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15 August 2023

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16 August 2023

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Abstract
Background – Endobronchial squamous cell carcinoma is one of the most common types of tumors with such a location. Patients often present in advanced stages of the disease, which leads to a targeted therapeutic attitude of pneumonectomy, most of the time. Practicing a lung parenchyma-preserving surgery led us to do this review. Material and Methods - We used three search platforms SCIENCE, MEDLINE and PubMed, in order to identify studies presenting case reports, studies and reviews on endobronchial squamous cell carcinoma. We identified clinical and paraclinical features of endobronchial squamous cell carcinoma. All selected articles were in English and contained clinical criteria of endobronchial squamous cell carcinoma, autofluorescence bronchoscopy in endobronchial squamous cell carcinoma, imaging features of endobronchial squamous cell carcinoma, blood tumor markers specific for lung squamous cell carcinoma, histopathological features of endobronchial squamous cell carcinoma. Results - 73 articles were analyzed, from which 47 articles were selected as bibliographic references. We have presented the criteria found for endobronchial squamous cell carcinoma in order to highlight the main characteristics and high reliability technologies for the detection of this type of cancer. Conclusions – The current literature review highlights the clinical and paraclinical characteristics of endobronchial squamous cell carcinoma. It aims to open new horizons for research and early detection, frequent practice of lung parenchymal preservation surgery.
Keywords: 
Subject: 
Medicine and Pharmacology  -   Pulmonary and Respiratory Medicine

1. Introduction

Endobronchial squamous carcinoma is a relatively rare entity within bronchopulmonary cancer [1,2], being one of the most common neoplasms located centrally, in the tracheal and bronchial lumen (primitive bronchi and lobar bronchi), causing partial obstruction or their total [1, 3]. Clinically, it frequently manifests with hemoptysis [4], being known as a bleeding neoplasm. Other known associated symptoms are: cough, recurrent pneumonia, wheezing and chest pain [3,4], among smokers [5]. Examination of serological tumor markers frequently found in squamous cell carcinoma, often they are: SCC-Ag (squamous cell carcinoma-associated antigen), Cyfra 21-1 (cytokeratin 19 fragment 21-1 antigen), CEA (carcinoembryonic antigen), TrxR (Thioredoxin reductase ) [6, 7,8]. Computed tomographic examination has no characteristic signs for squamous cell carcinoma. There are common characteristic signs for endobronchial tumors - the cutoff sign [5], the intratumoral air bronchogram, and the use of the Tsuboi classification to specify the type of intraluminal obstruction [9]. Bronchoscopic examination highlights changes in the mucosa, with several degrees of evolution - low-grade dysplasia (mild and moderate), high-grade (severe and in situ carcinoma) and invasive carcinoma [10]. Bronchoscopy also specifies the aspects of endobronchial tumors, nodular, polypoid lesions, with a large implantation base, bleeding, the segment of the bronchus where it is located, the degree of narrowing of the lumen [11]. Through bronchoscopy, biological samples of tumor tissue are taken for specifying the anatomopathological and immunohistochemical profile [3], including tests for the determination of immune cells, including the determination of PDL-1 [12]. From an anatomopathological-macroscopic point of view - squamous cell carcinoma represents about 20% of bronchopulmonary tumors and is most frequently centrally located [13].
Microscopically, squamous cell carcinoma has several characteristics: characteristic keratinization and intercellular bridges and shows a solidly involved growth pattern with hyperchromatic nuclei; tumor cells lack glandular structure or mucin production [13]. From an anatomopathological-macroscopic point of view - squamous cell carcinoma represents about 20% of bronchopulmonary tumors and it is most frequently centrally located [13].
This retrospective study aims to point out the clinical and paraclinical signs of squamous cell carcinoma for early diagnosis and initiation of personalized therapy with the goal of sparing lung parenchyma and increasing life expectancy among patients.

2. Material and Methods

We reviewed the Guidelines on Reviews and Meta-Analyses (PRISMA) to provide accuracy reports [14]. We used the recommendations from the preferred reporting elements systematically for the selection process.

