Molecular Diagnostics of Vascular Tumors of the Skin.

In this article, the authors have reviewed all the recent news regarding how the discovery of some novel and recurrent molecular and genetic changes has modified the classification of some entities and have addressed to the description of new variants of vascular tumors. And even more important, the authors also reviewed on how these findings, in addition to gain insight into the tumoral biology, portend significant clinical consequences not only regarding to their diagnosis but also to their management and prognosis because some of these mutations are potential targets for treatment. The authors have also highlighted immunohistochemical markers can help us as a surrogate marker of those molecular alterations.

Histopathology of vascular anomalies: update based on the revised 2014 ISSVA classification.

Precise diagnosis of childhood vascular anomalies is challenging, and requires careful correlation of clinical findings, diagnostic imaging, histopathology and genetic analysis. Skin and soft tissue biopsies remain an important element in the complete evaluation of many vascular anomalies included in the revised 2014 International Society for the Study of Vascular Anomalies (ISSVA) classification. Here we present an overview of the light microscopic and immunohistochemical features of the entities in this updated classification scheme, with emphasis on newly-included diagnoses such as PTEN hamartoma of soft tissue.

Mesenchymal tumors and tumor-like lesions of the breast: a contemporary approach review.

The classification of the breast tumors has been revised and recently published in 2012 in the WHO blue book. Contrary to the epithelial tumors in the breast, mesenchymal tumors are rare and the classification for benign and malignant tumors is based on the same criteria in both categories, since no other specific diagnostic criteria, which would have an impact on prognosis, exist to date. The present review deals with minor changes mirroring the recent developments in the benign mesenchymal tumors (new additions are nodular fasciitis and atypical vascular lesions, while the haemangiopericytoma is removed) focusing especially on criteria to diagnose sarcomas, which represent a wide spectrum including very difficult lesions. The majority of sarcomas of the breast arise as a component of a malignant phyllodes tumor, while the pure forms are very rare. When a pure primary sarcoma of the breast is diagnosed, pathologists are encouraged to categorize the lesion according to the type of differentiation and to provide to the clinicians all the important prognostic parameters for the best treatment choice.

Vascular anomalies: hemangiomas and beyond--part 1, Fast-flow lesions.

OBJECTIVE: The purpose of this study was to review the medical literature and the current classification of vascular anomalies to clarify common misconceptions and provide guidance for imaging and treatment. In this first article of a two-part series, we focus on the fast-flow vascular anomalies. CONCLUSION: Nonuniformity of terminology across the medical literature hampers understanding of the vascular anomalies. A familiarity with the classification and biology on which this terminology is based is essential for accurate and precise diagnosis.

Current classification and terminology of pediatric vascular anomalies.

OBJECTIVE: The purpose of this article is to review new terminology to diagnose, classify, and refer patients with vascular anomalies for additional imaging, intervention, and treatment. CONCLUSION: In recent decades, much has been learned regarding the histopathology, cause, and treatment of vascular anomalies. As information has been gleaned, a new classification system has emerged that divides vascular anomalies into neoplasms and malformations. Its utility is based on accurate initial diagnosis that correlates consistently with clinical presentation, disease course, and treatment.

Vulvar vascular tumors: a clinicopathologic study of 85 patients.

The subepidermal hormonally sensitive tissue of the vulva is anatomically unique and may give rise to a wide variety of vascular tumors. As a consequence, classifying vulvar vascular lesions has been challenging due both to the wide variety of lesions that may be encountered and the heterogeneity in reporting across several disciplines. The purpose of this study is to present an institutional experience of vulvar vascular lesions. Overall, 85 patients were identified over a 26-year period. Vascular lesions belonging to the following classes included (n, %total) benign vascular tumors (32, 38%), dilatations of preexisting vessels (31, 36%), hyperplasia/reactive (7, 8%), tumors with significant vascular component (11, 13%), malformations (3, 4%), and malignant vascular tumors (1, 1%). Two reaction patterns based on vulvar lymphatic pathology were identified: one is a stromal dominant pattern and the other is a vascular dominant pattern. Vulvar vascular malformations and true vascular malignancies, although rare, may have associated high morbidity. To accurately classify vulvar lymphatic lesions, the pathologist must carefully consider the patient's clinical history taking into account features such as preexisting lymphedema.

