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Introduction: Ovarian teratoma is a common occurrence in patients with anti‐NMDA receptor encephalitis (NMDARe), and its removal is crucial for a favorable prognosis. However, the initial pathogenesis of autoimmunity in the encephalitic teratoma remains unclear. In this study, we aimed to investigate the genomic landscape and microscopic findings by comparing NMDARe‐associated teratomas and non‐encephalitic control teratomas. Materials and Methods: A prospective consecutive cohort of 84 patients with NMDARe was recruited from January 2014 to April 2020, and among them, patients who received teratoma removal surgery at Seoul National University Hospital were enrolled. We conducted a comparison of whole‐exome sequencing data and pathologic findings between NMDARe‐associated teratomas and control teratomas. Results: We found 18 NMDARe‐associated teratomas from 15 patients and compared them with 17 non‐encephalitic control teratomas. Interestingly, the genomic analysis revealed no significant differences in mutations between encephalitic and non‐encephalitic teratomas. Pathologic analysis showed no discrepancies in terms of the presence of neuronal tissue and lymphocytic infiltration between the encephalitic teratomas (n = 14) and non‐encephalitic teratomas (n = 18). However, rituximab‐naïve encephalitic teratomas exhibited a higher frequency of germinal center formation compared to non‐encephalitic teratomas (80% vs. 16.7%, P = 0.017). Additionally, rituximab‐treated encephalitic teratomas demonstrated a reduced number of CD20+ cells and germinal centers in comparison to rituximab‐naïve encephalitic teratomas (P = 0.048 and 0.023, respectively). Discussion: These results suggest that the initiation of immunopathogenesis in NMDARe‐associated teratoma is not primarily attributed to intrinsic tumor mutations, but rather to immune factors present in the encephalitic patient group, ultimately leading to germinal center formation within the teratoma. [ABSTRACT FROM AUTHOR]

MPE, myxopapillary ependymoma; PFA-EPN, posterior fossa group A ependymoma; PFB-EPN, posterior fossa group B ependymoma; PF-SUBEPN, posterior fossa-subependymoma; PN, ependymoma; SP-EPN, spinal-ependymoma; SP-SUBEPN, spinal subependymoma; ST-EPN-ZFTA, supratentorial-ependymoma ZFTA fusion-positive; ST-SUBEPN, supratentorial subependymoma; YAP1-EPN, ST-ependymoma YAP1-positive gl Our case might be the first case of SP-EPN harboring a I ZFTA-YAP1 i fusion. ZFTA-YAP1 fusion-positive ependymoma can occur in the spinal cord: Letter to the editor Although I ZFTA i fusion-positive EPN occurs mainly in the supratentorial region, one I ZFTA i - I RELA i fusion-positive EPN in the cerebellum and one I ZFTA i - I MAML2 i fusion-positive EPN in the cervical junction have been reported [9]. Unsupervised t-SNE analysis with an overlay on the known ependymal tumor clusters revealed that our case belonged to ST-EPN- I RELA i (now the same as I ZFTA i -fusion-positive ST-EPN), not SP-EPN. [Extracted from the article]

We report an autopsy case of a 56‐year‐old male patient with the coexistence of dentatorubral‐pallidoluysian atrophy (DRPLA) and Parkinson's disease (PD). He presented with gait instability and dysarthria for 10 years. The removed brain showed general atrophy (988 g) with depigmentation of the substantia nigra. The neocortex and deep gray matter, including the red nucleus, subthalamic nuclei, and globus pallidus, were atrophic, and grumose degeneration of the cerebellar dentate nucleus was observed. Polyglutamine‐ and p62‐positive neuronal inclusions were present and widespread in the areas mentioned above. Interestingly, this case also had brainstem‐predominant PD pathology with α‐synuclein‐positive Lewy bodies and Lewy neurites. Generalized white matter atrophy with patchy loss of astrocytes in the white matter suggested glial dysfunction by elongated CAG repeats in the atrophin 1 gene (atrophin 1). Polymerase chain reaction (PCR) fragment analysis revealed increased CAG repeats (61) on atrophin 1 encoding atrophin 1. The patient had a family history of DRPLA, including his daughter, who was confirmed positive on genetic testing (CAG repeat: 65). His father, brother, and niece were suspected of having the disease. Clinicopathologically, all of the above findings are consistent with the coexistence of DRPLA and PD. So far, various overlapping neurodegenerative disorders have been reported, but the coexistence of DRPLA and PD has never been demonstrated in the published literature. Even though the exact time of PD development is unknown in this case, PD might develop after DRPLA, and the overwhelming symptoms of DRPLA might mask those of PD. Here, we report a clinicopathologically definite case of the coexistence of DRPLA and PD. White matter degeneration with patchy loss of astrocytes was another remarkable finding of this case. [ABSTRACT FROM AUTHOR]