2.1. Search Strategy

We used three online databases, SCIENCE, MEDLINE, and PubMed, since 1990 to identify studies presenting case reports, studies, and reviews of endobronchial squamous cell carcinoma. We analyzed clinical and paraclinical features of endobronchial squamous cell carcinoma. We used the following search terms in English: clinical criteria of endobronchial squamous cell carcinoma, autofluorescence bronchoscopy in endobronchial squamous cell carcinoma, imaging characteristics of endobronchial squamous cell carcinoma, blood tumor markers specific for lung squamous cell carcinoma, anatomopathological characteristics of endobronchial squamous cell carcinoma. I have identified few relevant specialized articles from which I have extracted important information. Information was synthesized according to the inclusion and exclusion criteria outlined below.

2.2. Selection Criteria

The authors independently analyzed the title, abstract and full text of the selected articles for each type of feature. Their eligibility for inclusion in this systematic review was assessed. The authors established the inclusion and exclusion criteria of the studies found to be eligible. Only articles considered eligible were studied; reading and information extraction was performed in accordance with the main aim and objective of this study.

2.3. Inclusion and Exclusion Criteria

As we aimed to analyze clinical and paraclinical characteristics of patients with squamous endobronchial lung carcinoma, only studies fulfilling the following criteria were included:
(a) the study included only patients with endobronchial squamous cell carcinoma;
(b) original reports of research studies describing the tomographic images, laboratory and/or clinical findings of this category of patients;
(c) studies published in a journal and in English;
(d) the study included features of autofluorescence bronchoscopy;
(e) studies published after 2005, up to now;
(f) studies reporting autofluorescence bronchoscopy, case reports, retrospective studies on pathologic anatomy, clinical, CT;
(g) studies that included laboratory analyzes of tumor markers in squamous cell carcinoma;
We excluded the following studies:
(a)
studies that did not report original data or clear diagnostic criteria;
(b)
editorials, comments, opinions;
(c)
letters and conference abstracts;
(d)
Scientific papers that described operative techniques for squamous bronchopulmonary cancer

2.4. Data Extraction

The authors independently screened the titles and abstracts of the identified articles. Articles were divided into the following categories: clinical characteristics, tumor markers, characteristics of autofluorescence bronchoscopy, imaging characteristics of CT scan. Articles were reviewed to determine inclusion criteria. The operative indication elements for lung parenchymal sparing surgery and the opportunity for resection with bronchoanastomosis were analyzed.

3. Results

73 articles were analyzed, from which 48 articles were selected. These were obtained through SCIENCEDIRECT, MEDLINE and PubMed electronic searches. They were distributed as follows: clinic - 6 citations, case reports - 11, autofluorescence bronchoscopy - 13, computed tomography - 15, biomarkers - 14, pathological anatomy - 4. Table 1 summarizes the most representative sensitivity and specificity articles we reviewed. Of the 48 cited articles, only 19 have presented diagnostic yield, specificity and sensitivity. 8 retrospective studies, 4 observational studies, 3 descriptive, 2 prospective, one meta-analysis and one review were representative.

