Primary Pulmonary Adenocarcinoma Research Articles

Solitary Pulmonary Nodule Under the Anonymity of COVID-19 Infection

Abstract We report the case of a 32-year-old male patient, a former smoker, with a known history of SARS-COV-2 infection, mild clinical form, condition that required follow-up evaluation. Despite being oligosymptomatic, the patient reports discreet respiratory symptoms, manifested by dry cough and a sensation of chest tightness. CT thoracic scan revealed a pseudo-nodular, diffusely contoured infiltrate of approximately 10 mm, in the apical left upper lobe segment (LUL), sequelae appearance, thought to represent SARS-COV-2 residual changes, with follow-up recommendation. Three months later, reassessment highlighted a slight progression of the lesion, with a spiculated appearance and umbilicated pleura, a context that mandated further respiratory-specific medical investigations, including bronchoscopic examination and positron emission tomography (PET CT). Given the diagnostic suspicion that included a pathology with neoplastic potential, the firm recommendation was to perform a nodular pulmonary biopsy through video-assisted thoracoscopy (VATS). Both the histopathological (HP) and immunohistochemical (IHC) examinations supported the diagnosis of primary pulmonary adenocarcinoma. The therapeutic course was completed by performing a left upper lobectomy with lymphadenectomy. The case is instructive, confirming that SARS-COV-2 infection is a perfect mimic (1), capable of imitating various other conditions. In this context, the optimal scenario is distinguished, where monitoring after infection contributes to the early and incidental identification of neoplasia, thus suggesting that SARS-COV-2 infection may also offer certain benefits.

Can tumour budding change the future of pulmonary adenocarcinoma?

BackgroundPulmonary adenocarcinoma shows different prognosis even in the same pathological subtype and stage. In this study, it is aimed to investigate the relationship between tumour budding and known prognostic values and clinicopathological features in pulmonary adenocarcinoma. MethodsIn this study, there have been 77 patients diagnosed with primary pulmonary adenocarcinoma. In the evaluation process, the number of budding between 0 and 4 is accepted as low budding (Bd1), the number of budding between 5 and 9 is considered as medium budding (Bd2), and the number of budding above 10 is considered as high budding (Bd3). ResultsAccording to the findings of the study, it can be seen that there is a statistical difference between tumour budding and stromal fibrosis (p < 0.001). The presence of pleural invasion, lymph vascular invasion and perineural invasion in patients with Bd3 is found to be statistically higher than the patients with Bd1 (p = 0.048) (p = 0.041) (p = 0.029). ConclusionsTumour budding has been associated with pleural invasion, lymph vascular invasion, perineural invasion, and stromal fibrosis. This study is the first to show the relationship between tumour budding and stromal fibrosis in pulmonary adenocarcinomas. The role of tumour budding in lung cancers remains to be clarified.

Prognosis of primary pulmonary adenocarcinoma after surgical resection in small-breed dogs: 52 cases (2005-2021).

Tumor size is an important prognostic factor in lung cancer in dogs, and the canine lung carcinoma stage classification (CLCSC) recently has been proposed to subdivide tumor sizes. It is unclear if the same classification scheme can be used for small-breed dogs. To investigate whether the tumor size classification of CLCS is prognostic for survival and progression outcomes in small-breed dogs with surgically resected pulmonary adenocarcinomas (PACs). Fifty-two client-owned small-breed dogs with PAC. Single-center retrospective cohort study conducted between 2005 and 2021. Medical records of dogs weighing <15 kg with surgically resected lung masses histologically diagnosed as PAC were examined. The numbers of dogs with tumor size ≤3 cm, >3 cm to ≤5 cm, >5 cm to ≤7 cm, or >7 cm were 15, 18, 14, and 5, respectively. The median progression-free interval (PFI) and overall survival time (OST) were 754 and 716 days, respectively. In univariable analysis, clinical signs, lymph node metastasis, margin, and histologic grade were associated with PFI, and age, clinical signs, margin, and lymph node metastasis were associated with OST. Tumor size classification of CLCS was associated with PFI in all categories, and tumor size >7 cm was associated with OST. In multivariable analysis, tumor size >5 cm to ≤7 cm and margin were associated with PFI, and age was associated with OST. The tumor size classification of CLCS would be an important prognostic factor in small-breed dogs with surgically resected PACs.

