Differential pericyte marker expression in craniofacial benign and malignant vascular tumors.

BACKGROUND: Vascular anomalies and tumors are common in the head, neck, and craniofacial areas and are associated with abnormalities in the angiomatous architecture. However, the etiology and molecular basis for the pathogenesis of most vascular lesions are still unknown. Pericytes are mural cells that surround endothelial cells. Besides angiogenesis and other physiological functions, pericytes play an important role in vascularized tissue repair and as resident mesenchymal stem/progenitor cells. Perivascular cells demonstrate a distinct immunohistochemical profile, including expression of alpha-smooth muscle actin (α-SMA), CD146, CD105, and PDGFRß, without endothelial differentiation (absence of CD31 and CD34 immunoreactivity). These pericyte markers have been shown to be expressed in soft tissue hemangiomas. However, they have not been fully examined in intraosseous hemangiomas. METHODS: In this study, we compared mesenchymal stem cell (MSC) expression of CD146 and α-SMA markers in pericytes from hemangiomas from different tissues and malignant vascular tumors. RESULTS: The results demonstrated an increased expression of pericyte markers in perivascular cells of benign hemangiomas, especially intraosseous hemangiomas and a significantly reduced expression of pericyte markers in malignant angiosarcomas. CONCLUSION: The evidence provides insight into the function of pericytes in vascular tumors and suggests their role in vascular tumor disease types.

Loss of expression of YAP1 C-terminus as an ancillary marker for epithelioid hemangioendothelioma variant with YAP1-TFE3 fusion and other YAP1-related vascular neoplasms.

Epithelioid hemangioendothelioma (EHE) with YAP1-TFE3 fusion is a recently characterized distinctive variant of EHE that accounts for a small subset (<5%) of cases. It is composed of nests of epithelioid cells with voluminous pale cytoplasm and often shows focally vasoformative architecture. TFE3 immunohistochemistry (IHC) can be used to support the diagnosis; however, studies have questioned its specificity. Yes-associated protein 1 (YAP1), part of the Hippo signaling pathway, is expressed in normal endothelial cells, but becomes disrupted in EHE variant with YAP1-TFE3, such that only a small N-terminal region of YAP1 is expressed in the fusion protein. A recent study also reported YAP1 rearrangements in a subset of retiform and composite hemangioendotheliomas (RHE and CHE). In this study, we evaluated the diagnostic utility of an antibody directed against the C-terminus of YAP1 (YAP1-CT) for EHE with YAP1-TFE3, RHE, and CHE. In total, 78 tumors were included in the study: EHE variant with YAP1-TFE3 (n = 13), conventional (CAMTA1-positive) EHE (n = 20), pseudomyogenic hemangioendothelioma (n = 10), epithelioid hemangioma (n = 19), epithelioid angiosarcoma (n = 10), RHE (n = 4), and CHE (n = 2). IHC was performed using a rabbit monoclonal anti-YAP1 C-terminus antibody. EHE variant showed complete loss of YAP1-CT expression in 10 of 13 (77%) cases. All cases of RHE and CHE, with previously confirmed YAP1 rearrangements, also showed loss of YAP1-CT expression. Loss of YAP1-CT was seen in one conventional EHE (1/20; 5%). All other epithelioid vascular tumors showed retained YAP1-CT expression. Loss of expression of YAP1-CT appears to be associated with good sensitivity and specificity for EHE variant with YAP1-TFE3 fusion and may provide additional support along with TFE3 and CAMTA1 IHC in challenging cases. This marker may also be useful in the diagnosis of RHE and CHE.

Congenital vascular lesions, could MAPK and PI3K inhibitors pave the way to new therapies?

PURPOSE OF REVIEW: Superficial vascular anomalies are a heterogeneous group of malformative and tumoral lesions, developed from various types of abnormal lymphatic and/or blood vessels. They are mostly benign but their clinical evolution can lead to dramatic cosmetic concern, functional impairment and even life-threatening conditions. Until recently, treatments relied on invasive procedures such as embotherapy/sclerotherapy and/or surgery. Recent molecular findings pave the way of new medical therapies. RECENT FINDINGS: Two main signaling pathways PI3K-AKT-mTOR and RAS-MAPK-ERK are now identified to encounter for the causative pathogenic genetic variants of most vascular anomalies. Involved genes are also responsible for several common neoplasms for which targeted therapies are already available or under development. Repurposing treatment strategy is considered for vascular anomalies treatment with promising results. SUMMARY: The mTOR inhibitor sirolimus is the most used targeted therapy so far but new molecules are tested currently.

