Lepidic Predominant Lung Adenocarcinoma Research Articles

Prognostic implications, genomic and immune characteristics of lung adenocarcinoma with lepidic growth pattern

AimsConflicting data were provided regarding the prognostic impact and genomic features of lung adenocarcinoma (LUAD) with lepidic growth pattern (LP+A). Delineation of the genomic and immune characteristics of LP+A could...

Hypertrophic osteoarthropathy mimicking a reactive arthritis: a case report and review of the literature

BackgroundHypertrophic osteoarthropathy (HOA) is a syndrome characterized by abnormal proliferation of skin and periosteal tissues of the extremities. It can be a rare hereditary disease (pachydermoperiostosis) or can be secondary to various diseases, though mostly lung malignancies. Here, we report an unusual clinical presentation of HOA.Case presentationA 77-year-old man presented with fever, diarrhea, and an oligoarthritis involving the left knee and the ankles. Since left knee synovial fluid aspiration revealed an aseptic synovitis and Clostridium Difficile toxin was detectable in stool samples, a reactive arthritis secondary to a Clostridium Difficile induced colitis was initially suspected. However, the presence of a worsened digital clubbing and the lack of a good clinical response to steroid therapy led us to perform a radionuclide bone scanning, which revealed HOA. This turned out to be associated with a lepidic predominant lung adenocarcinoma, which was clinically and radiologically difficult to distinguish from a relapse of pneumonia.ConclusionConsistent with the literature, HOA tends to have a variable clinical presentation, mimicking that of various rheumatic diseases. This clinical case shows that HOA can present as a presumptive acute reactive arthritis, and it highlights the importance of patient’s follow-up in the differential diagnosis of inflammatory arthritis, especially when a worsened digital clubbing is present.

Successful pulmonary arterial embolization followed by curative surgery for a lepidic predominant lung adenocarcinoma with severe hypoxemia

BackgroundLepidic predominant adenocarcinoma is characterized by frequent refractory hypoxemia due to intrapulmonary shunting. Severe hypoxemia can induce perioperative complications in case of thoracic surgery.Case presentationWe report a case of a 67 year-old woman with localized lepidic adenocarcinoma in the right lower lobe with severe hypoxemia. A selective arterial lung embolization allowed an instantaneous correction of the hypoxemia, and a curative lobectomy was safely performed 1 week after without any complication. The staging was pT3N0M0, and the patient received adjuvant chemotherapy.ConclusionsThis is the first case-report of successful endovascular embolization before curative surgery for a lepidic predominant lung adenocarcinoma.

Reversed Halo Sign in a Middle-Aged Female With Neutropenic Sepsis Following Chemotherapy for Acute Lymphoblastic Leukaemia

