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Treatment challenges persist in advanced lung cancer despite the development of therapies beyond the traditional platinum-based chemotherapy. The early 2000s marked a shift to tyrosine kinase inhibitors targeting epidermal growth factor receptor, ushering in personalized genetic-based treatment. A further significant advance was the development of immune checkpoint inhibitors (ICIs), especially for non–small cell lung cancer. These target programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4, which enhanced the immune response against tumor cells. However, not all patients respond, and immune-related toxicities arise. This review emphasizes identifying biomarkers for ICI response prediction. While PD-L1 is a widely used, validated biomarker, its predictive accuracy is imperfect. Investigating tumor-infiltrating lymphocytes, tertiary lymphoid structure, and emerging biomarkers such as high endothelial venule, Human leukocyte antigen class I, T-cell immunoreceptors with Ig and ITIM domains, and lymphocyte activation gene-3 counts is promising. Understanding and exploring additional predictive biomarkers for ICI response are crucial for enhancing patient stratification and overall care in lung cancer treatment.
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Background@#The importance of molecular pathology tests has increased during the last decade, and there is a great need for efficient training of molecular pathology for pathology trainees and as continued medical education. @*Methods@#The Molecular Pathology Study Group of the Korean Society of Pathologists appointed a task force composed of experienced molecular pathologists to develop a refined educational curriculum of molecular pathology. A 3-day online educational session was held based on the newly established structure of learning objectives; the audience were asked to score their understanding of 22 selected learning objectives before and after the session to assess the effect of structured education. @*Results@#The structured objectives and goals of molecular pathology was established and posted as a web-based interface which can serve as a knowledge bank of molecular pathology. A total of 201 pathologists participated in the educational session. For all 22 learning objectives, the scores of self-reported understanding increased after educational session by 9.9 points on average (range, 6.6 to 17.0). The most effectively improved items were objectives from next-generation sequencing (NGS) section: ‘NGS library preparation and quality control’ (score increased from 51.8 to 68.8), ‘NGS interpretation of variants and reference database’ (score increased from 54.1 to 68.0), and ‘whole genome, whole exome, and targeted gene sequencing’ (score increased from 58.2 to 71.2). Qualitative responses regarding the adequacy of refined educational curriculum were collected, where favorable comments dominated. @*Conclusions@#Approach toward the education of molecular pathology was refined, which would greatly benefit the future trainees.
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Background@#Although the Korean Society for Cytopathology has developed educational goals as guidelines for cytopathology education in Korea, there is still no systematic approach to cytopathology education status for pathology residents. Furthermore, satisfaction with cytopathology education and with the outcome of the current training/educational program has not been investigated in Korea. This study aimed to obtain comprehensive data on the current state of cytopathology education for residents and evaluate education outcomes. @*Methods@#An online survey was conducted in December 2020 for the board-certified pathologists and training residents registered as members of the Korean Society for Cytopathology. The questionnaire comprised questions that investigated the current status of cytopathology at each training institution, the degree of satisfaction with the work and education related to cytopathology, outcomes of cytopathology training, and educational accomplishments. @*Results@#Of the participants surveyed, 12.3% (132/1,075) completed the questionnaire, and 36.8% (32/87) of cytopathology residents participated. The mean overall satisfaction with cytopathology education was 3.1 points (on a 1- to 5-point scale, 5: very satisfied). The most frequent suggestion among the free description format responses was to expand educational opportunities, such as online education opportunities, outside of the individual institutions. @*Conclusions@#Our results showed that cytopathology training in Korea needs further improvement. We expect that this study will inform systematic training of competent medical personnel armed with broad cytopathology knowledge and strong problem-solving abilities.
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Choristoma, also known as a hairy polyp, is a rare benign mass that commonly occurs in the nasopharynx and oropharynx in the head and neck region. It is usually diagnosed in children and has rarely been reported in adults. In this study, we describe a nasopharyngeal choristoma in an adult man. The mass was located at the lateral nasopharyngeal wall, and the patient expressed intermittent nasal stuffiness and ear fullness. The mass was successfully removed using an endoscopic approach. Since nasopharyngeal choristoma in adults is rare, it is important to distinguish it from other benign tumors located in the nasopharynx or nasal cavity. In this report, we describe the radiologic characteristics of nasopharyngeal choristoma and summarize the importance of differential diagnosis from other benign masses.
