Eyelid Kaposi Sarcoma in HIV-Negative Patient

Introduction: Kaposi sarcoma disease is a proliferative and multifocal disorder with dual components, vascular and fibroblastic cellular, cutaneous and visceral expression. Kaposi Sarcoma can affect the ocular surface and adnexa and can masquerade as other entities, delaying prompt diagnosis can lead to diagnostic wandering delaying treatment. Our aim is to describe a case of KS of the eyelid in an HIV seronegative patient. Case Presentation: A seventy-year-old man developed a bilateral growing tumoral reddish purple vascular mass on both the lower and upper eyelid involving rapidly for 6 months. Both feet and the two shanks show the presence of a brown-violet tumor-shaped formation. The patient was negative for HIV. Histology examination showed a nodular tumor-like mass with a fibro hemangioma-epitheliomatous. Polymerase chain reaction was positive for human herpes virus 8. Initial chemotherapy followed by surgery was proposed to the patient. Unfortunately, the patient rejected treatment and was lost to follow-up. Conclusion: This case reports the difficulty of managing KS in developing countries.

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

Kaposi’s Sarcoma Associated with Gastrointestinal Bleeding: A Rare Complication of Long-Term Corticosteroid Therapy

Corticosteroid therapy has revolutionized the treatment of many diseases in medicine. The most concerned diseases are chronic inflammatory diseases. Its use may be either short-term or long-term, thus generating several side effects, some of which are conventional and known, but others are rare, such as Kaposi’s sarcoma. We report here a particular clinical observation. Observation: This is a patient of 37 years, who consults in Internal Medicine for the treatment of mucocutaneous lesions, papular nodular, hyper pigmented, budding and disseminated appeared after six months of corticosteroid therapy. This treatment was introduced for the treatment of acoustic neurinoma. The patient is not diabetic or alcoholic and has a negative HIV status. The diagnosis of Kaposi’s sarcoma was made by histology of biopsied skin lesions which concluded for a regular proliferation without atypia spindle cell or mitosis. The lesions persisted over a month despite discontinuation of corticosteroid therapy. Treatment with Bleomycin was necessary. The outcome was favorable under treatment with progressive and complete disappearance of lesions after 15 treatments. Conclusion: The classical side effects of long-term corticosteroid are known, but Kaposi sarcoma complicating long-term corticosteroid is rare in the literature. It is vital that any long-term corticosteroid should be the subject of careful and regular monitoring.

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.

Current status of the adjuvant therapy in uterine sarcoma: A literature review

Uterine sarcomas (US) are rare mesenchymal tumours accounting approximately for 3%–7% of all uterine cancers. Histologically, US are classified into mesenchymal tumours or mixed epithelial and mesenchymal tumours. The group of mesenchymal tumours includes uterine leiomyosarcoma (uLMS, 65% of cases), endometrial stromal sarcoma (ESS, 21%)– traditionally divided into low grade (LG-ESS) and high grade–undifferentiated uterine sarcoma (5%) and other rare subtypes such as alveolar or embryonal rhabdomyosarcoma. Despite the fact that several drugs demonstrated clinical activity in advanced or metastatic settings, the role of postoperative therapy in US remains controversial. In this review, we have summarised the current state of the art, including the chief trials on adjuvant treatment modalities in US, especially focusing on uLMS, LG-ESS and other rare histotypes.

Human herpesvirus-8 positive iatrogenic Kaposi's sarcoma in the setting of refractory ulcerative colitis

Although Kaposi sarcoma(KS) has been more traditionally considered an AIDS-defining illness,it may also be seen in individuals on immunosuppresive therapy.We report a case of a patient who presented to the hospital in the setting of increasingly refractory ulcerative colitis.Computed tomography scan of the abdomen was consistent with sigmoid diverticulititis and blood cultures were positive for Klebsiella.After a course of antibiotics with resolution of infection,a colonoscopy was performed to evaluate his diverticulitis and incidentally revealed a new rectal tumor.Immunohistochemistry showed the tumor was consistent with KS,with cells staining strongly positive for human herpesvirus-8.This case not only illustrates a rare case of KS found in an HIV-negative individual,but it also highlights the importance of considering an alternative diagnosis in a patient refractory to medical treatment.We discuss the management and care of an ulcerative colitis patient diagnosed with KS on immunosuppressive therapy.

Establishment of an ELISA to Detect Kaposi's Sarcoma-associated Herpesvirus Using Recombinant ORF73

Kaposi's sarcoma-associated herpesvirus (KSHV) is causally related to Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and a proportion of cases of multicentric Castleman's disease (MCD). The ORF73 protein was cloned into pQE80L-orf73 and expressed in E.coli and purified. The expressed recombinant ORF73 was identified by sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE). A protein of about 27 kDa was expressed as expected. Western Blotting showed that the purified recombinant ORF73 reacted with KSHV positive serum. The immunogenicity of the recombinant ORF73 was further analysed by ELISA and the optimal conditions were determined. The ORF73 ELISA was used to compare the KSHV seroprevalence between Hubei and Xinjiang Han people. The Han people in Xinjiang have significantly higher KSHV seroprevalence than their counterparts in Hubei (6.7% vs 2.9%, P = 0.005).

