Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Imaging features and clinical significance of atypical pleural plaques mimicking bone tumors: a retrospective case series.

This study aimed to examine the imaging characteristics and clinical implications of atypical pleural lesions that mimic bone tumors and form along the inner margins of consecutive ribs. This retrospective analysis included 45 atypical pleural lesions arising from 13 patients who underwent chest computed tomography (CT) between April 2021 and March 2023. The clinical features, CT findings, and radiologic diagnoses prior to pathologic identification were examined. Pathological findings were reviewed in the surgically resected case. Subgroup analysis was performed based on the presence of concurrent typical pleural plaques. The mean age of the patients was 69.3±8.4 years with a predominance of males (76.9%). The lesions primarily exhibited unilateral involvement (84.6%), being most frequently located in the right mid-level posterior region. Calcification was present in 75.6% of cases, typically seen continuously along the ribs (82.4%). Adjacent rib changes were observed in 28.9% of cases. These lesions were frequently misdiagnosed as osteochondromas or bony spurs (55.6%) by thoracic radiologists. No significant growth was observed during follow-up (n=11, 47±41 months), and the pathological findings were consistent with pleural plaques. Patients with concurrent typical pleural plaques had more atypical pleural lesions without statistical significance (P=0.071) and showed a more even distribution (P=0.039). In conclusion, atypical pleural lesions resembling bone tumors along consecutive ribs represent a distinct subset of pleural plaques. Their unique distribution and morphology should be recognized by radiologists to avoid misinterpretation and unnecessary interventions.

Enlarging pulmonary cyst: a rare form of alveolar adenoma.

BACKGROUND: Alveolar adenoma is a rare benign tumour, usually presenting as a peripherally located solid mass, sometimes mimicking malignancy. CASE PRESENTATION: A 37-year-old woman presented with chronic intermittent vague chest discomfort. The chest x-ray showed a simple cyst in the left lower lung field, and serial computed tomography (CT) over the following 2-year period showed rapid growth of the cyst, from 3.5 to 9.0 cm in diameter. The CT scan suggested bronchiolar communication, which was suspected to be the cause of growth, via check-valve mechanism. Thoracoscopic surgery was performed, and we found a thin-walled cyst in the lingular segment. Wedge resection was performed and the pathology was an unexpected alveolar adenoma which had grown on the terminal bronchiole, causing the alveolus to rupture and the cyst to grow. In 48 months of follow-up, there was no evidence of recurrence and the patient's symptoms resolved. CONCLUSIONS: Rapidly growing pulmonary cysts can lead to complications including rupture with pneumothorax and haemothorax, and surgery is always indicated. Abnormally rapid growth may indicate an underlying pathology such as alveolar adenoma. Surgical resection is the treatment of choice and there have been no reported cases of recurrence. Here we present a rare form of alveolar adenoma, which was a form of rapidly growing pulmonary cyst.

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

BACKGROUND: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. METHODS: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. RESULTS: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. CONCLUSIONS: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

Radiological and pathological analysis of the galaxy sign in patients with pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma.

BACKGROUND: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma sometimes presents as large pulmonary nodules composed of small nodular opacities (galaxy sign) on computed tomography (CT). The aim of this study was to assess the presence, usefulness, and pathological characteristics of the galaxy sign on CT of pulmonary MALT lymphoma. METHODS: From January 2011 to December 2021, chest CTs of 43 patients with pulmonary MALT lymphoma were reviewed by two radiologists for the galaxy sign and various other findings. Interreader agreement to characterize the galaxy sign and factors associated in making a correct first impression on CT prior to pathological diagnosis were assessed. Resected specimens were reviewed by two pathologists, and the proportion of peripheral lymphoma infiltrates was compared between lesions with and without the galaxy sign. RESULTS: Of 43 patients, 22 patients (44.2%) showed the galaxy sign (κ = 0.768, p < 0.0001). The galaxy sign (p = 0.010) was associated with making a correct first impression on CT prior to pathological diagnosis. On pathological examination, lesions showing the galaxy sign on CT demonstrated a significantly higher proportion of peripheral lymphoma infiltrates (p = 0.001). CONCLUSION: The galaxy sign can be seen on CT of pulmonary MALT lymphoma with a higher proportion of peripheral lymphoma infiltrates and may be useful in making a correct diagnosis of pulmonary MALT lymphoma.

Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor.

BACKGROUND: The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM). METHODS: A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary's Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results. RESULTS: Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively. CONCLUSIONS: We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor's molecular pathology.

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.

Computed Tomography Findings for Predicting Invasiveness of Lung Adenocarcinomas Manifesting as Pure Ground-Glass Nodules.