Objective To explore the potential preoperative ultrasonography ( US) and cytopathological features to avoid total thyroidectomy in NIFTP. Context Recently, it has been proposed that that noninvasive follicular thyroid neoplasms with papillary-like nuclear features ( NIFTP) be classified as tumours, rather than cancer. Patients A total of 142 surgically proven follicular variant papillary thyroid carcinomas ( FVPTCs; 45 NIFTP, 97 non- NIFTP; mean size: 20.4±11.0 mm, range: 10.0-65.0 mm) from 142 patients were included in this study. Measurements Three preoperative features of thyroid nodules (each US finding, US and Bethesda category) were compared in NIFTP and non- NIFTP groups. The preoperative decision-making process to avoid total thyroidectomy in NIFTP was evaluated based on combination of those features. Results In each US finding, there was only significantly less macrocalcification in the NIFTP group than in the non- NIFTP group (8.8% [4/45] vs 32.0% [31/97], P = .006). In US category, all of the NIFTP nodules were a low or intermediate suspicion (100% [45/45]). In Bethesda category, 26.7% [12/45] of the NIFTP was diagnosed as either suspicious malignancy or malignant, which increased the risk of a total thyroidectomy. In our study, a total thyroidectomy might be avoided in all of the NIFTP cases if lobectomy was selected for the nodules classified as a low or intermediate suspicion in US, despite being classified as a suspicious malignancy or malignant by cytopathology. Conclusions Combining the US and cytopathological results could sensitively reduce total thyroidectomy in cases of NIFTP. [ABSTRACT FROM AUTHOR]

