A Rare Case of Pulmonary Artery Sarcoma.

Pulmonary artery sarcoma (PAS) is a rare and aggressive mesenchymal tumor with an overall poor prognosis1-5. Due to similar clinical and radiologic findings, PAS is often misdiagnosed as a pulmonary embolism (PE) frequently leading to prolonged anticoagulation therapy, which delays the correct diagnosis 1-3. By presenting this clinical case our objective is to emphasize characteristic CT findings that favour a neoplastic origin of a pulmonary intravascular filling defect. PET-CT and MRI have also an important potential role in its diagnosis and therapeutical management.

Liver mesenchymal neoplasms: something old, something new.

Histological examination of liver biopsies and resection specimens remains the gold standard to establish a definitive diagnosis of liver lesions. While hepatocellular carcinoma remains the most commonly encountered liver lesion on mass-directed biopsies, surgical pathologists must be aware of other entities that may pose diagnostic challenges, as an accurate diagnosis is key for patient management. Mesenchymal tumours of the liver are relatively uncommon, therefore many pathologists are unfamiliar with these tumours. While the clinical presentation and radiological features of these lesions often overlap, careful attention to histological clues can assist in weeding out various congeners to arrive at the most accurate diagnosis. An additional challenge when diagnosing mesenchymal tumours is the specimen type, as mass-directed core biopsies are limited and have become standard clinical practice. Besides careful attention to histological features, radiological findings and clinical history, immunohistochemical analysis and molecular studies have become of immense diagnostic value. In this review, we discuss several common and rare mesenchymal hepatic lesions as defined in the current World Health Organization (WHO) classification and most up-to-date literature. We also discuss immunohistochemistry panels and relevant molecular findings that may assist in rendering an accurate diagnosis when encountering these lesions in daily practice.

Hexokinase 2-driven glycolysis in pericytes activates their contractility leading to tumor blood vessel abnormalities.

Defective pericyte-endothelial cell interaction in tumors leads to a chaotic, poorly organized and dysfunctional vasculature. However, the underlying mechanism behind this is poorly studied. Herein, we develop a method that combines magnetic beads and flow cytometry cell sorting to isolate pericytes from tumors and normal adjacent tissues from patients with non-small cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC). Pericytes from tumors show defective blood vessel supporting functions when comparing to those obtained from normal tissues. Mechanistically, combined proteomics and metabolic flux analysis reveals elevated hexokinase 2(HK2)-driven glycolysis in tumor pericytes, which up-regulates their ROCK2-MLC2 mediated contractility leading to impaired blood vessel supporting function. Clinically, high percentage of HK2 positive pericytes in blood vessels correlates with poor patient overall survival in NSCLC and HCC. Administration of a HK2 inhibitor induces pericyte-MLC2 driven tumor vasculature remodeling leading to enhanced drug delivery and efficacy against tumor growth. Overall, these data suggest that glycolysis in tumor pericytes regulates their blood vessel supporting role.

Intravascular emboli relates to immunosuppressive tumor microenvironment and predicts prognosis in stage III colorectal cancer.