Purpose: To comprehensively evaluate qualitative and quantitative features for predicting invasiveness of pure ground-glass nodules (pGGNs) using multiplanar computed tomography. Methods: Ninety-three resected pGGNs (16 atypical adenomatous hyperplasia [AAH], 18 adenocarcinoma in situ [AIS], 31 minimally invasive adenocarcinoma [MIA], and 28 invasive adenocarcinoma [IA]) were retrospectively included. Two radiologists analyzed qualitative and quantitative features on three standard planes. Univariable and multivariable logistic regression analyses were performed to identify features to distinguish the pre-invasive (AAH/AIS) from the invasive (MIA/IA) group. Results: Tumor size showed high area under the curve (AUC) for predicting invasiveness (.860, .863, .874, and .893, for axial long diameter [AXLD], multiplanar long diameter, mean diameter, and volume, respectively). The AUC for AXLD (cutoff, 11 mm) was comparable to that of the volume (P = .202). The invasive group had a significantly higher number of qualitative features than the pre-invasive group, regardless of tumor size. Six out of 59 invasive nodules (10.2%) were smaller than 11 mm, and all had at least one qualitative feature. pGGNs smaller than 11 mm without any qualitative features (n = 16) were all pre-invasive. In multivariable analysis, AXLD, vessel change, and the presence or number of qualitative features were independent predictors for invasiveness. The model with AXLD and the number of qualitative features achieved the highest AUC (.902, 95% confidence interval .833-.971). Conclusion: In adenocarcinomas manifesting as pGGNs on computed tomography, AXLD and the number of qualitative features are independent risk factors for invasiveness; small pGGNs (<11 mm) without qualitative features have low probability of invasiveness.

Molecular and immunohistochemical comparison between primary gastrointestinal mucosal melanomas and atypical gastrointestinal stromal tumors.

BACKGROUND: It is sometimes challenging to differentiate between gastrointestinal (GI) mucosal melanoma and gastrointestinal stromal tumors (GISTs) because they share some similarities in histological and molecular features. In this study, we investigated their clinicopathological and molecular features. METHODS: Four primary GI mucosal melanomas and 4 atypical GISTs resected from 2017 to 2019 were included. Electronic medical records and histology slides were reviewed and, if needed, immunohistochemical stainings were additionally done. Somatic mutations were analyzed using whole exome sequencing (WES) with tumors and matched normal tissues. RESULTS: By immunohistochemistry, GISTs were positive for CD117 (4 of 4), DOG1 (4 of 4), and CD34 (2 of 4). In contrast, melanomas were positive for CD117 (2 of 4), HMB-45 (4 of 4), Melan-A (4 of 4), and S100 protein (3 of 4). Using WES, the KIT mutation was detected in 2 of 4 GISTs and 1 of 4 melanomas, all of which showed strong CD117 immunoreactivity. PDGFRA mutation was detected in 2 of 4 GISTs but 0 of 4 melanomas. TP53, NF1, RB1, TERT, and KMT2D mutations were detected in 1 of 4 melanomas but 0 of 4 GISTs. A patient with KIT-mutated melanoma was treated with Gleevec and has remained disease-free for 1 year. CONCLUSIONS: GISTs and GI melanomas have a wide histopathological spectrum. Appropriate ancillary studies can be helpful for proper diagnosis and optimal treatment.

18 F-Flutemetamol PET/CT for Transthyretin Amyloid Cardiomyopathy : Timing Matters.

ABSTRACT: We report 18 F-flutemetamol PET/CT finding in an 88-year-old man with cognitive impairment and transthyretin amyloid cardiomyopathy. Early phase PET/CT images showed significantly increased myocardial uptake, but there was no myocardial uptake in delayed phase PET/CT images. A dual-time-point amyloid PET/CT imaging may be helpful to diagnose and differentiate subtypes of amyloid cardiomyopathy in patients with suspected cardiac amyloidosis.

Prognostic Role of Systemic Inflammatory Markers in Patients Undergoing Surgical Resection for Oral Squamous Cell Carcinoma.

Background: A high platelet−lymphocyte ratio (PLR) is a marker of systemic inflammation and, together with the neutrophil−lymphocyte ratio (NLR), is associated with poor outcomes in several cancers. We investigated the prognostic value of PLR and other systemic inflammatory markers, such as NLR, systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI), in oral squamous cell carcinoma (OSCC) patients undergoing surgical resection. Methods: We derived PLR, NLR, SII, and SIRI from a retrospective chart review of 269 consecutive OSCC patients. The complete blood count examined in the immediate preoperative period was used to compute PLR, NLR, SII, and SIRI. We analyzed the relationship between these systemic inflammatory markers and the clinicopathologic characteristics, disease-specific survival (DSS), and progression-free survival (PFS) of patients. Results: In the univariate analysis, high PLR and SII were significantly associated with worse DSS and PFS (all p < 0.05). In the multivariate analysis, PLR (HR 2.36, 95% CI 1.28−4.36 for DSS; HR 1.80, 95% CI 1.06−3.06 for PFS) was an independent predictor of survival outcomes. When PLR was analyzed as a continuous variable, the relationship between the outcome and preoperative PLR was not monotonically linear. In the subgroup analysis, PLR was more strongly associated with DSS and PFS in patients who were male, had stage III/IV OSCC, or had lymph node metastasis. Conclusion: Our data suggest that in OSCC patients, the pretreatment PLR is an independent predictor of DSS and PFS. The PLR is a readily available biomarker that will improve prognostication and risk stratification in OSCC.