Angiosarcomas: histology, immunohistochemistry and molecular insights with implications for differential diagnosis.

Angiosarcomas (AS) represent a heterogenous group of tumors with variable clinical presentation. AS share an important morphologic and immunohistochemical overlap with other sarcomas, hence the differential diagnosis is challenging, especially in poorly-differentiated tumors. Although molecular studies provide significant clues, especially in the differential diagnosis with other vascular neoplasms, a thorough hematoxylin and eosin analysis remains an essential tool in AS diagnosis. In this review, we discuss pathological and molecular insights with emphasis on implications for differential diagnosis in cutaneous, breast, soft tissue and visceral AS.

Intravascular schwannoma: A review of a rare diagnosis.

While schwannoma is one of the most common types of benign peripheral nerve tumors in adults, a very unique and specific variant of schwannoma, the intravascular variant, is exceedingly rare. There have only been three previously published cases of intravascular schwannomas. Here we describe a fourth case of an intravascular schwannoma in a 47-year-old man with an enlarging subcutaneous nodule on his posterior calf. This is the second case of an intravascular schwannoma contained within a vein. Also included is an overview of intravascular schwannomas, including a description and discussion of the histopathological diagnosis, differential diagnoses, and schwannoma variants.

Pulmonary Artery Sarcoma With Low 18F-FDG Uptake.

ABSTRACT: A 75-year-old man presented with dyspnea for more than 2 months, with blood test showing low platelet count and cardiac ultrasound showing severe pulmonary hypertension (>54 mm Hg). A CT pulmonary angiogram showed a filling defect in the pulmonary trunk, right and left pulmonary arteries, raising the possibilities of pulmonary embolism or artery sarcoma. FDG PET/CT was performed for further evaluation and showed low uptake in the pulmonary wall, which supported the diagnosis of pulmonary embolism. Patient was treated with anticoagulants with no changes on repeated CT pulmonary angiogram. Patient underwent surgery, and histopatological examination revealed a pulmonary artery sarcoma.

Vascular Tumor Recapitulated in Endothelial Cells from hiPSCs Engineered to Express the SERPINE1-FOSB Translocation.

Chromosomal translocations are prevalent among soft tissue tumors, including those of the vasculature such as pseudomyogenic hemangioendothelioma (PHE). PHE shows endothelial cell (EC) features and has a tumor-specific t(7;19)(q22;q13) SERPINE1-FOSB translocation, but is difficult to study as no primary tumor cell lines have yet been derived. Here, we engineer the PHE chromosomal translocation into human induced pluripotent stem cells (hiPSCs) using CRISPR/Cas9 and differentiate these into ECs (hiPSC-ECs) to address this. Comparison of parental with PHE hiPSC-ECs shows (1) elevated expression of FOSB, (2) higher proliferation and more tube formation but lower endothelial barrier function, (3) invasive growth and abnormal vessel formation in mice after transplantation, and (4) specific transcriptome alterations reflecting PHE and indicating PI3K-Akt and MAPK signaling pathways as possible therapeutic targets. The modified hiPSC-ECs thus recapitulate functional features of PHE and demonstrate how these translocation models can be used to understand tumorigenic mechanisms and identify therapeutic targets.

Remodeling of Kv7.1 and Kv7.5 Expression in Vascular Tumors.

Voltage-dependent potassium (Kv) channels contribute to the excitability of nerves and muscles. In addition, Kv participates in several cell functions, including cell cycle progression and proliferation. Kv channel remodeling has been associated with neoplastic cell growth and cancer. Kv7 channels are expressed in blood vessels, and they participate in the maintenance of vascular tone and are implicated in myocyte proliferation. Although evidence links Kv7 remodeling to different types of cancer, its expression in vascular tumors has never been studied. Endothelium-derived vascular neoplasms range from indolent lesions to highly aggressive and metastasizing cancers. Here, we show that Kv7.1 and Kv7.5 are evenly distributed in tunicas as well as the endothelium of healthy veins and arteries. The layered structure of vessels is lost in vascular tumors. By studying eight vascular tumors with different origins and characteristics, we found that Kv7.1 and Kv7.5 expression was changed in vascular cancers. While both channels were generally downregulated, Kv7.5 expression was clearly correlated with neoplastic malignancy. The vascular tumors did not contract; therefore, the role of Kv7 channels is probably related to proliferation rather than controlling vascular tone. Our results identify vascular Kv7 channels as targets for cancer detection and anticancer therapies.