3.1. Study Characteristics

Clinical findings – The symptomatology described in the literature is specified for endobronchial tumors [2]. Clinical presentation of patients with endobronchial squamous cell carcinoma revealed cough, chest pain, shortness of breath, blood in sputum, wheezing, hoarseness, recurrent chest infections (including bronchitis and pneumonia), weight loss and loss of appetite, and fatigue [4], cough, dyspnoea, atelectasis, post-obstructive pneumonia, wheezing, and hemoptysis [15, 16]. Omar Elsaca & all specified of squamous cell carcinomas (SCCs) are the most common type of central tumor and can cause cough, dyspnea, atelectasis, postobstructive pneumonia, wheezing, and hemoptysis [15].
Laboratory findings – In patients with squamous cell carcinoma, hypercalcemia is frequently encountered [15, 17]. The analysis of blood tumor markers revealed the presence of SCC-Ag, CYFRA21-1 [6, 18, 19, 20], CEA, TrxR [6,7]. Although uncharacteristic of this type of cancer, elevated levels of CA 125 have been reported [18]. The blood determinations of these tumor markers can be performed by ELISA biochemical tests, electrochemical determinations on different sensors. Studies on stochastic sensors are known. Stochastic sensors based on maltodextrins with different dextrose equivalent were proposed for the assay of three lung cancer biomarkers: neuron specific enolase, carcinoembryonic antigen and epidermal growth factor receptor. The two sensors proposed can determine simultaneously NSE, CEA and HER-1 in whole blood samples (qualitative and quantitative), with recoveries higher than 97.00 %. This screening test may serve for fast and early detection of lung cancer. [21] Biochemical analysis by ELISA technique has 50% sensitivity at >90% specificity [22] .
A special place has represented by the determination of serological tumor markers for PD-L1 immunity, which demonstrated the superiority of PD-1/PD-L1 inhibitors for patients with advanced squamous NSCLC compared to chemotherapy [12, 23, 24]. Rui-Lian Chen and all conducted thismeta-analysis to investigate the efficacy of PD-1/PD-L1 inhibitors versus chemotherapy for squamous NSCLC patients. Their study included 11 clinical trials involving 3112 patients, which compared the efficacy of PD-1/PD-L1 inhibitors with chemotherapy for advanced squamous NSCLC patients. Their observed that PD-1/PD-L1 inhibitors significantly improved OS and PFS of advanced squamous-cell lung cancer when compared with chemotherapy [23].
The analyzed articles for tumor markers were 6, which included both separate markers and groups of markers. 12 markers were found. The analysis of articles is in Table 2.
In the analyzed studies, 6 groups of tumor markers were found analyzed together, depending on the result of which the diagnosis was established.

3.2. Anatomopathological Characteristics

Macroscopically it is located centrally, frequently at the tracheo-bronchial level, along the major airways, exophytic [13], with a tendency to exfoliation [17], frequently on the membranous area [25], bleeding [3]. Microscopically: cellular changes extend to the entire epithelium of the airways but without reaching the surface. Lesions progressing to CIS show grossly aberrant cytology (including patchy chromatin, variable nuclear size and shape, dyskaryosis, and other abnormal nuclear shapes) that extend throughout the airway epithelium but do not infiltrate the basement membrane [26]. Images of sheets or lobules composed of polygonal malignant cells with eosinophils, cytoplasm and pleomorphic nuclei, with atypical mitosis, along with the existence of pearls of keratosis and the presence of intercellular junctions, have also been encountered [27]. Omar Elsaca and all, stated that acinar, papillary or micropapillary, leptic or solid growth patterns represent the majority of neoplastic gland production in squamous carcinoma [15] . The presence of keratin synthesis by tumor cells, which may also include intercellular desmosomes, is used to diagnose squamous cell carcinoma [15, 28]. Gold-standard for confirmation of neoplasia by bronchoscopy remain biopsy and perform histopathological examination with a positive diagnosis rate in 82% of cases [10].

3.3. Immunohistochemical Markers

Specific for squamous cell carcinoma - p40, CK5/6 and TP63 (p63) [29]; which is also argued by Omar Elsaca & all - expression of p40, p63, CK5 and desmoglein appears in squamous cell carcinoma on immunohistochemical examination [15]. Squamous cell carcinomas confined to the bronchial wall are also known to exhibit two distinct patterns of growth: superficial spread and endobronchial mass lesions. In these cases, the immunohistochemical expressions of p53 and Ki-67 are correlated with survival rates [30].

