T1 and T2 Mapping for Characterization of Mediastinal Masses: A Feasibility study.

Purpose: To evaluate the feasibility and usefulness of T1 and T2 mapping in characterization of mediastinal masses. Methods: From August 2019 through December 2021, 47 patients underwent 3.0-T chest MRI with T1 and post-contrast T1 mapping using modified look-locker inversion recovery sequences and T2 mapping using a T2-prepared single-shot shot steady-state free precession technique. Mean native T1, native T2, and post-contrast T1 values were measured by drawing the region of interest in the mediastinal masses, and enhancement index (EI) was calculated using these values. Results: All mapping images were acquired successfully, without significant artifact. There were 25 thymic epithelial tumors (TETs), 3 schwannomas, 6 lymphomas, and 9 thymic cysts, and 4 other cystic tumors. TET, schwannoma, and lymphoma were grouped together as "solid tumor," to be compared with thymic cysts and other tumors ("cystic tumors"). The mean post-contrast T1 mapping (P < .001), native T2 mapping (P < .001), and EI (P < .001) values showed significant difference between these two groups. Among TETs, high risk TETs (thymoma types B2, B3, and thymic carcinoma) showed significantly higher native T2 mapping values (P = .002) than low risk TETs (thymoma types A, B1, and AB). For all measured variables, interrater reliability was good to excellent (intraclass coefficient [ICC]: .869∼.990) and intrarater reliability was excellent (ICC: .911∼.995). Conclusion: The use of T1 and T2 mapping in MRI of mediastinal masses is feasible and may provide additional information in the evaluation of mediastinal masses.

Current state of cytopathology residency training: a Korean national survey of pathologists.

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.

The prognostic utility of the histologic subtype of stage I lung adenocarcinoma may be diminished when using only the invasive component to determine tumor size for tumor node metastasis (TNM) staging.

BACKGROUND: Histologic subtypes were considered prognostic factors in early-stage lung adenocarcinoma in the 7th edition of the tumor node metastasis (TNM) staging system (TNM-7). However, the T-staging system has changed and now measures only the size of the invasive component to determine tumor size. The aim of this study was to determine whether the histologic subtype is still a prognostic factor in the 8th edition of the TNM staging system (TNM-8). METHODS: From 2010 to 2017, 788 patients who underwent curative surgery for stage I lung adenocarcinoma according to TNM-8 were analyzed retrospectively. Survival rates were compared among predominant patterns of adenocarcinoma. Prognostic factors were analyzed according to risk factors for recurrence in stage I lung adenocarcinoma. RESULTS: The 5-year recurrence-free survival rates among predominant histologic subtypes were statistically different, especially between the lepidic/acinar/papillary group and the micropapillary/solid group. Total tumor size was not significantly different between the two groups, but invasive component size was different (1.5 vs. 2.3 cm, P<0.001). In the multivariate analysis that adopted total tumor size as a variable, visceral pleural invasion (VPI), lymphovascular invasion (LVI), and micropapillary-predominant adenocarcinoma were significant predictors for recurrence. Conversely, adenocarcinoma subtypes were not significant risk factors for recurrence in the multivariate analysis that adopted invasive component size as a variable. CONCLUSIONS: The importance of adenocarcinoma subtype for prognosis may be reduced when only the invasive component of a tumor is used to determine tumor size, as described in the TNM-8 staging system.

Metachronous double primary neuroendocrine tumors in larynx and lung: a case report.

When a patient harbors two or more neuroendocrine tumors (NETs), it can be difficult to determine whether they are double primary tumors or metastases. A 60-year-old man complained of voice change lasting 1 month. On physical examination and imaging, a 1.8-cm mass was observed in his epiglottis, and a laser epiglottectomy was performed. Upon microscopic examination, the tumor consisted of medium-sized ovoid or short spindle cells. Immunohistochemical staining of the tumor cells was positive for synaptophysin, chromogranin, and calcitonin but negative for CD56; the Ki-67 proliferation index was approximately 5%. The patient was diagnosed with atypical carcinoid tumor. In 2015, a hypermetabolic endobronchial tumor was identified in the left lower lobe by positron emission tomography-computed tomography. Bronchoscopic biopsy revealed palisading large tumor cells with high nuclear-cytoplasmic ratio, frequent mitoses, and necrosis. The tumor cells were positive for CD56 and negative for cytokeratin-7, thyroid transcription factor-1, P40, synaptophysin, chromogranin, and calcitonin; the Ki-67 proliferation index was approximately 90%. Overall histologic findings were consistent with large cell neuroendocrine carcinoma rather than metastatic atypical carcinoid tumor. Detailed clinical and pathological review are essential to differentiate between metastatic NET and double primary NETs and, therefore, to provide the best management of the patient.

