Immunohistochemical characterization of mesothelioma in 6 large felids

2021 ◽  
pp. 104063872110156
Author(s):  
Sarah E. Coe ◽  
Michael M. Garner ◽  
Matti Kiupel

Mesothelioma has been reported frequently in large felids. These neoplasms present a diagnostic challenge given their highly variable morphology that mimics carcinomas or sarcomas at different locations. Our goal was to characterize mesotheliomas morphologically and immunohistochemically to determine if a panel of antibodies could be used to more accurately support the diagnosis of these neoplasms in large felids. Mesotheliomas from 6 large felids, including 4 clouded leopards, 1 Bengal tiger, and 1 cheetah, were immunohistochemically labeled for vimentin, E-cadherin, pancytokeratin, Wilms tumor 1 (WT1), MUC-1, and calretinin. The mesotheliomas of the 4 clouded leopards and the tiger were of the epithelial subtype; the mesothelioma from the cheetah was biphasic. All 6 mesotheliomas had strong immunohistochemical labeling for vimentin, E-cadherin, and pancytokeratin. All cases had cytoplasmic labeling for WT1, and 2 also had nuclear labeling. The 3 mesotheliomas with distinct papillary fronds were weakly positive for MUC-1. These and one other epithelial mesothelioma were also positive for calretinin. Our study demonstrates that the morphologic and immunohistochemical phenotypes of mesothelioma that have been identified in humans and domestic species can occur in large felids, and a panel of pancytokeratin, vimentin, WT1, and calretinin can be utilized to support the diagnosis of these neoplasms.

Cell Cycle ◽  
2020 ◽  
Vol 19 (20) ◽  
pp. 2662-2675
Author(s):  
Yun Han ◽  
Chao Song ◽  
Tingting Zhang ◽  
Qianqian Zhou ◽  
Xiaoqian Zhang ◽  
...  

2015 ◽  
Vol 123 (4) ◽  
pp. 989-997 ◽  
Author(s):  
Keiichi Sakai ◽  
Shigetaka Shimodaira ◽  
Shinya Maejima ◽  
Nobuyuki Udagawa ◽  
Kenji Sano ◽  
...  

OBJECT Dendritic cell (DC)-based vaccination is considered a potentially effective therapy against advanced cancer. The authors conducted a Phase I study to investigate the safety and immunomonitoring of Wilms’ tumor 1 (WT1)-pulsed DC vaccination therapy for patients with relapsed malignant glioma. METHODS WT1-pulsed and/or autologous tumor lysate-pulsed DC vaccination therapy was performed in patients with relapsed malignant gliomas. Approximately 1 × 107 to 2 × 107 pulsed DCs loaded with WT1 peptide antigen and/or tumor lysate were intradermally injected into the axillary areas with OK-432, a streptococcal preparation, at 2-week intervals for at least 5–7 sessions (1 course) during an individual chemotherapy regimen. RESULTS Ten patients (3 men, 7 women; age range 24–64 years [median 39 years]) with the following tumors were enrolled: glioblastoma (6), anaplastic astrocytoma (2), anaplastic oligoastrocytoma (1), and anaplastic oligodendroglioma (1). Modified WT1 peptide–pulsed DC vaccine was administered to 7 patients, tumor lysate-pulsed DC vaccine to 2 patients, and both tumor lysate–pulsed and WT1-pulsed DC vaccine to 1 patient. The clinical response was stable disease in 5 patients with WT1-pulsed DC vaccination. In 2 of 5 patients with stable disease, neurological findings improved, and MR images showed tumor shrinkage. No serious adverse events occurred except Grade 1–2 erythema at the injection sites. WT1 tetramer analysis detected WT1-reactive cytotoxic T cells after vaccination in patients treated with WT1-pulsed therapy. Positivity for skin reaction at the injection sites was 80% (8 of 10 patients) after the first session, and positivity remained for these 8 patients after the final session. CONCLUSIONS This study of WT1-pulsed DC vaccination therapy demonstrated safety, immunogenicity, and feasibility in the management of relapsed malignant gliomas.


