Purpose: Neuro-oncological ventral antigen 1 (NOVA1), a neuron-specific pre-mRNA splicing factor, is involved in neuronal development and oncogenesis. NOVA1 overexpression is associated with favorable prognosis in head and neck squamous cell carcinoma (HNSCC) and gastric adenocarcinoma, whereas its downregulation correlates with poor outcomes. High NOVA1 levels in these cancers correlate with increased CD3+ and CD8+ T lymphocyte densities, suggesting involvement in tumor immune-inflammatory signals. This study explores NOVA1's role in regulating the immune-inflammatory cGAS-STING pathway in HNSCC cells and clinical tissues. Materials and Methods: HNSCC cell lines (FaDu, YD-10B, SNU-1066, and SNU-1076) were transfected with NOVA1 and poly(dA:dT). Quantitative real-time polymerase chain reaction and Western blot analysis were used to assess gene/protein expression. Enzymelinked immunosorbent assay quantified cytokine levels, and immunoprecipitation assessed protein interactions. Clinical tissue samples from 234 HNSCC patients were analyzed using immunohistochemistry to correlate NOVA1 and STING pathway markers with immune cell infiltration. Results: NOVA1 overexpression in HNSCC cells increased phosphorylation of STING (p-STING) without altering cGAS or TBK1. Immunoprecipitation showed an interaction between NOVA1 and p-STING. Overexpression of NOVA1, particularly with poly(dA:dT) treatment, tended to elevate CCL5 and CXCL10 expression. In clinical samples, NOVA1 expression strongly correlated with p-STING levels (r=0.749, p<0.001). Higher NOVA1 and p-STING expressions were linked to increased infiltration of CD3+ T cells, CD8+ T cells, and FOXP3+ regulatory T cells. Conclusion NOVA1 modulates the cGAS-STING pathway through STING phosphorylation and associated immune responses in HNSCC, providing a potential therapeutic target for enhancing anti-tumor immunity.

Chronic active Epstein-Barr virus (CAEBV) can induce complications in various organs, including the brain and gastrointestinal tract. A 3-year-old boy was referred to the hospital with a history of fever and seizures for 15 days. A diagnosis of encephalitis based on computed tomography (CT) and magnetic resonance imaging findings and clinical correlation was made. Laboratory tests showed positive serology for Epstein-Barr virus (EBV) and negative for Rotavirus antigen and IgG and IgM antibodies for cytomegalovirus, herpes simplex virus, and varicella zoster virus, respectively. Abdominal CT showed diffuse wall thickening with fluid distension of small bowel loops, lower abdomen wall thickening, and a small amount of ascites. The biopsy demonstrated positive Epstein-Barr encoding region in situ hybridization in cells within the crypts and lamina propria. The patient was managed with steroids and hematopoietic stem cell transplantation (HSCT). This case showed histopathological characteristics of concurrent EBV-associated encephalitis and colitis in CAEBV infection. The three-step strategy of immunosuppressive therapy, chemotherapy, and allogeneic HSCT should be always be considered for prevention of disease progression.

Chronic active Epstein-Barr virus (CAEBV) can induce complications in various organs, including the brain and gastrointestinal tract. A 3-year-old boy was referred to the hospital with a history of fever and seizures for 15 days. A diagnosis of encephalitis based on computed tomography (CT) and magnetic resonance imaging findings and clinical correlation was made. Laboratory tests showed positive serology for Epstein-Barr virus (EBV) and negative for Rotavirus antigen and IgG and IgM antibodies for cytomegalovirus, herpes simplex virus, and varicella zoster virus, respectively. Abdominal CT showed diffuse wall thickening with fluid distension of small bowel loops, lower abdomen wall thickening, and a small amount of ascites. The biopsy demonstrated positive Epstein-Barr encoding region in situ hybridization in cells within the crypts and lamina propria. The patient was managed with steroids and hematopoietic stem cell transplantation (HSCT). This case showed histopathological characteristics of concurrent EBV-associated encephalitis and colitis in CAEBV infection. The three-step strategy of immunosuppressive therapy, chemotherapy, and allogeneic HSCT should be always be considered for prevention of disease progression.

