Canine Perivascular Wall Tumors Research Articles

Survivin, β-catenin, and ki-67 immunohistochemical expression in canine perivascular wall tumors: Preliminary assessment of prognostic significance.

High survivin expression has been correlated with poor outcomes in several canine tumors but not in soft tissue tumors (STTs). Survivin is a target gene of the Wnt/β-catenin pathway, which is involved in human STT oncogenesis. Immunohistochemistry for survivin, β-catenin, and Ki-67 was performed on 41 canine perivascular wall tumors (cPWTs), and statistical associations of protein expression and histopathologic and clinical variables with clinical outcomes were investigated. Immunohistochemically, there was nuclear positivity (0.9%-12.2% of tumor cells) for survivin in 41/41 (100%), cytoplasmic positivity (0 to > 75% of tumor cells) for survivin in 31/41 (76%), nuclear positivity (2.9%-67.2% of tumor cells) for β-catenin in 24/41 (59%), and cytoplasmic positivity (0% to > 75% of tumor cells) for β-catenin in 23/41 (56%) of cPWTs. All tumors expressed nuclear Ki-67 (2.2%-23.5%). In univariate analysis and multivariate analysis (UA and MA, respectively), every 1% increase of nuclear survivin was associated with an increase of the instantaneous death risk by a factor of 1.15 [hazard ratio (HR) = 1.15; P = .007]. Higher nuclear survivin was associated with grade II/III neoplasms (P = .043). Expression of cytoplasmic survivin, nuclear and cytoplasmic β-catenin, and nuclear Ki-67 were not significantly associated with prognosis in UA nor MA. Tumor size was a significant prognostic factor for local recurrence in UA [subdistribution HR (SDHR) = 1.19; P = .02] and for reduced overall survival time in MA. According to UA and MA, a unitary increase of mitotic count was associated with an increase of the instantaneous death risk by a factor of 1.05 (HR = 1.05; P = .014). Nuclear survivin, mitotic count, and tumor size seem to be potential prognostic factors for cPWTs. In addition, survivin and β-catenin may represent promising therapeutic targets for cPWTs.

Keeping Pathologists in the Loop and an Adaptive F1-Score Threshold Method for Mitosis Detection in Canine Perivascular Wall Tumours

Performing a mitosis count (MC) is the diagnostic task of histologically grading canine Soft Tissue Sarcoma (cSTS). However, mitosis count is subject to inter- and intra-observer variability. Deep learning models can offer a standardisation in the process of MC used to histologically grade canine Soft Tissue Sarcomas. Subsequently, the focus of this study was mitosis detection in canine Perivascular Wall Tumours (cPWTs). Generating mitosis annotations is a long and arduous process open to inter-observer variability. Therefore, by keeping pathologists in the loop, a two-step annotation process was performed where a pre-trained Faster R-CNN model was trained on initial annotations provided by veterinary pathologists. The pathologists reviewed the output false positive mitosis candidates and determined whether these were overlooked candidates, thus updating the dataset. Faster R-CNN was then trained on this updated dataset. An optimal decision threshold was applied to maximise the F1-score predetermined using the validation set and produced our best F1-score of 0.75, which is competitive with the state of the art in the canine mitosis domain.

Survivin immunohistochemical expression in canine perivascular wall tumours: preliminary assessment

Survivin immunohistochemical expression in canine perivascular wall tumours: preliminary assessment

Deep learning for necrosis detection using canine perivascular wall tumour whole slide images

Necrosis seen in histopathology Whole Slide Images is a major criterion that contributes towards scoring tumour grade which then determines treatment options. However conventional manual assessment suffers from inter-operator reproducibility impacting grading precision. To address this, automatic necrosis detection using AI may be used to assess necrosis for final scoring that contributes towards the final clinical grade. Using deep learning AI, we describe a novel approach for automating necrosis detection in Whole Slide Images, tested on a canine Soft Tissue Sarcoma (cSTS) data set consisting of canine Perivascular Wall Tumours (cPWTs). A patch-based deep learning approach was developed where different variations of training a DenseNet-161 Convolutional Neural Network architecture were investigated as well as a stacking ensemble. An optimised DenseNet-161 with post-processing produced a hold-out test F1-score of 0.708 demonstrating state-of-the-art performance. This represents a novel first-time automated necrosis detection method in the cSTS domain as well specifically in detecting necrosis in cPWTs demonstrating a significant step forward in reproducible and reliable necrosis assessment for improving the precision of tumour grading.