Correlation between ALK, ROS1 Biomarkers and EGFR Oncogene Mutations in Lung Tumours: Our Observations in an Apex Oncopathology Laboratory

Introduction: Analysis of Anaplastic lymphoma receptor tyrosine kinase gene (ALK), Repressor of Silencing 1 (ROS1) gene are determined by immunohistochemistry (IHC) and it is an easily applicable, cost-effective assay for potential treatment with crizotinib. Mutations of Epidermal growth factor receptor (EGFR) genes are evaluated by IHC/Multiplex RT-PCR. The purpose of this study is to assess the frequencies of ALK, ROS1 and their association with EGFR fusion gene mutations in a spectrum of lung tumours. Materials and methods: A total of 202 cases of lung tumours reported at our Center for Oncopathology from September 1st 2020 to 31st August 2021, were retrospectively analyzed for ALK, ROS1 and EGFR fusion genes based on Immunohistochemistry (IHC) and Multiplex PCR findings. ALK was tested using D5F3 clone, and ROS1 was analyzed using Cell Signalling’s D4D6 clone on the Ventana immunohistochemistry platform. EGFR status was analyzed using EGFR mutation test V2 real-time multiplex PCR assay on Roche Cobas Z480. Results: 202 biopsy samples and cellblocks of fluid aspirates were analyzed. 175/202 were histologically and immunologically proved as Non-small cell lung carcinoma (Primary pulmonary adenocarcinoma) and its metastases. 09/199 (5.23%) were Positive for ALK IHC and 03/199 (1.74%) cases had equivocal results. 06/179 (3.85%) cases were Positive for ROS1 IHC and 03/179 (1.92%) cases had equivocal results. Other histo-morphological diagnoses i.e., adenosquamous, squamous, small cell, mucinous carcinoma etc (27 cases) were all ALK and ROS1 Negative. 188/202 tumours were analyzed for EGFR mutation status, which showed 70/188 (37.23%) had specific EGFR mutations. 118/188 (62.76%) cases were EGFR wildtype. Conclusion: We observed that age related incidence of EGFR mutations was highest in elderly females, of 61 to 70 years. ALK gene mutations occurred in 6.03% and ROS1 gene mutations occurred in 5.02% of lung tumours and their metastases. EGFR-mutations were associated with ROS1 mutated lung adenocarcinomas. There are no coexistent ALK-EGFR or ALK-ROS1 mutations. All ALK IHC positive pulmonary adenocarcinomas are ROS1 negative and are mutually exclusive.

First Analysis of Expression of Napsin-A in Ovine Pulmonary Adenomatosis of Sheep and Goat at Duhok Governorate

Ovine Pulmonary Adenomatosis is a chronic respiratory disease of sheep or contagious lung cancer of sheep, and less commonly of goats. A total of 4061 lung samples were selected randomly from slaughtered sheep and goats. All samples of lungs with typical lesions were fixed in 10% neutral buffered formalin and examination is performed by macrocsopical and microscopical observation. To perform IHC technique, we used TMA with a polymer system by application of specific markers Napsin A. Results showed 35 lungs suspected from natural cases are diagnosed as OPA. Histologically results showed that the presence of multiple proliferations foci of neoplastic cells in the epithelial cell of alveoli and bronchi, these proliferations appears either papillary or as impression of solid growths appearance or acinar shape which is classified as classical and atypical form. The current study found that the expression of Nnapsin A was observed in 85.71% of the OPA as a granular cytoplasmic staining but there was staining in the nucleus of tumor cells. In conclusion, these findings indicate for the first time that Napsin A is extremely specific for adenocarcinoma of lung in primary origin and use of this important biomarker is guaranteed to help disconnect primary pulmonary adenocarcinoma for diagnosis from other types of lung cancer.

Refined Diagnosis of Pleural Effusions by Immunocytochemistry of Cell Blocks.

