Complex vascular anomalies and tissue overgrowth of limbs associated with increased skin temperature and peripheral venous dilatation: parks weber syndrome or PROS?

AbstractPIK3CA-related overgrowth spectrum (PROS) is a series of congenital, sporadic disorders that are associated with segmental overgrowth phenotypes and postzygotic, somatic gene mutations in the PIK3CA-ATK-mTOR pathway. The variability and overlapping phenotypes between PROS and other complex vascular malformations make the differential diagnosis confusing and challenging. PROS should be considered for the differential diagnosis with other complex vascular malformations and syndromes with a tissue overgrowth phenotype, such as Parkes-Weber syndrome (PWS).Herein, we diagnosed one unique clinically challenging case manifested as capillary malformation (CM), limb overgrowth, as well as increased skin temperature and peripheral venous dilatation of lower limb that indicated a potential fast-flow lesion. The patient was initially diagnosed with PWS. Contrary to the previous diagnosis, based on further MR imaging and digital subtraction angiography (DSA), which ruled out the existence of AVMs and AVFs, and molecular analysis with targeted next-generation sequencing (NGS) revealing a somatic PIK3CA mutation, we ultimately diagnosed that the patient had a unique form of PROS simulating PWS phenotypes. We suggest that it is important to propose the differential diagnosis of PWS and PROS, two diseases that share a common overgrowth phenotype. We recommended radiological diagnosis such as MRI, CT and DSA as well as further molecular diagnosis to provide more information for the assessment of vascular lesions and to further guide clinical treatment strategies.

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Clinicopathological, Radiological, and Molecular Features of Primary Lung Adenocarcinoma with Morule-Like Components

Disease Markers ◽

10.1155/2021/9186056 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Li-Li Wang ◽

Li Ding ◽

Peng Zhao ◽

Jing-Jing Guan ◽

Xiao-Bin Ji ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Egfr Mutation ◽

Pik3ca Mutation ◽

Gene Mutations ◽

Invasive Adenocarcinoma ◽

Targeted Next Generation Sequencing ◽

Molecular Features ◽

Solid Nodule ◽

Primary Lung Adenocarcinoma ◽

Lung Adenocarcinomas

Background. Morule-like component (MLC) was a rare structure in primary lung adenocarcinoma. We aimed to reveal the clinicopathological, radiological, immunohistochemical, and molecular features of lung adenocarcinoma with MLCs. Methods. Twenty lung adenocarcinomas with MLCs were collected, and computed tomographic and histological documents were reviewed. Immunohistochemistry, targeted next-generation sequencing, and Sanger sequencing for β-catenin gene were performed. Results. There were 9 lepidic adenocarcinomas, 8 acinar adenocarcinomas, 2 papillary adenocarcinomas, and 1 minimally invasive adenocarcinoma. Most patients (16/17) were shown a pure solid nodule, and 1 patient was shown a partly solid nodule on chest computed tomography (CT). Nine cases were accompanied with micropapillary components, and 3 were with cribriform components in which 2 suffered a worse prognosis. No significant association was found between the MCLs and the overall survival of lung adenocarcinoma ( P = 0.109 ). The MLCs were often arranged in whorled or streaming patterns. The cells in MLCs showed syncytial and mild appearance. The MLCs were positive for E-cadherin, CK7, TTF-1, napsin-A, vimentin, and β-catenin (membrane), and negative for CK5/6, p40, p63, Synaptophysin, chromogranin A, and Cdx-2. EGFR mutation, ALK-EML4 fusion, HER2 amplification, and PIK3CA mutation were detected in 16 cases, 2 cases, 1 case, and 1 case, respectively. EGFR mutation was more frequent in adenocarcinomas with MLCs than those without MLCs ( P = 0.040 ). β-catenin gene mutation was not detected in any patients. Conclusions. MLC is often observed in the background of acinar, lepidic, and papillary adenocarcinomas. Lung adenocarcinomas with MLCs tend to appear as a solid mass on CT and harbor EGFR gene mutations. The micropapillary components and cribriform components may cause poor prognosis of lung adenocarcinomas with MLCs. Vimentin is always positive in MLCs, and it is a useful marker for the identification of MLCs.