SESSION TITLE: Other Infections SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: The reversed halo sign (RHS) has been described with increasing incidence in pulmonary mucormycosis in immunocompromised hosts, which has a high risk of morbidity and mortality.1 CASE PRESENTATION: A 58-year-old woman with acute lymphoblastic leukaemia who had completed her first cycle of hyper-CVAD chemotherapy presented with persistent fever for 3 days and neutropenia. She was empirically started on piperacillin-tazobactam for neutropenic sepsis. Chest CT scan showed a left upper lobe lesion with central ground-glass density surrounded by denser consolidation, corresponding to the RHS (Fig.1). It involved the mediastinum and abutted the pericardium and main pulmonary trunk. She underwent a bronchoscopy with BAL and transbronchial lung biopsy for which microbiology and histology were unremarkable. Post-bronchoscopy, she was started on ambisome and had a brain MRI which was normal. However, she continued to be febrile. She underwent a left VATS which was converted to a posterolateral thoracotomy with upper lobectomy and abscess resection. Intraoperatively, there was abscess invasion into the anterior chest wall, pericardium and right ventricular outlet tract. Histology showed a cavitatory nodule surrounded by geographic necrosis with mucormycosis and fungal angioinvasion (Fig 2). She completed 2 months of ambisome before conversion to posaconazole. Post-operative recovery was uneventful and she underwent her second cycle of chemotherapy on post-operative day 24 with further plans for haematopoetic stem cell transplant following completion of chemotherapy. DISCUSSION: The RHS may be seen on chest CT in a range of conditions. It was originally described in cryptogenic organising pneumonia;2 but can be seen in invasive pulmonary infections, Pneumocystis jirovecii pneumonia, sarcoidosis, lipoid pneumonia, lymphomatoid granulomatosis, granulomatosis with polyangiitis and lepidic predominant lung adenocarcinoma.2,3 It has been described with an increasing incidence in pulmonary mucormycosis, particularly in immunocompromised patients with haematologic disease. Pulmonary mucormycosis has high morbidity and mortality. Early diagnosis and prompt treatment with amphotericin B and surgical resection can improve outcomes.1 CONCLUSIONS: The RHS in an immunocompromised host should prompt consideration of invasive fungal infections, including pulmonary mucormycosis. Reference #1: Legouge C, Caillot D, Chrétien ML, et al. The reversed halo sign: Pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia? Clin Infect Dis. 2014;58(5):672-8. Reference #2: Raju S, Ghosh S, Mehta AC. Chest Computed Tomography Signs in Pulmonary Disease - A Pictorial Review. CHEST Pulm Dis - A Pict Rev CHEST [Internet]. 2016;12. http://dx.doi.org/10.1016/j.chest.2016.12.033 Reference #3: Marchiori E, Zanetti G, Meirelles GS, et al. The reversed halo sign on high-resolution CT in infectious and noninfectious pulmonary diseases. Am J Roentgenol. 2011 Jul;197(1):W69-75 DISCLOSURE: The following authors have nothing to disclose: Michelle Kam, Lionel Cheng, Norman Chan, Denise Tan, Heng Joo Ng, Keng Leong Tan No Product/Research Disclosure Information

Prognostic Impact of the Findings on Thin-Section Computed Tomography in Patients with Subcentimeter Non–Small Cell Lung Cancer

IntroductionSubcentimeter NSCLC is not always an early-stage disease despite its small tumor size. We investigated the prognostic impact of such cancers on the basis of the findings of thin-section computed tomography (CT). MethodsWe evaluated the clinicopathological features and prognosis of 328 surgically resected clinical-N0 NSCLCs 1.0 cm or less in size. Consolidation-to-tumor ratio (CTR) was evaluated for all, and tumors were classified into three groups, namely, pure ground glass opacity (GGO) (CTR = 0 [n = 139]), part solid (0 < CTR < 1.0 [n = 123]), and pure solid (CTR = 1.0 [n = 66]). ResultsPathological nodal involvement was observed in seven patients, with all cases found exclusively in pure solid subcentimeter NSCLC (10.9%). Furthermore, a multivariate analysis revealed that the presence of GGO was an independently significant clinical factor in overall survival (OS) and recurrence-free survival (RFS) (OS: p = 0.0340; RFS: p = 0.0018). Histological examination revealed that 134 of the 139 cases of pure GGO (97%), 99 of the 123 cases of part solid tumor (81%), and 16 of the 66 cases of pure solid tumor (25%) were lepidic predominant lung adenocarcinoma. Evaluation of the oncological outcomes on the basis of CTR revealed that 5-year OS and RFS rates were significantly better in patients with nonsolid tumors (OS and RFS = 100%) or part solid tumors (OS = 97.5% and RFS=94.9%), whereas the OS and RFS rates of patients with pure solid subcentimeter NSCLC were 87.6% and 79.3%, respectively (OS: p = 0.0015; RFS: p < 0.0001). ConclusionsThe findings of thin-section CT are extremely important when considering the prognosis of subcentimeter NSCLC. Radiologically determined solid subcentimeter NSCLCs should be treated as invasive tumors regardless of their small size.

Pro-tumoural CXCL10/CXCR3-A autocrine loop in invasive mucinous lung adenocarcinoma.

