Flanagan's condensed protocol for neurodegenerative diseases. Implementation in a clinical autopsy setting with partial supervision of a neuropathologist.

The Condensed Protocol (CP) was originally developed for the evaluation of Alzheimer's Disease (AD) and other neurodegenerative diseases as a workable alternative to the complex and costly established autopsy guidelines. The study objective is to examine the degree of implementation of the CP in the pathology department of a third level university hospital in a period of 5 years. Clinical autopsies performed between 2016 and 2021 on patients aged 65 years or over and did not require a specific neuropathological examination were reviewed. Histological screening and staging of neurodegenerative diseases was performed using the original immunohistochemical stains. Out of 255 autopsies, 204 met the inclusion criteria and 190 could be reviewed. The CP was applied to 99 cases; histological signs of neurodegenerative disease were observed in 92. Sampling errors were detected in 59 cases. Immunohistochemical studies were performed in 68 cases. The diseases identified were: 31 cases of AD (12 low grade; 19 intermediate), 18 amyloid angiopathy, 15 primary age-related tauopathy, 6 argyrophilic grain disease, 3 progressive supranuclear palsy, 1 Lewy body disease (of 22 cases), and 2 limbic-predominant age TDP43 encephalopathy (of 5 cases). In 30 out of 83 cases, there was more severe vascular pathology in complete sections of frontal cortex and lentiform nucleus. The CP allows reliable detection and staging of AD and related neurodegenerative diseases in clinical autopsies. However, supervision by a neuropathologist seems necessary for a fully successful implementation of the CP in a clinical hospital setting.

Post-mortem neuropathologic examination of a 6-case series of CAR T-cell treated patients.

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for the treatment of refractory hematopoietic malignancies. Adverse events are common, and neurotoxicity is one of the most important. However, the physiopathology is unknown and neuropathologic information is scarce. Materials and methods: Post-mortem examination of 6 brains from patients that underwent CAR T-cell therapy from 2017 to 2022. In all cases, polymerase chain reaction (PCR) in paraffin blocks for the detection of CAR T cells was performed. Results: Two patients died of hematologic progression, while the others died of cytokine release syndrome, lung infection, encephalomyelitis, and acute liver failure. Two out of 6 presented neurological symptoms, one with extracranial malignancy progression and the other with encephalomyelitis. The neuropathology of the latter showed severe perivascular and interstitial lymphocytic infiltration, predominantly CD8+, together with a diffuse interstitial histiocytic infiltration, affecting mainly the spinal cord, midbrain, and hippocampus, and a diffuse gliosis of basal ganglia, hippocampus, and brainstem. Microbiological studies were negative for neurotropic viruses, and PCR failed to detect CAR T -cells. Another case without detectable neurological signs showed cortical and subcortical gliosis due to acute hypoxic-ischemic damage. The remaining 4 cases only showed a mild patchy gliosis and microglial activation, and CAR T cells were detected by PCR only in one of them. Conclusions: In this series of patients that died after CAR T-cell therapy, we predominantly found non-specific or minimal neuropathological changes. CAR T-cell related toxicity may not be the only cause of neurological symptoms, and the autopsy could detect additional pathological findings.

Minimally Invasive Tissue Sampling Findings in 12 Patients With Coronavirus Disease 2019.

BACKGROUND: Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure. METHODS: From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs. CONCLUSIONS: MITS is useful for evaluating COVID-19-related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA.

Minimally Invasive Autopsy Practice in COVID-19 Cases: Biosafety and Findings.

Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening the body, which may be a valid alternative in these cases. We aimed to: (a) provide biosafety guidelines for conducting MIAs in COVID-19 cases, (b) compare the performance of MIA versus complete autopsy, and (c) evaluate the safety of the procedure. Between October and December 2020, MIAs were conducted in six deceased patients with PCR-confirmed COVID-19, in a basic autopsy room, with reinforced personal protective equipment. Samples from the lungs and key organs were successfully obtained in all cases. A complete autopsy was performed on the same body immediately after the MIA. The diagnoses of the MIA matched those of the complete autopsy. In four patients, COVID-19 was the main cause of death, being responsible for the different stages of diffuse alveolar damage. No COVID-19 infection was detected in the personnel performing the MIAs or complete autopsies. In conclusion, MIA might be a feasible, adequate and safe alternative for cause of death investigation in COVID-19 cases.

Osteosarcoma del tercio proximal de la tibia

Se presenta el caso clínico de un niño de 12 años de edad, con una neoplasia en el tercio proximal de la tibia izquierda, cuyo análisis histopatológico reveló la presencia de un osteosarcoma esclerosante. Se exponen los principales hallazgos clínicos y radiológicos de este paciente y se revisa la literatura relativa a esta entidad poco frecuente en el niño.(AU)