Papillary Endothelial Hyperplasia (Masson Tumor) of the Hand. Surgical and Pathological Consideration from Seven Cases Using New Vascular Markers.

Although papillary endothelial hyperplasia may occur at almost any site, one of the most common sites is the hand. It is generally regarded as a reactive vascular proliferation i.e. exuberant form of organizing thrombus. Diagnosis of Masson tumor can be challenging due to its close clinical, radiological and even histopathological resemblance to angiosarcoma. We present seven cases of Masson tumor of the hand; wanting to reveal its nature using new vascular markers and discuss the treatment options and expected outcomes, present clinical and radiological features that may aid diagnosis and also offer treatment plans. A multicenter retrospective study was performed between January 2014 and November 2019. Immunohistochemical stains of Glut1, WT1, ERG, CD31 and alpha smooth muscle actin (ASMA) were performed on each cases. We found seven cases during the examined period. 4 out of 7 cases were women. All lesions occurred in the hands. 3 out of 7 cases appeared in a previously present vascular malformation. All cases were treated with surgical excision and the diagnosis of papillary endothelial hyperplasia was made by histology. Pre-operative testing (radiograph/MRI/US/fine needle aspiration biopsy) did not suggest the diagnosis of Masson tumor; however, aspiration cytology could rule out malignancy. The proliferative endothelial cells proved to be Glut1 negative and WT1 positive and the accompanying pericytic cells were ASMA positive in all cases. Though Masson tumor is a rare vascular lesion in the hand among other vascular tumors, it should be considered in the differential diagnostics even in the case of previously existing vascular malformation. WT1 positivity of the endothelial cells and the accompanying pericytic cells raises the question whether the initially reactive endothelial proliferation may transform into a true benign vascular tumor.

Prognostic Determinants Analysis and Nomogram for Bone Malignant Vascular Tumors: A Surveillance, Epidemiology and End Results (SEER) Analysis.

BACKGROUND The aim and objective of our investigations were to explore the prognostic value of various clinical and pathological factors of bone malignant vascular tumors and establish a nomogram for their outcome predictions. MATERIAL AND METHODS All data of primary bone malignant vascular tumors (MVTs) patients were randomly selected from the Surveillance, Epidemiology and End Results (SEER) database. However, selected patients were clinically diagnosed with various cancers during 1988-2015. The potential prognostic factors were analyzed using SPSS (Windows, version 22.0). All prognostic factors were combined to formulate a nomogram to predict the overall survival (OS). RESULTS A total of 266 selected patients were included in our study. In the univariate model, age (P.

Falso positivo en estudio de tomografía de emisión de positrones con fluorodesoxiglucosa-F18 de un leiomioma de vena cava inferior en paciente con sospecha de paraganglioma / False positive in fluorodeoxyglucose-F18 positron emission tomography computed tomography scan of inferior vena cava leiomyoma in patient with a suspected paraganglioma

Los leiomiomas son tumores benignos derivados de tejido muscular liso que rara vez se presentan fuera del útero. Estos tumores no suelen mostrar captación de FDG. Presentamos el caso de un paciente con hipertensión arterial refractaria al tratamiento y una lesión dependiente de vena cava inferior que muestra una intensa captación de FDG en el estudio PET/TC, sugestivo de paraganglioma, con un diagnóstico histológico final de leiomioma

Leiomyomas are benign tumors derived from smooth muscle tissue that rarely present outside the uterus. These tumors do not usually show FDG uptake. We present the case of a patient with hypertension refractory to treatment and a lesion arising from inferior vena cava, that shows intense FDG uptake in PET/CT scan, suggestive of paraganglioma, with a final histological diagnosis of leiomyoma

A concise review of angiofibroma of soft tissue: A rare newly described entity that can be encountered by dermatopathologists.

Angiofibroma of soft tissue (AFST) is a newly described, rare mesenchymal neoplasm with fibroblastic and vascular components; it can be seen in both sexes and in a broad age range. It presents as a slowly enlarging mass, most often in the deep tissues of the upper and lower extremities, but occasionally in a superficial location where it may be encountered by dermatopathologists. It has a benign clinical course with a very low probability of recurrence after complete excision. This lesion has a prominent vasculature and may have an infiltrative growth pattern. These features could lead to a misdiagnosis, such as malignant vascular tumor, by an unwary dermatopathologist. The diagnosis of AFST initially relied solely on morphology and immunohistochemistry but, more recently, molecular studies have begun to play a role. Because of the potential for misdiagnosis, we present this review to raise awareness.