DeepRePath: Identifying the Prognostic Features of Early-Stage Lung Adenocarcinoma Using Multi-Scale Pathology Images and Deep Convolutional Neural Networks.

The prognosis of patients with lung adenocarcinoma (LUAD), especially early-stage LUAD, is dependent on clinicopathological features. However, its predictive utility is limited. In this study, we developed and trained a DeepRePath model based on a deep convolutional neural network (CNN) using multi-scale pathology images to predict the prognosis of patients with early-stage LUAD. DeepRePath was pre-trained with 1067 hematoxylin and eosin-stained whole-slide images of LUAD from the Cancer Genome Atlas. DeepRePath was further trained and validated using two separate CNNs and multi-scale pathology images of 393 resected lung cancer specimens from patients with stage I and II LUAD. Of the 393 patients, 95 patients developed recurrence after surgical resection. The DeepRePath model showed average area under the curve (AUC) scores of 0.77 and 0.76 in cohort I and cohort II (external validation set), respectively. Owing to low performance, DeepRePath cannot be used as an automated tool in a clinical setting. When gradient-weighted class activation mapping was used, DeepRePath indicated the association between atypical nuclei, discohesive tumor cells, and tumor necrosis in pathology images showing recurrence. Despite the limitations associated with a relatively small number of patients, the DeepRePath model based on CNNs with transfer learning could predict recurrence after the curative resection of early-stage LUAD using multi-scale pathology images.

Early risk-assessment of patients with nasopharyngeal carcinoma: the added prognostic value of MR-based radiomics.

OBJECTIVES: To assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC) METHODS: Patients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores. RESULTS: This study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72-0.80; p=0.04), stage (iAUC, 0.70-0.79; p=0.001), and combined models (iAUC, 0.76-0.81; p<0.001). In the test cohort, the radiomics and combined survival models were robustly validated for their ability to predict PFS. CONCLUSION: Integration of MR-based radiomic features with clinical and stage variables improved the prediction PFS in patients diagnosed with NPC.

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.

Delayed periprosthetic seroma in a male Poland syndrome patient: A case report.

RATIONALE: Custom-made implant is an accepted treatment option for treatment of chest deformity in Poland syndrome. Unlike the raised concerns and awareness for the long-term consequences of breast implants, the long-term complications of customized implants for special purposes like Poland syndrome has not been reported in the literature. PATIENT CONCERNS: A 44-year-old male with Poland syndrome presented to our institution complaining of a large bulge and fluctuation on the right chest wall. This occurred after 14 years from the initial implant surgery for correction of chest wall deformity. Upon failure of resolution by multiple aspirations, workup was carried out under suspicion of implant associated malignancy. INTERVENTION: Total Capsulectomy and implant removal was done. OUTCOMES: Histology revealed chronic inflammation with fibrosis. Implant-associated malignancy was not found. He is being followed up with no signs of recurrence. LESSONS: For rare cases of implant insertion such as Poland syndrome, awareness of delayed complications and workups based on suspicion of implant-associated malignancy is needed. Surgeon awareness and patient education is required.

Proposal of a scoring system for predicting pathological risk based on a semiautomated analysis of whole slide images in oral squamous cell carcinoma.

BACKGROUND: The study aimed to evaluate the risk factors based on pathological findings comprehensively in oral squamous cell carcinoma (OSCC) using image analysis. METHODS: Scanned images of hematoxylin and eosin-, pan-cytokeratin-, CD3-, and CD8-stained slides of OSCC cases from 256 patients were analyzed, and six variables were obtained including the tumor-stroma ratio, tumor budding per tumor bed area, and tumor infiltrating lymphocytes-associated variables. We determined the "score" of all cases based on the variables, and all cases were classified into low-, intermediate-, and high-risk groups. RESULTS: A significant difference in prognosis was confirmed between the risk groups (p < 0.001), and even when evaluated within different tumor-node-metastasis (TNM) stages, the high-risk groups were associated with poor survival. CONCLUSIONS: We report our work on a possible descriptive model that can predict prognosis based on pathological and imaging findings regardless of the TNM stage.

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.