Invasive mucinous adenocarcinoma of the lung: Serial CT findings, clinical features, and treatment and survival outcomes.

BACKGROUND: Invasive mucinous adenocarcinoma (IMA) of the lung is a rare and distinct subtype of adenocarcinoma that can appear as airspace opacities on computed tomography (CT). In daily practice, we have occasionally encountered spontaneous regression of airspace opacities (SRAs) without treatment on serial CTs in patients with IMAs, which has not previously been described in the literature. Here, we describe serial CT findings with emphasis on SRAs in relation to clinicopathological features and treatment outcomes in patients with IMAs. METHODS: A total of 46 patients with pathologically-confirmed IMAs of the lung from January 2013 to June 2018 were included. Serial CT scans were reviewed and the patients were classified into SRA and no-SRA groups according to the presence of SRA. Radiological features, clinicopathological characteristics, and treatment outcomes were compared between the SRA and no-SRA groups. RESULTS: A total of 32 patients were included in the no-SRA group and 14 patients in the SRA group. IMAs in the SRA group were mostly pneumonic (P < 0.001), larger (P < 0.001), multifocal (P = 0.001), and showed higher stage (P < 0.001) on initial CT. Of seven patients who died during follow-up, six were from the SRA group (P < 0.001). Mean overall survival for all IMAs was 86.6 months (range, 0-110 months), and the SRA group showed significantly worse overall survival (P < 0.001). CONCLUSIONS: IMAs of the lung showing SRAs on serial CTs are larger and multifocal, and tend to be pneumonic in type on initial CT. Patients present at a higher stage of disease, with higher mortality rate and reduced overall survival. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Invasive mucinous adenocarcinomas (IMAs) of the lung can show spontaneous regression of airspace opacities (SRAs) on serial CTs, without being correlated to the administration of anticancer drugs. IMAs that showed SRAs demonstrated reduced overall survival in patients. WHAT THIS STUDY ADDS: When airspace opacities show regression on CT, IMA should still be included in the differential diagnosis. A more careful application of RECIST 1.1 is needed in the assessment of tumor response of IMAs.

TGF-ß induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer.

Transforming growth factor-ß (TGF-ß) promotes tumor invasion and metastasis by inducing epithelial-mesenchymal transition (EMT). EMT is often related with acquisition of stemness characteristics. The objective of this study was to determine whether EMT and stemness characteristics induced by TGF-ß might be associated with epigenetic regulation in lung cancer. A human normal lung epithelial cell line and four lung cancer cell lines were treated with TGF-ß. Transcriptome analysis of BEAS-2B and A549 cells incubated with TGF-ß were analyzed through next-generation sequencing (NGS). Western blotting was carried out to investigate expression levels of epithelial and mesenchymal markers. Wound healing and Matrigel invasion assay, sphere formation assay, and in vivo mice tumor model were performed to evaluate functional characteristics of EMT and stemness acquisition. To investigate whether activation of EMT and stem cell markers might be involved in epigenetic regulation of lung cancer, experiment using a DNA methyltransferase inhibitor (5-azacytidine, AZA), methylation-specific PCR (MSP) and bisulfite sequencing were performed. NGS revealed changes in expression levels of EMT markers (E-cadherin, N-cadherin, fibronectin, vimentin, slug and snail) and stem cell markers (CD44 and CD87) in both BEAS-2B and A549 cells. Functional analysis revealed increased migration, invasion, sphere formation, and tumor development in mice after TGF-ß treatment. Expression of slug and CD87 genes was activated following treatment with AZA and TGF-ß. MSP and bisulfite sequencing indicated DNA demethylation of slug and CD87 genes. These results suggest that TGF-ß induced EMT and cancer stemness acquisition could be associated with activation of slug and CD87 gene by their promoter demethylation.

Peripheral type squamous cell carcinoma of the lung: clinicopathologic characteristics in comparison to the central type.

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.

Pathologic properties of SOD3 variant R213G in the cardiovascular system through the altered neutrophils function.