Vascular bone tumors: a proposal of a classification based on clinicopathological, radiographic and genetic features.

The classification of vascular bone tumors remains challenging, with considerable morphological overlap spanning across benign to malignant categories. The vast majority of both benign and malignant vascular tumors are readily diagnosed based on their characteristic histological features, such as the formation of vascular spaces and the expression of endothelial markers. However, some vascular tumors have atypical histological features, such as a solid growth pattern, epithelioid change, or spindle cell morphology, which complicates their diagnosis. Pathologically, these tumors are remarkably similar, which makes differentiating them from each other very difficult. For this rare subset of vascular bone tumors, there remains considerable controversy with regard to the terminology and the classification that should be used. Moreover, one of the most confusing issues related to vascular bone tumors is the myriad of names that are used to describe them. Because the clinical behavior and, consequently, treatment and prognosis of vascular bone tumors can vary significantly, it is important to effectively and accurately distinguish them from each other. Upon review of the nomenclature and the characteristic clinicopathological, radiographic and genetic features of vascular bone tumors, we propose a classification scheme that includes hemangioma, hemangioendothelioma, angiosarcoma, and their epithelioid variants.

Modified primary tumour/vessel tumour/nodal tumour classification for patients with invasive ductal carcinoma of the breast.

BACKGROUND: We previously reported that the primary tumour/vessel tumour/nodal tumour (PVN) classification is significantly superior to the UICC pTNM classification and the Nottingham Prognostic Index for accurately predicting the outcome of patients with invasive ductal carcinoma of the breast in a manner that is independent of the nodal status and the hormone receptor status. METHODS: The purpose of the present study was to compare the outcome predictive power of a modified PVN classification to that of the newly devised pathological UICC pTNM classification and the reclassified Nottingham Prognostic Index in a different group of patients with invasive ductal carcinoma (n=1042) using multivariate analyses by the Cox proportional hazard regression model. RESULTS: The modified PVN classification clearly exhibited a superior significant power, compared with the other classifications, for the accurate prediction of tumour recurrence and tumour-related death among patients with invasive ductal carcinoma in a manner that was independent of the nodal status, the hormone receptor status, and adjuvant therapy status. CONCLUSION: The modified PVN classification is a useful classification system for predicting the outcome of invasive ductal carcinoma of the breast.

The controversial histologic classification of canine subcutaneous whorling tumours: The path to perivascular wall tumours.

Subcutaneous spindle cell tumours characterized by whorling growth patterns are common in dogs and are identified as a distinct entity. These tumours were misnamed as hemangiopericytomas (HPCs) because of some minor morphological parallels with their human counterparts. In veterinary medicine, the cell of origin of HPC has been under debate for a long time. Some authors have suggested a perivascular origin while others a perineural one. The evidence of the orientation of the neoplastic cells around the vessels and the expression of contractile proteins supported a perivascular origin while S100 expression and an inconsistent vascular connection supported a perineural origin. Despite the morphological similarities with peripheral nerve sheath tumours in humans, the perineural origin was supported mainly by the expression of markers with low specificity. On the contrary, the majority of studies have supported the perivascular origin of 'old' canine HPC. Since a variable degree of myoid-pericytic differentiation was described, the term perivascular wall tumours (PWTs) were suggested to substitute HPC. Once the diagnostic criteria of PWTs were defined, the clinical behaviour and prognostic variables were investigated, demonstrating differences as compared with the group of canine soft tissue sarcomas (STSs) in general. PWTs are less aggressive, mostly locally invasive, and rarely metastasizing. Their behaviour seems to be less influenced by histological grade, suggesting that canine STSs are heterogeneous. The study of the biological behaviour of specific STS tumour types may be valuable in detecting differences which have passed unnoticed when STSs have been studied concomitantly.

Primary Vascular Tumors of Bone: A Monoinstitutional Morphologic and Molecular Analysis of 427 Cases With Emphasis on Epithelioid Variants.