BACKGROUND Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC. METHODS Targeted next-generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and transforming growth factor β [TGF-β]) was performed for 516 patients with stage III or high-risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy. The associations between critical pathway mutations and relapse-free survival (RFS) and overall survival were analyzed. The associations were further analyzed according to the tumor location. RESULTS The mutation rates for the WNT, P53, RTK-RAS, PI3K, and TGF-β pathways were 84.5%, 69.0%, 60.7%, 30.0%, and 28.9%, respectively. A mutation in the PI3K pathway was associated with longer RFS (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36-0.99), whereas a mutation in the RTK-RAS pathway was associated with shorter RFS (adjusted HR, 1.60; 95% CI, 1.01-2.52). Proximal tumors showed a higher mutation rate than distal tumors, and the mutation profile was different according to the tumor location. The mutation rates of Kirsten rat sarcoma viral oncogene homolog ( KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α ( PIK3CA), and B-Raf proto-oncogene serine/threonine kinase ( BRAF) were higher in proximal tumors, and the mutation rates of adenomatous polyposis coli ( APC), tumor protein 53 ( TP53), and neuroblastoma RAS viral oncogene homolog ( NRAS) were higher in distal tumors. The better RFS with the PI3K pathway mutation was significant only for proximal tumors, and the worse RFS with the RTK-RAS pathway mutation was significant only for distal tumors. CONCLUSIONS A PI3K pathway mutation was associated with better RFS for CRC patients treated with adjuvant chemotherapy, and an RTK-RAS pathway mutation was associated with worse RFS. The significance of the prognostic impact differed according to the tumor location. Cancer 2017;123:3513-23. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Recent reports suggest that mutations in the promoter of the gene encoding telomerase reverse transcriptase (TERT) affect thyroid cancer outcomes.Methods: In all, 551 patients with differentiated thyroid cancer (DTC) enrolled in this study. The median follow-up duration was 4.8 years (interquartile range, 3.4-10.6 years).Results: TERT promoter mutations were detected in 25 DTCs (4.5%): 2.8% in neither BRAF-mutated nor RAS-mutated tumors, 4.8% in BRAF-mutated tumors, and 11.3% in RAS-mutated tumors. Moreover, they were frequently observed in American Thyroid Association (ATA) high-risk and TNM stage III/IV groups (9.1% and 12.9%, respectively). The coexistence of BRAF or RAS with TERT promoter mutations increased aggressive clinicopathologic features, recurrence (hazard ratio [HR] for BRAF, 4.64; 95% confidence interval [CI], 1.42-15.18; HR for RAS, 5.36; 95% CI, 1.20-24.02), and mortality (HR for BRAF, 15.13; 95% CI, 1.55-148.23; HR for RAS, 14.75; 95% CI, 1.30-167.00), even after adjustments for the age at diagnosis and sex, although the significance was lost after additional adjustments for pathologic characteristics. Furthermore, TERT promoter mutations significantly increased the risk of both recurrence and mortality in the ATA high-risk (HR for recurrence, 5.79; 95% CI, 2.07-16.18; HR for mortality, 16.16; 95% CI, 2.10-124.15) and TNM stage III/IV groups (HR for recurrence, 3.60; 95% CI, 1.19-10.85; HR for mortality, 9.06; 95% CI, 2.09-39.26).Conclusions: The coexistence of BRAF or RAS mutations enhanced the prognostic effects of TERT promoter mutations. Furthermore, TERT promoter mutations strengthened the predictions of mortality and recurrence by the ATA and TNM staging systems, particularly for high-risk patients with DTC. Cancer 2016;122:1370-1379. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate the factors associated with diagnostic accuracy of preoperative fine-needle aspiration (FNA) for follicular variant papillary thyroid carcinoma (FVPTC). Methods The patients with FVPTC who underwent thyroidectomy were divided into 2 groups: 'group A' (Bethesda category II, III, or IV) versus 'group B' (category V or VI). Results A total of 225 patients (117 in group A and 108 in group B) were included. Group B was associated with older age, malignant ultrasonographic features, smaller tumor size, extrathyroidal extension, higher stage, and B-type Raf (BRAF)V600E mutation compared with group A. In multivariable analysis, malignant ultrasonographic features and tumor size ≤3.0 cm were independent predictive factors for group B. Conclusion FVPTCs >3.0 cm are unlikely to be diagnosed as category V or VI. Clinicians should keep FVPTC in mind and consider diagnostic lobectomy for the nodules regardless of FNA or ultrasonographic findings. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1467-E1471, 2016 [ABSTRACT FROM AUTHOR]

ABSTRACT Background and aim: Using machine learning methods can be helpful in the clinical decision processes such as pathological diagnosis with the aid of microscopic feature datasets. In the present study using the Breast Cancer Wisconsin dataset, an optimal algorithm (classifiers) which can predict both diagnosis (benign vs malignant) and prognosis (recur vs non-recur) was devised by comparing several classification algorithms. Methods: The performance of a two-step algorithm, which sequentially decides diagnosis and prognosis, was compared with that of a multi-class classifier, which divides classes simultaneously. Results: In the two-step classifier, it was discovered that the functional trees (FT) algorithm is the best for the first step of classification, and Naïve Bayes is the best for the second step of classification. On the other hand, the one-step classifier shows better accuracy and better prediction on benign and non-recurring cases than the two-step classifier, but it shows lower accuracy on predicting recurring cases, leading to lower sensitivity. Conclusions: We conclude that the two-step classifier with FT and Naïve Bayes is better than the one-step classifier. This work will be helpful in setting the automated screening system in real clinics and highlight clues to improve the accuracy by refining data and algorithm selection in data mining or machine learning processes. [ABSTRACT FROM AUTHOR]

