Cushing's syndrome caused by giant Ewing's sarcoma of the kidney:A case report and review of literature

BACKGROUND Primary renal Ewing’s sarcoma(ES)is extremely rare,and only two cases causing Cushing’s syndrome(CS)have been reported to date.We report that the case of an 18-year-old patient is diagnosed primary renal ES with typical CS characterized by purple stripes,weight gain,and hypertension.CASE SUMMARY CS was first diagnosed by laboratory testing.A huge tumor was revealed in the kidney following an imaging examination.Moreover,brain and bone metastases were observed.After comprehensive treatment,primarily based on surgery,primary renal ES was pathologically diagnosed with a typical EWSR1-FLI1 genetic mutation through genetic testing.Furthermore,the glucocorticoid level returned to normal.By the ninth postoperative month of follow-up,the patient was recovering well.Cushing-related symptoms had improved,and a satisfactory curative effect was achieved.CONCLUSION Primary renal ES,a rare adult malignant tumor,can cause CS and a poor prognosis.

Unlocking epigenetics for precision treatment of Ewing’s sarcoma

Ewing’s sarcoma(EWS)is a highly aggressive malignant bone tumor primarily affecting adolescents and young adults.Despite the efficacy of chemoradiotherapy in some cases,the cure rate for patients with metastatic and recurrent disease remains low.Therefore,there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS treatment.Epigenetic regulation,a crucial factor in physiological processes,plays a significant role in controlling cell proliferation,maintaining gene integrity,and regulating transcription.Recent studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS.A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug development.This review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS,integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

Perigastric extraskeletal Ewing's sarcoma: A case report

Ewing's sarcoma (ES) is a neoplasm of undifferentiated small round cells, which occurs in the bones and deep soft tissues of children and adolescents. We present a rare case of a 44-year-old woman with gastric ES presenting with epigastric pain and weight loss. Ultrasound and computed tomography scans indicated a solid/cystic mass in the pancreatic tail. At laparotomy, the tumor was found attached to the posterior surface of the stomach, completely free from the pancreas, with no lymphadenopathy or local metastases. The polynodal, partly pseudocystic, dark-red soft tumor was excised. Histopathology revealed an anaplastic small-round-cell tumor with strong membranous CD99 immunoexpression. Additionally, there was patchy immunostaining for S-100 protein, vimentin, protein gene product (PGP) 9.5 and neuron-specifi c enolase, and weak focal CD117 cytoplasmic immunoreactivity. The patient had no adjuvant chemotherapy; her postoperative recovery was uneventful, and she remains symptom-free, and without any sign of recurrence at 20 mo. To the best of our knowledge, this is only the third ever case of gastric ES.

Extraskeletal Ewing sarcoma of the stomach:A rare case report

BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors.We herein present a rare case of ES involving the gastric area.CASE SUMMARY We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d.Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach;the mass was connected to the gastric antrum.Then,the mass was surgically excised completely.Upon histopathological,immunophenotype and molecular analysis,the mass was identified to be a primary gastric ES.CONCLUSION EES is an aggressive tumor with poor prognosis.Therefore,early diagnosis and timely intervention are essential for a good prognosis.It is imperative for us to raise awareness about this rare tumor.Surgical resection is still the best treatment option.

Primary extraosseous Ewing's sarcoma of the lung in a 36-year-old female patient:clinical,imaging,and pathologic findings

Primary extraosseous Ewing's sarcoma is a very rare clinical entity. In the report, we present the case of a 36year-old female patient who underwent resection of lung mass and was diagnosed as having Ewing's sarcoma by pathological examination. The clinical, imaging, and pathologic features of the case are described and discussed.

Extraosseous Ewing's sarcoma arising from the pterygomandibular space

Extraosseous Ewing’s sarcoma (EES) arising in head and neck is extremely rare. We report on a rare case of EES originating from the pterygomandibular space. A 15-year-old boy was seen with a rapidly growing mass in the right upper neck, difficulty in opening mouth, dysphagia, numbness in the right lower lip and buccal skin. Clinical and radiological examinations indicated that a soft tissue mass origi-nated from the pterygomandibular space with the submandibular space and mouth floor extension. Histological and immunohistochemical evaluations of the biopsy specimen revealed poorly differentiated small blue round cells with positive stains for CD99 and neuron-specific enolase. According to the clinical manifestation, CT and MRI findings, histological pattern and the results of the immunohistochemical studies, the final diagnosis was EES. Our patient was treated with chemotherapy and radiotherapy. The lesion recurred locally after 10 months and he died of multiple distant metastases 22 months later. Early and confident diagnosis coupled with combined surgical excision and modern chemotherapy/radiotherapy appears to be the most effective treatment plan.