Chronic active Epstein-Barr virus (CAEBV) can induce complications in various organs, including the brain and gastrointestinal tract. A 3-year-old boy was referred to the hospital with a history of fever and seizures for 15 days. A diagnosis of encephalitis based on computed tomography (CT) and magnetic resonance imaging findings and clinical correlation was made. Laboratory tests showed positive serology for Epstein-Barr virus (EBV) and negative for Rotavirus antigen and IgG and IgM antibodies for cytomegalovirus, herpes simplex virus, and varicella zoster virus, respectively. Abdominal CT showed diffuse wall thickening with fluid distension of small bowel loops, lower abdomen wall thickening, and a small amount of ascites. The biopsy demonstrated positive Epstein-Barr encoding region in situ hybridization in cells within the crypts and lamina propria. The patient was managed with steroids and hematopoietic stem cell transplantation (HSCT). This case showed histopathological characteristics of concurrent EBV-associated encephalitis and colitis in CAEBV infection. The three-step strategy of immunosuppressive therapy, chemotherapy, and allogeneic HSCT should be always be considered for prevention of disease progression.

Histiocytic and dendritic cell neoplasms comprise diverse tumors originating from the mononuclear phagocytic system, which includes monocytes, macrophages, and dendritic cells. The 5th edition of the World Health Organization (WHO) classification updating the categorization of these tumors, reflecting a deeper understanding of their pathogenesis.In this updated classification system, tumors are categorized as Langerhans cell and other dendritic cell neoplasms, histiocyte/macrophage neoplasms, and plasmacytoid dendritic cell neoplasms. Follicular dendritic cell neoplasms are classified as mesenchymal dendritic cell neoplasms within the stroma-derived neoplasms of lymphoid tissues.Each subtype of histiocytic and dendritic cell neoplasms exhibits distinct morphological characteristics. They also show a characteristic immunophenotypic profile marked by various markers such as CD1a, CD207/langerin, S100, CD68, CD163, CD4, CD123, CD21, CD23, CD35, and ALK, and hematolymphoid markers such as CD45 and CD43.In situ hybridization for EBV-encoded small RNA (EBER) identifies a particular subtype. Immunoprofiling plays a critical role in determining the cell of origin and identifying the specific subtype of tumors. There are frequent genomic alterations in these neoplasms, especially in the mitogen-activated protein kinase pathway, including BRAF (notably BRAFV600E), MAP2K1, KRAS, and NRAS mutations, and ALK gene translocation.This review aims to offer a comprehensive and updated overview of histiocytic and dendritic cell neoplasms, focusing on their ontogeny, morphological aspects, immunophenotypic profiles, and molecular genetics. This comprehensive approach is essential for accurately differentiating and classifying neoplasms according to the updated WHO classification.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Purpose: To assess the diagnostic potential of whole-exome sequencing (WES) and elucidate the clinical and genetic characteristics of primary ciliary dyskinesia (PCD) in the Korean population. Materials and Methods: Forty-seven patients clinically suspected of having PCD were enrolled at a tertiary medical center. WES was performed in all patients, and seven patients received biopsy of cilia and transmission electron microscopy (TEM). Results: Overall, PCD was diagnosed in 10 (21.3%) patients: eight by WES (8/47, 17%), four by TEM. Among patients diagnosed as PCD based on TEM results, two patients showed consistent results with WES and TEM of PCD (2/4, 50%). In addition, five patients, who were not included in the final PCD diagnosis group, had variants of unknown significance in PCD-related genes (5/47, 10.6%).The most frequent pathogenic (P)/likely pathogenic (LP) variants were detected in DNAH11 (n=4, 21.1%), DRC1 (n=4, 21.1%), and DNAH5 (n=4, 21.1%). Among the detected 17 P/LP variants in PCD-related genes in this study, 8 (47.1%) were identified as novel variants. Regarding the genotype–phenotype correlation in this study, the authors experienced severe PCD cases caused by the LP/P variants in MCIDAS, DRC1, and CCDC39. Conclusion Through this study, we were able to confirm the value of WES as one of the diagnostic tools for PCD, which increases with TEM, rather than single gene tests. These results will prove useful to hospitals with limited access to PCD diagnostic testing but with relatively efficient in-house or outsourced access to genetic testing at a pre-symptomatic or early disease stage.