Gastrointestinal Kaposi's sarcoma: Case report and review of the literature

Kaposi's sarcoma(KS) of the gastrointestinal tract is not an uncommon disease among individuals with acquired immunodeficiency syndrome(AIDS). The majority is asymptomatic, and for this reason, gastrointestinal KS(GI-KS) remains undiagnosed. With continued tumor growth, considerable variation in clinical presentation occurs including abdominal pain, nausea, vomiting, iron deficiency anemia(either chronic or frank gastrointestinal bleeding), and rarely mechanical obstruction alone or combined with bowel perforation. Endoscopy with biopsy allows for histological and immunohistochemical testing to confirm the diagnosis of GI-KS among those with clinical symptoms. In previous studies, dual treatment with highly active antiretroviral therapy and systemic chemotherapy have been associated with improved morbidity and mortality in individuals with visceral KS. Therefore, investigators have suggested performing screening endoscopies in select patients for early detection and treatment to improve outcome. In this review, we describe a 44 years old man with AIDS and cutaneous KS who presented for evaluation of postprandial abdominal pain, vomiting, and weight loss. On upper endoscopy, an extensive, infiltrative,circumferential, reddish mass involving the entire body and antrum of the stomach was seen. Histologic examination later revealed spindle cell proliferation, and confirmatory immunohistochemical testing revealed human herpes virus 8 latent nuclear antigen expression consistent with a diagnosis of gastric KS. Following this, we present a comprehensive review of literature on KS with emphasis on gastrointestinal tract involvement and management.

Immunogenicity Analysis of Prokaryotic Expression Products of Kaposi's Sarcoma Associated Herpesvirus orf65

To purify the protein encoding the small capsid protein (SCP) of KSHV and analyze its immunogenicity, the carboxyl terminus of orf65 of Kaposi's sarcoma associated-herpesvirus (KSHV) was expressed in a prokaryotic expression system. The expression of recombinant E.coli containing pQE-80L-orf65 was induced by isopropyl-β-D-thiogalactopyranoside (IPTG) and the fusion protein was purified by chromatography. The expressed protein and its purified product were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and showed that 9 kDa was the expected size of the purified orf65 protein. The antiserum was produced in rabbit which was immunized by purified orf65 protein. An ELISA assay was established to analyze the immunogenicity of the purified orf65 protein. The ELISA analysis demonstrated that orf65 protein has strong immune activity, and the immune activity of polyclonal antibody against orf65 was more than 4 fold higher than that in the serum of the non-immunized rabbit. These results demonstrate that purified orf65 protein has very strong immunogenicity and can be used in screening KSHV infection in the general population using ELISA.

Fertility-sparing surgeries without adjuvant therapy through term pregnancies in a patient with low-grade endometrial stromal sarcoma:A case report

BACKGROUND Low-grade endometrial stromal sarcoma(LGESS)is a rare indolent tumor with a favorable prognosis.With the importance of improving quality of life recognized,fertility-sparing surgery may be an option for those young women.However,most of the reports suggested that stage IA patients might be candidates for fertility-sparing surgery,and adjuvant hormonal treatment was considered a feasible adjuvant therapy for reducing the recurrence risk of patients with LGESS and hysterectomy was recommended after the completion of pregnancy and delivery.CASE SUMMARY A 28-year-old pregnant woman diagnosed with stage IB LGESS was treated by fertility-sparing surgery when term cesarean section delivery was performed.Without any adjuvant treatment,she had the other successful term pregnancy and cesarean section 45 mo after first fertility-sparing surgery.Moreover,only hysteroscopic resection was performed to retain fertility again even when the tumor recurred after 6 years.So far the patient’s fertility and disease-free status have remained for more than 8 years without any adjuvant therapy despite local resection of the sarcoma.And the two babies were in good health.CONCLUSION For young patients with stage I LGESS,it seems that repeated fertility-sparing surgeries could be performed even after two term deliveries and the tumor recurrence,and it might be attempted without adjuvant therapy but the counseling should be considered as mandatory.