The main objective of microscopic examination of pleural effusions is to ascertain the presence of malignant cells. Effusions prepared routinely using May-Grünwald-Giemsa (MGG)- and Papanicolaou (PAP)-staining can, in a number of cases, provide inconclusive cytological results regarding malignancy. This report describes the refined diagnosis of such cases based on immunocytochemical analysis of pleural effusion cell blocks. Of the 340 pleural effusions obtained during 2019 at the Department of Clinical Cytology, Gävle Hospital, Sweden, 63 (18.5%) contained atypical cells of undetermined significance or potentially malignant cells. This diagnosis could be refined using Epithelial Cell Adhesion Molecule/EPCAM (BEREP4) immunocytochemical analysis of effusion cell blocks, allowing previously inconclusive effusions to be classified as clearly benign 42/63 (66.7%) or malignant 21/63 (33.3%). Effusions initially diagnosed as clearly malignant (27/340; 7.9%) were all 27 (100%) BEREP4-immuno-stained. Most BEREP4-positive effusions (37/48; 77.1%) were also carcinoembryonic antigen (CEA) positive. The number of BEREP4-positive cells, however, tended to exceed that of CEA-positive cells. The BEREP4 positive effusions were further examined using different monoclonal antibodies, such as Thyroid transcription factor 1 (TTF-1) for primary pulmonary adenocarcinoma, to determine the original site of the primary tumour. Immunohistochemical staining of pleural effusion cell blocks significantly refines the diagnosis of serous pleural effusions, especially in cases where the preliminary diagnosis was atypical cells of undetermined significance or potentially malignant cells. Furthermore, in the cases of malignancy, the origin of the primary tumour could most often be determined.

Nadir and Finical-Minimally Invasive Adenocarcinoma Lung

Minimally invasive adenocarcinoma emerges as a miniature, solitary, localized, primary pulmonary adenocarcinoma ≤ 3.0 centimetre magnitude and ≤ 0.5 centimetre zone of stromal invasion or non-invasive (lepidic) pattern of neoplastic evolution. Minimally invasive adenocarcinoma lung is predominantly comprised of non-mucinous component and is confined within peripheral pulmonary parenchyma. Preponderantly asymptomatic, poorly defined areas appear concurrent with lepidic pattern of tumour growth whereas solid foci are concordant with focal tumour invasion. Cogent histopathological subtypes appear as non-mucinous variant, mucinous variant and mixed variant. Stromal invasion configures acinar, papillary, micropapillary, solid, colloid, foetal or invasive mucinous lesions. Neoplastic cells appear immune reactive to CK7, thyroid transcription factor1(TTF-1) or Napsin A and immune non-reactive to p40. Minimally invasive adenocarcinoma lung requires segregation from neoplasms such as invasive pulmonary adenocarcinoma, lepidic predominant pattern, adenocarcinoma in situ or atypical adenomatous hyperplasia lung. The gradually progressive neoplasm demonstrates ‘ground glass’ opacities. Appropriate neoplastic discernment necessitates comprehensive histological assessment of entire surgical resection specimens. Minimally invasive adenocarcinoma lung can be appropriately treated with surgical extermination of the neoplasm followed by extensive monitoring. Neoplasm is devoid of lymphatic invasion, vascular invasion, tumour necrosis or pleural invasion.

Primary Pulmonary Colloid Adenocarcinoma: A Case Report with Literature Review

Pulmonary colloid adenocarcinomas are uncommon tumors individualized as a distinct entity in the histological classification of World Health Organisation of lung tumors characterized by extensive pool of extracellular mucin distending and destroying alveolar walls.

Microwave ablation therapy assisted by artificial pneumothorax and artificial hydrothorax for lung cancer adjacent to the vital organs.

ObjectivesThis study aimed to investigate the technical methods and safety of artificial pneumothorax and artificial hydrothorax in the treatment of lung cancer adjacent to vital organs by CT-guided microwave ablation.Subjects and MethodsThree of the six patients were men and three were women, with a mean age of 66.0 years (range 47–78 years). There patients had primary pulmonary adenocarcinoma, one had lung metastasis from liver cancer, one had lung metastasis from colon cancer, and one had lung metastasis from bladder cancer. There were four patients with a single lesion, one with two lesions, and one with three lesions. The nine lesions had a mean diameter of 1.1 cm (range 0.4–1.9). In three patients, the lung cancer was adjacent to the heart, and in the remaining three, it was close to the superior mediastinum. Six patients were diagnosed with lung cancers or lung metastases and received radical treatment with microwave ablation (MWA) assisted by artificial pneumothorax and artificial hydrothorax in our hospital. Postoperative complications were observed and recorded; follow-up was followed to evaluate the therapeutic effect.ResultsThe artificial pneumothorax and artificial hydrothorax were successfully created in all six patients. A suitable path for ablation needle insertion was also successfully established, and microwave ablation therapy was carried out. 2 patients developed pneumothorax after operation; no serious complications such as operation-related death, hemothorax, air embolism and infection occurred.Moreover, 4–6 weeks later, an enhanced CT re-examination revealed no local recurrence or metastasis, and the rate of complete ablation was 100%.ConclusionsMicrowave ablation, assisted by artificial pneumothorax, artificial hydrothorax, is a safe and effective minimally invasive method for treating lung cancer adjacent to the vital organs, and optimizing the path of the ablation needle and broadening the indications of the ablation therapy

