vascular tumours and malformations: A single-centre experience.

OBJECTIVES: To assess the safety and efficacy of rapamycin in treating children with vascular tumours and malformations. STUDY DESIGN: We performed a retrospective review at a large tertiary care paediatric centre to assess the efficacy and safety of using rapamycin to treat vascular tumours and malformations. Response to therapy was defined by patient-reported symptom improvement, radiological reduction in size of lesions, and/or improvement of laboratory parameters. RESULTS: Forty-two patients (7 with vascular tumours and 35 with vascular malformations) have been treated with rapamycin. Despite 33 of 42 patients being diagnosed in the first year of life, the median age of initiating rapamycin was 11 years. Of the 38 children treated for a minimum of 4 months, 29 (76%) exhibited a clinical response. Twenty-one patients had follow-up imaging studies and of these, 16 (76%) had radiographic decrease in lesion size. Median time to demonstration of response was 49 days. All five children with vascular tumours and all three children with vascular malformations under the age of 4 years showed a clinical response. Response rate was lower for children ≥ 4 years of age (0/2, 0% for vascular tumours; 21/28, 75% for vascular malformations). No patient experienced an infection directly related to rapamycin or discontinued rapamycin due to toxicity. CONCLUSIONS: Rapamycin is safe and efficacious in most children with select vascular tumours and malformations. Young children appear to respond better, suggesting that early initiation of rapamycin should be considered.

TFE3 rearranged epithelioid hemangioendothelioma of bone: A clinicopathological, immunohistochemical and molecular study of two cases.

Epithelioid hemangioendothelioma (EHE) is a rare malignant angiocentric vascular neoplasm. Around 90% of classic EHE has a t(1;3)(p36;q25) that results in a WWTR1-CAMTA1 fusion gene, a histologically distinctive subset of EHE has been recently shown to have a t(10;14)(p13;q42)that results in a different fusion gene, YAP1-TFE3. Twenty-one cases of TFE3 Rearranged Epithelioid Hemangioendothelioma have been reported in the literature, and only two cases occurred in bone. In the report, we report additional two cases occurred in the femur and skull and review the related literature.

An integrated multidisciplinary team approach to the management of vascular anomalies: challenges and benefits.

BACKGROUND: Vascular anomalies comprise highly variable pathophysiology and commonly pose diagnostic and management dilemmas. Consequently, patients often benefit from input from multiple specialists. This study describes the inception of a multidisciplinary team (MDT) Vascular Anomaly Clinic (VAC) in a tertiary paediatric centre, and the subsequent experience managing this complex patient group. METHODS: This was a retrospective study of paediatric patients (< 18 years old) attending an MDT VAC from its inception in October 2012 until November 2019. Patient demographics, presentation, diagnosis and management were reviewed. RESULTS: One hundred and thirty-three paediatric patients were seen over 7 years with a median age of 9.8 years. Vascular malformations were the most common diagnosis (88%), with venous malformations predominating (27%). The most common symptoms were pain (46%) and swelling (34%). Patients often required ≥ 2 investigations, with Doppler ultrasound (86%) and magnetic-resonance imaging (61%) being most common. Management included surgery (27%), sclerotherapy (26%), compression garments (23%), analgesia (12%), laser (15%), embolisation (5%) and sirolimus (3%). CONCLUSIONS: The complex nature of vascular anomalies and high proportion of patients requiring multi-specialty management justified the establishment of an MDT VAC in our centre. Our experience demonstrates the success of an efficient one-stop MDT environment in the management of these challenging conditions. LEVEL OF EVIDENCE: IV.

Up-to-date imaging review of paediatric soft tissue vascular masses, focusing on sonography.