3.4. Tomography Findings

On computed tomography scan (CT), primary endobronchial malignancies manifest as a polypoid lesion, a focal sessile lesion, eccentric narrowing of the airway lumen, or circumferential wall thickening [31]. Lung squamous cell carcinoma has a higher incidence of central localization with internal cavities, compared to the rest of lung cancers [32]. Sometimes, the CT examination of endobronchial squamous carcinomas presents as a localized bronchial thickening with a long outgrowth, plated on the wall of the bronchus of about 5 cm [33]. Central mass lesions may show either sheath and occlusion of the segmental or lobar bronchus/endobronchial component or sheath of adjacent vessels [34]. As distinct signs for endobronchial tumors, we frequently encounter the sign of the bronchus [35]. Chang Min Park stated in the study ‟Tumors in the Tracheobronchial Tree: CT and FDG PET Features‟, at computed tomography (CT), primary malignant tumors manifest as a polypoid lesion, a focal sessile lesion, eccentric narrowing of the airway lumen, or circumferential wall thickening. Because SCC arises from the surface epithelium, the tumor surface is typically irregular. At fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET), most squamous cell carcinomas show high uptake, whereas adenoid cystic carcinoma and mucoepidermoid carcinoma show variable uptake depending on the grade of differentiation [31]. Yoonah Song conducted a study on 310 patients who presented with lung squamous cell carcinoma simulating benign infectious or inflammatory diseases. Pulmonary squamous cell carcinoma may present as localized, long, continuous, bronchial thickening on CT [33].
Only 4 representative scientific reports were found and analyzed. Bronchial sign, bronchial cutoff sign, polypoid lesion, focal lesion, sessile lesions were followed, wich sensitivity and specificity. All analyzed elements were specified in Table 3.

3.5. Bronchoscopy Findings

Bronchoscopy with autofluorescence and that with fluoroscopy detects precancerous bronchial lesions located at the level of the bronchial tree, for squamous cell lung cancer [10, 36]. During these examinations, pathological tissues appear reddish-brown in color, invasive lesions appear as defects easily recognized by bronchial fluorescence [37]. These characteristics specified to the thoracic surgeon help to decide the therapeutic decision of tumor resection with preservation of the lung parenchyma. Autofluorescence bronchoscopy allows the detection of pathological changes by using spectral differences in fluorescence and absorption properties at different levels of normal versus dysplastic epithelium [37].

3.6. Flexible Autofluorescence Bronchoscopy

(AFB) is necessary for the diagnosis of endobronchial tumor formations. This examination highlights mucosal changes in several degrees of evolution - low-grade (mild and moderate) dysplasias, high-grade (severe and in situ carcinoma) and invasive carcinoma [9], and evaluates suspicious endobronchial tumors - malignant changes, by detecting irregularity bronchial mucosa, nodular or polypoid lesions and carina thickening [10]. Sometimes there may also be false-positive imaging aspects of the neoplasm, due to areas of inflammation or a thickened epithelium [38]. Malignant tissues on autofluorescence examination have much less green color and may appear as shades of red, brown, or magenta depending on the AFB system used [39]. Xiaoxuan Zheng and all conducted a retrospective study on 218 cases with 1208 biopsies, by white-light bronchoscope and autofluorescence bronchoscopy, in ‟Application of Quantitative Autofluorescence Bronchoscopy Image Analysis Method in Identifying Bronchopulmonary Cancer‟. The paper specified the characteristics of the techniquewhite-light bronchoscope associated with autofluorescence bronchoscopy was able to differentiate between benign and malignant lesion with a high sensitivity, specificity, positive predictive value, and negative predictive value (92.1%, 59.3%, 87.3%, and 71.1%, respectively) [40].