Histiocytic and dendritic cell neoplasms comprise diverse tumors originating from the mononuclear phagocytic system, which includes monocytes, macrophages, and dendritic cells. The 5th edition of the World Health Organization (WHO) classification updating the categorization of these tumors, reflecting a deeper understanding of their pathogenesis.In this updated classification system, tumors are categorized as Langerhans cell and other dendritic cell neoplasms, histiocyte/macrophage neoplasms, and plasmacytoid dendritic cell neoplasms. Follicular dendritic cell neoplasms are classified as mesenchymal dendritic cell neoplasms within the stroma-derived neoplasms of lymphoid tissues.Each subtype of histiocytic and dendritic cell neoplasms exhibits distinct morphological characteristics. They also show a characteristic immunophenotypic profile marked by various markers such as CD1a, CD207/langerin, S100, CD68, CD163, CD4, CD123, CD21, CD23, CD35, and ALK, and hematolymphoid markers such as CD45 and CD43.In situ hybridization for EBV-encoded small RNA (EBER) identifies a particular subtype. Immunoprofiling plays a critical role in determining the cell of origin and identifying the specific subtype of tumors. There are frequent genomic alterations in these neoplasms, especially in the mitogen-activated protein kinase pathway, including BRAF (notably BRAFV600E), MAP2K1, KRAS, and NRAS mutations, and ALK gene translocation.This review aims to offer a comprehensive and updated overview of histiocytic and dendritic cell neoplasms, focusing on their ontogeny, morphological aspects, immunophenotypic profiles, and molecular genetics. This comprehensive approach is essential for accurately differentiating and classifying neoplasms according to the updated WHO classification.

Histiocytic and dendritic cell neoplasms comprise diverse tumors originating from the mononuclear phagocytic system, which includes monocytes, macrophages, and dendritic cells. The 5th edition of the World Health Organization (WHO) classification updating the categorization of these tumors, reflecting a deeper understanding of their pathogenesis.In this updated classification system, tumors are categorized as Langerhans cell and other dendritic cell neoplasms, histiocyte/macrophage neoplasms, and plasmacytoid dendritic cell neoplasms. Follicular dendritic cell neoplasms are classified as mesenchymal dendritic cell neoplasms within the stroma-derived neoplasms of lymphoid tissues.Each subtype of histiocytic and dendritic cell neoplasms exhibits distinct morphological characteristics. They also show a characteristic immunophenotypic profile marked by various markers such as CD1a, CD207/langerin, S100, CD68, CD163, CD4, CD123, CD21, CD23, CD35, and ALK, and hematolymphoid markers such as CD45 and CD43.In situ hybridization for EBV-encoded small RNA (EBER) identifies a particular subtype. Immunoprofiling plays a critical role in determining the cell of origin and identifying the specific subtype of tumors. There are frequent genomic alterations in these neoplasms, especially in the mitogen-activated protein kinase pathway, including BRAF (notably BRAFV600E), MAP2K1, KRAS, and NRAS mutations, and ALK gene translocation.This review aims to offer a comprehensive and updated overview of histiocytic and dendritic cell neoplasms, focusing on their ontogeny, morphological aspects, immunophenotypic profiles, and molecular genetics. This comprehensive approach is essential for accurately differentiating and classifying neoplasms according to the updated WHO classification.