Inhibition of p38/MK2 Signaling Prevents Vascular Invasion of Melanoma.

Melanoma cells can switch between distinct gene expression profiles, resulting in proliferative or invasive phenotypes. Signaling pathways involved in this switch were analyzed by gene expression profiling of a cohort of 22 patient-derived melanoma cell lines. CDH1 negativity was identified as a surrogate marker for the invasive phenotype. CDH1 expression could be turned on and off by modulating activity of p38 or its downstream target MK2, suggesting that this pathway controls melanoma progression. Mechanistically, MK2 inhibition prevented melanoma-induced vascular barrier disruption, reduced the expression of PODXL and DEL-1, and prevented vascular dissemination in vivo. PODXL and DEL-1 expression in patients with melanoma were associated with poor survival and thus can be used as prognostic markers. Downstream targets of MK2 may thus serve as candidate therapeutics.

False positive in fluorodeoxyglucose-F18 positron emission tomography computed tomography scan of inferior vena cava leiomyoma in patient with a suspected paraganglioma. / Falso positivo en estudio de tomografía de emisión de positrones con fluorodesoxiglucosa-F18 de un leiomioma de vena cava inferior en paciente con sospecha de paraganglioma.

Leiomyomas are benign tumors derived from smooth muscle tissue that rarely present outside the uterus. These tumors do not usually show FDG uptake. We present the case of a patient with hypertension refractory to treatment and a lesion arising from inferior vena cava, that shows intense FDG uptake in PET/CT scan, suggestive of paraganglioma, with a final histological diagnosis of leiomyoma.

[Reversible cerebral vasoconstriction syndrome secondary to secreting jugular paraganglioma]. / Sindrome de vasoconstriccion cerebral reversible secundario a un paraganglioma yugular secretor de metanefrinas.

TITLE: Sindrome de vasoconstriccion cerebral reversible secundario a un paraganglioma yugular secretor de metanefrinas.

Congenital cutaneous pyogenic granuloma: Report of two cases and review of the literature.

Congenital cutaneous pyogenic granuloma is a rare benign vascular tumor with clinical and histopathological features similar to infantile hemangioma. It usually presents as a red, pedunculated and highly friable papule. On histopathological analysis, one can see a capillary vessel proliferation with lobular pattern and endothelial proliferation. The differential diagnosis is based on negativity of glucose transporter 1 (GLUT1) immunochemistry studies. We report two infants with congenital pyogenic granuloma, one with a unique cutaneous lesion and the other with multiple lesions affecting both skin and mucosal surfaces. These two cases highlight the importance of the differential diagnosis based on the GLUT1 immunochemistry analysis considering the distinct treatments required to these infant vascular tumors.

Prognostic Value and Prediction of Extratumoral Microvascular Invasion for Hepatocellular Carcinoma.

BACKGROUND: There are few reports on microvascular invasion (MVI) located intra- or extratumorally and prognosis of hepatocellular carcinoma (HCC). OBJECTIVE: The aim of this study was to evaluate patient outcome according to the location of MVI, and to build a nomogram predicting extratumoral MVI. METHODS: We included 681 consecutive patients who underwent hepatic resection (HR) or liver transplantation (LT) for HCC from January 1994 to June 2012, and evaluated patient outcome according to the degree of vascular invasion (VI). A nomogram for predicting extratumoral MVI was created using 637 patients, excluding 44 patients with macrovascular invasion, and was validated using an internal (n = 273) and external patient cohort (n = 256). RESULTS: The 681 patients were classified into four groups based on pathological examination (148 no VI, 33 intratumoral MVI, 84 extratumoral MVI, and 29 macrovascular invasion in patients who underwent HR; 238 no VI, 50 intratumoral MVI, 84 extratumoral MVI, and 15 macrovascular invasion in patients who underwent LT). Multivariate analysis revealed that extratumoral MVI was an independent risk factor for overall survival in patients who underwent HR (hazard ratio 2.62, p < 0.0001) or LT (hazard ratio 1.99, p = 0.0005). Multivariate logistic regression analysis identified six independent risk factors for extratumoral MVI: α-fetoprotein, tumor size, non-boundary type, alkaline phosphatase, neutrophil-to-lymphocyte ratio, and aspartate aminotransferase. The nomogram for predicting extratumoral MVI using these factors showed good concordance indices of 0.774 and 0.744 in the internal and external validation cohorts, respectively. CONCLUSIONS: The prognostic value of MVI differs according to its invasiveness. The nomogram allows reliable prediction of extratumoral MVI in patients undergoing HR or LT.