The genomic and transcriptome characteristics of lung adenocarcinoma patients with previous breast cancer

BackgroundBreast cancer and lung cancer are the top two malignancies in the female population and the number of patients with breast cancer and subsequent primary lung cancer has increased significantly in recent years. However, the unique molecular characteristics of this group of patients remains unclear.PurposeTo identify the genomic and transcriptome characteristics of primary lung adenocarcinoma patients with previous breast cancer by comparison with single primary lung adenocarcinoma (SPLA) patients.MethodsThe tumor and normal pulmonary tissue specimens of ten primary pulmonary adenocarcinoma patients with previous breast cancer (multiple primary cancer, MPC) and ten SPLA patients were prospectively collected. The whole exome sequencing (WES) and RNA sequencing (RNA-seq) were performed to analyze the gene mutation and expression differences between MPC and SPC patients.ResultsThe results of WES indicated that the mutations of TRIM73, DLX6 and CNGB1 only existed in MPC patients. The results of RNA-seq manifested the occurrence of second primary lung adenocarcinoma in breast cancer patients was closely associated with cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Besides, the expression levels of FGF10 and VEGFA genes were significantly increased in MPC patients.ConclusionThe occurrence of second primary lung adenocarcinoma may be related to the cytokine-cytokine receptor action, autophagy, PI3L-Akt, cAMP and calcium ion signaling pathways. Furthermore, the mutations of TRIM73, DLX6 and CNGB1 and high expression of FGF10 and VEGFA might play an important role in the development of lung adenocarcinoma in breast cancer patients. However, more in-depth investigations are needed to verify above findings.

PRIMARY MUCINOUS ADENOCARCINOMA OF THE LUNG WITH SIGNET-RING CELLS AND ALK REARRANGEMENT: A CASE REPORT

TYPE: Case Report TOPIC: Lung Pathology INTRODUCTION: The presence of malignant signet-ring cells is more commonly seen in the adenocarcinomas, particularly those of the gastrointestinal tract and breast. In a study with 24,171 patients with signet-ring cell carcinoma (SRCC), it was found that only 3.1% of the cases have a primary pulmonary origin, making the study of SRCC of the lung restricted to reports and case series. CASE PRESENTATION: We present the case of a 70-year-old patient with a history of retroperitoneal liposarcoma and papillary thyroid carcinoma in whom a primary pulmonary adenocarcinoma of mucinous pattern with signet-ring cells and ALK rearrangement was diagnosed. DISCUSSION: The World Heart Organization (WHO) had included the SRCC subtype. However, since 2015 WHO classification, it is recognized only as cytologic features rather than primary histologic subtype. The incidence of primary SRCC of the lung is between 0.14 to 1.9% of all lung tumors. The differences in incidence rates lie in the definition since clear diagnostic criteria have not been established. Its presentation is slightly more common in men (52.7%) and Caucasian patients (82.2%), with a mean overall survival duration of 8 months. Patients presenting with the EML4-ALK fusion protein have unique pathological and physiological characteristics. Several reports have shown that it predominates in a young female population with adenocarcinoma and without exposure to tobacco. However, these are not consistent data in all studies. CONCLUSIONS: Lung cancer has a very heterogeneous presentation. We emphasize the importance of approaching these patients with histopathological, immunohistochemical, and molecular biology studies. DISCLOSURE: Nothing to declare. KEYWORD: pulmonary signet ring cell carcinoma

Critical diagnostic and cancer stem cell markers in neoplastic cells from canine primary and xenografted pulmonary adenocarcinoma.

It is challenging to diagnose metastatic tumors whose cellular morphology is different from the primary. We characterized canine primary pulmonary adenocarcinoma (PAC) and its xenografted tumors by histological and immunohistochemical analyses for critical diagnostic and cancer stem cell (CSC) markers. To generate a tumor xenograft model, we subsequently transplanted the tissue pieces from the PAC into athymic nude mice. Immunohistochemical examination was performed for diagnostic (TTF-1, Napsin A, and SP-A) and CSC markers (CD44 and CD133). The use of CSC markers together with diagnostic markers can improve the detection and diagnosis of canine primary and metastatic adenocarcinomas.