The purpose of this article is to provide an up-to-date overview on imaging of paediatric vascular soft tissue masses, including both neoplastic and non-neoplastic lesions. We describe the-often challenging-imaging diagnosis-mainly performed by ultrasound (and secondarily by MRI) and differential diagnosis of vascular soft tissue lesions in children. We underline how important it is to determine whether a vascular anomaly has a regional vascular origin, or if there are other entities, ranging from benign to malignant lesions, which have flow-signal or blood degradation products. Even though clinical examination and patient's history are the first and indispensable steps in the initial diagnosis, the role of imaging is crucial, not only to determine whether a mass represents a true tumour/pseudo-tumour, but also to achieve a more correct diagnosis and determine the extension of the tumour/pseudo-tumour and its relation with the nearby anatomic structures.

Clinical and Pathologic Features of Primary Angiosarcoma of the Kidney.

PURPOSE OF REVIEW: Primary angiosarcoma of the kidney is extremely rare; hence, relatively little is known regarding its clinicopathologic features and prognosis. Herein, we review the literature on primary renal angiosarcoma with emphasis on the clinical and pathologic features. RECENT FINDINGS: Approximately 64 cases have been reported in the literature, and most cases occur in the 6th-7th decade with a strong male predominance. The aetiology is unknown. Patients present with flank pain, haematuria, abdominal mass and weight loss. A considerable number of patients develop metastatic disease at diagnosis or shortly afterwards. Grossly, the tumour comprises ill-defined haemorrhagic spongy masses often with necrosis. Microscopically, the tumour is composed of anastomosing capillary-sized vessels which are lined by malignant endothelial cells. The mainstay of treatment is surgery followed by radiation therapy with or without chemotherapy. Renal angiosarcomas are highly aggressive tumours with dismal outcome, and they must be distinguished from morphologically similar lesions of the kidney.

Dermoscopy of arteriovenous tumour: A morphological study of 39 cases.

BACKGROUND/OBJECTIVES: Arteriovenous tumour is a distinct, benign, acquired vascular lesion that can be misdiagnosed. METHODS: A dermoscopic examination of 39 cases of arteriovenous tumours collected from four Spanish hospitals was performed to evaluate specific dermoscopic criteria and patterns. RESULTS: The most common structures found were vascular, 95% of cases (37/39); 90% (35/39) were non-arborising telangiectasia. All the lesions except two (95%) had a homogeneous pigmentation background that was red in 30 cases (77%), bluish-red in three (8%), brown in two (5%) and blue or multicoloured in one case each. Lacunae were seen in only three cases (8%). Non-arborising telangiectasia on a reddish background was identified in 72% of cases. CONCLUSIONS: Dermoscopy is helpful in improving the diagnosis of arteriovenous tumours and allows the observer to differentiate them from other cutaneous lesions such as other vascular tumours, basal cell carcinomas and melanomas.

Dermoscopy of lymphangioma circumscriptum: A morphological study of 45 cases.

BACKGROUND/OBJECTIVES: The dermoscopy of lymphangioma circumscriptum, also known as superficial lymphatic malformation, remains to be clarified. METHODS: Digital dermoscopic images of 45 histopathologically confirmed cases of lymphangioma circumscriptum collected from nine hospitals in Spain, Italy and Turkey were evaluated for the presence of dermoscopic structures and patterns. RESULTS: Our study shows that the most common structure found in lymphangioma circumscriptum was the presence of lacunae (89% of cases). The latter were red or dark-coloured in 18 cases (45%), yellowish or whitish in 14 cases (35%) and multicoloured in eight cases (20%). The second most common dermoscopic structure was the presence of vascular structures, which were found in 82% of cases, followed by white lines (47%), the hypopyon sign or two-tone lacunae (42%) and scales (7%). CONCLUSIONS: Dermoscopy is useful in improving the diagnosis of lymphangioma circumscriptum with characteristic structures and patterns and could assist in elucidating the presence of blood in lymphatic channels.

Giant cranionasal epithelioid haemangioendothelioma with invasive growth pattern mimicking a skull base chondrosarcoma.