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C3 glomerulonephritis (C3GN), a rare condition associated with dysregulation of the alternative pathway of the complement system, is histopathologically characterized by isolated or dominant C3 deposition in the renal glomeruli. We report a case of C3GN associated with anti-complement factor H (CFH) autoantibodies and CHF-related protein deficiency in an adolescent male. A 16-year-old adolescent male was admitted to a hospital with a 1-month history of generalized edema prior to presentation. Persistent microscopic hematuria and low serum C3 levels were incidentally detected at 7 and 10 years of age, respectively. Laboratory test results revealed hypoalbuminemia, nephrotic-range proteinuria, microscopic hematuria, and normal serum creatinine levels. The serum C3 and C4 levels were 17 mg/dL (normal 80–150 mg/dL) and 22 mg/mL (17–40 mg/mL), respectively. Renal biopsy showed typical features of C3GN. Further investigations revealed positive results on plasma anti-CFH autoantibody testing and a homozygous deletion of CFHR1 and CFHR3, which encode CFH-related proteins 1 and 3, respectively. Proteinuria persisted despite treatment with intravenous methylprednisolone, mycophenolate mofetil, and angiotensin-receptor blocker; however, his renal function remained stable. In conclusion, anti-CFH autoantibodies serve as important contributors to C3GN. This is the first case report that describes C3GN in an adolescent Korean male with anti-CFH autoantibodies and homozygous CFHR1 and CFHR3 deletion.
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C3 glomerulonephritis (C3GN), a rare condition associated with dysregulation of the alternative pathway of the complement system, is histopathologically characterized by isolated or dominant C3 deposition in the renal glomeruli. We report a case of C3GN associated with anti-complement factor H (CFH) autoantibodies and CHF-related protein deficiency in an adolescent male. A 16-year-old adolescent male was admitted to a hospital with a 1-month history of generalized edema prior to presentation. Persistent microscopic hematuria and low serum C3 levels were incidentally detected at 7 and 10 years of age, respectively. Laboratory test results revealed hypoalbuminemia, nephrotic-range proteinuria, microscopic hematuria, and normal serum creatinine levels. The serum C3 and C4 levels were 17 mg/dL (normal 80–150 mg/dL) and 22 mg/mL (17–40 mg/mL), respectively. Renal biopsy showed typical features of C3GN. Further investigations revealed positive results on plasma anti-CFH autoantibody testing and a homozygous deletion of CFHR1 and CFHR3, which encode CFH-related proteins 1 and 3, respectively. Proteinuria persisted despite treatment with intravenous methylprednisolone, mycophenolate mofetil, and angiotensin-receptor blocker; however, his renal function remained stable. In conclusion, anti-CFH autoantibodies serve as important contributors to C3GN. This is the first case report that describes C3GN in an adolescent Korean male with anti-CFH autoantibodies and homozygous CFHR1 and CFHR3 deletion.
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Background@#Squamous cell carcinomas (SqCCs) of the lung are known to arise more often in a central area but reports of peripheral SqCCs have increased, with a pathogenesis that is obscured. In this study, the clinicopathologic characteristics of peripheral lung SqCCs were studied and compared with those of the central type. @*Methods@#This study included 63 peripheral lung SqCCs and 48 randomly selected central cases; hematoxylin and eosin-stained slides of surgically resected specimens were reviewed in conjunction with radiologic images and clinical history. Cytokeratin-7 immunohistochemical staining of key slides and epidermal growth factor receptor (EGFR)/KRAS mutations tested by DNA sequencing were also included. @*Results@#Stages of peripheral SqCCs were significantly lower than central SqCCs (p=.016). Cystic change of the mass (p=.007), presence of interstitial fibrosis (p=0.007), and anthracosis (p=.049) in the background lung were significantly associated with the peripheral type. Cytokeratin-7 positivity was also higher in peripheral SqCCs with cutoffs of both 10% and 50% (p=.011). Pathogenic mutations in EGFR and KRAS were observed in only one case out of the 72 evaluated. The Cox proportional hazard model indicated a significantly better disease-free survival (p=.009) and the tendency of better overall survival (p=.106) in the peripheral type. @*Conclusions@#In peripheral type, lower stage is a favorable factor for survival but more frequent interstitial fibrosis and older age are unfavorable factors. Multivariate Cox analysis revealed that peripheral type is associated with better disease-free survival. The pathogenesis of peripheral lung SqCCs needs further investigation, together with consideration of the background lung conditions.