The SOD3 variant, SOD3R213G, results from substitution of arginine to glycine at amino acid 213 (R213G) in its heparin binding domain (HBD) and is a common genetic variant, reported to be associated with ischemic heart disease. However, little is understood about the role of SOD3R213G in innate immune function, and how it leads to dysfunction of the cardiovascular system. We observed pathologic changes in SOD3R213G transgenic (Tg) mice, including cystic medial degeneration of the aorta, heart inflammation, and increased circulating and organ infiltrating neutrophils. Interestingly, SOD3R213G altered the profile of SOD3 interacting proteins in neutrophils in response to G-CSF. Unexpectedly, we found that G-CSF mediated tyrosine phosphatase, SH-PTP1 was down-regulated in the neutrophils of SOD3R213G overexpressing mice. These effects were recovered by reconstitution with Wt SOD3 expressing bone marrow cells. Overall, our study reveals that SOD3R213G plays a crucial role in the function of the cardiovascular system by controlling innate immune response and signaling. These results suggest that reconstitution with SOD3 expressing bone marrow cells may be a therapeutic strategy to treat SOD3R213G mediated diseases.

Risk Factors for Occult Lymph Node Metastasis in Peripheral Non-Small Cell Lung Cancer with Invasive Component Size 3 cm or Less.

BACKGROUND: In the seventh edition TNM staging system for lung cancer, a high maximum standardized uptake value (SUVmax) on positron emission tomography was regarded as a risk factor for occult lymph node metastasis in clinical T1N0 non-small cell lung cancer (NSCLC). However, in the eighth edition TNM classification, tumors are classified according to the size of the invasive component only, and those with invasive component size ≤3 cm are diagnosed as stage T1. The aim of this study was to reassess the risk factors for occult lymph node metastasis under the eighth edition TNM classification for lung cancer. METHODS: From 2010 to 2017, 553 patients with clinical N0 peripheral NSCLC with invasive component size ≤3 cm underwent anatomical lobectomy with systematic lymph node dissection. We analyzed these cases retrospectively to identify risk factors for postoperative nodal upstaging. RESULTS: Among 553 study patients, 54 (9.8%) had nodal upstaging after surgery. In multivariate analysis adopting the eighth edition TNM classification for lung cancer, serum carcinoembryonic antigen (CEA) level (hazard ratio [HR] = 1.113, p = 0.002), invasive component size (HR = 2.398, p = 0.004), visceral pleural invasion (HR = 2.901, p = 0.005), and lymphatic invasion (HR = 9.336, p < 0.001) were significant risk factors for nodal upstaging, but SUVmax was not. CONCLUSION: SUVmax is not a predictor of nodal upstaging in clinical N0 peripheral NSCLC with invasive component size ≤3 cm under the eighth edition TNM classification for lung cancer. Significant risk factors of occult lymph node metastasis are serum CEA level, tumor invasive component size, visceral pleural invasion, and lymphatic invasion.

The Effect of Resection Margin Distance and Invasive Component Size on Recurrence After Sublobar Resection in Patients With Small (≤2 Cm) Lung Adenocarcinoma.

BACKGROUND: When performing sublobar resection for lung cancer, the margin distance should exceed the tumor size. However, instead of total tumor size, the 8th edition TNM staging system has adopted the size of invasive component for the T stage. The aim of this study was to determine whether the prognosis was satisfactory when the resection margin distance was greater than the invasive component size instead of the total tumor size. METHODS: From 2008 to 2017, 193 consecutive patients were diagnosed with lung adenocarcinoma (invasive component size ≤2 cm) and underwent sublobar resection. We analyzed risk factors for recurrence using clinicopathological factors including margin/invasive component ratio (resection margin distance/invasive component size). RESULTS: Mean tumor size was 1.4 (±0.5) cm and the mean invasive component size was 0.8 cm (±0.5). In the multivariate analysis, neither resection margin distance (cm) nor margin/tumor ratio (resection margin distance/tumor size) was significant risk factors for recurrence. On the other hand, the margin/invasive component ratio (hazard ratio =0.035, p = 0.043) and the SUVmax (hazard ratio =1.993, p = 0.033) were significant risk factors for recurrence. CONCLUSIONS: When sublobar resection is performed for small (invasive component size ≤2 cm) adenocarcinomas of the lung, the resection margin distance should be larger than the invasive component size. Sublobar resection is not an appropriate treatment for lung adenocarcinoma with high SUVmax.

