scholarly journals Differential diagnosis of multiple primary lung cancers and intra-lung metastasis of lung cancer by multiple gene detection

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Liu-Yang Xu ◽  
Jin Chen ◽  
Yu-Peng Zeng ◽  
Xiao Li ◽  
Zhi-Hong Zhang
2020 ◽  
Author(s):  
Xu Liuyang ◽  
Chen Jin ◽  
Zeng Yupeng ◽  
Ji Pan ◽  
Zhuo Shuaishuai ◽  
...  

Abstract Objective To study the differential diagnosis of MPLC and IM by detecting the different lesions of the same patient. To explore the differences in prognosis between MPLC and IM, and to explore the factors affecting the prognosis of multi-focal lung cancer. Methods Fifty patients with multi-focal lung cancer were screened, and the relevant clinical information was noted; the patients were diagnosed by ACCP standard. Mutations of the lesions were detected by ARMS-PCR, and the detected genes included EGFR, ALK, ROS1, MET, KRAS, RET, HER-2, BRAF, NRAS and PIK3CA. The results of genetic testing were compared with those of ACCP standard diagnosis. Results We analyzed a total of 101 tumors from 50 patients. Classification based on gene testing contradicted the clinicopathologic diagnosis in 10 (20%) of the comparisons, identifying independent primaries in 6 cases diagnosed as metastasis and metastases in 4 cases diagnosed as independent primaries. Another 7(14%) tumor pairings were assigned an “equivocal” result based on gene testing. The results of gene testing of the remaining 33(66%) tumor pairings were consistent with the clinicopathologic diagnosis. The mutant heat map indicated that IM patients have a higher rate of mutation consistency than MPLC patients. Conclusion Multi-gene detection of multi-focal lung cancer has a certain auxiliary effect on the differential diagnosis of MPLC and IM, which can complement the clinical standards, but also has some limitations.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Changjiang Liu ◽  
Chengang Liu ◽  
Xiao Zou ◽  
Lin Shao ◽  
Ying Sun ◽  
...  

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.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1551
Author(s):  
Katsuo Usuda ◽  
Masahito Ishikawa ◽  
Shun Iwai ◽  
Yoshihito Iijima ◽  
Nozomu Motono ◽  
...  

The purpose of this study is to determine whether the combination assessment of DWI and T2-weighted imaging (T2WI) improves the diagnostic ability for differential diagnosis of lung cancer from benign pulmonary nodules and masses (BPNMs). The optimal cut-off value (OCV) for differential diagnosis was set at 1.470 × 10−3 mm2/s for apparent diffusion coefficient (ADC), and at 2.45 for T2 contrast ratio (T2 CR). The ADC (1.24 ± 0.29 × 10−3 mm2/s) of lung cancer was significantly lower than that (1.69 ± 0.58 × 10−3 mm2/s) of BPNM. The T2 CR (2.01 ± 0.52) of lung cancer was significantly lower than that (2.74 ± 1.02) of BPNM. As using the OCV for ADC, the sensitivity was 83.9% (220/262), the specificity 63.4% (33/52), and the accuracy 80.6% (253/314). As using the OCV for T2 CR, the sensitivity was 89.7% (235/262), the specificity 61.5% (32/52), and the accuracy 85.0% (267/314). In 212 PNMs which were judged to be malignant by both DWI and T2WI, 203 PNMs (95.8%) were lung cancers. In 33 PNMs which were judged to be benign by both DWI and T2WI, 23 PNMs (69.7%) were BPNMs. The combined assessment of DWI and T2WI could judge PNMs more precisely and would be acceptable for differential diagnosis of PNMs.


2019 ◽  
pp. 1-3
Author(s):  
Lucman Anwer ◽  
Akram Nurhussen ◽  
Javairia Anwer ◽  
Khaled M. AlKattan ◽  
Lucman Anwer ◽  
...  