Epithelioid haemangioendothelioma (EHE) is a rare low-grade vascular neoplasm that is composed of mostly epithelioid cells. EHE may arise as a solitary tumour or in the form of multiple body lesions, and commonly occurs in soft tissues, liver, pleura, lung, peritoneum, lymph nodes, breast, and many other sites. EHE in the cranionasal region is extremely rare. There are very few reports of cases of skull-base EHE. We discuss an extremely rare presentation of an aggressive EHE that originated from the sellar region. Based on literature review, our patient is the first reported case of a giant solitary EHE with prepontine cistern invasion and abducens nerve encroachment mimicking a chondrosarcoma. We treated this rare tumour by near subtotal surgical excision with subsequent radiotherapy, considering that complete tumour resection with free margins in both cavernous sinus and clival region avoiding neural and vascular structure encroachment becomes technically difficult.

Phosphoinositide 3-kinase: a new kid on the block in vascular anomalies.

Vascular anomalies are broadly divided into vascular tumours and malformations. These lesions are composed of abnormal vascular elements of various types, and mainly affect infants, children, and young adults. Vascular anomalies may be painful, may be complicated by bleeding, infection, or organ dysfunction, and can have secondary effects on other tissues. Current treatment strategies include surgical excision, pulsed laser, and sclerotherapy, which are invasive, with risks of recurrence. There are growing pharmacological options for these vascular anomalies, but, to date, no specific targeted therapies have been developed. Phosphoinositide 3-kinases (PI3Ks) constitute a family of lipid kinases that are involved in signal transduction and vesicular traffic, and that modulate important cellular processes such as proliferation, growth, and migration. Recent findings have indicated that the PI3K signalling pathway is important in the pathogenesis of vascular anomalies. This provides an opportunity to use PI3K inhibitors, which are in clinical trials for cancer treatment, for such lesions. Here, we provide an update on the classification of vascular anomalies, with their major features, and discuss the role of the PI3K signalling pathway in the pathogenesis of vascular anomalies, and their clinical implications and therapeutic opportunities. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Risk factors and morbidity of infantile haemangioma: preterm birth promotes ulceration.

AIM: We identified the characteristics of an infantile haemangioma (IH) that predispose children to complications, interventions and long-term morbidity and examined perinatal risk factors for IH. METHODS: We studied children with IHs admitted to Helsinki University Hospital's paediatric vascular anomaly clinic in Finland in 2004-2007 and registered perinatal records, IH characteristics, complications and interventions. These patients received a questionnaire on perinatal data and long-term morbidity resulting from IH. We analysed factors related to complications, interventions and morbidity and compared our cohort's perinatal data to the Finnish Medical Birth Register (FMBR) figures. RESULTS: We approached 185 families, of which 136 replied to the questionnaire. Children with facial, segmental and indeterminate IHs showed more complications, interventions and higher long-term morbidity. Preterm birth predisposed infants to ulceration of IHs, with a 95% confidence interval (CI) of 1.02-5.14 and odds ratio (OR) of 2.29. In addition to earlier known risks, maternal gestational diabetes mellitus rate was higher in our IH cohort than the rate in the FMBR (95% CI 1.39-4.95, OR 2.62). CONCLUSION: Physicians treating IHs should consider the elevated ulceration risk in preterm infants. The association between gestational diabetes mellitus and child's risk for an IH is uncertain and requires further research.

Infantile cardiac vascular tumour: from prenatal diagnosis to postnatal treatment.

Primary vascular tumour of the heart is rare, especially in neonates and infants. We report a male premature newborn with a right atrial tumour associated with a large amount of pericardial effusion detected by screening foetal echography. Diagnosis of capillary haemangioma was confirmed by histopathological examination after complete surgical resection. Other vascular tumours in the neonates and infants reported in the English literatures are reviewed, and one algorithm for both prenatal and postnatal management is proposed.

Radiation-induced angiosarcoma of the breast: A case report.

