Preoperative diagnosis of clear cell sarcoma of the kidney by detection of BCOR internal tandem duplication in circulating tumor DNA

Clear cell sarcoma of the kidney (CCSK) is the second most common renal malignancy in children. The prognosis is poorer in CCSK than in Wilms’ tumor, and multimodal treatment including surgery, intensive chemotherapy, and radiation is required to improve the outcome for children with CCSK. Histological evaluation is required for the diagnosis. However, biopsies of tumors to obtain diagnostic specimens are not routinely performed because of the risk of spreading tumor cells during the procedure. Recently, internal tandem duplication (ITD) of BCOR has been recognized as a genetic hallmark of CCSK. We herein established a novel BCOR‐ITD‐specific polymerase chain reaction method with well‐designed primers, and then performed a liquid biopsy for cell‐free DNA (cfDNA) obtained from plasma of three children with nonmetastatic renal tumors (stage II) and from one control. BCOR‐ITD was positively detected in the cfDNA of two cases, both of which were later diagnosed as CCSK based on histological feature of the resected tumor specimen, while it was not detected for a normal control and a patient diagnosed with Wilms’ tumor. Our study is the first one of preoperative circulating tumor DNA assay in pediatric renal tumors. The liquid biopsy method enables less invasive, preoperative diagnosis of CCSK with no risk of tumor spillage, which can avoid iatrogenic upstaging.     

Cytological findings of ROS1‐rearranged lung adenocarcinoma

ROS1‐rearranged lung adenocarcinoma has been recently identified. We report a case of ROS1‐rearranged lung adenocarcinoma with special emphasis on cytological findings. Here, we report a case of young woman with ROS1‐rearranged lung adenocarcinoma diagnosed by cytology and discuss the clinical, cytological, and molecular findings. Cytologically, the tumor consisted of small tight clusters of cells with high nuclear/cytoplasmic ratio. Nuclei were enlarged and small nucleoli were occasionally observed. Signet‐ring cells were focally identified. Neoplastic cells were positive for ROS1 immunocytochemistry. Subsequently, the translocation of ROS1 gene was confirmed in a histological specimen. In conclusion, the specific histology of adenocarcinoma on cytological materials should promote testing for ROS1 immunohistochemistry. Immunocytochemical detection of ROS1 protein helps identify patients suitable for molecular targeted therapy.     

Novel eosinophilic neuronal cytoplasmic inclusions in the external cuneate nucleus of humans

We report the occurrence of neuronal cytoplasmic inclusions (NCIs) in the external cuneate nucleus of humans. The NCIs appeared as accumulations of eosinophilic rod‐like structures in the neuronal somata in 20 (9.5%) of 211 consecutive autopsy cases. Histochemically, the NCIs were stained bright red with Gomori trichrome, Azan‐Mallory and methyl green‐pyronin, indicating that they contain protein and RNA. Immunohistochemically, the NCIs were positive for stress granule marker proteins, including Hu‐antigen R, eukaryotic translation initiation factor 3 and poly(A)‐binding protein 1, but negative for ubiquitin‐ and autophagy‐related proteins. Ultrastructurally, the NCIs were composed of randomly oriented arrays of parallel fibrillar crystalline material with a well‐defined substructure consisting of longitudinal striations, and were often associated with ribosome‐like granules. These NCIs are morphologically, immunohistochemically and topographically distinct from any other inclusions previously described. Their incidence was found to increase with age. A high incidence was also observed in individuals with noninfectious inflammatory disease. These findings suggest that eosinophilic NCIs in the external cuneate nucleus are novel inclusions and might be formed under stress conditions.     

Application of a wearable switch to perform a mouse left click for a child with mix type of cerebral palsy: a single case study

Abstract

Purpose: Children with cerebral palsy may face difficulties using handheld pointing devices, due to involuntary muscle movements. This study aimed at describing the idea of the new wearable sensor switch and assessing its feasibility as an access solution in a case of mixed-type cerebral palsy.

Methods: The study participant was a 17-year-old male with mixed-type cerebral palsy characterized by chorea-athetotic movements and bilateral spasticity with gross motor function classification system level V. He exhibited sudden and irregular involuntary upper limb movements when sitting. Because spastic finger movements limited his ability to use a handheld mouse, he used a trackball near his neck as a pointing device (previous input method). The wearable switch system using a stretchable strain sensor was introduced; the sensor was attached to a groove worn on the dorsal regions of the right hand crossing the proximal interphalangeal and metacarpophalangeal joints of the middle finger (new input method). The switch turned on when the subject flexed his middle finger.

Results: The user successfully turned the switch on and typed almost the same numbers of characters per trial compared with the previous input method. The speed of his head movements during typing reduced (p?<?.01), and his sitting posture was nearly upright during computer operation (p?<?.01). No involuntary movement, requiring physical assistance, was observed when using the wearable switch.

Conclusion: The new switch system can be a new option for people with difficulty using standard handheld input devices due to paralysis and involuntary muscle movements.

• Implications for rehabilitation

• Cerebral palsy is a major cause of motor dysfunction and spasticity and dyskinesia in the fingers and upper limbs may prevent children with cerebral palsy from using handheld input devices.

• Wearable devices may be useful for children with cerebral palsy who have limited access to handheld pointing devices.

• We developed a new wearable switch to control devices using a flexible stretchable sensor.

• The wearable switch contributed to the improvement of sitting posture and reduction of neck burden during the typing task at the speed equivalent to that using the previous method in a child with mixed type of cerebral palsy exhibiting choreoathetotic movements and bilateral spasticity.

     

Discrepancy in polysomnography scoring for a patient with obstructive sleep apnea hypopnea syndrome

Overnight polysomnography (PSG) is indispensable for diagnosis of obstructive sleep apnea hypopnea syndrome. However, studies on interscorer agreement on PSG scoring between laboratories are few. The purpose of this study was to examine the reliability of interscorer agreement on PSG scoring among 16 sleep laboratories in Japan. We found a relatively moderate interscorer reliability of the index of oxygen desaturation and arousal during sleep, but a relatively low reliability of the index of transient reduction in and complete cessation of breathing (apnea hypopnea index). The median rate of interscorer coincidence of sleep staging was the lowest for slow wave (deep) sleep (23.5%), followed by those for Stage 1 (59.8%), Wake (73.2%) and Stage 2 (74.2%) in this order, and rapid eye movement was the most reliably identified stage (91.3%). The median rate of interscorer coincidence for all stages was 71.8%. The present study demonstrates that scorers tend to analyze PSG data according to a relatively empirical decision as opposed to a rule-dependent decision. Further detailed scoring manuals are required to decrease the interscorer discrepancy in PSG scoring.