Invasive mucinous adenocarcinoma (IMA) is a mucinous variant of lepidic predominant lung adenocarcinoma (LPA) and associated with a worse prognosis. We postulated that cytokine expression would enable us to differentiate IMA from LPA in terms of prognosis and acquisition of pro-tumoural capacities.A 30-cytokine panel was assessed in bronchoalveolar lavage fluids (BALF) from IMA (n=38), LPA (n=25) and control samples (n=7). We investigated the expression of differentially expressed cytokines and splice variants of their receptors in surgical samples. The presence of EGFR and KRAS mutations were determined. We also examined the expression of cytokines and splice variants of their receptors in different cell lines, exploring their functional impact on signalling pathways, proliferation and migration.Only C-X-C motif chemokine 10 (CXCL10) was differentially expressed, namely overexpressed in IMA BALF compared with LPA. CXCL10 overexpression in BALF was linked to a worse prognosis. In surgical samples, CXCL10 and its receptor C-X-C motif chemokine receptor 3 (CXCR3) were overexpressed in IMA compared to LPA. A pro-tumoural CXCR3-A splice variant was overexpressed in IMA, suggesting a CXCL10/CXCR3-A autocrine loop in IMA. CXCL10 and CXCR3 expression were not correlated with EGFR or KRAS status. CXCL10 up-regulated CXCR3-A expression, Erk1/2 phosphorylation and enhanced migration in the mucinous H2228 cell line.CXCL10/CXCR3-A may play a pro-tumoural role in IMA via an autocrine mechanism.

JCES01.19 Clinicopathologic Characteristics, Genetic Variability and Therapeutic Options of RET Rearrangement Patients in Lung Adenocarcinoma

RET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few data are available about the prevalence, clinicopathologic characteristics, genetic variability and therapeutic options in RET-positive lung adenocarcinoma patients. For 615 patients with lung adenocarcinoma, RET status was detected by reverse transcription-polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) and FISH were performed in positive cases. Thymidylate synthetase (TS) mRNA level was assayed by RT-PCR. Overall survival (OS) was evaluated by Kaplan-Meier method and compared with log-rank test. Twelve RET-positive patients were identified by RT-PCR. However, one patient failed the detection of RET arrangement by FISH and NGS. Totally, 11 patients (1.8%) confirmed with RET rearrangements by three methods, including six females and five males with a median age of 54 years. The presence of RET rearrangement was associated with lepidic predominant lung adenocarcinoma subtype in five of 11 patients. RET rearrangements comprised of nine KIF5B–RET and two CCDC6–RET fusions. Four patients had concurrent gene variability by NGS detection, including EGFR (n=1), MAP2K1 (n=1), CTNNB1 (n=1) and AKT1 (n=1). No survival difference existed between RET-positive and negative patients (58.1 vs. 52.0 months, P=0.504). The median progression-free survival of first-line pemetrexed/platinum regimen was 7.5 months for four recurrent cases, and longer than RET-negative patients (7.5 vs. 5.0 months, P=0.026). The level of TS mRNA was lower in RET-positive patients than that in those RET-negative counterparts (239±188×10-4 vs. 394±457×10-4, P=0.019). The prevalence of RET fusion is approximately 1.8% in Chinese patients with lung adenocarcinoma. RET arrangement is characterized by lepidic predominance and a lower TS level. RET-rearranged patients may benefit more from pemetrexed-based regimen.