3.7. Other Bronchoscopy Techniques

Performed for the detection of endobronchial squamous carcinoma: narrow-band imaging bronchoscopy (NBI), confocal laser endomicroscopy and laser Raman spectroscopy (LRS), high-magnification bronchoscopy (HMB) and high-definition bronchoscopy (HD) [39].
-
NBI uses narrow-band filters that enhance visualization of mucosal and submucosa vessels and assess the abnormal angiogenesis seen in malignant lesions [41]. On NBI examination, tortuous and steeply terminated vessels are more common in squamous cell carcinoma [42].
-
Optical coherence tomography (OCT) uses near-infrared light, interacts with tissue architecture as a function of depth, and allows for cross-sectional imaging with specificity close to a histological examination by optical interferometry, with spatial resolution of 3 to 15.
Table 4. The representative scientific research carried out by us for the bronchoscopic examinations used in the discovery and biopsy of lung squamous carcinoma.
Table 4. The representative scientific research carried out by us for the bronchoscopic examinations used in the discovery and biopsy of lung squamous carcinoma.
1 2 3 4 5 6 7 8 9 10 11
REFERENCES 3 9 10 11 27 35 38 40 42 44 47
AUTHOR Saibin Wang Tatsuya Imabayashi Camelia Bădescu Zheng Liu Viorel Biciușcă Semra Bilaçeroğlu Jiayuan Sun Xiaoxuan Zheng Bojan Zaric Ankit Gupta Hongling Wang
NR PATIENTS 531 1021 156 708 38 92 232 218 65 0 38
STUDY TYPE retrosp retrosp prospect retrospect descriptive prospective meta-analysis retrospect descript review descript
DIAGNOSTIC YELD 95% 75,9% 84% 89,30% 0 68,00% 95,00% 92,10% 0 95% 93,4%
SENSITIVITY 95% 0 84% 95,70% 0 68% 95% 92,10% 0 95% 93,4%
SPECIFICITY 95% 0 84% 89,30% 0 68% 95% 87,30% 0 95% 93,4%
BRONHOSCOPY/ AFB 0 0 84% 89,30% 0 0 95% 92,10% 0 95% 93,4%
BRONHOSCOPY/NBI 0 0 0 0 0 0 0 0 NBI 95% 0
FIBEROPTIC BRONHOSCOPY exam 0 0 0 exam exam 0 0 0 0 0
WHITE LIGHT BRONHOSCOPY 0 0 69,49% 75,60% 0 0 88,53% 62,20% 0 0 86,8%
FLUOROSCOPIC BRONHOSCOPY 0 exam 0 0 0 exam 0 0 0 0 0
MUCOSAL CHANGES modified mucosa modified mucosa modified mucosa 99% modified mucosa modified mucosa modified mucosa modified mucosa Tortuous blood vessels were identified in 72 % Abnormal vascular patterns include increased vessel growth, tortuous vessels, dotted vessel, and spiral or screw-type vessels 0

4. Discussion

In this review we wanted to establish a correlation of clinical and paraclinical features for endobronchial squamous cell carcinoma. Clinical and paraclinical features were reviewed. These features are vaguely approached in lung cancer diagnosis and treatment guides.
Endobronchial squamous cell carcinoma is one of the most common tumors with this location [15], being the most common type of cancer that is located in the tracheobronchial tree [46]. Symptoms are common to endobronchial tumors: cough, chest pain, recurrent pneumonia [3,4], atelectasis, post-obstructive pneumonia, wheezing [15] and hemoptysis, especially after bronchoscopy with biopsy [3,15], compared to other types of endobronchial tumors [3].
Usual laboratory analyzes revealed the presence of hypercalcemia in the blood [15,17], compared to the assessment of analyzes for lung adenocarcinoma. Analysis of blood tumor markers detected increased levels of SCC-Ag, CYFRA21-1, CEA [6,18,19,20], in patients with squamous cell carcinoma of the lung, compared to those who presented with adenocarcinoma [18].
CT scans have highlighted the characteristic signs of endobronchial tumors, with different degrees of obstruction of the bronchial tree, the bronchus sign, the cutoff sign, with the prominence of the endobronchial tumor formation [5,9,31,32,33,34,35]. On closer examination, there are signs of localized thickening of the bronchial wall in squamous cell carcinoma [33], but it is not mentioned in the literature as a specific feature.
Bronchoscopic examinations with autofluorescence highlight the color changes at the level of the basement membrane in malignant formations, due to an abundant vascularization. Neoplastic lesions are represented as dark red images due to mucosal hypertrophy that decrease fluorescence by increasing blood flow to the malignant tissue [47]. Squamous cell carcinoma in situ is detected on bronchoscopic examination with superficial autofluorescence, even if the basement membrane is not involved [46]. Most often, lesions can be detected in the central airways. Sometimes, the therapeutic approach may consist of bronchoscopic interventions [44]. Central squamous cell carcinoma lesions are known to invade the basement membrane but maintain the bronchus cartilage and do not invade it [44]. Squamous cell carcinomas confined to the bronchial wall show two distinct patterns of growth: superficial spread and endobronchial mass lesions [30]. Compared with lung squamous cell carcinoma, adenocarcinoma in situ, the preinvasive form, is mostly located in the lung parenchyma; it is usually diagnosed on resected tissue [44,47].
Bronchoscopy with Narrow Band Imaging (NBI) demonstrated tortuous blood vessels in 72% of patients with squamous cell carcinoma of the lung, compared with 8% in adenocarcinoma [42].
Taking biological biopsy samples of tumor tissue or suspected to be tumor tissue, by autofluorescence bronchoscopy, has a high accuracy in the diagnosis of anatomopathological certainty "gold standard", immunohistochemistry [48].
Confirmation of histologic diagnosis determines the surgical resection of early-stage disease, while pathologic grading and molecular testing allow for personalized tumor type selection, adjuvant therapy, and genotype-based treatment regimen, meant to improve survival in advanced-stage patients [13].
Recognition of clinical signs, circulating tumor markers, characteristics of computed tomographic examination and types of bronchoscopic investigations, participate in an early detection of this type of tumor. The approach of a personalized therapy, with a view to a surgical treatment to preserve the lung parenchyma, led us to carry out this review.