A Mesoporous Chelating Polymer-Carbon Composite for the Hyper-Efficient Separation of Heavy Metal Ions.

The removal of heavy-metal ions from wastewater is an important objective from a public-health perspective, and chelating agents can be used to achieve this aim. Herein, we report the synthesis of mesoporous carbon as a chelating polymer host using nanoarchitectonics approach. Carboxymethylated polyethyleneimine, a chelating polymer, was incorporated into the mesopore walls of mesoporous carbon to create a polymer-mesoporous-carbon composite. Nitrogen adsorption- desorption experiments and scanning electron microscopy (SEM) were used to illustrate the structural advantages of the composite. Co2+ adsorption by the composite material was examined using cobalt nitrate solutions at pH 3. The study revealed that the Co2+-absorption data are most closely modeled by the Langmuir isotherm. The maximum adsorption capacity, calculated by linear regression, was determined to be about 40 mg-Co/g-composite at pH 3. The composite exhibited about a six-times higher adsorption capacity toward a dilute Co solution (12.5 ppm) than that of the pristine mesoporous carbon. In addition, the composite showed a substantially higher distribution coefficient (Kd = 1.54×105) compared to that (Kd = 2.05×10²) of the mesoporous carbon. Overall, we expect that the mesoporous composite, with its large mesopores (~20 nm), will be in high demand for adsorption applications.

Prognosis after wedge resection in patients with 8th edition TNM stage IA1 and IA2 non-small cell lung cancer.

BACKGROUND: According to the 8th edition TNM classification for non-small cell lung cancer (NSCLC), tumor stage (T) is determined by the maximum size of the invasive component, without the lepidic component, and the T category has been further subdivided. We investigated the indications for wedge resection using the 8th edition TNM staging system, which measures only the size of the invasive component in tumor size. METHODS: We compared 5-year disease-free survival (DFS) rates in 429 consecutive patients with 8th edition stage IA1 and IA2 NSCLC who underwent lobectomy or wedge resection from 2007 to 2017. We also analyzed the risk factors for recurrence after surgical resection. RESULTS: There were no significant differences in clinicopathological factors or 5-year DFS in patients with stage IA1 disease (5-year DFS 95.0%, lobectomy, vs. 91.6%, wedge resection; P=0.435). For patients with stage IA2 tumors, the 5-year DFS was 88.3% after lobectomy and 74.0% after wedge resection (P=0.118). There were significant differences in clinicopathological characteristics between lobectomy and wedge resection groups in stage IA2 NSCLC. On multivariate analysis, serum CEA level [hazard ratio (HR) =1.040, P=0.046] and lymphovascular invasion (HR =2.664, P=0.027), but not wedge resection, were significant risk factors for recurrence in stage IA2 NSCLC. On multivariate analysis for recurrence risk after wedge resection in stage IA1 and stage IA2 NSCLC, only the width of the resection margin was associated with recurrence. CONCLUSIONS: Wedge resection may be an acceptable procedure in stage IA1 NSCLC. When performing wedge resection, it is necessary to ensure a sufficient resection margin distance.

A case of early diagnosis of pulmonary capillary hemangiomatosis in a worker with exposure to silica.

BACKGROUND: Pulmonary capillary hemangiomatosis (PCH) is a progressive and refractory vascular disease in the lung. Pulmonary hypertension is frequently combined with PCH when capillary proliferation invades to nearby pulmonary vascular systems. It is difficult to differentiate PCH from other diseases such as pulmonary venoocclusive disease and pulmonary arterial hypertension that cause pulmonary hypertension as they frequently overlap. CASE PRESENTATION: A 29-year-old female who had worked at a bathtub factory presented with progressive exertional dyspnea for the past 2 years. Computed tomography revealed centrilobular, diffusely spreading ground-glass opacities sparing subpleural parenchyma with some cystic lesions and air-trapping in both lungs, suggesting a peculiar pattern of interstitial lung disease with airway involvement. There was not any evidence of right heart failure or pulmonary hypertension on echocardiogram, as well as radiography. Microscopic examination of the lung by thoracoscopic resection showed atypical proliferation of capillary channels within alveolar walls and interlobar septa, without invasion of large vessels. CONCLUSION: We experienced a pathologically diagnosed PCH in a young female complaining progressive dyspnea with prior exposure to occupational silica or organic solvent without elevated right ventricular systolic pressure (RVSP) who showed atypical pattern of radiologic findings.