BACKGROUND: Stage III colorectal cancer (CRC) patients experience varying degrees of prognosis even if receiving standard therapeutic regimes. Intravascular emboli (IVE), a type of vascular invasion, impacts the clinical outcome in CRC. In this study, we confirmed the role of IVE in predicting the prognosis of stage III CRC patients and characterized the tumor microenvironment (TME) of CRC with IVE. METHODS: Data from 220 consecutive patients (cohort 1) with stage III CRC undergoing radical surgery was collected retrospectively between January 2009 to December 2014. According to the presence of IVE, which was confirmed by two independent pathologists, patients were classified into two groups. Univariate and multivariate Cox regression analyses were performed to evaluate the relation of IVE presence to patients' prognosis. The association between IVE and clinicopathological factors was also analyzed. Furthermore, differentially expressed genes (DEGs) and gene set enrichment analyses (GSEA) were performed to describe features of the TME based on microarray data consisting of 6 patients. Tumor tissues from a separate cohort of 73 patients with stage III CRC (cohort 2) collected between June 2014 and December 2015 were used to analyze tumor-infiltrating lymphocyte (TIL) by immunohistochemistry (IHC) staining. RESULTS: IVE was observed in 126 (57.3%) patients and could serve as an unfavorable independent prognostic predictor (P < 0.001) as well as lymph node metastasis (P < 0.05) and tumor location (P < 0.05). Additionally, patients with IVE had a higher neutrophil percentage (P = 0.002) and lower lymphocyte percentage (P = 0.002) relative to those without IVE. CRC with IVE had a significantly different profile of DEGs compared to CRC without IVE, and GSEA showed chronic inflammatory and immunosuppressive TME may promote IVE development. In cohort 2, tumors with IVE had fewer CD3+ TILs in the stromal region, as well as fewer CD8+ TILs in both stromal and tumoral regions relative to those without IVE. CONCLUSION: IVE, which was related closely to a chronic inflammatory and immunosuppressive TME, forecasted a worse prognosis of stage III CRC patients and may be taken into consideration when a therapeutic strategy is decided upon.

A unique epithelioid vascular neoplasm of bone characterized by EWSR1/FUS-NFATC1/2 fusions.

An increasing number of epithelioid vascular lesions, in particular tumors from the benign and low-grade end of the spectrum, have been characterized by recurrent gene fusions. As a result, the detection of these molecular markers have improved the classification of diagnostically challenging cases. However, despite the significant progress, there are occasional lesions that do not fit in known histologic or molecular groups. Herein, we present five such unclassified epithelioid vascular lesions, which occurred in the bone and showed a distinct morphology composed of alternating vasoformative and solid growth and mild to moderate nuclear pleomorphism. The variegated morphologic appearance resembled that of composite hemangioendothelioma, being distinct from both epithelioid hemangioma and epithelioid hemangioendothelioma, and consistently showed cytologic atypia. Due to their unusual morphologic appearance and negative molecular work-up, targeted transcriptome sequencing was performed in two cases showing the presence of NFATC2 fusions with either EWSR1 or FUS genes. Three additional bone tumors with EWSR1 gene rearrangements were identified by FISH screening of a large cohort of 45 fusion-negative epithelioid vascular neoplasms, one fused to NFATC2 while two others to NFATC1. There were three females and two males, with a wide age range at presentation, mean of 44 years. The lesions occurred in the pelvis, maxillary sinus, and humerus. Two patients presented with polyostotic disease, both located in the pelvic bones. Two patients had available follow-up, one developed two local recurrences in the humerus over a 15-year period, while the other showed no recurrence 4 years subsequent to an en-bloc resection. Tumors were positive for CD31 and ERG, while negative for EMA, CK, synaptophysin, and chromogranin. FISH confirmed this abnormality in all cases, none of them being associated with gene amplifications. Further studies are needed to establish the pathogenetic relationship of this rare molecular subset with other epithelioid vascular tumors and to determine its clinical behavior.

Aberrant cytoplasmic connexin43 expression as a helpful marker in vascular neoplasms.

BACKGROUND: Gap junctions consisting of connexins (Cx) are fundamental in controlling cell proliferation, differentiation, and cell death. Cx43 is the most broadly expressed Cx in humans and is attributed an important role in skin tumor development. Its role in cutaneous vascular neoplasms is yet unknown. METHODS: Fifteen cases each of cutaneous angiosarcoma (cAS), Kaposi sarcoma (KS), and cherry hemangioma (CH) were assessed by immunohistochemistry for expression of Cx43. Expression pattern, intensity, and percentage of positively stained cells were analyzed. Solid basal cell carcinomas served as positive and healthy skin as negative controls. RESULTS: Most cases of cAS presented with a strong Cx43 staining of almost all tumor cells, whereas endothelia of KS showed medium expression and CH showed mostly weak expression. In comparison with KS or cAS, the staining intensity of CH was significantly lower (P ≤ 0.001). All tissue sections of both cAS and KS were characterized by a mostly diffuse, cytoplasmic staining pattern of the vascular endothelia. None of those showed nuclear staining. CONCLUSION: The high-to-intermediate expression of Cx43 observed in all cases of cAS and KS suggests that this Cx may play a role in the development of malignant vascular neoplasms and serve as a helpful diagnostic marker.