5. Limitation

The specialized literature has a small number of researches on this topic.

6. Conclusions

Endobronchial squamous cell carcinoma is one of the most common tumors with endoluminal development, which overcomes the structure of the bronchus more difficult. Knowledge of clinical and paraclinical features can contribute to early detection. Patients can benefit from personalized therapy and lung parenchymal-conserving surgery. The update of clinical and paraclinical characteristics of endobronchial squamous cell carcinoma opens new horizons for scientific research with the aim of early detection. Lung parenchymal conserving surgery with resection with bronchoanastomosis will be able to be practiced more frequently, so as to increase the survival rate of this type of patients.

Author Contributions

Conceptualization: R.S.M, C.S.G. and D.P.; data curation: A.M.I., A.O.B, C.S.S. and A.F.N; investigation: C.S.G.and D.P.; methodology: C.S.G. and D.P.; project administration: R.S.M., C.S.G. and D.P.; supervision: R.S.M., C.S.G. and A.O.B.; writing—original draft: C.S.G. and A.O.B.; writing—review and editing: R.S.M., C.S.G.,D.P., A.F.N. and A.O.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable (This systematic review did not require ethical approval as it was based on previously published studies).

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors would like to thank "Marius Nasta" Institute of Pneumophtiziology, Bucharest, Romania and "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania; for the use of online facilities to complete this research.

Conflicts of Interest

The authors declare that they have no conflict of interest regarding the publication of this article.

Ethical Consideration

This systematic review did not require ethical approval as it was based on previously published studies.

