Newcomers in Vascular Anomalies.

Vascular anomalies are composed of tumors and malformations and with overlapping histologies, thus are often misdiagnosed or labeled with imprecise terminology. Lesions are common and usually diagnosed during infancy or childhood; the estimated prevalence is 4.5%. Vascular tumors rapidly enlarge postnatally and demonstrate endothelial proliferation. Malformations are errors in vascular development with stable endothelial turnover; they are typically named based on the primary vessel that is malformed (capillary, arterial, venous, lymphatic). This article reviews the pathologic and molecular genetic characteristics for select recently described vascular anomalies.

Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies.

BACKGROUND: Vascular anomalies are a diagnostic and therapeutic challenge. They require dedicated interdisciplinary management. Optimal patient care relies on integral medical evaluation and a classification system established by experts in the field, to provide a better understanding of these complex vascular entities. METHOD: A dedicated classification system according to the International Society for the Study of Vascular Anomalies (ISSVA) and the German Interdisciplinary Society of Vascular Anomalies (DiGGefA) is presented. The vast spectrum of diagnostic modalities, ranging from ultrasound with color Doppler, conventional X-ray, CT with 4 D imaging and MRI as well as catheter angiography for appropriate assessment is discussed. RESULTS: Congenital vascular anomalies are comprised of vascular tumors, based on endothelial cell proliferation and vascular malformations with underlying mesenchymal and angiogenetic disorder. Vascular tumors tend to regress with patient's age, vascular malformations increase in size and are subdivided into capillary, venous, lymphatic, arterio-venous and combined malformations, depending on their dominant vasculature. According to their appearance, venous malformations are the most common representative of vascular anomalies (70 %), followed by lymphatic malformations (12 %), arterio-venous malformations (8 %), combined malformation syndromes (6 %) and capillary malformations (4 %). CONCLUSION: The aim is to provide an overview of the current classification system and diagnostic characterization of vascular anomalies in order to facilitate interdisciplinary management of vascular anomalies. KEY POINTS: · Vascular anomalies are comprised of vascular tumors and vascular malformations, both considered to be rare diseases.. · Appropriate treatment depends on correct classification and diagnosis of vascular anomalies, which is based on established national and international classification systems, recommendations and guidelines.. · In the classification, diagnosis and treatment of congenital vascular anomalies, radiology plays an integral part in patient management.. CITATION FORMAT: · Sadick M, Müller-Wille R, Wildgruber M et al. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies. Fortschr Röntgenstr 2018; 190: 825 - 835.

Recent advances in the diagnosis of soft tissue tumours.

Soft tissue tumours are relatively rare, but are diagnostically challenging as they comprise a large spectrum of diagnostic entities. Substantial advances have been made in recent years in identifying the underlying recurrent chromosomal and genomic alterations in a significant subset of soft tissue tumours, and this continues to enrich our understanding of the biological mechanisms of tumour development and progression. Ongoing validation and integration of these findings into existing pathological-diagnostic algorithms has led to re- or subclassification of diagnostic categories and will continue to shape a more nuanced (and hopefully clinically relevant) tumour classification system in the future. This review provides a selective overview of recent diagnostic or conceptual advances in the categories of peripheral nerve sheath tumours, vascular and adipocytic tumours, round cell and myogenic sarcomas, and gastrointestinal stromal tumours, as well as their underlying molecular mechanisms, some of which have been translated successfully into useful immunohistochemical stains. A thorough and critical validation of newly identified diagnostic markers-acknowledging the fact that some genetic alterations may not necessarily be tumour-specific-and ongoing correlation with clinical and prognostic implications will be necessary in this regard.

Clinical and sonographic features of pediatric soft-tissue vascular anomalies part 1: classification, sonographic approach and vascular tumors.

Sonography can be used in the management of pediatric soft-tissue vascular anomalies for diagnosing, for assessing lesion extent and for evaluating complications and response to therapy. The sonographic technique includes a combination of gray-scale imaging with color and spectral Doppler techniques. However the interpretation of the sonographic findings requires correlation with the clinical findings, some of which can be easily obtained at the time of scanning. This has to be combined with the use of appropriate nomenclature and the most updated classification in order to categorize these children into the appropriate management pathway. In this article, which is part 1 of a two-part series, the authors review the current classification of vascular anomalies, provide a clinical and a sonographic approach to these lesions, and review the most relevant clinical and sonographic features of vascular tumors including infantile and congenital hemangiomas, tufted angioma, kaposiform hemangioendothelioma, pyogenic granuloma, intramuscular capillary-type hemangioma and angiosarcoma.