生物信息大分子功能的研究——酵母甘露聚糖对鼠Sarcoma-180瘤生长的抑制效应

酵母甘露聚糖(Mannan,简称Man)是能参与生物信息流影响生物体、特别是在糖基化方面起着重要调控作用的生物信息大分子。它是否能在抑制生物机体中肿瘤生长方面具有重要作用?研究结果表明:酵母甘露聚糖既能使患S-180瘤鼠的体质增强的同时又有抑制其体内所患S-180瘤生长的功效。Man抑制患鼠机体内的S-180瘤生长的功效(抑瘤率)随用量的增加而提高,当Man用量达360 mg(40 mg/Kg/d·9d)时,其抑瘤率达98.4%的最高水平,此时鼠体重增加1.66倍。Man的抑瘤功效有最佳适用量并存在性别敏感性,通常是雄性鼠的抑瘤率高于雌性鼠。Man抑制鼠S-180肿瘤生长的作用优于市售5-氟尿嘧啶的作用。

Genotypic analysis on the ORF-K1 gene of human herpesvirus 8 from patients with Kaposi's sarcoma in Xinjiang,China

Human herpesvirus 8 （HHV-8） is thought to be essential for the development of all forms of Kaposi＇s sarcoma （KS）. HHV-8 DNA is present virtually in all KS tumor biopsy samples. Genes at both ends of the HHV-8 genome have been shown to vary considerably. Seven major molecular subtypes of HHV-8 were defined based on the amino acid sequence of the open reading frame K1 （ORF-K1）, generally known as A, B, C, D, E, F, and Z. Most strains collected worldwide were clustered into two subtypes （A and C）. Here, the K1/VRI region of HHV-8 was amplified by nested PCR in 22 （81.48%） of 27 cases from Xinjiang Uygur Autonomous Region, a province in northwestern China. Phylogenetic analysis on the basis of the K1/VR1 amino acid sequence indicated that the majority of these KS patients were infected by subtype C HHV-8 （n = 18, including 15 belonging to the C2 group）, and several by subtype A （n = 4, including 3 being the A1 group）. This is the first report of subtype A HHV-8 in China. Furthermore, the correlations between different forms and lesions of KS and different subtypes of HHV-8 were analyzed. The findings showed that subtype A HHV-8 resulted in significantly more frequent mucosal KS lesions than subtype C. However, there was no obvious correlation between different forms of KS and different subtypes of HHV-8.

Antitumor effect and mechanism of Gecko on human esophageal carcinoma cell lines in vitro and xenografted sarcoma 180 in Kunming mice

AIM: To investigate the anti-tumor effect of Chinese medicine Gecko on human esophageal carcinoma cell lines and xenografted sarcoma 180 in Kunming mice and its mechanism. METHODS: The serum pharmacological method was used in vitro . The growth rates of the human esophageal carcinoma cells (EC9706 or EC1) were measured by a modifi ed 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The transplanted tumor model of the mouse S180 sarcoma was established. Fifty mice were randomly divided into fi ve groups (n = 10). Three Gecko groups were treated respectively with oral administration of Gecko powder at a daily dose of 13.5 g/kg, 9 g/kg, and 4.5 g/kg. The negative group (NS group) was treated with oral administration of an equal volume of saline and the positive group (CTX group) was treated with 100 mg/kg Cytoxan by intraperitoneal injection at the fi rst day. After 2 wk of treatment, the anti-tumor activity was evaluated by tumor tissue weighing. The impact on immune organ was detected based on the thymus index, spleen index, phagocytic rate and phagocytic index. The protein expression of vascular endothelingrowth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected by immunohistochemistry. The cell apoptotic rate was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The A value in each group treated with Gecko after 72 h was reduced signif icantly in EC9706 and in EC1. The tumor weight in each group of Gecko was decreased signifi cantly (1.087 ± 0.249 vs 2.167 ± 0.592; 1.021 ± 0.288 vs 2.167 ± 0.592; 1.234 ± 0.331 vs 2.167 ± 0.592; P < 0.01, respectively). However, the thymus index and Spleen index of mice in Gecko groups had no significant difference compared with the NS group. The immunoreactive score of VEGF and bFGF protein expression of each Gecko group by immunohistochemical staining were lowered signifi cantly. The apoptosis index (AI) of each group was increased progressively with increase of dose of Gecko by TUNEL. CONCLUSION: Gecko has anti-tumor effects in vitro and in vivo; induction of tumor cell apoptosis and the down-regulation of protein expression of VEGF and bFGF may be contributed to anti-tumor effects of Gecko.