References

  1. Ulusan, A.; Tunca, I.E.; Şanlı, M.; Işık, A.F. ; Endobronchial lesions cases treated with interventional bronchoscopic techniques: Our single-center experiences. Turkish Journal of Thoracic and Cardiovascular Surgery 2020, 28, 352–358. [Google Scholar] [CrossRef] [PubMed]
  2. Li, Z.; Zarogoulidis,P. ; Kougioumtzi, I.; Darwiche, K.; Tsakiridis, K.; Katsikogiannis, N.; Stylianaki, A.; Kesisis, G.; Machairiotis, N.; Zarogoulidis, K.; Surgical approaches of endobronchial neoplasms. J Thorac Dis 2013, 5, S378–S382. [Google Scholar] [CrossRef] [PubMed]
  3. Wang, S.; Ye, Q.; Tu, J.; Song, Y. ; The location, histologic type, and stage of lung cancer are associated with bleeding during endobronchial biopsy. Cancer Management and Research 2018, 10, 1251–1257. [Google Scholar] [CrossRef] [PubMed]
  4. Pandey,K. ; Vaidya, P.J.; Kate, A.H.; Chavhan, V.B.; Jaybhaye, P.; Patole, K.; Deshpande, R.K.; Chhajed, P.N.; Bronchoscopic and surgical management of rare endobronchial tumors- Brief Communication. J Can Res Ther 2016, 12, 1093–7. [Google Scholar] [CrossRef]
  5. Zhang, X.; Lv, F.; Fu, B.; Li, W.; Lin, R.; Chu, Z. ; Clinical and Computed Tomography Characteristics for Early Diagnosis of Peripheral Small-cell Lung Cancer. Cancer Management and Research 2022, 14, 589–601. [Google Scholar] [CrossRef]
  6. Nistor, C.E.; Stanciu-Găvan, C. ; Clinical Implications of Early Molecular Diagnosis in Lung Cancer- brief review. J Addict Med Ther Sci 2020, 6, 026–029. [Google Scholar] [CrossRef]
  7. Zhao, W.; Yu, H.; Han, Z.; Gao, N.; Xue, J.; et al. l.; Original Article Clinical signifi cance of joint detection of serum CEA, SCCA, and bFGF in the diagnosis of lung cancer. Int J Clin Exp Pathol. 2015, 8, 9506–9511. [Google Scholar]
  8. Ye, S.; Chen, X.; Yao, Y.; Li, Y.; Sun, R.; et al. l.; Thioredoxin Reductase as a Novel and Effi cient Plasma Biomarker for the Detection of Non-Small Cell Lung Cancer: a Large-scale, Multicenter study. Sci Rep 2019, 9, 2652. [Google Scholar] [CrossRef]
  9. Imabayashi, T.; Matsumoto, Y.; Uchimura, K.; Furuse, H.; Tsuchida, T. ; Computed Tomography Bronchus Sign Subclassification during Radial Endobronchial Ultrasound-Guided Transbronchial Biopsy: A Retrospective Analysis. Diagnostics 2023, 13, 1064. [Google Scholar] [CrossRef]
  10. Bădescu, C.; Mihălțan, F. ; Autofluorescence bronchoscopy and lung cancer diagnosis. Pneumologia 2020, 69, 135–141. [Google Scholar] [CrossRef]
  11. Liu, Z.; Zhang,Y. ; Li, Y-P.; Ma, J.; Shi, F.; Zhao, D-F.; Li, J-M.; Zhang, Y-Z.; Clinical relevance of using autofluorescence bronchoscopy and white light bronchoscopy in different types of airway lesions. Journal of Cancer Research and Therapeutics 2016, 12, 69–72. [Google Scholar] [CrossRef] [PubMed]
  12. Janzic, U.; Kern, I.; Janzic, A.; Cavka, L.; Cufer, T. ; PD-L1 expression in squamous-cell carcinoma and adenocarcinoma of the lung. Radiol Oncol 2017, 51, 357–362. [Google Scholar] [CrossRef] [PubMed]
  13. Zheng, M. ; Classification and Pathology of Lung Cancer. Surg Oncol Clin N Am 2016, 25, 447–468. [Google Scholar] [CrossRef] [PubMed]
  14. Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. ; PRISMA Group Preferred reporting items for systematic reviews and metaanalyses: The PRISMA statement. PLoS Med. 2009, 6, e1000097. [Google Scholar] [CrossRef] [PubMed]
  15. Elsaka,O. ; Noureldean, M.A.; Gamil, M.A.; Mostafa Tarek Ghazali, M.T.; Al-Razik, A.H.A.; Hisham,D.; Etiology, Investigations, and Treatment in Cases of Non-Small Cell Lung Cancer. Asian Basic and Applied Research Journal 2022, 4, 96–122. [Google Scholar]