2017 ◽  
Vol 59 (6) ◽  
pp. 700-708
Author(s):  
Mohamed Ragab Nouh ◽  
Hanan Abd El-Aziz Amr ◽  
Rola H Ali

Background Soft-tissue chondroma (STC) is a rare benign soft tissue tumor that arises primarily in acral extra-skeletal locations. Occasionally, STCs may arise in more proximal non-acral locations, accompanied by non-classic features that label them as indeterminate lesions and pose diagnostic challenge for both radiologists and pathologists alike. Purpose To explicate the potential of diagnostic imaging in the identification and characterization of appendicular non-acral STCs with emphasis on their morphologic magnetic resonance imaging (MRI) enhancement. Material and Methods Our clinical database records were searched for patients with histologically proven primary soft-tissue chondroid lesions over a five-year period. Two musculoskeletal (MSK) trained radiologists evaluated the imaging studies and an MSK pathologist revised the pathological findings. Results The study included six cases of appendicular non-acral STCs (mean age = 40.5 years). The mean size of the tumors was 5.6 cm, with four localized to the knee region, one in the thigh, and one in the sternoclavicular region. All cases showed high signal intensity matrix with low-signal intensity septa on T2-weighted MRI and post-contrast marginal/septal enhancement. The lesions were lobulated and lacked host tissue reaction except for one showing subjacent mild soft-tissue edema. Histologically, the cases lacked overt features of malignancy although one was originally misdiagnosed as chondrosarcoma. Conclusion Non-acral STCs are benign cartilaginous tumors that may pose a diagnostic challenge, both radiologically and pathologically. Collaborative imaging and pathologic workup is needed for better characterization of non-aggression of these lesions, and to avoid diagnostic pitfalls and unnecessary radical resections.


2020 ◽  
Vol 58 (3) ◽  
pp. 198-207
Author(s):  
Elżbieta Zarychta ◽  
Katarzyna Lepinay ◽  
Sebastian Szubert ◽  
Jakub Jozwicki ◽  
Jan Misiak ◽  
...  

2021 ◽  
Author(s):  
Ayana Morales ◽  
Caitlyn Genovese ◽  
Matthew Bott ◽  
Julio Alvarez ◽  
Sung Soo Mun ◽  
...  

AbstractPurposeWilms’ tumor 1 (WT1) is overexpressed in several cancers, and WT1 expression levels are associated with poor prognosis. As a host protein that functions as an oncogene, it represents an important immunotherapeutic target. This study evaluated WT1 expression in Kaposi sarcoma (KS) tumors to assess whether immunotherapy targeting WT1 is a potential therapeutic approach for KS. We also investigated the role of the causal agent of KS, Kaposi sarcoma herpesvirus (KSHV/HHV-8) in regulating WT1 expression.Experimental designImmunohistochemistry for WT1, KSHV, and B and T cells subsets, followed by image analysis, was performed in 363 KS tumor biopsies. Expression of KSHV vFLIP was evaluated by immunofluorescence. Primary endothelial cell cultures and cell lines were infected with KSHV in vitro, or transduced with an inducible vFLIP vector and induced with doxycycline, and then assessed for WT1 expression. Binding of ESK-1, a T cell receptor mimic therapeutic antibody that recognizes WT1 peptides presented on MHC HLA-A0201, was assessed using flow cytometry.ResultsWe report overexpression of WT1 in KS tumors, which was associated with increased with increasing histopathologic stage and the proportion of KSHV-infected cells. Areas with high WT1 expression showed sparse T cell infiltrates. KSHV infection in vitro resulted in WT1 upregulation, mediated by the viral protein vFLIP, which resulted in stronger binding of ESK1.ConclusionsKS lesions express high levels of WT1, a process regulated by the KSHV-encoded vFLIP. These findings suggest that immunotherapy directed against WT1 may represent a therapeutic approach for this cancer.Translational RelevanceKaposi sarcoma (KS) is a vascular neoplasm caused by the Kaposi sarcoma herpesvirus (KSHV/HHV-8). People living with HIV are not only at a significantly higher risk of developing KS, but also often have a more aggressive clinical course. Although antiretroviral therapy may cause regression of HIV-associated KS lesions, advanced cases of KS also require chemotherapy, which is rarely curative. Wilms’ tumor 1 (WT1) has been reported to be overexpressed in various cancers, functioning as an oncogene and associated with a poor prognosis. WT1 is also an important immunotherapeutic target, with several WT1-directed therapies showing promising results in early clinical trials for leukemias and solid tumors. Here we report high expression of WT1 in KS, especially in higher histological stages. Our findings provide pre-clinical evidence that supports conducting anti-WT1 immunotherapy trials in KS, and evaluating WT1 expression as a potential biomarker to identify individuals most likely to benefit.


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