Project description:Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. METHODS: In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results. RESULTS: The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. CONCLUSION: The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages. Keywords: other
Project description:Kaposi's sarcoma (KS) is generally considered a neoplastic disorder of vascular origin and occurs in patients with acquired immunodeficiency syndrome (AIDS) or who have received immunosuppressive treatments after an organ transplant (Soulier et al., Blood 86(4):1276-80, 1995; Viejo-Borbolla and Schulz, AIDS Rev 5(4):222-9, 2003; Schulz, J Antimicrob Chemother 45(Suppl T3):15-27, 2000; Aversa et al. Crit Rev Oncol Hematol 53(3):253-65, 2005; Mbulaiteye and Engels, Int J Cancer 119(11):2685-91, 2006; Tessari et al., Eur J Dermatol 16(5):553-7, 2006). Several Kaposi's sarcoma case reports involving eyelids and conjunctiva have been published (Bavishi et al., Int J STD AIDS 23(3):221-2, 2012; Baumann et al., Ger J Ophthalmol 4(4):239-45, 1995).we report a 13 years old asian male patient rare case of ocular KS that was initiated from the sclera and progressed into the cornea and conjunctiva without an human Immunodeificiency Virus (HIV) or HHV-8 infection after a peripheral blood stem cells transplantation. In this case, anti- vascular endothelial growth factor (VEGF) therapy was attempted to stop the advance of ocular lesions and failed. Eventually, the KS was cured by a limbo-corneal lamellar graft, an amniotic membrane and scleral allograft transplantation plus intraoperative mitomycin C(MMC) after the complete excision of the tumors.A compete surgical excision combined with the intraoperative application of MMC, as well as grafts to repair the scleral, conjunctival, and corneal surfaces, could prevent a recurrence of KS.
Project description:RationaleMyeloid sarcoma (MS) involves the proliferation of extramedullary blasts from 1 or more myeloid lineages, replacing the original tissue structures, and these neoplasias are called granulocytic sarcoma, chloroma, or extramedullary myeloid neoplasms. These tumors develop in lymphoid organs, bones, skin, soft tissues, various mucous membranes, organs, and the central nervous system. MS is rare in non-leukemic patients, while MS patient with effusion as the first manifestation is even rare.Patient concernsWe report the case of 44-year-old woman with abdominal pain, diarrhea, and vomiting.DiagnosisUltrasound examination and computed tomography of the chest revealed large pericardial effusions and bilateral pleural effusions. Cytomorphological examination of the pericardial and pleural effusion, flow cytometry, and immunohistochemical markers suggested myeloid tumor cells. However, concurrent peripheral blood and bone marrow examinations showed no evidence of acute myeloid leukemia. The patient was eventually diagnosed with isolated MS.Interventions and outcomesAfter chemotherapy with pirarubicin + cytarabine and high-dose cytarabine + etoposide, the pericardial effusion and pleural effusion were absorbed, and the mediastinal mass significantly shrunk. One year after patient gave up treatment, acute myeloid leukemia (AML) was confirmed by bone marrow examinations.ConclusionThe early manifestations of the patient lacked specificity and were highly susceptible to misdiagnosis. Cytomorphology and flow cytology indicated important directions for the diagnosis of the disease in the early stage. Administration of chemotherapy regimen containing cytarabine could prolong disease-free survival and time before progress to AML.
Project description:IntroductionAcute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML), with myeloid sarcoma (MS) seldom occurring at onset. Myelofibrosis (MF) is a condition characterized by megakaryocytic proliferation and atypia with an array of clinical findings, but MF secondary to APL treatment is extremely rare. MF secondary occurring after treatment of APL with MS as the initial presentation has not been reported.Case reportA 73-year-old male was admitted to our hospital in August 2016, presenting with a pain in his left shoulder, followed by right shoulder and bilateral hip pain. A progressive increase in a mass in the right sternoclavicular joint was also observed. After comprehensive examines, he was diagnosed as APL with MS as the initial manifestation in April 2017. The patient then underwent induction, consolidation, and maintenance therapies until August 2019 and achieved complete remission. However, twice examinations in December 2020 and September 2022 confirmed that MF was present.ConclusionThis is the first case of MF secondary occurring after treatment of APL with MS. Early recognition of MS in APL patients is crucial for timely intervention and treatment initiation. Meticulous diagnostic work-up and careful monitoring during treatment are necessary to detect potential complications, which may significantly impact the patients' outcome. Also, a comprehensive management approach encompassing induction, consolidation, and maintenance therapies should be adopted to ensure optimal therapeutic responses and reduce the risk of recurrence or treatment-related complications.