Mutational profiles of primary pulmonary adenocarcinoma and paired brain metastases disclose the importance of KRAS mutations

BackgroundBrain metastases present a significant complication in lung cancer with an unmet therapeutic need. MethodsIn this single-centre, retrospective study, we genotyped a clinico-pathologically well-annotated cohort of consecutively resected brain metastases of lung adenocarcinomas and paired primary tumours, diagnosed from 2000 to 2015, using the Ion Torrent Oncomine Comprehensive Cancer Panel v3. ResultsAmong 444 consecutive brain metastases, 210 (49%) originated from lung cancer. Analysis was successful in 111 samples, including 54 pairs of brain metastasis and primary tumour. Most driver alterations were preserved in brain metastases. Private alterations exclusive to primary tumours, brain metastases or both sites (intersecting cases) were present in 22%, 26% and 26% of cases, respectively. Seven percent had no shared mutations. KRAS mutations were more frequent in primary tumours metastasised to the brain (32/55, 58%) compared to TCGA (33%, p < 0.005) and own data from routine diagnostics, independent from clinical or pathological characteristics. Fourteen cases showed alterations in the EGFR signalling pathway including additional KRAS alterations that were private to brain metastases. KRAS G12C was detected most frequently (26% of patients) and KRAS G12C and G13C variants were significantly enriched in brain metastases. Synchronous and metachronous cases had a similar mutation profile. ConclusionsOur results suggest an important role of KRAS alterations in the pathobiology of brain metastases from lung adenocarcinomas. This has direct therapeutic implications as inhibitors selectively targeting KRAS G12C are entering the clinics.

Diagnosis and treatment of primary pulmonary enteric adenocarcinoma: Report of Six cases

BACKGROUNDPrimary pulmonary enteric adenocarcinoma (PEAC) is a very rare subtype of invasive adenocarcinoma, and there have been no large studies on PEAC to date. Therefore, it is necessary to obtain much more information about the clinical and pathological features, diagnosis, differential diagnosis, and treatment of PEAC.CASE SUMMARYAll clinical data of six patients with confirmed PEAC from 2013 to 2018 were collected, and data on diagnosis, differential diagnosis, and treatment of PEAC are discussed combined with all the associated literature. The mean age of six patients was 64.0 ± 5.6 (59-73) years old. Their clinical manifestations were heterogeneous, and during their disease course, there were no gastrointestinal symptoms. There was no evidence from colonoscopy or imaging studies to suggest digestive tract tumors or new metastases. The most commonly mutated gene was KRAS (50.0%), and the pathological features of the six cases were similar to those of colorectal cancer. CDX2 (83.3%) and CK7 (66.7%) had the highest positive rates upon immunohistochemical examination. In the associated literature, 252 cases were identified, and the most commonly mutated gene was KRAS (42.9%). Additionally, CDX2 (68.3%) and CK7 (85.8%) had the highest positive rates. Patients mainly received surgery, chemotherapy, and radiotherapy, immunotherapy was not included.CONCLUSIONPositive results for CDX2 and CK7 play an important role in the diagnosis and differential diagnosis of PEAC, and immunotherapy or targeted therapy focused on KRAS needs to be further studied for the treatment of PEAC.

Primary Warthin’s-like adenocarcinoma of the lung: A clinicopathological, immunohistochemical, and molecular analysis of three cases

Three cases of primary pulmonary adenocarcinoma with prominent lymphoid stroma and papillary features mimicking Warthin’s tumor are presented. The patients are two women and one man ages 52, 62, and 74 years respectively. Clinically, the patients presented with non-specific symptoms of cough, dyspnea, and chest pain. Imaging showed the presence of an intrapulmonary mass in the right lower, right upper and left lower lobe. All patients underwent lobectomy. Histologically, the tumors were characterized by the presence of and oncocytic papillary growth pattern embedded in a lymphoid rich background. Immunohistochemical stains for TTF-1, keratin 7, and beta-catenin were positive in the epithelial component, while CD20 showed strong positive staining in the lymphoid component. In addition, CD4 and CD8 also showed positive staining in a ratio of 3–4:1, EBER was negative. Kras mutations with wild type EGFR were identified in one case. Clinical follow-up ranging from 8 to 24 months was obtained showing that all patients are alive without recurrence. The cases herein presented represent an unusual histological variant of primary lung adenocarcinoma, which closely mimics Warthin’s tumor.