INTRODUCTION AND IMPORTANCE: Today, breast-conserving surgery (BCS) and adjuvant radiotherapy are preferred treatments for patients with early invasive breast cancer. Radiation-induced angiosarcoma (RIAS) of the breast is a rare but serious complication of radiotherapy. CASE PRESENTATION: Seventy-one-year-old woman is presented to our department with a locally advanced dark red polypoid lesion on her left breast. She had left BCS, axillary dissection, and adjuvant radiotherapy for invasive breast cancer 8 years before presentation. A small tissue sample from the breast lesions was sent for histopathologic examination that the diagnosis was angiosarcoma of the breast. She had neoadjuvant chemotherapy. Following the completion of chemotherapy, a total mastectomy was performed as surgical treatment. The final histopathologic diagnosis was well-differentiated angiosarcoma. CLINICAL DISCUSSION: RIAS of the breast is rare disease that develops after a several-year latency period. Locally advanced disease was initially treated with neoadjuvant chemotherapy which appears to be effective for significant disease regression. Patients who respond well to chemotherapy in vivo may have higher disease-specific survival rates. After chemotherapy-induced regression of locally advanced sarcoma, total mastectomy was performed for radical treatment. CONCLUSION: RIAS of the breast is defined as the histological diagnosis of angiosarcoma in an irradiated region after a long latency period in a patient who has previously received radiotherapy for breast carcinoma. Based on clinical and nuclear imaging data, we may conclude that neoadjuvant chemotherapy can result in significant disease regression, and following neoadjuvant chemotherapy the treatment of angiosarcoma is completed by radical breast surgery.

A Young Female with a Hepatic Epithelioid Hemangioendothelioma.

Background: Primary hepatic epithelioid hemangioendothelioma (HEHE) is an extremely rare tumour of vascular origin with an incidence of <0.1 cases per 100,000 people worldwide. Case description: A 29-year-old female with the history of epigastric pain and unintentional weight loss (3 kg over six months) was referred for upper endoscopy. The examination was without visual pathological findings, but a rapid urease test was positive. First-line treatment with clarithromycin-containing triple therapy for Helicobacter pylori infection was given. After completion of eradication therapy, diffuse abdominal pain developed. An abdominal computed tomography (CT) showed multiple liver nodules. Three consecutive core liver biopsies were performed and were inconclusive. A subsequent surgical liver nodule resection was performed. Histopathology of the specimen revealed grade 2 hepatocellular carcinoma; bone scintigraphy was negative for metastasis. A multidisciplinary team (MDT) recommended giving the patient sorafenib, which was poorly tolerated. The histology was reviewed using immunohistochemistry staining at the request of the oncologist, which showed expression of CD31 and CD34. Based on clinical, morphological and immunohistochemistry findings, a diagnosis of hepatic epithelioid hemangioendothelioma was made. Based on the multidisciplinary team's findings, liver transplantation was indicated as the only curative treatment. Conclusion: Because of the rarity of this disease, combining clinical, radiological and histopathological methods as well as an MDT approach can help to reach the correct final diagnosis. As demonstrated in this clinical case, it is crucial to perform immunohistochemistry of a liver biopsy to confirm a HEHE diagnosis. LEARNING POINTS: Hepatic epithelioid hemangioendothelioma is a rare vascular tumour that is often misdiagnosed and mismanaged.This case emphasises the critical importance of interdisciplinary teamwork and the use of non-invasive and invasive techniques to achieve a definitive diagnosis.

Epithelioid Hemangioma Masquerading as a Clavicular Mass: A Diagnostic Conundrum.

Epithelioid hemangioma (EH), a rare benign tumor, is documented in only a few cases in the medical literature. The complications of epithelioid hemangioma depend on the site of their presentation. If located in the eye, epithelioid hemangiomas may lead to amblyopia; in the larynx, they can cause respiratory issues; and if affecting bone, they can result in osteolytic lesions. Here, we present a case of a 40-year-old male who presented with swelling in the medial end of the right clavicle. Following clinical evaluation and a computed tomography scan, an excision biopsy was performed. The excised lesion measured 3 x 2.5 cm, and histopathological examination confirmed the finding as an epithelioid hemangioma.