Project description:BACKGROUND:Kaposi's Sarcoma (KS) is a proliferation of aberrant vascular structures lined by spindle cells, and is caused by a gammaherpes virus (HHV8/KSHV). Its course is aggravated by co-infection with HIV-1, where the timing of infection with HIV-1 and HHV8 is important for the clinical outcome. METHODS:In order to better understand the pathogenesis of KS, we have analysed tissue from two AIDS-KS lesions, and from normal skin by serial analysis of gene expression (SAGE). Semi-quantitative RT-PCR was then used to validate the results. RESULTS:The expression profile of AIDS-related KS (AIDS-KS) reflects an active process in the skin. Transcripts of HHV8 were found to be very low, and HIV-1 mRNA was not detected by SAGE, although it could be found using RT-PCR. Comparing the expression profile of AIDS-KS tissue with publicly available SAGE libraries suggested that AIDS-KS mRNA levels are most similar to those in an artificially mixed library of endothelial cells and leukocytes, in line with the description of KS lesions as containing spindle cells with endothelial characteristics, and an inflammatory infiltrate. At least 64 transcripts were found to be significantly elevated, and 28 were statistically downregulated in AIDS-KS compared to normal skin. Five of the upregulated mRNAs, including Tie 1 and sialoadhesin/CD169, were confirmed by semi-quantitative PCR to be elevated in additional AIDS-KS biopsies. Antibodies to sialoadhesin/CD169, a known marker of activated macrophages, were shown to specifically label tumour macrophages. CONCLUSION:The expression profile of AIDS-KS showed 64 genes to be significantly upregulated, and 28 genes downregulated, compared with normal skin. One of the genes with increased expression was sialoadhesin (CD169). Antibodies to sialoadhesin/CD169 specifically labelled tumour-associated macrophages, suggesting that macrophages present in AIDS-KS lesions belong to a subset of human CD169+ macrophages.
Project description:BackgroundStatus epilepticus in patients with hepatic encephalopathy (HE) is a rare but serious condition that is refractory to antiepileptic drugs, and current treatment plans are vague. Diagnosis may be difficult without a clear history of cirrhosis. Liver transplantation (LT) is effective to alleviate symptoms, however, there are few reports about LT in the treatment of status epilepticus with HE. To our knowledge, this is the first report of status epilepticus present as initial manifestation of HE.Case summaryA 59-year-old woman with a 20-year history of heavy drinking was hospitalized for generalized tonic-clonic seizures. She reported no history of episodes of HE, stroke, spontaneous bacterial peritonitis, ascites or gastrointestinal bleeding. Neurological examination revealed a comatose patient, without papilledema. Laboratory examination suggested liver cirrhosis. Plasma ammonia levels upon admission were five times normal. Brain computed tomography (CT) was normal, while abdominal CT and ultrasound revealed mild ascites, liver cirrhosis and splenomegaly. Electroencephalography (EEG)showed diffuse slow waves rhythm, consistent with HE, and sharp waves during ictal EEG corresponding to clinical semiology of focal tonic seizures. The symptoms were reversed by continuous antiepileptic treatment and lactulose. She was given oral levetiracetam, and focal aware seizures occasionally affected her 10 mo after LT.ConclusionStatus epilepticus could be an initial manifestation of HE. Antiepileptic drugs combined with lactulose are essential for treatment of status epilepticus with HE, and LT is effective to prevent the relapse.