A case of steroid-dependent myeloid granulocytic sarcoma masquerading as Crohn's disease

Small bowel tumors and Crohn's disease are common causes of small bowel obstruction.Early stage neoplasms can easily be mistaken for Crohn's disease.Therefore,thorough work-ups including imaging studies and endoscopic evaluation with biopsies are critical for accurate diagnosis.Here we report a case of an otherwise healthy female with progressive onset of multiple,recurrent obstructive symptoms secondary to terminal ileal narrowing who was referred for management of steroid-dependent Crohn's disease.After thorough evaluation,the diagnosis was revised to myeloid granulocytic sarcoma involving the terminal ileum.In this case,a delay in diagnosis can be detrimental for prognosis,as myeloid granulocytic sarcoma is highly predictive of underlying acute myeloid leukemia and needs urgent referral for chemotherapy and/or resection.

Ureteral Ewing’s sarcoma in an elderly woman: A case report

BACKGROUND Ewing’s sarcoma(ES)is regarded as a skeletal tumor,with few instances of extraskeletal ES.A primary ES in the ureter is extremely rare.CASE SUMMARY We report the case of a 69-year-old woman who presented with intermittent flank pain and hematuria and was found to have a mass in the left ureter.Pathology of the excised mass indicated ES.The clinical treatment and pathologic characteristics in this case,and a review of the literature describing ES in the urinary system,are presented.CONCLUSION Due to the rarity and malignancy of ES in ureter,early diagnosis and prompt surgical treatment are critical.

EWS Knockdown and Taxifolin Treatment Induced Differentiation and Removed DNA Methylation from p53 Promoter to Promote Expression of Puma and Noxa for Apoptosis in Ewing’s Sarcoma

Ewing’s sarcoma is a pediatric tumor that mainly occurs in soft tissues and bones. Malignant characteristics of Ewing’s sarcoma are correlated with expression of EWS oncogene. We achieved knockdown of EWS expression using a plasmid vector encoding EWS short hairpin RNA (shRNA) to increase anti-tumor mechanisms of taxifolin (TFL), a new flavonoid, in human Ewing’s sarcoma cells in culture and animal models. Immunofluorescence microscopy and flow cytometric analysis showed high expression of EWS in human Ewing’s sarcoma SK-N-MC and RD-ES cell lines. EWS shRNA plus TFL inhibited 80% cell viability and caused the highest decreases in EWS expression at mRNA and protein levels in both cell lines. Knockdown of EWS expression induced morphological features of differentiation. EWS shRNA plus TFL caused more alterations in molecular markers of differentiation than either agent alone. EWS shRNA plus TFL caused the highest decreases in cell migration with inhibition of survival, angiogenic and invasive factors. Knockdown of EWS expression was associated with removal of DNA methylation from p53 promoter, promoting expression of p53, Puma, and Noxa. EWS shRNA plus TFL induced the highest amounts of apoptosis with activation of extrinsic and intrinsic pathways in both cell lines in culture. EWS shRNA plus TFL also inhibited growth of Ewing’s sarcoma tumors in animal models due to inhibition of differentiation inhibitors and angiogenic and invasive factors and also induction of activation of caspase-3 for apoptosis. Collectively, knockdown of EWS expression increased various anti-tumor mechanisms of TFL in human Ewing’s sarcoma in cell culture and animal models.