Expression of Kaposi's Sarcoma-associated Herpesvirus ORFK8.1 and Its Preliminary Diagnostic Application

The ORFK8.1 of Kaposi's sarcoma associated-herpesvirus(KSHV) was expressed in a prokaryotic expression system. The expression of recombinant E.coli containing pQE-80L-orf K8.1 was induced by isopropyl-b-D-thiogalactopyranoside(IPTG) . The fusion protein was purified by chromatyography. The expressed protein and its purified product were identified by sodium dodecyl sulfate-polyacrylamide gel eletrophoresis(SDS-PAGE) . SDS-PAGE showed that a protein of 26 kDa was visualized as expected. A western blot assay was established to analyze the immunogenicity of purified recombinant ORFK8.1 protein. The optimal condition of the recombinant ORFK8.1 ELISA assay was confirmed:the concentration of antigen was 5 μg/mL,the dilution of serum was 1:200. We used the ELISA method to investigate the recombinant ORF K8.1 protein's specificity,the data showed that the specificity of ORF K8.1 to detect KSHV was 100%. At the same time,560 sera samples from Hubei province were detected by using ORFK8.1 ELISA to investigate KSHV seroprevalence in this region. The KSHV seroprevalence in Hubei province is shown to be 6.80%.

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.

Pathogenesis and Associated Diseases of Kaposi's Sarcoma-associated Herpesvirus

Kaposi's sarcoma-associated herpesvirus(KSHV)is the primary etiological agent of Kaposi's sarcoma,primary effusion lymphoma and muticentric Castleman's disease.In common with the other herpesviruses,KSHV exhibits both latent and lytic life cycles,both of which are characterized by distinct gene expression profiles and programs.KSHV encodes proteins which play essential roles in the inhibition of host adaptive and innate immunity,the inhibition of apoptosis,and the regulation of the cell cycle.KSHV also encodes several proteins which have transforming and intrcellular signalling activity.

The Biology of Kaposi’s Sarcoma-Associated Herpesvirus and the Infection of Human Immunodeficiency Virus

Kaposi sarcoma-associated herpesvirus (KSHV),also known as human herpesvirus 8 (HHV-8),is discovered in 1994 from Kaposi's sarcoma (KS) lesion of an acquired immunodeficiency syndrome (AIDS) patient. In addition to its association with KS,KSHV has also been implicated as the causative agent of two other AIDS-associated malignancies: primary effusion lymphoma (PEL) and multicentric Castleman’s disease (MCD). KSHV is a complex DNA virus that not only has the ability to promote cellular growth and survival for tumor development,but also can provoke deregulated angiogenesis,inflammation,and modulate the patient’s immune system in favor of tumor growth. As KSHV is a necessary but not sufficient etiological factor for KS,human immunodeficiency virus (HIV) is a very important cofactor. Here we review the basic information about the biology of KSHV,development of pathogenesis and interaction between KSHV and HIV.

Hepatic Kaposi sarcoma: A case report and review of the literature

Kaposi sarcoma(KS) is an aggressive cancer caused by human herpesvirus-8, primarily seen in immunocompromised patients. As opposed to the well-described cutaneous manifestations and pulmonary complications of KS, hepatic KS is rarely reported before death as most patients with hepatic KS do not manifest symptoms or evidence of liver injury. In patients with acquired immune deficiency syndrome, hepatic involvement of KS is present in 12%-24% of the population on incidental imaging and in approximately 35% of patients with cutaneous KS if an autopsy was completed after their death. Patients with clinically significant hepatic injury due to hepatic KS usually have an aggressive course of disease with hepatic failure often progressing to multi-organ failure and death. Here we report an unusual presentation of acute liver injury due to hepatic KS and briefly review the published literature on hepatic KS.

Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for the treatment of undifferentiated embryonal sarcoma of the liver in children

BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare and aggressive mesenchymal tumor in children.Herein,we describe our experience in neoadjuvant therapy(NAT)and subsequent surgery for the treatment of UESL in children.AIM To evaluate the efficacy of NAT and explore a new choice for successful operation of UESL in children.METHODS We retrospectively analyzed six patients newly diagnosed with unresectable UESL who received NAT and then surgery at our center between January 2004 and December 2019.The tumor was considered unresectable if it involved a large part of both lobes of the liver or had invaded the main hepatic vessels or inferior vena cava.The NAT included preoperative transcatheter arterial chemoembol ization(TACE)and systemic chemotherapy.The patients were 4 boys and 2 girls with a mean age of 7 years.The longest tumor at presentation ranged from 8.6 to 14.8 cm(mean,12 cm).Extrahepatic metastases were present in 2 cases.Preoperative systemic chemotherapy was administered 3 wk after TACE.Tumor resection was performed 3 wk after one or two cycles of NAT.The patients received systemic chemotherapy after surgery.RESULTS All patients successfully underwent NAT and complete resection.The tumor volumes decreased by 18.2%–68.7%,with a mean decrease of 36%after 1 cycle of NAT(t=3.524,P=0.017).According to the Response Evaluation Criteria In Solid Tumors criteria,4 patients had a partial response and underwent surgery,while 2 had stable disease and received another cycle of NAT before surgery.Massive tumor necrosis was seen on pathological examination of the surgical specimen:>90%necrosis in two,>50%necrosis in three,and 25%necrosis in 1,with an average of 71.8%.Post-NAT complications included fever,nausea and vomiting,and mild bone marrow suppression.Elevated alanine transaminase levels occurred in all patients,which returned to normal within 7–10 d after treatment.No cardiac or renal toxicity,severe hepatic dysfunction,bleeding and nontarget embolization were observed in the patients.The median follow-up period was 8 years with an overall survival of 100%.CONCLUSION NAT effectively reduced tumor volume,cleared the tumor margin,and caused massive tumor necrosis.This may be a promising choice for successful surgery of UESL in children.