Computed tomography radiomic features hold prognostic utility for canine lung tumors: An analytical study.

Quantitative analysis of computed tomography (CT) radiomic features is an indirect measure of tumor heterogeneity, which has been associated with prognosis in human lung carcinoma. Canine lung tumors share similar features to human lung tumors and serve as a model in which to investigate the utility of radiomic features in differentiating tumor type and prognostication. The purpose of this study was to correlate first-order radiomic features from canine pulmonary tumors to histopathologic characteristics and outcome. Disease-free survival, overall survival time and tumor-specific survival were calculated as days from the date of CT scan. Sixty-seven tumors from 65 dogs were evaluated. Fifty-six tumors were classified as primary pulmonary adenocarcinomas and 11 were non-adenocarcinomas. All dogs were treated with surgical resection; 14 dogs received adjuvant chemotherapy. Second opinion histopathology in 63 tumors confirmed the histologic diagnosis in all dogs and further characterized 53 adenocarcinomas. The median overall survival time was longer (p = 0.004) for adenocarcinomas (339d) compared to non-adenocarcinomas (55d). There was wide variation in first-order radiomic statistics across tumors. Mean Hounsfield units (HU) ratio (p = 0.042) and median mean HU ratio (p = 0.042) were higher in adenocarcinomas than in non-adenocarcinomas. For dogs with adenocarcinoma, completeness of excision was associated with overall survival (p<0.001) while higher mitotic index (p = 0.007) and histologic score (p = 0.037) were associated with shorter disease-free survival. CT-derived tumor variables prognostic for outcome included volume, maximum axial diameter, and four radiomic features: integral total, integral total mean ratio, total HU, and max mean HU ratio. Tumor volume was also significantly associated with tumor invasion (p = 0.044). Further study of radiomic features in canine lung tumors is warranted as a method to non-invasively interrogate CT images for potential predictive and prognostic utility.

Clinicopathological Features and Survival Outcomes of Primary Pulmonary Invasive Mucinous Adenocarcinoma.

Simple SummaryPulmonary invasive mucinous adenocarcinoma (IMA) is a recognized variant of lung adenocarcinoma (ADC) that has unique histological patterns. Comprehensively clinical studies and pathological analyses on IMAs have been limited because IMA is rarely diagnosed compared with other subtypes. We compared the clinical characteristics, pathological features, and survival outcomes of 77 IMA patients with 520 non-IMA-type ADC patients. Currently, IMAs lack a simple pathological prognostic grading system to predict survival. We therefore proposed a simple two-tier grading system, which was modified from the low- and high-grade PanIN grading system, to evaluate its prognostic value. We found that IMAs have more distinct clinicopathological characteristics compared to non-IMA-type ADCs. For patients with stage I–IIIA IMA, a new two-tier grading system might be useful in predicting recurrence-free survival. We demonstrated that stage I and II IMAs have better overall survival compared with non-IMA-type ADCs.Pulmonary invasive mucinous adenocarcinoma (IMA) has unique histological patterns. This study aimed to comprehensively evaluate the clinicopathological features, prognosis, and survival outcomes of IMAs. We retrospectively identified 77 patients with pulmonary IMA and reviewed their clinical and pathological features. Another 520 patients with non-IMA-type ADC were retrieved for comparison with patients with IMA. A new two-tier grading system (high-grade and low-grade IMAs) modified from the pancreatic intraepithelial neoplasia classification system was used for survival analyses. Compared to patients with non-IMA-type ADC, patients with IMA tended to have never smoked (p = 0.01) and had early-stage IMA at initial diagnosis (p < 0.001). For stage I–II diseases, the five-year overall survival (OS) rates were 76% in IMAs and 50% in non-IMA-type ADCs, and a longer OS was observed in patients with IMA (p = 0.002). KRAS mutations were the most commonly detected driver mutations, which occurred in 12 of the 28 (43%) patients. High-grade IMAs were associated with a shorter recurrence-free survival (RFS) for stage I–IIIA diseases (p = 0.010) than low-grade IMAs but not for OS. In conclusion, patients with stage I and II IMA had better OS than those with non-IMA-type ADC. A new two-tier grading system might be useful for predicting RFS in stage I–IIIA IMAs.

