Next-generation sequencing facilitates differentiating between multiple primary lung cancer and intrapulmonary metastasis: a case series

Abstract Background In lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP. Case presentation Case 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months. Conclusion Our cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions.

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Molecular Identification and Genetic Characterization of Early-Stage Multiple Primary Lung Cancer by Large-Panel Next-Generation Sequencing Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.653988 ◽

2021 ◽

Vol 11 ◽

Author(s):

Guotian Pei ◽

Mingwei Li ◽

Xianjun Min ◽

Qiang Liu ◽

Dasheng Li ◽

...

Keyword(s):

Lung Cancer ◽

Next Generation Sequencing ◽

Early Stage ◽

Primary Lung Cancer ◽

Advanced Stage ◽

Next Generation ◽

Molecular Method ◽

Multiple Primary ◽

Large Panel ◽

Generation Sequencing

ObjectiveThe incidence of early stage multiple primary lung cancer (MPLC) has been increasing in recent years, while the ideal strategy for its diagnosis and treatment remains controversial. The present study conducted genomic analysis to identify a new molecular classification method for accurately predicting the diagnosis and therapy for patients with early stage MPLC.MethodsA total of 240 tissue samples from 203 patients with multiple-non-small-cell lung cancers (NSCLCs) (n = 30), early stage single-NSCLC (Group A, n = 94), and advanced-stage NSCLC (Group B, n = 79) were subjected to targeted multigene panel sequencing.ResultsThirty patients for whom next-generation sequencing was performed on >1 tumor were identified, yielding 45 tumor pairs. The frequencies of EGFR, TP53, RBM10, ERBB2, and CDKN2A mutations exhibited significant differences between early and advanced-stage NSCLCs. The prevalence of the EGFR L858R mutation in early stage NSCLC was remarkably higher than that in advanced-stage NSCLC (P = 0.047). The molecular method classified tumor pairs into 26 definite MPLC tumors and four intrapulmonary metastasis (IM) tumors. A high rate of discordance in driver genetic alterations was found in the different tumor lesions of MPLC patients. The prospective Martini histologic prediction of MPLC was discordant with the molecular method for three patients (16.7%), particularly in the prediction of IM (91.7% discordant).ConclusionsComprehensive molecular evaluation allows the unambiguous delineation of clonal relationships among tumors. In comparison, the Martini and Melamed criteria have notable limitations in the recognition of IM. Our results support the adoption of a large panel to supplement histology for strongly discriminating NSCLC clonal relationships in clinical practice.

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Clinicopathologic Characteristics and Outcomes of Simultaneous Multiple Primary Lung Cancer

Journal of Oncology ◽

10.1155/2021/7722231 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Ying Liu ◽

Yu-Ping Zhou ◽

Mai Zhang ◽

Li Li ◽

Hu Liao ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Confidence Interval ◽

Primary Lung Cancer ◽

Histological Type ◽

Recurrence Free Survival ◽

Clinicopathologic Characteristics ◽

Free Survival ◽

Histological Types ◽

Multiple Primary

Background. Simultaneous multiple primary lung cancer has been detected increasingly nowadays with the development of image technology. However, the clinicopathologic characteristics and outcomes are not clear. Methods. All consecutive patients diagnosed as simultaneous multiple primary lung cancer according to Martini–Melamed and American College of Chest Physicians criteria from June 2010 to June 2019 in our center were enrolled. The clinicopathologic characteristics and outcomes were compared between patients with the same histological type and different histological types. Results. A total of 336 patients were enrolled, consisting of 297 (88.4%) patients with the same histological type and 39 (11.6%) patients with different histological types. Compared to patients with the same histological type, patients with different histological types were more commonly males (87.2% vs. 34.0%; p < 0.001 ) with an older age (65 [62–69] vs. 59 [52–65] yrs; p < 0.001 ) at diagnosis. Also, patients with different histological types showed worse respiratory function and more advanced stage according to TNM staging. The 1-, 2-, and 3-year overall survival of overall patients was 97.7%, 96.1%, and 92.2%, and the 1-, 2-, and 3-year recurrence-free survival of overall patients was 96.8%, 92.9% and 85.7%, respectively. Importantly, patients with different histological types showed worse overall survival ( p < 0.001 ) and recurrence-free survival ( p = 0.002 ) than patients with same histological type. The multivariable Cox proportional hazard model revealed that presence of different histological types was significant predictor for worse overall survival (adjusted hazard ratio: 10.00; 95% confidence interval: 2.92–34.48; p < 0.001 ) and recurrence-free survival (adjusted hazard ratio: 2.59; 95% confidence interval: 1.14–5.88; p = 0.023 ). Conclusions. Although relatively less common in simultaneous multiple primary lung cancer, patients with different histological types showed worse clinical characteristics and outcomes.