P2.03b-046 Clinicopathologic Characteristics, Genetic Variability and Therapeutic Options of RET Rearrangement Patients in Lung Adenocarcinoma: Topic: Biomarkers

RET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few data are available about the prevalence, clinicopathologic characteristics, genetic variability and therapeutic options in RET-positive lung adenocarcinoma patients. For 615 patients with lung adenocarcinoma, RET status was detected by reverse transcription-polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) and FISH were performed in positive cases. Thymidylate synthetase (TS) mRNA level was assayed by RT-PCR. Overall survival (OS) was evaluated by Kaplan-Meier method and compared with log-rank test. Twelve RET-positive patients were identified by RT-PCR. However, one patient failed the detection of RET arrangement by FISH and NGS. Totally, 11 patients (1.8%) confirmed with RET rearrangements by three methods, including six females and five males with a median age of 54 years. The presence of RET rearrangement was associated with lepidic predominant lung adenocarcinoma subtype in five of 11 patients. RET rearrangements comprised of nine KIF5B–RET and two CCDC6–RET fusions. Four patients had concurrent gene variability by NGS detection, including EGFR (n=1), MAP2K1 (n=1), CTNNB1 (n=1) and AKT1 (n=1). No survival difference existed between RET-positive and negative patients (58.1 vs. 52.0 months, P=0.504). The median progression-free survival of first-line pemetrexed/platinum regimen was 7.5 months for four recurrent cases, and longer than RET-negative patients (7.5 vs.5.0 months, P=0.026). The level of TS mRNA was lower in RET-positive patients than that in those RET-negative counterparts (239±188×10-4 vs. 394±457×10-4, P=0.019). The prevalence of RET fusion is approximately 1.8% in Chinese patients with lung adenocarcinoma. RET arrangement is characterized by lepidic predominance and a lower TS level. RET-rearranged patients may benefit more from pemetrexed-based regimen.

Clinicopathologic characteristics, genetic variability and therapeutic options of RET rearrangements patients in lung adenocarcinoma

BackgroundRET fusion gene is identified as a novel oncogene in a subset of non-small cell lung cancer (NSCLC). However, few data are available about the prevalence, clinicopathologic characteristics, genetic variability and therapeutic options in RET-positive lung adenocarcinoma patients. Patients and methodsFor 615 patients with lung adenocarcinoma, RET status was detected by reverse transcription-polymerase chain reaction (RT-PCR). Next-generation sequencing (NGS) and FISH were performed in positive cases. Thymidylate synthetase (TS) mRNA level was assayed by RT-PCR. Overall survival (OS) was evaluated by Kaplan-Meier method and compared with log-rank test. ResultsTwelve RET-positive patients were identified by RT-PCR. However, one patient failed the detection of RET rearrangement by FISH and NGS. Totally, 11 patients (1.8%) confirmed with RET rearrangements by three methods, including six females and five males with a median age of 54 years. The presence of RET rearrangements was associated with lepidic predominant lung adenocarcinoma subtype in five of 11 patients. RET rearrangements comprised of nine KIF5B–RET and two CCDC6–RET fusions. Four patients had concurrent gene variability by NGS detection,including EGFR(n=1),MAP2K1 (n=1), CTNNB1 (n=1) and AKT1 (n=1). No survival difference existed between RET-positive and negative patients (58.1 vs. 52.0 months, P=0.504). The median progression-free survival of first-line pemetrexed/platinum regimen was 7.5 months for four recurrent cases. And the level of TS mRNA was lower in RET-positive patients than that in those RET-negative counterparts (239±188×10−4 vs. 394±457×10−4, P=0.019). ConclusionThe prevalence of RET fusion is approximately 1.8% in Chinese patients with lung adenocarcinoma. RET rearrangements are characterized by lepidic predominance and a lower TS level. RET-rearranged patients may benefit more from pemetrexed-based regimen.

Ground-glass opacity of the lung in a patient with melanoma: “The radiological seed of doubt”