Optimizing palliative chemotherapy for advanced invasive mucinous adenocarcinoma of the lung

BackgroundA primary pulmonary invasive mucinous adenocarcinoma (IMA) is a rare subtype of invasive adenocarcinoma of the lung. The prognosis of advanced IMA depending on chemotherapy regimen has not been fully investigated. Here, we compared the clinical outcomes of patients with advanced IMA treated with different palliative chemotherapies that included novel therapeutics.MethodsThis single-center retrospective study included a total of 79 patients diagnosed with IMA and treated with palliative chemotherapy. The primary outcome was the comparison of overall survival according to palliative chemotherapy type. Risk factors associated with death were evaluated as a secondary outcome.ResultsThe study cohort of 79 patients comprised 27 progressive or recurrent cases and 52 initial metastatic patients. Thirteen patients (16.5%) received targeted therapy and 18 cases (22.8%) received immunotherapy. When we compared the survival outcomes of the different treatment regimens, patients with IMA treated by immunotherapy (undefined vs. non-immunotherapy 17.0 months, p < 0.001) had better overall survival rates. However, there was no difference in the prognosis between the cases treated with a targeted therapy (35.6 vs. non-targeted therapy 17.0 months, p = 0.211). None of the conventional regimens produced a better outcome. By multivariable analysis, immunotherapy (HR 0.28; 95% CI 0.11–0.74; P = 0.008) was found to be an independent prognostic factor for death.ConclusionsThis study suggests that immunotherapy for patients with advanced IMA may provide favorable outcomes than other chemotherapy options.

EGFR mutation status yield from bronchoalveolar lavage in patients with primary pulmonary adenocarcinoma compared to a venous blood sample and tissue biopsy.

BackgroundIn recent years, there has been a revolution in the genomic profiling and molecular typing of lung cancer. A key oncogene is the epidermal growth factor receptor (EGFR). The gold standard for determining EGFR mutation status is tissue biopsy, where a histological specimen is taken by a bronchoscopic or surgical method (transbronchial biopsy, forceps biopsy, etc.). However, in clinical practice the tissue sample is often insufficient for morphological and molecular analysis. Bronchoalveolar lavage is a validated diagnostic method for pathogenic infections in the lower respiratory tract, yet its diagnostic value for oncogenic mutation testing in lung cancer has not been extensively investigated. This study aims to compare the prevalence of EGFR mutation status in bronchoalveolar lavage and peripheral blood referring to the gold standard - tissue biopsy in patients with primary lung adenocarcinoma.MethodsTwenty-six patients with adenocarcinoma were examined for EGFR mutation from tissue biopsy, peripheral blood sample and bronchoalveolar lavage.ResultsThirteen patients had wild type EGFR and the other 13 had EGFR mutation. EGFR mutation from a peripheral blood sample was identified in 38.5% (5/13) of patients, whereas EGFR mutation obtained from bronchoalveolar lavage (BAL) was identified in 92.3% (12/13). This study demonstrates that a liquid biopsy sample for EGFR status from BAL has a higher sensitivity compared to a venous blood sample.

The prevalence of tumour markers in malignant pleural effusions associated with primary pulmonary adenocarcinoma: a retrospective study

ABSTRACT Background Oncological treatment of primary pulmonary adenocarcinoma (AC) includes drugs targeting the pathways involving programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK). The aim of the study was to report the prevalence of these tumour markers in pleural fluid with cytology positive for pulmonary AC and the potential influence of volume pleural fluid tested. Methods We retrospectively reviewed all thoracenteses performed in a two-year period at our interventional unit at Department of Respiratory Medicine at Zealand University Hospital Naestved, Denmark. ALK and PD-L1 testing was done using immunohistochemistry and EGFR testing using next-generation sequencing. We included pleural fluid specimens containing malignant cells originating from primary pulmonary AC and with at least one tumour marker requested by the clinicians. Results When screening 927 pleural fluid specimens, we identified 57 in accordance with the inclusion criteria. PD-L1, ALK and EGFR were obtained in 35/55 (64%), 38/57 (67%) and 26/47 (55%), respectively. The prevalence did not increase when analysing volumes > 50 mL (p = 0.21–0.58) Conclusion Tumour markers in pleural fluid specimens containing cells from pulmonary AC can be demonstrated in more than half of the cases. Therefore, supplementary invasive procedures than thoracentesis could potentially await these analyses.