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Mutational distinction between adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma in lung cancer patients with multiple tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e21089 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e21089-e21089

Author(s):

Jixian Liu ◽

Yingmei Li ◽

Yuancai Xie ◽

Xinyu Luan ◽

Xuxing Peng ◽

...

Keyword(s):

Lung Cancer ◽

Minimally Invasive ◽

Driver Mutations ◽

Adenocarcinoma In Situ ◽

Cancer Type ◽

Invasive Adenocarcinoma ◽

Multiple Tumors ◽

Origin And Evolution ◽

Minimally Invasive Adenocarcinoma

e21089 Background: Lung adenocarcinoma is the most popular lung cancer type, and it can be classified as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA) based on histology. The mutational similarities and differences have not been discussed in these subtypes. Methods: Targeted deep sequencing was performed on 31 lung adenocarcinomas with matched blood samples from 15 patients with multiple tumors. We compared mutations among each subtype. Results: The 31 tumors consisted of 10 AIS, 6 MIA and 15 IA subtypes; the median mutation number in each type was 1, 1 and 3 respectively. Eleven, six and fifty-three mutations were identified in AIS, MIA, and IA respectively. Among all the 67 mutations, only EGFR_p.L858R was found in all three types; BRAF_p.K601E was found in AIS and IA. Conclusions: AIS, MIA and IA harbor distinct mutational signatures, except for several popular driver mutations, suggesting their distinct origin and evolution path.

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A Clinicopathological Study of Small Lung Adenocarcinoma 1 cm or Less in Size: Emphasis on Histological Subtypes Associated With Lymph Node Metastasis and Recurrence

International Journal of Surgical Pathology ◽

10.1177/1066896917721649 ◽

2017 ◽

Vol 26 (1) ◽

pp. 4-11 ◽

Cited By ~ 6

Author(s):

Wei Zhao ◽

Hui Wang ◽

Jun Xie ◽

Bo Tian

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Lung Adenocarcinoma ◽

Who Classification ◽

Limited Resection ◽

Adenocarcinoma In Situ ◽

Invasive Adenocarcinoma ◽

Node Metastasis ◽

Minimally Invasive Adenocarcinoma

Background. The aim of this study was to assess the prognostic significance of the newly proposed 2015 World Health Organization (WHO) lung adenocarcinoma classification for patients undergoing resection for small (≤1 cm) lung adenocarcinoma. We also investigated whether lobectomy offers prognostic advantage over limited resection for this category of tumors. Methods. A retrospective study of resected pulmonary adenocarcinomas (n = 83) in sizes 1 cm or less was carried out in which comprehensive histologic subtyping was assessed according to the 2015 WHO classification on all consecutive patients who underwent lobectomy or limited resection between 1998 and 2012. Correlation between clinicopathologic parameters and the difference in recurrence between lobectomy and limited resection group was evaluated. Results. Our data show that the proposed 2015 WHO classification identifies histological subsets of small lung adenocarcinomas with significant differences in prognosis. No recurrence was noted for patients with adenocarcinoma in situ and minimally invasive adenocarcinoma. Invasive adenocarcinomas displayed high heterogeneity and the presence of micropapillary component of 5% or greater in adenocarcinomas was significantly related to lymph node involvement and recurrence ( P < .001). Stage IA patients who underwent limited resection had a higher risk of recurrence than did those treated by lobectomy ( P < .05). Conclusions. Application of the 2015 WHO classification identifies patients with adenocarcinoma in situ and minimally invasive adenocarcinoma had excellent prognosis. Micropapillary pattern was associated with high risk of lymph node metastasis and recurrence.

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Radiopathologic correlation of collision lung cancer with ground-glass opacity

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492318811549 ◽

2018 ◽

Vol 27 (1) ◽

pp. 45-48

Author(s):

Shinsuke Uchida ◽

Koji Tsuta ◽

Masahiko Kusumoto ◽

Kouya Shiraishi ◽

Takashi Kohno ◽

...

Keyword(s):

Lung Cancer ◽

Ground Glass Opacity ◽

Ground Glass ◽

Adenocarcinoma In Situ ◽

Invasive Adenocarcinoma ◽

Ki 67 ◽

Lung Cancers ◽

Collision Tumors ◽

Minimally Invasive Adenocarcinoma ◽

Epidermal Growth

Pulmonary collision tumors have been described as a special entity of synchronous multiple lung cancer. There have been no reports detailing the chronological changes in primary collision lung cancers on chest computed tomography. We report a case of ground-glass lung nodules gradually colliding with each other. The collision tumors of the lung were composed of minimally invasive adenocarcinoma and adenocarcinoma in situ with epidermal growth factor mutations. Immunohistochemically, the Ki-67 labeling indices were different in the 2 components. Ki-67 staining was useful to distinguish the 2 components. The 2 dominant ground-glass tumors grew slowly with radiologic and pathologic heterogeneity.

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