Cutaneous intravascular natural killer/T cell lymphoma with peculiar immunophenotype.

Intravascular lymphoma (IVL) is a rare entity. Most cases are a variant of extranodal diffuse large B cell lymphoma, and fewer than 10% of the published cases are of T cell origin. Only intravascular B cell lymphoma is recognized as a distinct entity in the most recent World Health Organization (WHO) classification of lymphoproliferative disorders. We describe a case of cutaneous natural killer (NK)/T IVL, with a cytotoxic immunophenotype and Epstein-Barr virus (EBV) positivity. However, our case was immunohistochemically negative not only for T cell receptor (TCR)-ßF1 and TCR-γ (TCR-silent), but also for CD56, making it the first triple-negative NK/T IVL case to be described. We urge recognition of this NK/T cell lineage intravascular lymphoma due to its particular immunophenotypical profile and its unvarying relationship with EBV. Its occurrence should not be considered a coincidence, but rather a key aspect of the pathogenic background of this haematological neoplasm.

Vascular Tumors of Bone: The Evolvement of a Classification Based on Molecular Developments.

The classification of vascular tumors of bone has been under debate over time. Vascular tumors in bone are rare, display highly overlapping morphology, and, therefore, are considered difficult by pathologists. Compared with their soft tissue counterparts, they are more often multifocal and sometimes behave more aggressively. Over the past decade, with the advent of next-generation sequencing, recurrent molecular alterations have been found in some of the entities. The integration of morphology and molecular changes has led to a better characterization of these separate entities.

Rho kinase proteins display aberrant upregulation in vascular tumors and contribute to vascular tumor growth.

BACKGROUND: The serine/threonine protein kinases ROCK1 and 2 are key RhoA-mediated regulators of cell shape and cytoskeletal dynamics. These proteins perform multiple functions in vascular endothelial cell physiology and are attractive targets for cancer therapy based on their roles as oncogenes and metastatic promoters. Given their critical functions in both of these processes, we hypothesized that molecular targeting of ROCK proteins would be exceedingly effective against vascular tumors such as hemangiomas and angiosarcomas, which are neoplasms composed of aberrant endothelial cells. METHODS: In this study, we compared ROCK1 and 2 protein expression in a large panel of benign and malignant vascular tumors to that of normal vasculature. We then utilized shRNA technology to knockdown the expression of ROCK1 and 2 in SVR tumor-forming vascular cells, and evaluated tumor size and proliferation rate in a xenograft model. Finally, we employed proteomics and metabolomics to assess how knockdown of the ROCK paralogs induced alterations in protein expression/phosphorylation and metabolite concentrations in the xenograft tumors. RESULTS: Our findings revealed that ROCK1 was overexpressed in malignant vascular tumors such as hemangioendotheliomas and angiosarcomas, and ROCK2 was overexpressed in both benign and malignant vascular tumors including hemangiomas, hemangioendotheliomas, hemangiopericytomas, and angiosarcomas. shRNA-mediated knockdown of ROCK2, but not ROCK1, in xenograft vascular tumors significantly reduced tumor size and proliferative index compared to control tumors. Proteomics and metabolomics analysis of the xenograft tumors revealed both overlapping as well as unique roles for the ROCK paralogs in regulating signal transduction and metabolite concentrations. CONCLUSIONS: Collectively, these data indicate that ROCK proteins are overexpressed in diverse vascular tumors and suggest that specific targeting of ROCK2 proteins may show efficacy against malignant vascular tumors.

[Infiltration of Cardiac Vessels by Lung Cancer: Incidence, Classification, Operative Technique with Heart Lung Bypass, and Results]. / Infiltration der herznahen Gefäße durch Lungenkarzinome: Inzidenz, Klassifikationen, operative Technik unter Einsatz der Herz-Lungen-Maschine und Ergebnisse.