Haemangiopericytomas in dogs: Epidemiological analysis of 136 cases

Perivascular wall tumors (PWTs or haemangiopericytomas) are common in dogs, and they are clinically important in veterinary oncology, but there is no data on the occurrence of these tumors in dogs in Poland. The aim of the present study was an epidemiological analysis of canine perivascular wall tumors. The study included 136 dogs with recognized PWTs (whose frequency of occurrence was the same in females and males). The mean age of the dogs was 9.8±3.0 years, with no statistically significant difference between sexes. Among the dogs, 40.7% were mongrels, and 59.3% were purebred. Among the purebred dogs, 21 (26.3%) were German Shepherds, 17 (21.3%) were Boxers, 5 (6.3%) were Doberman pinchers and Rottweilers. Statistical analysis revealed that four breeds were predisposed to perivascular wall tumors in comparison to the general dog population: German Shepherds, Boxers, Doberman pinchers and Rottweilers. Moreover, large-breed (but not giant-breed) dogs were shown to be predisposed to PWTs. Tumors were located in the skin or subcutis of the entire body, mostly on the legs, more seldom on the trunk or the head. The most typical location for PWTs was the elbow area (11% of all cases).

Growth Factors and COX2 Expression in Canine Perivascular Wall Tumors.

Canine perivascular wall tumors (PWTs) are a group of subcutaneous soft tissue sarcomas developing from vascular mural cells. Mural cells are involved in angiogenesis through a complex crosstalk with endothelial cells mediated by several growth factors and their receptors. The evaluation of their expression may have relevance since they may represent a therapeutic target in the control of canine PWTs. The expression of vascular endothelial growth factor (VEGF) and receptors VEGFR-I/II, basic fibroblast growth factor (bFGF) and receptor Flg, platelet-derived growth factor B (PDGFB) and receptor PDGFRβ, transforming growth factor β1 (TGFβ1) and receptors TGFβR-I/II, and cyclooxygenase 2 (COX2) was evaluated on frozen sections of 40 PWTs by immunohistochemistry and semiquantitatively scored to identify their potential role in PWT development. Statistical analysis was performed to analyze possible correlations between Ki67 labeling index and the expression of each molecule. Proteins of the VEGF-, PDGFB-, and bFGF-mediated pathways were highly expressed in 27 (67.5%), 30 (75%), and 19 (47.5%) of 40 PWTs, respectively. Proteins of the TGFβ1- and COX2-mediated pathways were highly expressed in 4 (10%) and 14 (35%) of 40 cases. Statistical analysis identified an association between VEGF and VEGFR-I/II (P = .015 and .003, respectively), bFGF and Flg (P = .038), bFGF and PDGFRβ (P = .003), and between TGFβ1 and COX2 (P = .006). These findings were consistent with the mechanisms that have been reported to play a role in angiogenesis and in tumor development. No association with Ki67 labeling index was found. VEGF-, PDGFB-, and bFGF-mediated pathways seem to have a key role in PWT development and growth. Blockade of tyrosine kinase receptors after surgery could represent a promising therapy with the aim to reduce the PWT relapse rate and prolong the time to relapse.

Canine Perivascular Wall Tumors

Canine perivascular wall tumors (cPWTs) arise from vascular mural cells and are included among soft tissue sarcomas (STSs). Most prognostic studies are performed on canine STSs as a general group and regardless of their specific histotype. The aim of this study was to identify pathological parameters and profiles with prognostic impact for cutaneous/subcutaneous cPWTs. Anatomical location, type of growth, surgical margins, and size and depth of the tumor were collected in 56 cPWTs. The association between each pair of variables was evaluated by χ(2) test. Multiple correspondence analysis (MCA) was performed to describe the multivariate association of variables and was followed by cluster analysis to identify specific pathological profiles. The prognostic impact of variables and profiles was assessed by Cox regression model. Size and depth were significantly associated with increased relapse probability. Cases with complete surgical margins did not recur. Other single variables were not significantly associated with relapse. Cluster analysis on MCA considering site, depth, margins, and type of growth identified 3 pathological profiles associated with PWT relapse and having a high prognostic impact. Major prognostic factors for cPWTs were tumor size, depth of growth, and pathological profiles.

The Effects of Tumor Location on Diagnostic Criteria for Canine Malignant Peripheral Nerve Sheath Tumors (MPNSTs) and the Markers for Distinction Between Canine MPNSTs and Canine Perivascular Wall Tumors

Canine malignant peripheral nerve sheath tumors (MPNSTs) occur not only in the peripheral nervous system (PNS) but also in soft tissue and various organs (non-PNS). The most important diagnostic criterion is proof of peripheral nerve sheath origin. This is difficult in non-PNS MPNSTs, and its differential diagnosis is challenging. Canine perivascular wall tumors (PWTs) also commonly arise in soft tissue. Their histopathological features are quite similar to those of canine MPNSTs, making their differential diagnosis challenging. To elucidate whether the morphological features are applicable to diagnose non-PNS MPNSTs and to demonstrate useful markers for distinction between canine MPNSTs and PWTs, the authors examined 30 canine MPNSTs and 31 PWTs immunohistochemically for S100, nestin, NGFR, Olig2, claudin-1, CD57, PRX, α-SMA, desmin, and calponin. Among canine MPNSTs, the PNS tumors displayed significantly higher S100 and Olig2 expression than the non-PNS tumors. The expression levels of the other markers did not differ significantly, suggesting that the same morphological diagnostic criteria are applicable regardless of their location. The PWT cells displayed significantly weaker immunoreactivity than MPNSTs to markers used except α-SMA and desmin. Cluster analysis sorted most canine MPNSTs and PWTs into 2 distinctly different clusters, whereas 3 MPNSTs and 6 PWTs were assigned to the opposing cluster. These 3 MPNSTs were negative for almost all markers, while these 6 PWTs were positive for only neuronal markers. In particular, NGFR and Olig2 were almost negative in the rest of PWT cases. These findings suggest that NGFR and Olig2 are useful to distinguish these 2 tumors.

