Multiple Undifferentiated Pleomorphic Sarcoma (Malignant Fibrous Histiocytoma) with Extradural Involvement in a 7-Year-Old Labrador Retriever

A 7-year-old castrated male Labrador retriever was referred for evaluation of progressive hind limb paresis of 4 weeks’ duration. On computed tomography and magnetic resonance imaging examination, masses were found in several regions including the lung, right kidney, and peritoneum. Additionally, an extradural mass at the region of T13–L1 was identified, which is assumed to related to the chief complaint, progressive hind limb paresis. With the consent of the owner, a dorsal laminectomy was performed to remove the mass and surrounding tissues for the palliation of the hind limb paresis. Hematoxylin and eosin staining and immunohistochemical examination revealed the mass to be consistent with an undifferentiated (high-grade) pleomorphic sarcoma. The patient presented with recurrence of the hind limb paresis, respiratory discomfort, and urinary incontinence. The owner declined treatment and the dog was euthanized. Systemic metastasis was confirmed on postmortem microscopic examination. To the authors’ knowledge, this is the first report describing multiple undifferentiated high-grade pleomorphic sarcoma with extradural involvement developing into the vertebral canal through the intervertebral space, resulting in spinal damage, in a dog.

CS-6 A case of poorly differentiated chordoma with systemic metastasis

A case report: The patient was a 32-year-old man with diplopia. He was diagnosed as sphenoid sinusitis on MRI by a local doctor and visited an otolaryngologist. MRI showed extensive extension of neoplastic lesions from the clivus to the sphenoid sinus to the anterior ethmoid sinuses, bilateral cavernous sinuses, and the right medial and lateral pterygoid muscles. The right Lebiere’s lymph node was enlarged and thought to be a metastatic site. Based on the rapid growth and extension of the tumor, the patient was referred to the Department of Otolaryngology at our hospital on suspicion of sinonasal carcinoma. The possibility of chordoma could not be denied, so the patient was referred to our department. The patient underwent a joint endoscopic extended transsphenoidal tumor resection. The pathological diagnosis showed mitotic and necrotic features, and the majority of the cells showed highly atypical components without mucous substrate. However, brachyury, a marker for chordoma, was diffusely positive, and there was loss of INI1 (SMARCB1) expression. The final diagnosis was poorly differentiated chordoma. Postoperatively, the tumor in the right cavernous sinus grew rapidly, and the right eye became blind due to obstruction of the superior ophthalmic vein. The patient was treated with Gamma Knife as soon as possible in the hope of local control by high-dose irradiation, and after a total of three irradiations, the residual tumor shrank markedly and symptoms improved, but systemic metastasis occurred in a short period of time and the patient died. The number of cases of poorly differentiated chordoma has been reported rarely (more than 50), and it is more common in children and even rarer in adults. We report this case with a review of the literature.

A Case of Solitary Metastatic Deposit in the Orbital Rim from Follicular Thyroid Cancer

Follicular thyroid carcinoma (FTC) is the second most common thyroid cancer, following papillary carcinoma. Metastasis to the orbital rim from FTC is very rare. We recently experienced a case of FTC with metastasis to the orbital rim in a 74-year-old woman, who initially presented with a huge thyroid mass and an asymptomatic solitary orbital rim lesion. The solitary orbital rim lesion was suspected to be a separate disease entity such as lymphoma from the preoperative imaging, but bone metastasis from FTC was finally confirmed after orbital rim resection and total thyroidectomy. During follow-up, the patient presented multiple bone metastasis, so the solitary orbital rim lesion was considered a clinical sign of systemic metastasis from FTC. Therefore, we present this unique case with a review of the literature.

Identification of a Hypoxia-Related Gene Signature for Predicting Systemic Metastasis in Prostate Cancer

Background: Systemic metastasis is the main cause of death in patients with prostate cancer. It is necessary to establish a more accurate model to distinguish and predict patients with a high risk of metastasis to optimize individualized treatment.Methods: In this study, it was determined that hypoxia could affect the metastasis-free survival of patients with prostate cancer, and a hypoxia-related gene signature composed of seven genes for predicting metastasis was established and verified in different cohorts. The study further evaluated the effects of ALDOB expression on the proliferation and invasion of the LNCaP and DU145 cell lines under hypoxia and finally constructed a nomogram containing specific clinical characteristics of prostate cancer combined with the hypoxia gene signature to quantify the metastasis risk of individual patients.Results: The hypoxia-related gene signature was identified as an independent risk factor for metastasis-free survival in patients with prostate cancer. The expression of ALDOB increased under hypoxia and promoted the proliferation and invasion of LNCaP and DU145 cells. In addition, patients with a high risk score showed therapeutic resistance and immunosuppression. Compared with other parameters, the nomogram had the strongest predictive power and net clinical benefit.Conclusion: The study established a hypoxia-related gene signature and a nomogram to distinguish and predict patients with a high risk of prostate cancer metastasis, which may help to optimize individualized treatment and explore possible therapeutic targets.

