Taxonomic reclassification of Kaposi Sarcoma identifies disease entities with distinct immunopathogenesis.

BACKGROUND: The taxonomy of Kaposi Sarcoma (KS) is based on a classification system focused on the description of clinicopathological features of KS in geographically and clinically diverse populations. The classification includes classic, endemic, epidemic/HIV associated and iatrogenic KS, and KS in men who have sex with men (MSM). We assessed the medical relevance of the current classification of KS and sought clinically useful improvements in KS taxonomy. METHODS: We reviewed the demographic and clinicopathological features of 676 patients with KS, who were referred to the national centre for HIV oncology at Chelsea Westminster hospital between 2000 and 2021. RESULTS: Demographic differences between the different subtypes of KS exist as tautological findings of the current classification system. However, no definitive differences in clinicopathological, virological or immunological parameters at presentation could be demonstrated between the classic, endemic or MSM KS patients. Reclassifying patients as either immunosuppressed or non-immunosuppressed, showed that the immunosuppressed group had a significantly higher proportion of adverse disease features at presentation including visceral disease and extensive oral involvement, classified together as advanced disease (chi2 P = 0.0012*) and disseminated skin involvement (chi2 P < 0.0001*). Immunosuppressed patients had lower CD4 counts, higher CD8 counts and a trend towards higher HHV8 levels compared to non-immunosuppressed patients, however overall survival and disease specific (KS) survival was similar across groups. CONCLUSION: The current system of KS classification does not reflect meaningful differences in clinicopathological presentation or disease pathogenesis. Reclassification of patients based on the presence or absence of immunosuppression is a more clinically meaningful system that may influence therapeutic approaches to KS.

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. AIM: To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. METHODS: Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. RESULTS: A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P < .001). A more advanced albumin-bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P < .001). CONCLUSIONS: In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC.

Surgical excision alone for stage T1 anal verge cancers in people living with HIV.

INTRODUCTION: Anal cancer accounts for a small percentage of colorectal malignancies. Early stage (T1N0M0) cancers of the anal verge have been treated with local surgical excision alone in individuals without human immunodeficiency virus (HIV) infection. The risk of anal cancer is higher in people living with HIV (PLWH). We present results of the outcomes of T1 anal verge cancers treated by local excision only in a series of PLWH. METHODS: Demographic and clinicopathological data was prospectively collected from all HIV positive individuals with anal cancer, treated between 1986 and 2015. The date from anal cancer diagnosis until the date of the last follow up were collected. RESULTS: Fifteen patients had T1N0M0 cancer of the anal verge from a total of 92 patients with HIV-associated anal cancer. The mean age was 49 years (range 36-57). The average age of HIV diagnosis was 35 years (range 19-48) and four patients had a diagnosis of AIDS prior to the diagnosis of anal cancer. All patients were surgically managed with complete local excision of the tumour. There were no complications or need for any adjuvant therapy. No patients have relapsed and at a median follow up of 4 years (range 3-15), the overall survival was 100%. CONCLUSION: Surgical resection for early stage anal verge cancers is an effective strategy in PLWH. Increasing awareness of anal cancer and anoscopy surveillance in PLWH will hopefully continue to identify anal cancers at an early stage that are amenable to minimally invasive surgical management.

The clinical application of plasma Kaposi sarcoma herpesvirus viral load as a tumour biomarker: results from 704 patients.

OBJECTIVES: The aim of the study was to evaluate the role of plasma Kaposi sarcoma herpesvirus (KSHV) as a diagnostic and prognostic biomarker in people living with HIV (PLWH) and diagnosed with KSHV-associated diseases. METHODS: Using quantitative nested polymerase chain reaction (PCR) targeting the open reading frame-26 gene of KSHV, plasma levels of KSHV were measured in consecutive PLWH with KSHV-associated diseases or as part of the investigation of lymphadenopathy. RESULTS: Plasma KSHV assays were performed on samples from 684 PLWH and 20 HIV-seronegative people with KSHV-associated malignancies. In PLWH, plasma KSHV was detected in 39% of those with KS, 99% of those with multicentric Castleman disease (MCD), 9% of those with non-Hodgkin lymphoma (NHL), 2% of those with non-AIDS-defining malignancies and 0% of those with nonmalignant lymphadenopathy. There was no significant difference in plasma KSHV viral load among those with KS, MCD and KSHV-associated NHL. The 5-year overall survival rate from KS diagnosis of 335 PLWH was 95.2% (95% confidence interval 92.6-97.8%). Plasma KSHV viraemia did not predict overall survival in those with KS (P = 0.73), nor when those with T0 stage KS (P = 0.52) or T1 stage KS (P = 0.62) were analysed separately. CONCLUSIONS: Measuring the plasma levels of KSHV as a biomarker in KSHV-associated disease has a very limited value in either diagnosis or prognostication. The only potential role of clinical value is the suggestion that an undetectable plasma KSHV excludes a diagnosis of MCD in PLWH.

Severe raltegravir-associated rhabdomyolysis: a case report and review of the literature.

Raltegravir (RAL), an HIV integrase inhibitor, may uncommonly induce an increase of serum creatine kinase (CK) both in naïve and antiretroviral (ARV)-experienced HIV-positive patients. We report the case of severe rhabdomyolysis requiring hospitalization in an ARV-experienced HIV/hepatitis C co-infected patient treated with a RAL-containing drug regimen. Factors favouring a severe clinical occurrence of RAL-induced rhabdomyolysis from cases reported in literature are described.

[Variability in immunologic aspects of Whipple's disease. Is a unitary interpretation possible?]. / Variabilità degli aspetti immunologici nella malattia di Whipple. E possibile una interpretazione unitaria?

A case of Whipple's disease with histological and ultrastructural studies, characterized by unusual bacteriological and immunologic findings, is reported. Alpha hemolytic Streptococcus and Candida tropicalis were isolated from the culture of the intestinal biopsy specimens. The immunological function study showed a global defect both of humoral and cellular immunity. On the basis of the literature review, the Authors debate a unitary interpretation of the various immunological dysfunctions reported in this disease.

[Aplastic anemia and myelodysplasia: a not-always-easy distinction]. / Anemia aplastica e mielodisplasia: una distinzione non sempre agevole.

The differential diagnosis between Myelodysplasia and Aplastic anaemia may be sometimes difficult, because clinical and morphological features may appear similar. Two cases, a Myelodysplastic syndrome with hypocellular and an Aplastic anaemia with hypercellular BM aspirates, are described in this report. Reciprocal connections between these two pathological entities, some biological aspects and the value of BM biopsy are also discussed.

[Tissue polypeptide antigen: significance and prospective use in the clinical laboratory]. / L'antigene polipeptidico tessutale: significato e prospettive di impiego nel laboratorio clinico.

Sequential determination of tissue polypeptide antigen were carried out in patients with neoplastic diseases. Blood specimens were taken before surgery and one week, one month and every months after the operation. The values obtained were compared with those of a control group of blood donors and those of a control group of healthy persons. The values obtained in control groups suggest that alcohol could cause significant increase of tissue polypeptide antigen values.