Angioimmunoblastic T-cell lymphoma and Kaposi sarcoma: A fortuitous collision?

AIMS: Follicular helper T-cell (TFH) lymphoma of the angioimmunoblastic-type (AITL), one of the most prevalent T-cell lymphomas, typically encompasses proliferation of high endothelial venules and Epstein-Barr virus-positive immunoblasts, but neither infection with HHV8 nor association with Kaposi's sarcoma (KS) have been described. The aims of this study are to characterise the association between AITL and HHV8 infection or KS. METHODS AND RESULTS: Three male patients aged 49-76 years, HIV-negative, with concurrent nodal involvement by AITL and KS, were identified from our files and carefully studied. Two patients originated from countries where endemic KS occurs, including one with cutaneous KS. The lymphomas featured abundant vessels, expanded follicular dendritic cells and neoplastic TFH cells [PD1+ (three of three), ICOS+ (three of three), CXCL13+ (three of three), CD10+ (two of three), BCL6 (two of three)] but lacked EBV+ immunoblasts. The foci of KS consisted of subcapsular proliferations of ERG+, CD31+ and/or CD34+ , HHV8+ spindle cells. High-throughput sequencing showed AITL-associated mutations in TET2 (three of three), RHOA (G17V) (three of three) and IDH2 (R172) (two of three), which were absent in the microdissected KS component in two cases. Relapses in two patients consisted of AITL, without evidence of KS. No evidence of HHV8 infection was found in a control group of 23 AITL cases. CONCLUSION: Concurrent nodal involvement by AITL and KS is rare and identification of both neoplastic components may pose diagnostic challenges. The question of whether the association between AITL and KS may be fortuitous or could reflect the underlying immune dysfunction in AITL remains open.

Postmortem Cardiopulmonary Pathology in Patients with COVID-19 Infection: Single-Center Report of 12 Autopsies from Lausanne, Switzerland.

We report postmortem cardio-pulmonary findings including detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in formalin-fixed paraffin embedded tissue in 12 patients with COVID-19. The 5 women and 7 men (median age: 73 years; range 35-96) died 6-38 days after onset of symptoms (median: 14.5 days). Eight patients received mechanical ventilation. Ten patients showed diffuse alveolar damage (DAD), 7 as exudative and 3 as proliferative/organizing DAD. One case presented as acute fibrinous and organizing pneumonia. Seven patients (58%) had acute bronchopneumonia, 1/7 without associated DAD and 1/7 with aspergillosis and necrotic bronchitis. Microthrombi were present in 5 patients, only in exudative DAD. Reverse transcriptase quantitative PCR detected high virus amounts in 6 patients (50%) with exudative DAD and symptom-duration ≤14 days, supported by immunohistochemistry and in-situ RNA hybridization (RNAscope). The 6 patients with low viral copy levels were symptomatic for ≥15 days, comprising all cases with organizing DAD, the patient without DAD and one exudative DAD. We show the high prevalence of DAD as a reaction pattern in COVID-19, the high number of overlying acute bronchopneumonia, and high-level pulmonary virus detection limited to patients who died ≤2 weeks after onset of symptoms, correlating with exudative phase of DAD.

Meningeal Relapse of Nodular Lymphocyte Predominant Hodgkin Lymphoma Transformed to T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: A Case Report.

Central nervous system involvement in Hodgkin lymphoma is extremely rare, especially in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), which usually carries a favorable prognosis. Here we report a case of a young patient with NLPHL, who developed a progressive and fatal neurological deterioration requiring a very extensive work-up including two biopsies to obtain the diagnosis of T-cell/histiocyte-rich large B-cell lymphoma like transformation. This report, which includes post-mortem analysis, highlights the correlations between clinical, radiological, and biological data but also the difficulties encountered in reaching the correct diagnosis.

UCA1 overexpression is associated with less aggressive subtypes of bladder cancer.

Non­coding RNAs (ncRNAs) have been shown to serve important roles in carcinogenesis via complex mechanisms, including transcriptional and post­transcriptional regulation, and chromatin interactions. Urothelial carcinoma­associated 1 (UCA1), a long ncRNA, was recently shown to have tumorigenic properties in urothelial bladder cancer (UBC), as demonstrated by enhanced proliferation, migration, invasion and therapy resistance of UBC cell lines in vitro. These in vitro findings suggested that UCA1 is associated with aggressive tumor behavior and could have prognostic implications in UBC. The aims of the present study were to therefore to investigate the statistical associations between UCA1 RNA expression and UBC pathological features, patient prognosis and p53 and Ki­67 expression. Chromogenic in situ hybridization and immunohistochemistry were performed on UBC tissue microarrays to characterize UCA1 RNA, and p53 and Ki­67 expression in 208 UBC cases, including 145 non­muscle­invasive and 63 muscle­invasive cases. UCA1 was observed in the tumor cells of 166/208 (80%) UBC cases tested. No expression was noted in normal stromal and endothelium cells. Patients with UBC that overexpressed UCA1 (35%) had a significantly higher survival rate (P=0.006) compared with that in patients with UBC that did not overexpress UCA1. This prognostic factor was independent of tumor morphology, concomitant carcinoma in situ, tumor grade and tumor stage. In addition, the absence of UCA1 overexpression was significantly associated with a high Ki­67 proliferative index (P=0.008) and a p53 'mutated' immunoprofile (strong nuclear expression or complete absence of staining; P=0.003). In conclusion, the present results identified UCA1 as potentially being a novel independent prognostic marker in UBC that was associated with a better patient prognosis and that could serve a pivotal role in bladder cancer carcinogenesis.

Diagnostic value of the UCA1 test for bladder cancer detection: a clinical study.

PURPOSE: To evaluate the efficiency of the UCA1 test as a diagnostic tool for the detection of bladder cancer. METHODS: Between October 2009 and December 2011 the UCA1 test was performed on collected urine samples from 162 patients divided into screening and follow-up groups, based on the absence or presence of prior bladder cancer. The test performance was then evaluated in each group and compared to cystoscopy and urinary cytology. RESULTS: The overall sensitivity, specificity and positive and negative predictive values for the UCA1 test were 70, 70.7, 75.6 and 64.5%, respectively. We observed no difference in performance for tumours of higher grade or stage, but sensitivity was increased in the screening population compared to patients under follow-up (83.9 vs. 59%). The UCA1 test successfully detected all 7 cases of isolated carcinoma in situ and was more sensitive in this particular setting than cystoscopy or urinary cytology. CONCLUSION: The efficiency of the UCA1 test for the detection of primary and recurring bladder cancer in our study was lower than previously reported. We confirmed the role of UCA1 as a possible adjunct to cystoscopy and cytology when a primary bladder cancer is suspected, but its role in the follow-up of recurring tumours remains limited. Further studies are needed to investigate the role of the UCA1 test in the early detection of carcinoma in situ lesions.