Lung cancer remains the leading cause of cancer related deaths worldwide. Unfortunately, up to 20% of these patients go on to develop multiple primary lesions in the lung. This phenomenon, termed as multiple primary lung cancers, is currently on the rise. Approach to MPLC is unique as they require meticulous assessment by a multi-disciplinary team. However, literature and guidelines on MPLC remain limited. Our case sheds light over few important aspects of MPLC and calls for lung cancer committees to address the grey areas in their diagnosis and management.


2021 ◽  
Author(s):  
jieyu xu ◽  
Xiaorong Yang

Abstract Background: Multiple primary lung cancer is a rare type of tumor, which is necessary to differentiate from a metastatic tumor.Case presentation: We report a 67-year-old female with coughing and expectoration in the past eight days. Chest computed tomography revealed that there are two nodules in the patient's lung. Radiographic findings cannot distinguish between the two nodules and distinguish between primary and metastatic lesions.The patient underwent bronchoscopic biopsy and percutaneous lung puncture. Combined with morphological and immunohistochemical results, we concluded that this is a case of multiple primary lung cancers, consisting of adenocarcinoma and adenoid cystic carcinoma. In clinical practice, surgery is considered to be the first choice for the treatment of cases of multiple primary lung cancer. The patient received symptomatic treatment because of the metastases. Conclusions: The article aims to report a rare case and emphasize the role of immunohistochemistry in diagnosing multiple lung cancer.


2010 ◽  
Vol 53 (2) ◽  
pp. 115-118 ◽  
Author(s):  
Naohiro Kobayashi ◽  
Ryota Nakamura ◽  
Koichi Kurishima ◽  
Yukio Sato ◽  
Hiroaki Satoh

Background: Although sarcoidosis as well as lung cancer are frequently encountered common diseases, their metachronous or synchronous occurrence in the same patient is very rare. Methods: The charts of lung cancer patients, diagnosed between 1980 and 2007 in our hospital, were reviewed. Results: We found 3 cases with sarcoidosis and lung cancer. The first case had lung cancer 16 years after the diagnosis of sarcoidosis. The second case had two different metachronous lung cancers 18 and 10 years after the diagnosis of sarcoidosis. The third case detected these two diseases simultaneously. In simultaneously detected cases, it is difficult to determine whether noncaseating epithelioid cell granulomas coexisting with lung cancer represent sarcoid reaction or genuine systemic sarcoidosis. Conclusions: Either causality or coincidence, lung cancer, a condition that can be observed in patients with sarcoidosis, should be considered in the differential diagnosis when suspicious findings of it are discovered.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14103-e14103 ◽  
Author(s):  
Ailin Li ◽  
Jonathan E. Schoenhals ◽  
Hampartsoum B. Barsoumian ◽  
Xiaohong Wang ◽  
David R. Valdecanas ◽  
...  