Carcinomas of the lung that infiltrate the blood vessels close to the heart (left atrium, pulmonary artery and aorta) without spreading to mediastinal lymph nodes or developing distant metastases are rare overall. Such situations are often classified as primarily inoperable by interdisciplinary tumour boards. This is only the case if, for technical reasons, an experienced thoracic surgeon does not feel able to perform a resection with a surrounding margin of healthy tissue. The surgical strategy to be employed must be chosen individually depending on the infiltrated structure. Complete tumour staging should always be carried out. This also helps in deciding whether neoadjuvant chemotherapy should be given before resection. A heart-lung machine must always be used if larger defects occur due to the resection of blood vessels close to the heart. Using a heart-lung machine in the case of tumour resection does not lead to problems of tumour cell dissemination. Nevertheless, the duration of use of the heart-lung machine should be kept to a minimum, also because of the anticoagulation required. The cardiac defects can be closed securely with the bovine patching materials that are now available. Postoperative morbidity and mortality are low after such resections. Curative resection of blood vessels close to the heart infiltrated by carcinomas of the lung can lead to 5-year survival rates of up to 50 %.

Vascular anomalies: differential diagnosis and mimickers.

Vascular anomalies are very common in children and encompass a wide spectrum of diseases. Many vascular anomalies can be mistaken for infantile hemangioma (IH). In addition, there is a variety of rare disorders including benign and malignant tumors that may mimic IH and other types of vascular anomalies. Understanding the clinical features, natural history, and typical clinical course of different types of vascular anomalies is essential in order to make the correct diagnosis and guide management. Radiologic imaging plays an important role in establishing the diagnosis; and when the diagnosis remains in doubt, a biopsy performed by a surgical specialist with expertise may prove to be lifesaving.

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.

2014 Revised Classification of Vascular Lesions from the International Society for the Study of Vascular Anomalies: Radiologic-Pathologic Update.

Since the publication of the seminal work on the histology-based classification of vascular anomalies by Mulliken and Glowacki in 1982 and the subsequent adoption of an expanded and modified version in 1996 by the International Society for the Study of Vascular Anomalies, an increasing number of vascular lesions have been recognized as histologically distinct entities. Furthermore, there have been significant advances in detailing the behavior and underlying genetics of previously identified lesions. These developments have required restructuring and expansion of the classification scheme so that appropriate therapies may be studied and implemented in affected patients. The new classification retains the broad categories of neoplasms and malformations but now divides the tumor group into benign, locally aggressive or borderline, and malignant, with the malformation group being divided into simple, combined, those of major named vessels, and those associated with other anomalies. Additionally, a category has been created for lesions in which the histology and behavior do not yet allow clear separation into neoplasm or malformation (thus named "provisionally unclassified vascular anomalies"). The known clinical courses and imaging, histologic, and genetic findings of the most common and/or clinically relevant lesions in the newly adopted revised system are reviewed in this article. (©)RSNA, 2016.

Hepatic small vessel neoplasm, a rare infiltrative vascular neoplasm of uncertain malignant potential.

Characteristic but rare vascular neoplasms in the adult liver composed of small vessels with an infiltrative border were collected from an international group of collaborators over a 5-year period (N=17). These tumors were termed hepatic small vessel neoplasm (HSVN), and the histologic differential diagnosis was angiosarcoma (AS). The average age of patients was 54years (range, 24-83years). HSVN was more common in men. The average size was 2.1cm (range, 0.2-5.5cm). Diagnosis was aided by immunohistochemical stains for vascular lineage (CD31, CD34, FLI-1), which were uniformly positive in HSVN. Immunohistochemical stains (p53, c-Myc, GLUT-1, and Ki-67) for possible malignant potential are suggestive of a benign/low-grade tumor. Capture-based next-generation sequencing (using an assay that targets the coding regions of more than 500 cancer genes) identified an activating hotspot GNAQ mutation in 2 of 3 (67%) tested samples, and one of these cases also had a hotspot mutation in PIK3CA. When compared with hepatic AS (n=10) and cavernous hemangioma (n=6), the Ki-67 proliferative index is the most helpful tool in excluding AS, which demonstrated a tumor cell proliferative index greater than 10% in all cases. Strong p53 and diffuse c-Myc staining was also significantly associated with AS but not with HSVN or cavernous hemangioma. There have been no cases with rupture/hemorrhage, disseminated intravascular coagulation, or Kasabach-Merritt syndrome. Thus far, there has been no metastasis or recurrence of HSVN, but complete resection and close clinical follow-up are recommended because the outcome remains unknown.