CT-guided transthoracic needle biopsy for evaluation of PD-L1 expression: Comparison of 22C3 and SP263 assays.

BACKGROUND: Although there have been several studies on concordance of different assays testing programmed cell death ligand-1 (PD-L1) expression using surgical specimens, studies using real-world biopsy specimens are scarce. However, many of the non-small cell lung cancer (NSCLC) cases requiring immunotherapy and thus PD-L1 testing are unresectable having to rely on small biopsy results. Therefore, we sought to assess the concordance of two diagnostic assays (22C3 and SP263) in evaluating PD-L1 expression using specimens from CT-guided transthoracic needle biopsy (TNB) specimens in a routine clinical setting. METHODS: A total of 202 NSCLC cases that underwent CT-guided TNB from April 2017 to February 2018 were retrospectively reviewed. Biopsy specimens tested with both 22C3 and SP263 assays were included. Concordance of PD-L1 expression levels determined by two assays was assessed using intraclass correlation coefficient, and the agreement of dichotomized values at various cutoffs (1%, 25%, and 50%) were assessed using Cohen's κ coefficient of agreement. RESULTS: A total of 80 patients (M:F = 47:33, mean age: 68.0 years) were included in the study. Concordance of PD-L1 expression levels was high (intraclass coefficient: 0.892) between 22C3 and SP263 assays. Agreements at cutoff levels of 1%, 25%, and 50% were also good, with κ values of 0.878, 0.698, and 0.790, respectively. Positive percent agreement was 93.2%, 100.0%, and 95.2% for agreements at 1%, 25%, and 50%. CONCLUSION: There is a high concordance of PD-L1 expression evaluated with 22C3 and SP263 assays using CT-guided TNB specimens.

Prognostic Factors in Stage IIB Non-Small Cell Lung Cancer according to the 8th Edition of TNM Staging System.

BACKGROUND: The purposes of this study were to evaluate the appropriateness of the stage migration of stage IIA non-small cell lung cancer (NSCLC) in the seventh edition of the tumor, node, and metastasis classification for lung cancer to stage IIB lung cancer in the eighth edition, and to identify prognostic factors in patients with eighth-edition stage IIB disease. METHODS: Patients with eighth-edition stage IIB disease were subclassified into those with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease, and their recurrence-free survival and disease-specific survival rates were compared. Risk factors for recurrence after curative resection were identified in all included patients. RESULTS: Of 122 patients with eighth-edition stage IIB NSCLC, 101 (82.8%) had seventh-edition stage IIA disease and 21 (17.2%) had seventh-edition stage IIB disease. Nonsignificant differences were observed in the 5-year recurrence-free survival rate and the 5-year disease-specific survival rate between the patients with seventh-edition stage IIA disease and those with seventh-edition stage IIB disease. Visceral pleural invasion was a significant risk factor for recurrence in patients with eighth-edition stage IIB NSCLC. CONCLUSION: The stage migration from seventh-edition stage IIA NSCLC to eighth-edition stage IIB NSCLC was appropriate in terms of oncological outcomes. Visceral pleural invasion was the only prognostic factor in patients with eighth-edition stage IIB NSCLC.

High expression level of SOX2 is significantly associated with shorter survival in patients with thymic epithelial tumors.

OBJECTIVES: Thymic epithelial tumors (TET) are heterogenous tumors which are composed of thymoma (TM) and thymic carcinoma (TC). We attempted to determine differences in gene expression between TM and TC, and to determine the effect of such genes on the prognosis of patients with TET. MATERIALS AND METHODS: Gene expression profiles of SOX2, OCT-4, IGF-1, IGF-1R and IR mRNA transcripts in tumor tissues of TM and TC were determined using real-time PCR (RT-PCR). We constructed tissue microarray with 140 paraffin-embedded tumor tissues and performed immunohistochemistry (IHC) for IGF-1R-related signaling molecules, including SOX2, IGF-1, IGF-1R and pAKT. RESULTS: SOX2 mRNA expression was notably higher (216-fold) in TCs than in TMs. However, there was no significant difference in expression of IGF-1, IGF-1R, OCT-4 or IR between the two tumor types. In IHC results, SOX2 (HR: 7.57, P = 0.001) and IGF-1 (HR: 9.43, P = 0.001) expression levels in TC were significantly higher than those in TM. There was a significant correlation in expression of SOX2 with IGF-1 (P = 0.021) and pAKT (P = 0.026). In univariate analysis, clinical TNM stage, WHO classification, serum LDH, expression of SOX2, IGF-1R, IGF-1 and pAKT, were significantly correlated with overall survival (OS). Multivariate analysis using a forward-selection procedure revealed that clinical N stage (HR: 4.08, P < 0.001), M stage (HR: 3.37, P = 0.001) and SOX2 expression (HR: 4.53, P = 0.010) were significantly associated with OS. CONCLUSIONS: SOX2 is expressed significantly higher in TC than in TM. SOX2 expression is also closely related to IGF-1 and pAKT expression. The higher expression of SOX2 is significantly associated with shorter survival in patients with TET.