Detailed Analysis and Radiomic Prediction of First Progression Sites of First-Line Targeted Therapy for EGFR-Mutant Lung Adenocarcinoma Patients With Systemic Metastasis

BackgroundWe aimed to analyze the first progression sites of first-line tyrosine kinase inhibitor (TKI) treatment for EGFR-mutant lung adenocarcinoma patients with systemic metastasis to recognize the potential candidates who might benefit from radiotherapy and establish a radiomic-based model to predict the first progression sites.Materials and MethodsWe retrospectively collected the clinical information and pre-treatment chest CT images of patients in Shanghai Chest Hospital from 2013 to 2017. All patients were diagnosed with stage IV EGFR-mutant lung adenocarcinoma and received TKI as first-line treatment. The first progression sites and survival were analyzed. The pre-treatment chest non-contrast CT images were utilized to establish a radiomic-based model to predict the first progression sites.ResultsWe totally collected 233 patients with systemic metastasis, among whom, there were 84 (36.1%) and 149 (63.9%) patients developing first progression in original lesions (OP) and new lesions (NP), respectively. The PFS and OS of patients with OP were longer than those with NP (PFS 11 months vs. 8 months, p = 0.03, OS 50 months vs. 35 months, p = 0.046). For 67.9% of the patients with OF, disease progressed within five sites (oligoprogression). The radiomic-based model could predict the progression sites with an AUC value of 0.736, a specificity of 0.60, and a sensitivity of 0.750 in the independent validation set.ConclusionAmong patients with systemic metastasis, there were 36.1% of patients developing OP at first progression who had a better prognosis than those developing NP. Patients with OP may be potential candidates who might benefit from radiotherapy. Radiomics is a useful method to distinguish patients developing OP and could provide some indications for radiotherapy.

Natural History of Untreated Retinoblastoma

Treatment abandonment is a leading cause of death in children with retinoblastoma worldwide. We studied children who abandoned treatment upfront at diagnosis to delineate the natural history of untreated retinoblastoma. Studied were children who received no treatment, diagnosed between 2007 and 2017 at 29 Chinese centers. Data were retrospectively collected from medical chart reviews and interviews with each patient’s family. During the study period, 44 children received no treatment after diagnosis of retinoblastoma. Clinical or radiologic evidence of orbital extension was available for 25 children, and radiologic evidence of systemic metastasis was available for 12 children. Median times from diagnosis of intraocular tumor to orbital disease was 13.7 months, orbital disease to metastasis was 2.6 months, and metastasis to death was 2.0 months. Children with brain metastasis had shorter survival than those with metastasis to other sites (median 1.0 vs. 3.1 months; p = 0.015). Overall, 36% of patients died within 12 months of diagnosis, 77% within 24 months, 95% within 36 months and 100% within 48 months. While multiple factors influence refusal of treatment, insights into the natural history of retinoblastoma derived from real-world evidence can inform clinicians and parents that retinoblastoma is life-threatening and encourage urgent treatment at diagnosis.

WNT8B as an Independent Prognostic Marker for Nasopharyngeal Carcinoma

Background: Members of the Wnt signaling pathway have been shown to play a role in nasopharyngeal carcinoma (NPC) progression. Aim: The purpose of this study was to investigate WNT8B protein expression in NPC patients using tissue microarray (TMA) analysis and to evaluate its correlation with patient survival and clinical parameters. Methods: A total of 82 NPC cases, together with six normal nasopharyngeal tissue samples, were targeted to construct the TMA blocks. The WNT8B protein expression was evaluated by immunohistochemistry and its correlation to the clinicopathological features was investigated. Results: Sixty-two of 82 (75.6%) cases exhibited high WNT8B protein expression while 20/82 (24.4%) cases appeared to have low WNT8B expression. The univariate analysis revealed that systemic metastasis was associated with patient 5-year survival. The multivariate Cox proportional hazard regression analysis showed that WNT8B expression and systemic metastasis were significantly associated with the survival of NPC patients. Furthermore, there was no correlation found between the WNT8B protein expression and other clinicopathological parameters. Conclusion: Our results suggest that the expression of WNT8B is associated with NPC patients’ survival and could serve as an independent prognostic factor for NPC patients.

Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy

Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form “micro-thrombi” with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of “micro-thrombi”, and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.