Recent molecular discoveries have refined vascular bone tumor classification. To investigate the clinical relevance of these refinements, we reviewed all cases of primary vascular bone tumors treated at our Institute. On the basis of morphology, cases were assessed immunohistochemically and molecularly. A total of 427 cases of primary vascular tumor of bone with available follow-up and histologic material were retrieved and reclassified according to the most recent diagnostic criteria as follows: 289 hemangiomas, 38 epithelioid hemangiomas, 21 epithelioid hemangioendotheliomas, 2 retiform hemangioendotheliomas, 1 intraosseous papillary intralymphatic angioendothelioma, 24 pseudomyogenic hemangioendotheliomas, and 52 angiosarcomas (of these, 45 were epithelioid angiosarcomas and 7 spindle cell secondary angiosarcoma). Both epithelioid and classic hemangiomas behave as benign tumors with excellent prognosis. The distinction between cellular and conventional type of epithelioid hemangioma was not associated with a different clinical course. Conversely, epithelioid hemangioendothelioma exhibited a more aggressive clinical behavior than hemangioma, with higher rates of multifocality and distant spread. Immunohistochemical positivity for CAMTA1 or TFE3 did not have a prognostic implication. In epithelioid hemangioendothelioma, the presence of morphologic malignant features was associated with reduced disease-free (P=0.064) and overall survival (P=0.055). Pseudomyogenic hemangioendothelioma featured local aggressiveness in 5/24 patients exhibiting a clinical behavior closer to epithelioid hemangioma than epithelioid hemangioendothelioma. Last, 32/45 patients with epithelioid angiosarcoma died of disease with a median survival time of 10 months from diagnosis. In conclusion, the integration of morphologic, immunohistochemical, and molecular features allows a better stratification of primary vascular tumors of bone with significant prognostic and therapeutic implications.

Brief Description of ISSVA Classification for Radiologists.

Ongoing discovery regarding the origin and treatment of vascular anomalies requires standardized nomenclature which itself must undergo iterative updating. This article introduces the 2018 International Society for the Study of Vascular Anomalies (ISSVA) classification, emphasizing the biologic basis of vascular anomalies, summarizing the key features of commonly encountered entities, and serving as a foundation for subsequent articles presented herein. Vascular tumors are discussed to highlight their distinction from vascular malformations which will receive greater attention with respect to management and technical considerations within the issue.

Cutaneous vascular tumours: an update.

This review evaluates changes in vascular nomenclature particularly in the category of vascular tumours of intermediate malignancy that includes the various haemangioendotheliomas, Kaposi's sarcoma and giant cell angioblastoma. Recently described entities in this category, including the latter tumour and composite haemangioendothelioma, are described. Several newly characterized vascular tumours not included in recent classifications of vascular tumours are also summarized. These include acquired elastotic haemangioma, symplastic haemangioma, cutaneous epithelioid angiomatous nodule and cutaneovisceral angiomatosis with thrombocytopenia. The newly introduced clinical classification of congenital haemangiomas into non-involuting and rapidly involuting variants and radiation-induced atypical vascular lesions are also reviewed.

Perivascular myoid tumors of the oral region: a clinicopathologic re-evaluation of 35 cases.

BACKGROUND: Myopericytoma (MPC) is a generic denomination to describe tumors showing differentiation toward perivascular myoid cells /myopericytes. It has been suggested that MPC forms a morphologic continuum with glomus tumor (GT), solitary myofibroma (SMF), and angioleiomyoma (ALM). This proposed relationship has not yet been assessed in the oral region. METHODS: We reviewed our 28-year experience with 35 oral tumors, originally diagnosed as ALM (n = 28), SMF (n = 4), GT (n = 2), and MPC (n = 1) to analyze their overlapping microscopic features, with the assistance of immunohistochemistry. RESULTS: Myopericytoma showed a wide range of growth patterns; concentric perivascular whorls, hemangiopericytomatous areas, glomangiopericytoma (GPC)-type vessels and leiomyomatous foci. Intravascular growth was also seen. Among 28 cases studied, three ALM were reclassified as MPC (n = 2) and SMF (n = 1), based on the present diagnostic criteria. Additional MPC-type components, at varying degrees, were similarly found in four ALM and three SMF, at least focally. One GT featured intravascular whorls of spindle cells. These four interrelated groups of tumors had in common GPC-type vasculature and intraluminal cellular proliferation was nearly ubiquitously present. Diffuse immunoreactivity for alpha-smooth muscle actin and less staining intensity of muscle-specific actin were observed in all tumors. Only ALM displayed desmin positivity of variable extent. Neither case tested expressed CD34. CONCLUSIONS: Our data matches with the recent results in extraoral sites that MPC, GT, SMF, and ALM exhibit histologic and immunohistochemical overlap with each other. A common perivascular myoid differentiation between these tumor types is further reinforced by the present oral series.