Kaposi’s sarcoma manifested as lower gastrointestinal bleeding in a HIV/HBV-co-infected liver cirrhosis patient: A case report

BACKGROUND Kaposi’s sarcoma(KS)is one of the most common cancers in human immunodeficiency virus(HIV)-positive patients and leads to a high prevalence of morbidity and mortality.It usually appears as cutaneous or mucous lesions.Patients with visceral KS are asymptomatic and clinically silent.As the disease advances,patients may progress from a normal condition to exhibiting severe symptoms.CASE SUMMARY A 27-year-old man presented with a 2-mo history of fever,bearing-down pain,and rectal bleeding.His hepatitis B virus DNA level was 2.7×107 IU/mL.Abdominal computed tomography(CT)indicated liver cirrhosis.Before he was admitted to our hospital,he was diagnosed with HIV infection.His CD4 count was 24 cells/μL.Pelvic cavity CT suggested a thickened rectum wall accompanied by multiple enlarged lymph nodes.The patient was initially treated as having haemorrhoidal varices with bleeding,telbivudine for anti-hepatitis B virus treatment,and antibiotics for anti-infection.After half a month of treatment,the patient felt that his lower lumbus ache and bearing-down pain had not improved,and a colonoscopy was conducted.The result revealed a rectal mass that was histologically confirmed as KS with rectal spindle cells that were positive for cluster of differentiation 117(CD117),CD34,human herpes virus 8,and CD31.He was administered systemic chemotherapy with 36 mg/d liposomal doxorubicin six times.The patient experienced no sign of lower gastrointestinal bleeding again.CONCLUSION This case highlights the diagnosis of primary KS with lower gastrointestinal bleeding in HIV-positive patients,which means visceral KS could not be excluded.The gold standard relies on colonoscopy and biopsy findings.

A Case of Ewing’s Sarcoma of the Clavicle in Adults

The Clavicle is a rare primary site for Ewing sarcoma (ES). We report one case of patient with clavicular ES under our tracking and review the related literatures on management of this rare tumor. The patient was age of 35 years and were non metastaticat presentation. The patient received chemotherapy before and after the surgery. Claviculectomy was used. The patient had good functional outcomes with no pain of the shoulder at the follow-up of ten months. In conclusion, Ewing sarcoma of clavicle is a very rare tumor and different methods of surgical treatment can be used. Clavicle often can be resected without a need of reconstruction.

Modulation of MMP-2 and TIMP-2 by low dose radiation in mice bearing S180 sarcoma

Objective To investigate the inhibition of low dose radiation （LDR） on S180 sarcomas and its modulation of MMP-2 and TIMP-2 in mice. Methods $180 subcutaneously implanted tumor model mice were randomly divided into two groups： control （N） and low dose radiation （LDR） groups. N mice were sacrificed after 12 h, whereas LDR mice were sacrificed after 12 （LDR-12 h）, 24 （LDR-24 h）, 48 （LDR-48 h）, and 72 （LDR-72 h） h. Thereafter, we measured the tumor volumes. Histopathology was performed, and P-V immunohistochemistry was applied to assess MMP-2 and TIMP-2 expression. Results Compared with the control group, the tumor growth was significantly inhibited in the LDR groups （P 〈 0.05）. MMP-2 expression was considerably reduced in LDR-24h （P 〈 0.05） and LDR-48h （P 〈 0.05）, whereas the change of TIMP-2 was not obvious in the LDR groups （P 〉 0.05） in contrast to that of the control group. Conclusion LDR can effectively suppress the growth of S180 implanted tumors by reducing MMP-2, which is associated with invasion and metastasis.

The effect of ABV regimen on CD4 lymphocyte count in patients with advanced HIV related Kaposi’s sarcoma

Objective: The combination of highly active antiretroviral therapy (HAART) and chemotherapy with ABV regimen (doxorubicin, bleomycin and vincristine) is a promising approach for the treatment of advanced HIV-related Kaposi's sarcoma (KS). Here we analyzed the relationship between the CD4 lymphocyte cell count and the clinical response to chemotherapy. Methods: The 176 HIV infected patients with advanced KS who failed to respond to prior HAART were selected. All these patients were then preceded to chemotherapy with ABV regimen which was administered at 3 weekly intervals for 6 cycles. For each patient CD4 cell count was done before starting chemotherapy and after finishing 6 cycles of chemotherapy. The difference of CD4 cell counts pre chemotherapy and post chemotherapy was compared with the clinical progress of the patients after 6 cycles of chemotherapy. Results: The overall clinical remission was shown in 93.7% patients. Progressive disease (PD) and no change in clinical condition (NC) was shown in 6.3% patients. The increase in CD4 cell count post chemotherapy was found in 89.8% patients and the decrease in CD4 cell count was seen in 10.2% patients. The difference of the mean CD4 cell counts for patients in group CR + PR (complete relief + partial relief) before and after chemotherapy was highly significant. The difference of the mean CD4 cell counts for patients in group NC + PD before and after chemotherapy was not significant. The difference in CD4 cell counts in CR + PR and NC + PD groups before and after chemotherapy was highly significant. Conclusion: The HIV related KS patients on HAART benefit from the chemotherapy as it increases the CD4 cell count and it has positive impact on clinical remission of KS.