Vascular anomalies and wounds.

Vascular anomalies comprise vascular tumours and vascular malformations. Some vascular anomalies result in ulcerations and necrosis. In vascular tumours, infantile haemangiomas are predominant and ulceration is demonstrated in up to 16%. In vascular malformations, arteriovenous malformations predominate and frequently demonstrate either primary ulceration or skin necrosis after diagnostic and therapeutic procedures. Various diagnostic and therapeutic imaging methods, such as X-ray, computed tomography (CT), magnetic resonance imaging (MRI), duplex Doppler ultrasound, and angiography, are used to visualize vascular anomalies; angiograms are required when embolization is attempted and blood flow needs to be further investigated. Duplex Doppler ultrasound is useful for routine check-ups as a therapeutic tool; however, it has limited in precision and accuracy. The aim of the present review is to give an overview of wounds related to vascular anomalies, detailing the diagnostic imaging and treatment options.

Vascular tumors of the liver: A brief review.

Vascular tumors of the liver are mesenchymal lesions from endothelial cells. They range from common benign lesions such as haemangioma, intermediate tumors like Kaposi sarcoma, and perivascular epithelioid cell tumor to malignant tumors such as hepatic epithelioid hemangioendothelioma and hepatic angiosarcoma in adults. Pediatric vascular tumors of the liver also include benign, locally aggressive, borderline, and malignant masses with haemangiomas being the most common benign tumors and epithelioid hemangioendothelioma being an uncommon pediatric malignancy. The list of these lesions is completed by nodular regenerative hyperplasia, solitary fibrous tumour, and hepatic small vessel neoplasms (HSVN). Some of these tumors are uncommon and rare. This review article aimed to enumerate hepatic vascular tumors along with their imaging, histopathology, molecular findings for accurate diagnosis that can result in better management.

Equine conjunctival haemangiosarcoma: Clinical presentation, management, and outcome of seven cases in the United Kingdom.

Background: Only 27 cases of equine conjunctival haemangiosarcoma have been reported in the literature over the past 37 years. Out of these, 22% of cases were lost to follow-up, 52% were euthanized, and 26% survived. A scarcity of cases and information is available for this rarely seen conjunctival tumour. Aim: To describe the clinical features, management, and outcome of conjunctival hemangiosarcoma in seven horses in the UK. Methods: Optivet medical records were reviewed for equine cases seen or advised on with a histopathological diagnosis of conjunctival haemangiosarcoma between January 2013 and March 2023. Medical records were accessed for details of signalment, history, management, and follow-up. Histopathology was used to confirm the diagnosis of haemangiosarcoma and assess the surgical margins. Immunohistochemistry was performed in a minority of cases with poorly differentiated solid tumours to support vascular lineage. Results: Seven eyes from seven horses (five geldings and two mares) with a mean age of 16 years and median of 18 years (range 10-21 years) met the criteria. Serosanguinous discharge was seen in six eyes. All eyes were managed surgically; 4 by exenteration and 3 by conjunctivectomy/keratectomy. Adjunctive cryotherapy was performed in two eyes. Metastatic disease in the ipsilateral parotid salivary gland, confirmed with histopathology, was seen in one horse. Surgical margins were clear in all but one eye. Solar elastosis was noted in five eyes. All horses were healthy at the last follow-up (0.2-5 years, mean 2.9 years, and median 2 years). Conclusion: Equine conjunctival haemangiosarcoma is rare. Serosanguinous ocular discharge is a common clinical sign. Early surgical excision is highly effective. Solar elastosis is a common histopathological feature, suggesting a role for UV-light in the pathogenesis.