Verrucous lymphovascular malformation versus verrucous hemangioma: controversial nomenclature.

The International Society for the Study of Vascular Anomalies (ISSVA) divides congenital vascular anomalies into malformations and tumors and subclassified hemangiomas under tumors. However, evidence shows this accepted classification has not been widely employed. Particularly troublesome is the use of the term hemangioma, commonly used to describe a variety of vascular lesions (both malformations and tumors). The term verrucous hemangioma has been used to describe a congenital vascular anomaly with a progressive verrucous epidermal surface persisting throughout life unless surgically excised. Recent evidence suggests that some of these lesions may share histologic features of both hemangiomas and malformations, thereby causing nosologic confusion. We report a 15-year-old adolescent girl with such a lesion and review the literature and controversy of verrucous hemangiomas. In our case, the most appropriate diagnosis is verrucous lymphovascular malformation. Further testing of similar lesions will be necessary to fully understand the nature and classification of these lesions.

[Classification of vascular anomalies].

The classification of vascular anomalies has been revised, as physicians and researchers have recognised an increasing number of vascular anomalies. The International Society for the Study of Vascular Anomalies presents a classification distinguishing between tumours and malformations. Over the years, an inaccurate application of the term haemangioma has been used, which has led to confusion among physicians. By using the classification and combining it with a thorough history and objective examination a classification of the most common vascular anomalies should be possible.

[Benign aggressive vascular anomalies in children]. / Anomalies vasculaires bénignes agressives de l'enfant et de l'adolescent.

Superficial vascular anomalies constitute a large group of malformative and tumoral conditions developed from all types of vessels. Vascular tumors are the result of cellular hyperplasia, whereas vascular malformations (VMs) are constituted of dysplastic vessels. The classification from International Society for the Study of Vascular Anomalies (ISSVA) is based on this pathogenic difference. The most common vascular tumor is infantile hemangioma, which treatment, when necessary, is propranolol. Congenital hemangiomas and tumors that might be complicated with Kasabach-Merritt phenomenon, i.e. deep thrombocytopenia, are much rarer. Management of Kasabach-Merritt phenomenon is now largely based on sirolimus. Low-flow VMs include capillary, venous and lymphatic malformations; arteriovenous malformations are high-flow malformations. These different types of VMs might be combined. Currently, there is an increasing work in delineating the different entities based on molecular findings. Treatment of VMs depends on the impairment linked to them, and is decided case by case, in pluridisciplinary consultations. Interventional treatments, especially surgery and sclerotherapy, are usually partially efficient, and management of patients with VMs increasingly involves medical drugs. First-line treatment of coagulation disorders associated with venous malformations is based on low molecular weight heparin; sirolimus seems efficient in hemorrhagic complications refractory to usual treatment. Sirolimus is about to become the standard treatment in painful inflammatory manifestations of mixed and/or complicated lymphatic malformations.

Managing Vascular Tumors-Open Approaches.

The most common vascular tumors encountered by the otolaryngologist are rare chromaffin cell tumors termed paragangliomas. Within the head and neck region, they commonly arise from the carotid body, vagus nerve (glomus vagale), and jugular vein (glomus jugulare). Other vascular head and neck tumors include sinonasal malignancies, because of proximity to or involvement of the pterygoid plexus as well as the rich vascularity of the sinonasal mucosa; juvenile nasopharyngeal angiofibroma, a vascular tumor of male adolescents; unusual vascular tumors such as hemangiopericytoma; and metastatic renal cell cancer, which has a proclivity for an unusually rich blood supply.

Mesenchymal, non-meningothelial tumors of the central nervous system.

The spectrum of non-meningothelial mesenchymal tumors that may arise within the central nervous system is presented, based on the current classification of soft tissue tumors. Among malignant types, hemangiopericytoma, rhabdomyosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma are the most frequent ones. Rare tumor entities are mentioned. As in soft tissue sarcomas, diagnosis is mainly based on light and electron microscopy, while immunohistochemistry can improve accuracy of diagnosis.