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BACKGROUND: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. METHODS: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed. RESULTS: Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort. CONCLUSIONS: Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.
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Humanos , Neoplasias de la Mama , Mama , Estudios de Cohortes , Antígenos HLA , Evasión Inmune , Inmunohistoquímica , Inmunoterapia , Leucocitos , Linfocitos Infiltrantes de Tumor , Complejo Mayor de Histocompatibilidad , Pronóstico , Linfocitos T ReguladoresRESUMEN
No abstract available.
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Tumores del Estroma Gastrointestinal , Mesilato de ImatinibRESUMEN
We need to establish an informative guideline to increase inter-institutional and inter-observer reproducibility of renal transplant diagnosis, and to improve the diagnostic ability of pathologists in Korea. A first nation-wide survey for renal transplant pathology was conducted by Renal Pathology Study Group of the Korean Society of Pathologists in 2016, to provide the continued excellence in the transplantation pathology laboratory, and to improve the diagnostic ability for the best treatment of transplant patients. This survey revealed the significant variations in scale, work load and biopsy indications for the renal transplant pathology in various institutions in Korea. The Banff classification were used by all institutions for the diagnosis of renal transplant pathology, but different formats were used: most institutions (70%) used the “2013 Banff classification” while the others were using “2007 Banff classification” (20%) or even older formats. In daily diagnostic practice of the renal allografts, difficulties that pathologists encounter were quite diverse due to different environments they work in. Most respondents agreed that standardized diagnostic practice guidelines, regular education on renal transplant pathology and convenient ways of consultation are further needed. We are currently working toward the enhancement of the expertise of renal pathologists and to increase inter-institutional and inter-observer reproducibility by 1) development of a set of virtual slides of renal allograft biopsies for the training, 2) validation and gathering expert's consensus on the core variables of rejection diagnosis by using virtual slides, and 3) continued education by the developed virtual slide atlas.
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Humanos , Aloinjertos , Biopsia , Clasificación , Consenso , Diagnóstico , Educación , Riñón , Corea (Geográfico) , Patología , Encuestas y Cuestionarios , TrasplanteRESUMEN
We report a new α-Galactosidase A (αGal-A) mutation in a 39-year-old Korean born, male Fabry disease patient. Fabry disease is a devastating, progressive inborn error of metabolism caused by X-linked genetic mutations. In this case, the first clinical symptom to occur was in childhood consisting of a burning pain originating in the extremities then radiating inwards to the limbs. This patient also stated to have ringing in his ears, angiokeratomas on his trunk, and cornea verticillata. He visited an outpatient cardiologist due to intermittent and atypical chest discomfort at the age of 39. Electrocardiographic and echocardiographic examination showed left ventricular hypertrophy. A physical examination revealed proteinuria without hematuria. The patient's plasma αGal-A activity was markedly lower than the mean value of the controls. After genetic counseling and obtaining written informed consent, we identified one hemizygous mutation in exon 4 of galactosidase alpha, c.617T>C (p.Leu206 Pro). He was eventually diagnosed as having Fabry disease.