Diagnostic value of endothelial markers and HHV-8 staining in gastrointestinal Kaposi sarcoma and its difference in endoscopic tumor staging

AIM: To clarify the diagnostic values of hematoxylin and eosin (HE), D2-40, CD31, CD34, and HHV-8 immunohistochemical (IHC) staining in gastrointestinal Kaposi's sarcoma (GI-KS) in relation to endoscopic tumor staging. METHODS: Biopsy samples (n = 133) from 41 human immunodeficiency virus-infected patients were reviewed. GI-KS was defined as histologically negative for other GI diseases and as a positive clinical response to KS therapy. The receiver operating characteristic area under the curve (ROC-AUC) was compared in relation to lesion size, GI location, and macroscopic appearances on endoscopy. RESULTS: GI-KS was confirmed in 84 lesions (81.6%). Other endoscopic findings were polyps (n = 9), inflammation (n = 4), malignant lymphoma (n = 4), and condyloma (n = 2), which mimicked GI-KS on endoscopy. ROC-AUC of HE, D2-40, blood vessel markers, and HHV-8 showed results of 0.83, 0.89, 0.80, and 0.82, respectively. For IHC staining, the ROC-AUC of D2-40 was significantly higher (P < 0.05) than that of HE staining only. In the analysis of endoscopic appearance, the ROC-AUC of HE and IHC showed a tendency toward an increase in tumor staging (e.g. , small to large, patches, and polypoid to SMT appearance). D2-40 was significantly (P < 0.05) advantageous in the upper GI tract and for polypoid appearance compared with HE staining. CONCLUSION: The diagnostic value of endothelial markers and HHV-8 staining was found to be high, and its accuracy tended to increase with endoscopic tumor staging. D2-40 will be useful for complementing HE staining in the diagnosis of GI-KS, especially in the upper GI tract and for polypoid appearance.

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.

Target therapy in gastrointestinal tract sarcoma:What is new?

Soft tissue sarcoma are rare tumors arising mostly from embryonic mesoderm, that can affect almost any part of the human body, including the gastrointestinal tract. The prognosis associated with soft tissue sarcoma is still poor, mainly because of the low efficacy of traditional approaches based on surgery and chemotherapy. As a result of genetic and molecular analysis, several new target therapies have been developed, leading to a significant improvement in the survival of patients affected by advanced disease. In this review we aim to explore the therapeutic potential and benefit of target therapy in the management of gastrointestinal soft tissue sarcoma and the possible complications or pitfalls of such an approach.

Non-AIDS-related Kaposi’s sarcoma:A single-institution experience

AIM:To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome(AIDS)-related Kaposi’s sarcoma(KS).METHODS:Patients with histologically proven non-AIDS-related KS treated with systemic chemotherapy were included in this retrospective analysis.In some cases,the human herpes virus 8 status was assessed by immunohistochemistry.The patients were staged according to the Mediterranean KS staging system.A multivariable model was constructed using a forward stepwise selection procedure.A P value<0.05 was considered statistically significant,and all tests were two-sided.RESULTS:Thirty-two cases were included in this analysis.The average age at diagnosis was 70 years,with a male/female ratio of approximately 2:1.Eighty-four percent of the cases had classic KS.All patients received systemic chemotherapy containing one of the following agents:vinca alkaloid,taxane,and pegylated liposomal doxorubicin.Ten patients(31.5%)experienced a partial response,and a complete response was achieved in four patients(12.4%)and stable disease in sixteen cases(50%).Two patients(6.2%)were refractory to the systemic treatment.The median progression-free survival(PFS)was 11.7 mo,whereas the median overall survival was 28.5 mo.At multivariate analysis,the presence of nodular lesions(vs macular lesions only)was significantly related to a lower PFS(hazard ratio:3.09;95%CI:1.18-8.13,P=0.0133).CONCLUSION:Non-AIDS-related KS appears mostly limited to the skin and is well-responsive to systemic therapies.Our data show that nodular lesions may be associated with a shorter PFS in patients receiving chemotherapy.