S.E. Mitchell Vascular Anomalies Flow Chart (SEMVAFC): a visual pathway combining clinical and imaging findings for classification of soft-tissue vascular anomalies.

Classification of vascular anomalies (VAs) is challenging due to overlapping clinical symptoms, confusing terminology in the literature and unfamiliarity with this complex entity. It is important to recognize that VAs include two distinct entities, vascular tumours (VTs) and vascular malformations (VaMs). In this article, we describe SE Mitchell Vascular Anomalies Flow Chart (SEMVAFC), which arises from a multidisciplinary approach that incorporates clinical symptoms, physical examination and magnetic resonance imaging (MRI) findings to establish International Society for the Study of Vascular Anomalies (ISSVA)-based classification of the VAs. SEMVAFC provides a clear visual pathway for physicians to accurately diagnose Vas, which is important as treatment, management, and prognosis differ between VTs and VaMs.

Imaging of vascular tumors with an emphasis on ISSVA classification.

The International Society for the Study of Vascular Anomalies (ISSVA) classification is becoming the international standard classification system for vascular tumors and vascular malformations. The ISSVA classification strictly distinguishes vascular tumors (neoplastic lesions) from vascular malformations (non-neoplastic lesions) based on whether there is a proliferation of vascular endothelial cells present, and it is an extremely useful classification system for determining therapeutic measures. For vascular tumors, it is clinically significant in terms of discriminating infantile hemangioma and rapidly involuting congenital hemangioma, which are expected to spontaneously regress, from other vascular tumors requiring treatment. Needless to say, clinical courses are important for diagnosis, and it is also important for radiologists to understand imaging findings on vascular tumors because such tumors have unique findings on diagnostic images. In this paper, vascular tumors are classified based on the ISSVA classification, and clinical and imaging findings are reviewed.

Vascular anomalies in pediatric patients: updated classification, imaging, and therapy.

Recent advances in knowledge regarding histopathology, cause, and treatment of pediatric vascular anomalies have led to substantial changes in classification and terminology. Over the past two decades, various subspecialists have adopted a new classification system proposed by the International Society for the Study of Vascular Anomalies (ISSVA). The ISSVA classification of vascular anomalies divides vascular anomalies into two categories: vascular neoplasms and malformations. It has been widely adopted by various pediatric subspecialists, because it reliably correlates patient presentation and disease progression, with more accurate histology, diagnosis, imaging, and treatment.

Anomalías vasculares / Vascular anomalies

Las anomalías vasculares incluyen un amplio número de enfermedades de la red vascular que tiene similitudes en su manifestación clínica, esto ha llevado por años a una confusión en la nomenclatura, diagnóstico y tratamiento. A continuación se presenta una revisión del tema que pretende describir la nomenclatura y clasificación vigente así como revisar la sintomatología, complicaciones y manejo actualizado.

Clinical classification of cardiovascular tumors and tumor-like lesions, and its incidences.

Tumors of the heart and the great vessels are very rare disease, and there are many disorders such as tumors originated from the heart and great vessels, metastatic tumors, and tumor-like lesions which do not fit into the usual concept of tumor or neoplasm; thus, it is very difficult to classify these tumors. We proposed a new classification of cardiovascular tumors for clinical use based on the accumulated biological analyses and clinical data of the reported literatures and our own study as benign tumors, malignant tumors, ectopic hyperplasia/ectopic tumors/others, and tumors of great vessels, with reference to the series of Atlas of tumor pathology of the Armed Forces Institute of Pathology and the recent World Health Organization classification of cardiac tumors issued in 2004. More than 50 disorders have been reported as tumors originated from the cardiovascular system, and various metastatic tumors from nearby organs, distant lesions, and intravascular extension tumors to the heart were reported. Based on the new classification, we reviewed epidemiology and incidence of cardiovascular tumors. Metastatic tumors are more frequent than tumors originated from the heart and great vessels, and cardiac myxoma is the most frequent tumors in all cardiac tumors.