e14103 Background: Anti-PD1 inhibitors are effective in only a subset of lung cancers, and many that respond later develop resistance. We recently found in a mouse model of anti-PD1 resistance that tumor-infiltrating lymphocytes (TILs) overexpressed indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting step in the catabolism of tryptophan (Trp) to kynurenine (Kyn) often implicated in immunosuppression. We tested whether inhibiting IDO would affect anti-PD1 mediated resistance. Methods: We used our anti-PD1-resistant lung cancer model (344SQ_R), which involved treating the parental 344SQ cells (344SQ_P) with anti-PD1 antibody followed by passage in 129SV/ev mice. We treated 344SQ_P and 344SQ_R mice with or without a selective IDO1 inhibitor (INCB023843) and measured tumor growth and lung metastasis. Plasma Trp and Kyn levels were tested by liquid chromatography–tandem mass spectrometry. TILs from blood and tumor-draining lymph nodes were isolated, analyzed by flow cytometry, and RNA was extracted for qPCR. Plasma C-C motif chemokine 22 (CCL22) levels were tested by ELISA. Data were analyzed with Prism 5.0 (GraphPad Software) and Flowjo V-10. Results: In untreated mice, IDO1 expression was 12 times higher in TILs from 344SQ_R mice than 344SQ_P mice, and mean plasma Kyn and Kyn/Trp levels were 3 times higher in 344SQ_R than in 344SQ_P. IDO inhibition was effective only in the PD1-resistant mice, reducing both tumor growth and lung metastasis. A subpopulation of myeloid-derived suppressor cells (Gr1int/lo CD11b+F4/80+) showed the greatest increase in IDO1 expression when comparing 344SQ_R to 344SQ_P and decreased after INCB023843 treatment only in 344SQ_R. INCB023843 also increased infiltrating CD8+ T cells, decreased CCL22 and regulatory T cells only in 344SQ_R tumors. Conclusions: Our results suggest that IDO1 is overexpressed in TILs from tumors resistant to anti-PD1 therapy; that a high plasma Kyn/Try ratio may be a marker of anti-PD1 resistance; and that IDO1 inhibition could be a promising approach for treating lung cancer that does not respond to anti-PD1 therapy.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20510-e20510
Author(s):  
Naixin Liang ◽  
Xinyu Liu ◽  
Yadong Wang ◽  
Jianchao Xue ◽  
Ziqi Jia ◽  
...  

e20510 Background: As the incidence of lung cancer soars, the number of patients diagnosed with multiple primary lung cancers (MPLC) was also rising. It was already known that genetic and immune microenvironment were involved in oncogenesis and treatment of tumors. The aim of this study was to investigate genetic and T Cell Receptor (TCR) Repertoire characteristic in patients with multiple primary lung cancers. Methods: We queried 84 lesions analyzed by 1021 gene panel and TCRβ repertoire for 32 patients with MPLC profiled by NGS. Shannon index was calculated on the clonal abundance of all productive TCR sequences. T cell clonality was defined as 1 − (Shannon index)/ln(# of productive unique sequences). MOI was a measure of the similarity in the T cell repertoire between tissue and blood taking into account the specific rearrangements and their respective frequencies. Results: 98.7% (77/78) of lesions from 30 patients were detected somatic mutations and EGFR mutations were detected in 44.2% (34/77) lesions; BRAF were detected in 22.1% (17/77) lesions; and KRAS were detected in 14.3% (11/77) lesions. We found different combinations of three driving genes in 13 patients. Almost all lesions (97.4%) had mutations in the RAS-RTK pathway. Shared mutations were detected between different lesions from 8 patients, and two patients were intrapulmonary metastases; The others were more meet to convergent evolution. The overall immune characteristics of 76 lesions from 30 patients were further studied. The shannon index showed heterogeneity in difference lesions of each patients and the comparing the most and least shannon index lesions variations ranged between 0.066 to 3.344. The lesions with shared mutations showed higher Shannon index than the non-share lesions (7.31 vs 6.96; p = 0.011). The heterogeneity also identified in MOI and 55% MOI of lesions was less than 0.5. The lesions with MOI higher than 0.5 had some pathologically identical and some have shared mutations. Furthermore, the shared TCR between lesions in same patient were analyzed. The more than 78% of T cell clones were restricted to individual lesions, which indicated the presence of heterogeneity between lesions due to T cell clones distribution heterogeneity. Meanwhile, the shared TCR was significantly higher in identical pathology group than difference pathology group (17.18% vs 6.60%; p = 0.0006); Besides, we found that shared TCR was comparable in both shared mutations and non-shared mutations groups (13.1% vs 15.33%, p = 0.537). These results suggested that the pathology between lesions in patients was affected to 100% shared TCR. Conclusions: In conclusion, the multiple lesions of MPLC showed heterogeneity and this heterogeneity is due to the distribution of T cell clones between lesions. Besides, the MOI and shared TCR was higher in MPLC with same pathology, which may increase the understanding of MPLC and influence the treatment choice of MPLC patients.


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