Hiperplasia endotelial papilar intravascular en la región supraclavicular / Intravascular papillary endothelial hyperplasia in the supraclavicular region

La hiperplasia endotelial papilar intravascular (IPEH) es una lesión vascular benigna poco frecuente que se presenta habitualmente como una neoformación subcutánea eritemato-violácea inespecífica. El estudio histopatológico, necesario para el diagnóstico de confirmación, muestra proliferación papilar de células endoteliales asociada con material trombótico. La IPEH puede simular otras lesiones como el angiosarcoma, por lo que el diagnóstico correcto de esta entidad es esencial para evitar tratamientos agresivos. La resección con márgenes amplios suele ser suficiente

Intravascular papillary endothelial hyperplasia (IPEH) is a rare benign vascular lesion that usually presents as a nonspecific erythematous-violaceous subcutaneous neoformation. The histopathological study, necessary for the confirmatory diagnosis, shows papillary proliferation of endothelial cells associated with thrombotic material. IPEH can simulate other lesions such as angiosarcoma, so the correct diagnosis of this entity is essential to avoid aggressive treatments. The resection with wide margins is usually enough

Diagnostic Performance of a Sonographic Volume and Solid Vascular Tissue Score (VSVTS) for Preoperative Risk Assessment of Pediatric and Adolescent Adnexal Masses.

STUDY OBJECTIVE: To evaluate the diagnostic performance of a Volume and Solid Vascular Tissue Score (VSVTS) for preoperative risk assessment of pediatric and adolescent adnexal masses. DESIGN: A retrospective cohort study comprised of all female individuals who presented with an adnexal mass that was managed surgically between April 2011 and March 2016. SETTING: The Hospital for Sick Children (Toronto, Ontario, Canada). PARTICIPANTS: Female individuals 1-18 years of age who presented to a large tertiary pediatric hospital with an adnexal mass that was managed surgically. MAIN OUTCOME MEASURES: Main outcome measures included diagnostic performance of the VSVTS for malignancy via sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and receiver operating characteristic area-under-the-curve (AUC) analysis. RESULTS: A total of 179 masses in 169 subjects were included. The malignancy rate was 10.6%. The AUC for the VSTVS was 0.919. A VSTVS cut-off value of 4 achieved a sensitivity of 79% (95% CI 0.54-0.93), specificity of 88% (95% CI 0.82-0.93), PPV of 0.44 (95% CI 0.33-0.56), NPV of 0.97 (95% CI 0.94-0.99), LR+ of 6.77 (95% CI 4.18-10.97), and LR- of 0.24 (95% CI 0.10-0.57). CONCLUSIONS: A sonographic scoring system based on the volume and presence of solid vascular tissue improves PPV for preoperative risk stratification of adnexal masses in the pediatric and adolescent population compared to existing ultrasound-only approaches. Further prospective research is needed to determine how best to incorporate components of such scoring systems into clinical management algorithms.

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.

The histopathology of congenital haemangioma and its clinical correlations: a long-term follow-up study of 55 cases.

AIMS: Congenital haemangiomas (CHs) can be subdivided into different subtypes [rapidly involuting CHs (RICHs), non-involuting CHs (NICHs), and partially involuting CHs (PICHs)]. During the first few days of life, RICHs may be associated with transient but sometimes marked thrombocytopenia. We sought to assess the histological aspects and clinicopathological correlations of the three subtypes. METHODS AND RESULTS: We assessed the histopathological features of 10 RICHs, 25 NICHs, and 20 PICHs, described the patients' long-term clinical outcomes, and assessed clinicopathological correlations. All CHs were located in the dermis and hypodermis, and comprised both capillary lobules (with three distinct histopathological patterns) and extralobular large vessels. Most of the extralobular vessels were abnormal veins and abnormal lymphatic vessels. We did not observe significant correlations between the CH subtype, the histopathological pattern, and the time of the histopathological assessment. Interestingly, unexpected intralobular expression of podoplanin was found in neonatal biopsies of five RICHs and PICHs. Four of these five patients had concomitant thrombocytopenia. The podoplanin staining intensity decreased over time as the thrombocytopenia resolved and the tumour shrank. CONCLUSION: The histopathological features were similar in all three subtypes of CH, and were related to the time since disease onset; we consider that RICH, PICH and NICH form a single entity and differ only in their involuting potential. Along with the transient expression of intralobular podoplanin observed in some specimens from the newborn, the lobular architecture might lead to misdiagnosis of tufted haemangioma or kaposiform haemangioendothelioma.