CT-guided coaxial biopsy of malignant lung lesions: are cores from 20-gauge needle adequate for histologic diagnosis and molecular analysis?

BACKGROUND: To determine the number of cores adequate for histopathologic diagnosis as well as evaluate the success rate of molecular analyses in CT-guided percutaneous core needle biopsy (PCNB) for malignant pulmonary lesions using a 20-guage coaxial needle. METHODS: Biopsy records of 196 malignant lung lesions were reviewed. Core obtained from each needle pass was put in a separate container for individual pathological analysis. Types of molecular analysis attempted and their success rates were recorded for each patient. We categorized each patient into one of six groups according to the number of cores (n=1, n=2, n=3, n=4, n=5, n≥6) acquired, and diagnostic sensitivity for histopathologic diagnosis was calculated for each core in each group. In order to assess the increase in cumulative sensitivity up to 4th core, the data from 1st to 4th needle passes in 4-, 5-, and ≥6-core groups were pooled and cumulative diagnostic sensitivities up to 4th core were calculated. RESULTS: Of 196 cases of lung malignancies, five different types of molecular studies (EGFR mutation, ALK translocation, KRAS mutation, RET and ROS1 rearrangements) were attempted with PCNB specimens in 100 cases and successfully done in 96 cases (96.0%). In ≥4-core group (4-, 5-, and ≥6-core groups combined; n=148), cumulative sensitivity increased from 83.8% to 89.9% between 1st and 2nd cores, 89.9% to 93.2% between 2nd and 3rd cores, and 93.2% to 94.6% between 3rd and 4th cores. CONCLUSIONS: The cumulative diagnostic sensitivity for the histopathologic diagnosis increases significantly between the second and fourth sampling. Multiple samples obtained with a 20-guage coaxial needle are adequate and have a high success rate for various molecular studies for lung malignancy.

Comparison of PANAMutyper and PNAClamp for Detecting KRAS Mutations from Patients With Malignant Pleural Effusion.

BACKGROUND/AIM: KRAS is one of the frequently mutated genes in human cancers and often relates with drug resistance and poor prognosis. PANAMutyper™ is a novel technology that integrates PNAClamp™ and PANA S-Melting™. In the present study, PANAMutyper™ and PNAClamp™ were compared for the detection of KRAS mutations using different samples of patients with malignant pleural effusion. PATIENTS AND METHODS: A total of 103 patients (including 56 lung adenocarcinoma, 10 lung squamous carcinoma, 17 small cell lung cancer, 3 large cell lung cancer, 3 stomach cancer, 2 ovarian cancer, and others) with malignant pleural effusion were investigated using matched tumor tissue, cell block, and pleural effusion samples. The diagnostic performance of these two methods was compared. RESULTS: KRAS mutations were detected in 18 (17.5%) of 103 patients using tissue, cell block, and pleural effusion samples. All 18 patients with KRAS mutations were detected by PANAMutyper™ using any sample type, however, only 7 cases were detected by PNAClamp™. Among the subtypes of KRAS mutations, substitution in codon 12, 35G>T was the most frequent, followed by substitution in codon 12, 35G>A and codon 12, 34G>A. In pleural effusion specimens, PANAMutyper™ showed a better diagnostic performance compared to PNAClamp™. CONCLUSION: PANAMutyper™ had a diagnostic superiority for the detection of KRAS mutations in patients with malignant pleural effusion compared to PNAClamp™, although there was a concordance between PANAMutyper™ and PNAClamp™ results. Therefore, PANAMutyper™ can be used for a more sensitive and accurate detection of KRAS mutations.