EWING’S SARCOMA CAN EXPRESS BONE MORPHOGENETIC PROTEIN

Paraffin sections from 6 cases of Ewing's sarcoma were immunostained by ABC method using BMP -McAb for investigating the existence of BMP in Ewing' s sarcoma. All cases were positive. The result was coincided with human tumor transplants in athymic nude mouse by Bauer. It is shown that Ewing' s sarcoma can express BMP. So we support the hypothesis that Ewing' s sarcoma originates from primitive multipotential cells and can pluripotentially differentiate.

CT and multimodal imaging findings of primary orbital Ewing＇s sarcoma involving the middle cranial fossa： a case report

This report details the CT and MR imaging findings of a primary orbital Ewing＇s sarcoma case involving the middle cranial fossa in a 13-year old boy. CT showed an ill-circumscribed homogeneous soft-tissue density mass with needle-like bone reaction. On MRI, the mass showed homogeneous iso-intensity on T1WI, heterogeneous hyper- intensity on T2WI, and marked homogeneous enhancement. Meanwhile, the mass was hyper-intense on DWI, and ADC alue was 575x10-6 mm2/s. The mass showed as high rCBV and rCBF, prolonged MTT based on DCS- PWI, and wash-out pattern of TIC derived from the DCE-MRI. Our case suggests that functional MRI modalities, including DWI, DSC-PWI or DCE-MR, could provide additional information for differential diagnoses. Both CT and MRI should be performed and comprehensively analyzed for limiting differential diagnoses, determining lesion extension and facilitating operative approach.

Facial nerve palsy, headache, peripheral neuropathy and Kaposi's sarcoma in an elderly man

We present a case of an elderly man, who initially presented with right facial nerve palsy, ipsilateral headache, elevated erythrocyte sedimentation rate(ESR) and no fever. A presumptive diagnosis of giant cell arteritis was made and the patient was treated with highdose steroids. A temporal artery biopsy was negative. Several months later, while on 16 mg of methylprednisolone daily, he presented with severe sensorimotor peripheral symmetric neuropathy, muscle wasting and inability to walk, uncontrolled blood sugar and psychosis. A work-up for malignancy was initiated with the suspicion of a paraneoplastic process. At the same time a biopsy of the macular skin lesions that had appeared on the skin of the left elbow and right knee almost simultaneously was inconclusive, whereas a repeat biopsy from the same area of the lesions that had become nodular, a month later, was indicative of Kaposi'ssarcoma. Finally, a third biopsy of a similar lesion, after spreading of the skin process, confirmed the diagnosis of Kaposi's sarcoma. He was treated with interferon α and later was seen in very satisfactory condition, with no clinical evidence of neuropathy, normal muscle strength, no headache, normal electrophysiologic nerve studies, involution of Kaposi's lesions and a normal ESR.

Intestinal Kaposi's sarcoma may mimic gastrointestinal stromal tumor in HIV infection

Diffuse intestinal Kaposi＇s sarcoma shares macroscopic and histopathologic features with gastrointestinal stromal tumors. Correct diagnosis may pose a clinical challenge. We describe the case of a young HIV-1-infected African lady without advanced immunodeficiency, who presented with a diffuse spindle cell tumor of the gut. Initial diagnosis was of a gastrointestinal stromal tumor, based on endoscopy and histopathology. Further evaluation revealed evidence for human herpesvirus 8 （HHV8） and the diagnosis had to be changed to diffuse intestinal Kaposi＇s sarcoma. Antiretroviral triple therapy together with chemotherapy was commenced, and has led to the rapid remission of intestinal lesions. With a background of HIV infection, the presence of HHV8 as the causative agent of Kaposi＇s sarcoma should be determined, as distinct treatment is indicated.