As the relationship between inflammation and carcinogenesis grows stronger, the role of cyclooxygenase-2 (COX-2) and epidermal growth factor (EGFR) has been highlighted in the pathogenesis and progression of human cancer. In view of the fact that vulvar cancer is characterized by precancerous inflammatory changes in elderly patients, the expressions of COX-2 and EGFR are expected to show different patterns of distribution according to age and other prognostic factors. To verify whether there was a relationship between their expression and clinicopathologic parameters in vulvar cancer, we investigated the inflammatory cellular infiltration and the expression of COX-2 and EGFR by immunohistochemical analysis. Eleven of 19 samples (57.8%) were stained positive for COX-2, and 17 (89.4%) for EGFR. The portion of inflammatory cellular infiltration in adjacent normal tissue was also higher in the older age group, and showed a strong correlation with COX-2 positivity ( P= 0.002). Furthermore, COX-2 expression was significantly more frequent in patients over 60 years of age compared to those under 50 years ( P= 0.009). COX-2 expression was noted to be high in moderate and well-differentiated cases, whereas, poorly differentiated carcinoma was negative for COX-2 expression ( P= 0.023). However, EGFR expression was not differently distributed on the basis of stage, age, tumor grading, or presence of lymph node metastasis. Our article suggests that vulvar cancer in elderly patients may be associated with inflammation, and thus with increased COX-2 expression. In light of these findings, a clinical trial designed to assess the addition of COX-2 targeted therapy to conventional treatment in vulvar cancer would be helpful for consideration of additional treatment options and possibly avoiding the serious surgical morbidity in elderly patients. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) has a fatal prognosis because of its aggressive and invasive characteristics. Understanding the mechanism of invasion necessitates an elucidation of the relationship between tumor cells and the tumor microenvironment. However, there has been a scarcity of suitable models to investigate this. In this study, we established a glioblastoma‐cerebral organoid assembloid (GCOA) model by co‐culturing patient‐derived GBM tumoroids and human cerebral organoids. Tumor cells from the tumoroids infiltrated the cerebral organoids, mimicking the invasive nature of the parental tumors. Using time‐lapse imaging, various invasion patterns of cancer cells within cerebral organoids resembling a normal tissue milieu were monitored. Both single‐ and collective‐cell invasion was captured in real‐time. We also confirmed the formation of an intercellular tumor network and tumor–normal‐cell interactions. Furthermore, the transcriptomic characterization of GCOAs revealed distinct features of invasive tumor cells. Overall, this study established the GCOA as a three‐dimensional (3D) in vitro assembloid model to investigate invasion mechanisms and interactions between tumor cells and their microenvironment. [ABSTRACT FROM AUTHOR]

We evaluated the hemodynamics of tissue-engineered hybrid graft in vivo. The hybrid expanded polytetrafluoroethylene (ePTFE) scaffold was fabricated by coating the ePTFE graft with poly (lactide-co-glycolide) (PLGA) solution. This scaffold was turned into an engineered hybrid graft by culturing smooth muscle cells on its surface. Both the ePTFE (n = 6) and the engineered hybrid grafts (n = 8) were implanted in the carotid arteries of mongrel dogs. The length of intima in the engineered hybrid graft was greater than the ePTFE. The neoarterial thickness in the engineered hybrid group was greater, and the foreign body reaction was more severe. We compared the hemodynamics (diameter, flow rate, pulsatile index, mean velocity, shear stress, resistance index, and systolic/diastolic ratio) of the native arteries in the distal anastmosis. The shear rate in the engineered hybrid group was higher immediately after implantation, and the resistance index was lower, but there was no significant difference after 4 weeks. The engineered grafts demonstrated similar hemodynamics with the ePTFE grafts after 4 weeks implantation.