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.

Malignant glomus tumor of the index finger

Glomus tumor (GT) is a benign mesenchymal tumor with an estimated incidence of 1.5 to 2% of soft tissue tumors. The majority of glomus tumors are benign and are mostly seen in the superficial skin & soft tissue of upper and lower distal extremity. The malignant variant of the glomus tumor is scarce. We report a case of a recurrent glomus tumor diagnosed in a 28-year-old male patient, who complained of painful swelling in the proximal phalanx of the right index finger. The magnetic resonance imaging of the hand revealed a well-defined multilobulated soft tissue mass at the palmar aspect of the 2nd digit along the shaft of the proximal phalanx. Histopathology revealed a well-circumscribed tumor arranged in solid sheets, nests and cords interconnect by vessels of varying size. The tumor cells were round to oval, showed moderate nuclear pleomorphism, eosinophilic cytoplasm, atypical mitoses (>5/10HPF), and necrosis. Immunohistochemically tumor cells reveal diffuse and strong cytoplasmic positivity with smooth muscle actin (SMA). Based on histomorphology and immunohistochemistry, a final diagnosis of malignant glomus tumor was made. We report this case due to its rarity, and it to be included among the differential if the lesion is painful and recurrent.

Epithelioid Vascular Tumors: A Review.

Vascular tumors are a diagnostically challenging area. This is particularly true in the case of epithelioid vascular tumors. Not only is the distinction between different epithelioid vascular tumors challenging, but also the differential diagnosis may be substantially expanded by the inclusion of melanoma, carcinomas, and other epithelioid soft tissue tumors. Recently developed immunohistochemical markers and more comprehensive genetic characterizations continue to advance our understanding of epithelioid vascular tumors. The present paper briefly reviews and updates basic concepts with regard to the following epithelioid vascular tumors: epithelioid hemangioma, epithelioid angiomatous nodule, pseudomyogenic hemangioendothelioma, composite hemangioendothelioma, epithelioid hemangioendothelioma, and epithelioid angiosarcoma.

[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.

Bilateral Myelinated Retinal Nerve Fibers Associated With Bilateral Vitreous Cysts and Solitary Vasoproliferative Tumor: A New Syndrome.

The authors report a case of a 57-year-old male with high myopia, extensive bilateral myelination of the retinal nerve fiber layer, bilateral vitreous cysts, and a solitary vasoproliferative tumor in the right eye. He underwent pars plana vitrectomy and multiple transpupillary thermotherapy treatments for recurrent vitreous hemorrhages and subretinal exudation from the vasoproliferative tumor. To the authors' knowledge, this is the first description of this constellation of findings and suggests this represents a new syndrome. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:356-359.].

Resection of the largest reported hepatic small vessel neoplasm.

Hepatic small vessel neoplasm (HSVN) is a recently described vascular neoplasm of the adult liver. The neoplastic cells are positive for markers of vascular lineage (CD31, CD34, FLI-1). The distinctive morphology and infiltrative borders separate HSVN from benign vascular tumors such as cavernous hemangioma, while lack of atypical morphologic features, low to absent mitotic activity and low proliferation index distinguish it from malignant vascular tumors such as epithelioid hemangioendothelioma and angiosarcoma. Due to its infiltrative nature and lack of adequate follow-up information, the benign versus low-grade nature of this tumor is currently uncertain. We present a patient with resected HSVN involving all but the right posterior section of the liver, making this case the largest reported in the current literature.