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GNA14, GNA11, and GNAQ Mutations Are Frequent in Benign but Not Malignant Cutaneous Vascular Tumors

Frontiers in Genetics ◽

10.3389/fgene.2021.663272 ◽

2021 ◽

Vol 12 ◽

Author(s):

Philipp Jansen ◽

Hansgeorg Müller ◽

Georg C. Lodde ◽

Anne Zaremba ◽

Inga Möller ◽

...

Keyword(s):

Kaposi's Sarcoma ◽

Vascular Malformations ◽

Gene Mutations ◽

Kaposi’S Sarcoma ◽

Diagnostic Value ◽

Vascular Tumors ◽

Malignant Neoplasms ◽

Mutation Status ◽

Targeted Next Generation Sequencing ◽

Three Samples

Cutaneous vascular tumors consist of a heterogeneous group of benign proliferations, including a range of hemangiomas and vascular malformations, as well as heterogeneous groups of both borderline and malignant neoplasms such as Kaposi’s sarcoma and angiosarcomas. The genetics of these tumors have been assessed independently in smaller individual cohorts making comparisons difficult. In our study, we analyzed a representative cohort of benign vascular proliferations observed in a clinical routine setting as well as a selection of malignant vascular proliferations. Our cohort of 104 vascular proliferations including hemangiomas, malformations, angiosarcomas and Kaposi’s sarcoma were screened by targeted next-generation sequencing for activating genetic mutations known or assumed to be potentially relevant in vascular proliferations. An association analysis was performed for mutation status and clinico-pathological parameters. Frequent activating hotspot mutations in GNA genes, including GNA14 Q205, GNA11 and GNAQ Q209 were identified in 16 of 64 benign vascular tumors (25%). GNA gene mutations were particularly frequent (52%) in cherry (senile) hemangiomas (13 of 25). In angiosarcomas, activating RAS mutations (HRAS and NRAS) were identified in three samples (16%). No activating GNA or RAS gene mutations were identified in Kaposi’s sarcomas. Our study identifies GNA14 Q205, GNA11 and GNAQ Q209 mutations as being the most common and mutually exclusive mutations in benign hemangiomas. These mutations were not identified in malignant vascular tumors, which could be of potential diagnostic value in distinguishing these entities.

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Classification and Differential Diagnosis of Spinal Vascular Malformations

10.28962/01.3.138 ◽

2017 ◽

Author(s):

Andreas Grillhoesl

Keyword(s):

Differential Diagnosis ◽

Vascular Malformations ◽

Spinal Vascular Malformations

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CT angiography and MRI of hand vascular lesions: technical considerations and spectrum of imaging findings

Insights into Imaging ◽

10.1186/s13244-020-00958-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Alain G. Blum ◽

Romain Gillet ◽

Lionel Athlani ◽

Alexandre Prestat ◽

Stéphane Zuily ◽

...

Keyword(s):

Doppler Ultrasonography ◽

Spindle Cell ◽

State Of The Art ◽

Vascular Malformations ◽

Vascular Lesions ◽

Systemic Diseases ◽

Contrast Enhanced ◽

Vascular Compromise ◽

Exposure To Trauma ◽

Technical Considerations

AbstractVascular lesions of the hand are common and are distinct from vascular lesions elsewhere because of the terminal vascular network in this region, the frequent hand exposure to trauma and microtrauma, and the superficial location of the lesions. Vascular lesions in the hand may be secondary to local pathology, a proximal source of emboli, or systemic diseases with vascular compromise. In most cases, ischaemic conditions are investigated with Doppler ultrasonography. However, computed tomography angiography (CTA) or dynamic contrast-enhanced magnetic resonance angiography (MRA) is often necessary for treatment planning. MR imaging is frequently performed with MRA to distinguish between vascular malformations, vascular tumours, and perivascular tumours. Some vascular tumours preferentially affect the hand, such as pyogenic granulomas or spindle cell haemangiomas associated with Maffucci syndrome. Glomus tumours are the most frequent perivascular tumours of the hand. The purpose of this article is to describe the state-of-the-art acquisition protocols and illustrate the different patterns of vascular lesions and perivascular tumours of the hand.