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Adulto , Humanos , Masculino , Angioqueratoma , Quemaduras , Córnea , Oído , Ecocardiografía , Electrocardiografía , Exones , Extremidades , Enfermedad de Fabry , Galactosidasas , Asesoramiento Genético , Hematuria , Hipertrofia Ventricular Izquierda , Consentimiento Informado , Metabolismo , Pacientes Ambulatorios , Examen Físico , Plasma , Proteinuria , TóraxRESUMEN
Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease found in many organs including biliary tract, salivary gland, kidney, and lung. Tubulointerstitial nephritis is the most common renal manifestation, but hematologic involvement of IgG4-RD is rare. Here, we report on a case of a 57-year-old male with IgG4-related interstitial nephritis with bicytopenia, which was initially thought to be systemic lupus erythematosus. He presented with proteinuria, anemia, thrombocytopenia, and low complement levels. Histological findings showed an increased number of IgG4-positive plasma cells (>200/high power field), and an elevated IgG4/IgG ratio (>90%). Serum levels of IgG and IgG4 were also increased. This case emphasized the importance of differential diagnosis of IgG4-RD and immune complex glomerulonephritis.
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Humanos , Masculino , Persona de Mediana Edad , Anemia , Complejo Antígeno-Anticuerpo , Sistema Biliar , Proteínas del Sistema Complemento , Diagnóstico Diferencial , Glomerulonefritis , Inmunoglobulina G , Inmunoglobulinas , Riñón , Pulmón , Lupus Eritematoso Sistémico , Nefritis Intersticial , Células Plasmáticas , Proteinuria , Glándulas Salivales , TrombocitopeniaRESUMEN
We made a mistake in our recently published article.
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BACKGROUND: The tall cell variant of papillary thyroid carcinoma (TCVPTC) is more aggressive than classic papillary thyroid carcinoma (PTC), but the percentage of tall cells needed to diagnose TCVPTC remains controversial. In addition, little is known about the clinicopathologic features of classic PTC with tall cell features (TCF). METHODS: We retrospectively selected and reviewed the clinicopathologic features and presence of the BRAF mutation in 203 cases of classic PTC, 149 cases of classic PTC with TCF, and 95 cases of TCVPTCs, which were defined as PTCs having or =50% tall cells, respectively. RESULTS: TCVPTCs and classic PTCs with TCF did not vary significantly in clinicopathologic characteristics such as pathologic (p) T stage, extrathyroidal extension, pN stage, lateral lymph node metastasis, or BRAF mutations; however, these features differed significantly in TCVPTCs and classic PTCs with TCF in comparison to classic PTCs. Similar results were obtained in a subanalysis of patients with microcarcinomas (< or =1.0 cm in size). CONCLUSIONS: Classic PTCs with TCF showed a similar BRAF mutation rate and clinicopathologic features to TCVPTCs, but more aggressive characteristics than classic PTCs.
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Humanos , Clasificación , Ganglios Linfáticos , Tasa de Mutación , Metástasis de la Neoplasia , Estudios Retrospectivos , Neoplasias de la TiroidesRESUMEN
The most common BRAF mutation in thyroid cancer is c.1799T>A (p.Val600Glu), and other BRAF mutations are rarely reported. We investigated the clinicopathological features of thyroid cancer with rare BRAF mutations. A total of 2,763 patients with thyroid cancer underwent molecular testing by direct DNA sequencing for mutations in BRAF exon 15. Among them, 2,110 (76.4%) had BRAF mutations. The c.1799T>A mutation was found in 2,093 (76.9%) of 2,722 papillary carcinomas and in one of 7 medullary carcinomas. Sixteen cases (0.76%) harbored rare mutation types. Five cases had single-nucleotide substitutions, 5 cases had small in-frame deletion or insertion, and one harbored a two-nucleotide substitution. Of these mutations, 2 were novel (c.1797_1798insGAGACTACA, c.[1799T>A; 1801_1812del]). The c.1801A>C mutation was identified in 4 follicular variant papillary carcinomas and one follicular carcinoma. None of the patients with the c.1801A>C mutation showed extrathyroidal extension or lymph node metastasis. The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features. Although BRAF mutations are detected exclusively in papillary carcinoma, they are also found in medullary carcinoma and follicular carcinoma.