Project description:BackgroundKaposi's sarcoma (KS) in HIV negative patients is rare and has to be distinguished from AIDS associated KS. Two groups are at risk to develop non-AIDS related KS: elderly men mainly of Mediterranean origin and persons with iatrogenic immunosuppression.Patients and methodsIn order to define risk-groups and major clinical features we retrospectively evaluated clinical data of all patients with non-AIDS associated KS presenting to the Department of Dermatology, University Hospital Tuebingen between 1987 and 2009. Data were extracted from the tumor registry of the Comprehensive Cancer Center Tuebingen and from patient records.Results20 patients with non-AIDS KS have been identified. The average age at KS onset was 66.6 years; the male-to-female-ratio was 3:1. Most of the patients were immigrants from Mediterranean or Eastern European countries (60%). 15 cases of classic KS versus 5 cases of iatrogenic KS were observed. In 95% of the cases, KS was limited to the skin, without mucosal, lymph node or visceral manifestation. KS lesions were in all cases multiple and mostly bilateral, the most common localization was the skin of the lower extremities. Tumor control was achieved in nearly all cases by the use of local or systemic therapy. No patient died from KS.ConclusionsUnlike KS in AIDS patients, non-AIDS associated KS is a rather localized process which rarely involves lymph nodes or organs. It is mostly seen in elderly males from Mediterranean or Eastern European countries and in most cases responsive on local or systemic therapeutic strategies.
Project description:Cases of disseminated visceral Kaposi's sarcoma (KS) after allogenic hematopoietic stem cell transplantation (HSCT) are very rare worldwide, and disseminated visceral KS is often rapidly progressive and life-threatening, especially in paediatric patients. Here, the case of a 6-year-old female patient with disseminated visceral KS after allogeneic HSCT for treating severe aplastic anaemia is presented. The authors encountered difficulties in making the diagnosis due to lack of experience, but the diagnosis was achieved relatively quickly and accurately using metagenomic next-generation sequencing. After tapering and withdrawal of immunosuppressant drugs, the patient's condition was controlled. In conclusion, although HSCT-related KS is very rare, it should be considered during differential diagnosis.
Project description:Kaposi's sarcoma (KS) in HIV-infected individuals can have a wide range of clinical outcomes, from indolent skin tumors to a life-threatening visceral cancer. KS tumors contain endothelial-related cells and inflammatory cells that may be HIV-infected. In this study we tested if HIV evolutionary patterns distinguish KS tumor relatedness and progression. Multisite autopsies from participants who died from HIV-AIDS with KS prior to the availability of antiretroviral therapy were identified at the AIDS and Cancer Specimen Resource (ACSR). Two patients (KS1 and KS2) died predominantly from non-KS-associated disease and KS3 died due to aggressive and metastatic KS within one month of diagnosis. Skin and visceral tumor and nontumor autopsy tissues were obtained (n = 12). Single genome sequencing was used to amplify HIV RNA and DNA, which was present in all tumors. Independent HIV tumor clades in phylogenies differentiated KS1 and KS2 from KS3, whose sequences were interrelated by both phylogeny and selection. HIV compartmentalization was confirmed in KS1 and KS2 tumors; however, in KS3, no compartmentalization was observed among sampled tissues. While the sample size is small, the HIV evolutionary patterns observed in all patients suggest an interplay between tumor cells and HIV-infected cells which provides a selective advantage and could promote KS progression.
Project description:PurposeKaposi's sarcoma (KS) is a disease of multifocal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). Activation of the c-kit and platelet-derived growth factor (PDGF) receptors by autocrine/paracrine mechanisms follows endothelial cell KSHV infection. In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients.Patients and methodsThis multicenter phase II study was designed to estimate the response rate to imatinib in AIDS-KS. Secondary objectives included investigation of predictors of response and imatinib pharmacokinetics in patients on antiretrovirals. Patients received imatinib 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their disease was stable.ResultsThirty patients were treated at 12 AIDS Malignancy Consortium sites. Ten patients (33.3%) achieved partial response, six (20%) had stable disease, and seven (23.3%) exhibited KS progression. Nine patients completed 52 weeks of imatinib therapy. The median treatment duration was 22.5 weeks. Only five patients (16.7%) discontinued therapy owing to adverse events. Antiretroviral regimens did not significantly alter imatinib metabolism. Activating mutations in PDGF-R and c-kit were not found at baseline or at disease progression. We found no correlation with response with changes in any of the candidate cytokines.ConclusionImatinib has activity in AIDS-KS. Pharmacokinetic interactions with antiretroviral drugs did not correlate with toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest imatinib is well tolerated and may be an alternative therapy for some patients with AIDS-KS.