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THE CLASSIC TYPE OF EHLERS–DANLOS SYNDROME: DIFFERENTIAL DIAGNOSIS AND PECULIARITIES OF PATIENT MANAGEMENT

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2021-100-5-62-69 ◽

2021 ◽

Vol 100 (5) ◽

pp. 62-69

Author(s):

А.N. Semyachkina ◽

◽

E.А. Nikolaeva ◽

А.R. Zabrodina ◽

L.P. Melikyan ◽

...

Keyword(s):

Differential Diagnosis ◽

Adult Population ◽

Gene Mutations ◽

Hereditary Disease ◽

Ehlers Danlos Syndrome ◽

Severe Pathology ◽

Type V ◽

Danlos Syndrome

The Classic Ehlers–Danlos syndrome (cEDS) is an autosomal dominant hereditary disease caused by type V collagen defect. The incidence of pathology is estimated at 1:20,000 of the population. The results of a long-term (15 years) follow-up of a group of patients (n=18) with cEDS, including 5 boys and 13 girls aged from 3 to 18 years, are presented. The diagnosis was made based on the presence of 2 large and 5 small international diagnostic criteria in all patients. The progreduated character of the disease is shown, which is most obvious in the dynamics of the state of the musculoskeletal system. Genetic verification of the diagnosis was performed in 6 patients; 5 probands had mutations in the COL5A1 gene, and one in the COL5A2 gene. Mutations already registered in the database were detected only in 2 children. Previously unknown substitutions were found in 4 patients. The article presents the issues of differential diagnosis of this severe pathology and touches upon the issue of continuity between medical pediatric specialists and doctors of various specialties working with the adult population.

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Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab014 ◽

2021 ◽

Author(s):

Lingyun Zhang ◽

Zhixiang Ren ◽

Zhengzheng Su ◽

Yang Liu ◽

Tian Yang ◽

...

Keyword(s):

Thyroid Cancer ◽

Copy Number ◽

Treatment Strategies ◽

Gene Mutations ◽

Anaplastic Thyroid Cancer ◽

Chinese Patients ◽

Driver Gene ◽

Phosphatidylinositol 3 Kinase ◽

Entire Cohort ◽

Whole Exome

Abstract Background Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. Methods Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. Results The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. Conclusions This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

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Should hemangiomas be included in initial differential diagnosis for congenital vascular malformations?

Vascular Malformations ◽

10.1201/9780367255343-6 ◽

2019 ◽

pp. 25-29

Author(s):

Francine Blei

Keyword(s):

Differential Diagnosis ◽

Vascular Malformations

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Parkes-Weber syndrome in the emergency department

BMJ Case Reports ◽

10.1136/bcr-2021-241649 ◽

2021 ◽

Vol 14 (9) ◽

pp. e241649

Author(s):

Raj Patel ◽

Edward James Durant ◽

Robert Freed

Keyword(s):

Emergency Department ◽

Interventional Radiology ◽

Case Report ◽

Vascular Malformations ◽

Weber Syndrome ◽

The Common ◽

Work Up

This case report describes a 20-year-old woman presenting to the emergency department (ED) with unilateral leg swelling. After multiple visits to the ED and workups with rheumatology, dermatology, interventional radiology and genetics, she was finally diagnosed with Parkes-Weber syndrome. The purpose of this case report is to illustrate the common and uncommon presentations, mimickers and work-up of Parkes-Weber syndrome as well as provide a brief overview of vascular malformations in general.

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