Use of Electron Microscopy to Classify Canine Perivascular Wall Tumors

The histologic classification of canine perivascular wall tumors (PWTs) is controversial. Many PWTs are still classified as hemangiopericytomas (HEPs), and the distinction from peripheral nerve sheath tumors (PNSTs) is still under debate. A recent histologic classification of canine soft tissue sarcomas included most histologic types of PWT but omitted those that were termed undifferentiated. Twelve cases of undifferentiated canine PWTs were evaluated by transmission electron microscopy. The ultrastructural findings supported a perivascular wall origin for all cases with 4 categories of differentiation: myopericytic (n = 4), myofibroblastic (n = 1), fibroblastic (n = 2), and undifferentiated (n = 5). A PNST was considered unlikely in each case based on immunohistochemical expression of desmin and/or the lack of typical ultrastructural features, such as basal lamina. Electron microscopy was pivotal for the subclassification of canine PWTs, and the results support the hypothesis that canine PWTs represent a continuum paralleling the phenotypic plasticity of vascular mural cells. The hypothesis that a subgroup of PWTs could arise from a pluripotent mesenchymal perivascular wall cell was also considered and may explain the diverse differentiation of canine PWTs.

Expression of claudin-1 in canine peripheral nerve sheath tumours and perivascular wall tumours. Immunohistochemical study.

A peripheral nerve sheath tumour consists of neoplastic Schwann cells or perineurial cells, or a mixture of Schwann cells, perineurial cells and fibroblasts. The first aim of the present study was to characterise the expression of the claudin-1 tight junction protein in canine intact peripheral nerves, canine benign peripheral nerve sheath tumours (cBPNSTs), such as schwannomas, neurofibromas, perineuriomas and canine malignant peripheral nerve sheath tumours (cMPNSTs), and in different other benign and malignant canine spindle cell tumours. The second aim of the present study was to examine whether claudin-1 can help to distinguish the subgroups of canine perivascular wall tumours. The biopsy and necropsy samples (n=203) included 10 intact peripheral nerves, 20 cBPNSTs (4 schwannomas, 8 neurofibromas, 8 perineuriomas), 16 cMPNSTs, 6 psammomatous meningiomas, 6 dermatofibromas, 6 leiomyomas, 6 myxomas, 4 spindle cell hemangiomas, 2 spindle cell lipomas, 6 fibrohistiocytic nodules, 8 fibrosarcomas, 8 leiomyosarcomas, 6 myxosarcomas, 8 hemangiosarcomas, 8 anaplastic sarcomas, 8 amelanotic spindle cell melanomas, 8 histiocytic sarcomas, 8 spindle cell carcinomas, 8 myoepitheliomas, 8 complex carcinomas, 5 cardiac rhabdomyosarcomas, 4 synovial sarcomas, 5 osteosarcomas, 4 chondrosarcomas and 4 liposarcomas; 31 canine perivascular wall tumours: 10 hemangiopericytomas, 8 myopericytomas, 6 angioleiomyomas, 4 angioleiomyosarcomas, 3 angiofibromas. The immunohistochemical panel consisted of humanized antibodies: anti-claudin-1, anti-neuron specific enolase, anti-S-100 protein, anti-α-smooth muscle actin, anti-vimentin, anti-cytokeratin AE1-AE3, anti-claudin-5, anti-Melan-A and anti-heavy caldesmon, anti-calponin and anti-desmin. The intact perineurial cells, all perineuriomas, neurofibromas, cMPNSTs, spindle cell carcinomas and epithelial components of the complex carcinomas, all hemangiopericytomas and myo-pericytomas showed claudin-1 positivity. The schwannomas and other spindle shape cell tumours were negative for claudin-1. Our findings suggest that an antibody against claudin-1, in combination with other antibodies, can be used as a novel diagnostic tool to differentiate canine peripheral nerve sheath tumours from other fusocellular tumours, and anti-claudin-1, together with other antibodies, can also be used to subclassify cBPNSTs. Furthermore, analysis of claudin-1 expression can help to differentiate between subgroups of canine perivascular wall tumours.

Comparison of three different grading systems in canine Perivascular Wall Tumours

Comparison of three different grading systems in canine Perivascular Wall Tumours

Immunohistochemical expression of VEGF, Flk1 and CTGF in canine Perivascular Wall Tumours

Immunohistochemical expression of VEGF, Flk1 and CTGF in canine Perivascular Wall Tumours