Subcentimeter NSCLC is not always an early-stage disease despite its small tumor size. We investigated the prognostic impact of such cancers on the basis of the findings of thin-section computed tomography (CT).We evaluated the clinicopathological features and prognosis of 328 surgically resected clinical-N0 NSCLCs 1.0 cm or less in size. Consolidation-to-tumor ratio (CTR) was evaluated for all, and tumors were classified into three groups, namely, pure ground glass opacity (GGO) (CTR = 0 [n = 139]), part solid (0 < CTR < 1.0 [n = 123]), and pure solid (CTR = 1.0 [n = 66]).Pathological nodal involvement was observed in seven patients, with all cases found exclusively in pure solid subcentimeter NSCLC (10.9%). Furthermore, a multivariate analysis revealed that the presence of GGO was an independently significant clinical factor in overall survival (OS) and recurrence-free survival (RFS) (OS: p = 0.0340; RFS: p = 0.0018). Histological examination revealed that 134 of the 139 cases of pure GGO (97%), 99 of the 123 cases of part solid tumor (81%), and 16 of the 66 cases of pure solid tumor (25%) were lepidic predominant lung adenocarcinoma. Evaluation of the oncological outcomes on the basis of CTR revealed that 5-year OS and RFS rates were significantly better in patients with nonsolid tumors (OS and RFS = 100%) or part solid tumors (OS = 97.5% and RFS=94.9%), whereas the OS and RFS rates of patients with pure solid subcentimeter NSCLC were 87.6% and 79.3%, respectively (OS: p = 0.0015; RFS: p < 0.0001).The findings of thin-section CT are extremely important when considering the prognosis of subcentimeter NSCLC. Radiologically determined solid subcentimeter NSCLCs should be treated as invasive tumors regardless of their small size.

Impact of Lepidic Component Occupancy on Effects of Adjuvant Chemotherapy for Lung Adenocarcinoma

The prognosis of lepidic predominant lung adenocarcinoma is favorable. We postulated that lepidic predominant tumors might not require postoperative adjuvant chemotherapy. The present study aims to determine whether lepidic component occupancy affects overall survival after postoperative adjuvant chemotherapy for lung adenocarcinoma. Clinical and pathologic data were collected from a database and from the medical records of 964 patients with completely resected lung adenocarcinoma. We assessed the influence of lepidic component occupancy in the tumor on the outcomes of adjuvant chemotherapy. Among the patients, 270 received adjuvant chemotherapy and 694 did not, and 415 and 549 had lepidic predominant and non-lepidic predominant tumors, respectively. Adjuvant chemotherapy contributed to better overall survival compared with observation in non-lepidic predominant tumors (p = 0.025). Multivariate analyses revealed age, sex, stage, lepidic component occupancy, and adjuvant chemotherapy as independent prognostic factors for overall survival. The overall survival was significantly longer for patients with non-lepidic predominant tumors at stages IA, IB, and II-III under adjuvant chemotherapy compared with observation (p = 0.040, p = 0.007, and p = 0.012, respectively), whereas survival rates were similar for patients with all stages of lepidic predominant tumors even after propensity score matching study. Lepidic component occupancy reflected the effect of adjuvant chemotherapy for lung adenocarcinoma. Adjuvant chemotherapy did not have much impact for lepidic predominant tumors and could be considered for non-lepidic predominant tumors even at stage IA.

Prognostic Factors in Resected Ais, Mia and Lepidic Predominant Lung Adenocarcinoma

ABSTRACT Aim: The new International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society (IASLC/ATS/ERS) lung adenocarcinoma classification has been proposed in 2011. The aim of the study is to demonstrate the prognostic factors and pattern of recurrence in AIS, MIA and lepidic predominant lung adenocarcinoma. Methods: We retrospectively reviewed 545 patients undergoing surgical resection for lung adenocarcinoma in Taipei Veterans General Hospital between 2006 and 2010. Fifty-two patients with lepidic predominant lung adenocarcinoma were identified. The predictive factors and pattern of recurrence of these patients were investigated. Results: The 5-year overall survival and recurrence-free rates were 84.0% and 83.0%, respectively. During follow-up, 7 (13.5%) patients developed recurrence. The median time to recurrence was 28.7 months (range, 10.6 to 57.8 months). The percentage of T2-4 (P = 0.003), N1-2 (P Conclusions: The overall survival and freedom from recurrence rates were good in lepidic predominant adenocarcinoma. TNM stage (II-III vs. I) was a significant predictive factor of freedom from recurrence in these patients. Disclosure: All authors have declared no conflicts of interest.