  16. Umemura, S.; Kudo, K.; Ninomiya, T.; Shiote, Y.; Yamane, H.; Suwaki, T.; Shirakawa, A.; Kamei, H. ; Centrally Located Squamous Cell Carcinoma of the Lung Mimicking Endobronchial Tuberculosis. J Thorac Oncol. 2009, 4, 1178–1179. [Google Scholar] [CrossRef]
  17. AJ, A.; Brock, M.V.; Ford, J.G.; Samet, J.M.; Spivack, S.D. ; Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013, 143, e1S–29S. [Google Scholar]
  18. Liu, L.; Teng, J.; Zhang, L.; Cong, P.; Yao, Y.; Sun, G.; Liu, Z.; Yu, T.; Liu, M. ; The Combination of the Tumor Markers Suggests the Histological Diagnosis of Lung Cancer- Research Article. BioMed Research International 2017, 2013989. [Google Scholar] [CrossRef]
  19. Chen, Z.; Huang, L.; Zhu, B. ; Assessment of Seven Clinical Tumor Markers in Diagnosis of Non-Small-Cell Lung Cancer- Research Article. Disease Markers 2018, 9845123. [Google Scholar] [CrossRef]
  20. Molina, R.; Marrades, R. M.; Augé J., M.; and all. Assessment of a combined panel of six serum tumor markers for lung cancer. American Journal of Respiratory and Critical Care Medicine. 2016, 193, 427–437. [Google Scholar] [CrossRef]
  21. Comnea-Stancu, I.R.; Stefan-van Staden, R.I.; van Staden, J.F.; Stanciu-Gavan, C. ; Stochastic sensors based on maltodextrins for screening of whole blood for neuron specific enolase, carcinoembryonic antigen and epidermal growth factor receptor. Microsyst Technol 2016, 22, 25–29. [Google Scholar] [CrossRef]
  22. Pan, J.; Song, G. ; and all; Identification of Serological Biomarkers for Early Diagnosis of Lung Cancer Using a Protein Array-Based Approach. Molecular & Cellular Proteomics 2017, 16, 2069–2078. [Google Scholar]
  23. Chen, R-L. ; Zhou, J-X.; Cao, Y.; Li, S-H.; Li, Y-H.; Jiang, M.; Dong-Yan Lu, D-Y.; Li, P.; Lin, L-Z.; The efficacy of PD-1/PD-L1 inhibitors in advanced squamous-cell lung cancer: a meta-analysis of 3112 patients. Immunotherapy 2019, 11, 17. [Google Scholar] [CrossRef]
  24. Fernandez-Trujillo, L.; Garcia-Robledo, J.E.; Zúniga-Restrepo, V.; Sua, L.F. ; Clinical characteristics and PD-L1 expression in primary lung squamous cell carcinoma: A case series. Respiratory Medicine Case Reports 2020, 30, 101114. [Google Scholar] [CrossRef] [PubMed]
  25. Goto, T.; Maeshima, A.; Akanabe, K.; Kato, R. ; Bronchial sleeve resection for early-stage squamous cell carcinoma - case report. Journal of Cardiothoracic Surgery 2012, 7, 33. [Google Scholar] [CrossRef]
  26. Wisnivesky,J. P.; Yung, R.C-W.; Praveen N. Mathur; Zulueta, J.J.; Diagnosis and Treatment of Bronchial Intraepithelial Neoplasia and Early Lung Cancer of the Central Airways Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Supplement 2013, 143, e263S–e277S. [Google Scholar]
  27. Biciuşcă, V.; Popescu, I.A.S. ; and all; Diagnosis of lung cancer by flexible fiberoptic bronchoscopy: a descriptive study. Rom J Morphol Embryol 2022, 63, 369–381. [Google Scholar] [CrossRef]
  28. Detterbeck, F.C.; Lewis, S.Z.; Diekemper, R.; Addrizzo-Harris, D.; Alberts, W.M. ; Executive Summary: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013, 143, 7S–37S. [Google Scholar] [CrossRef]
  29. Inamura, K. ; Update on Immunohistochemistry for the Diagnosis of Lung Cancer- Review; Cancers 2018, 10, 72. 10. [CrossRef]
  30. Urer,H. N.; Kocaturk, C.I.; Gunluoglu, M.Z.; Arda, N.; Demir, A.; Ortakoylu, M.G.; Bedirhan, A.A.; Dincer, S.I.; Squamous cell carcinomas confined to the bronchial wall: the effect of growth patterns. Thorac Cardiovasc Surg. 2014, 62, 120–125. [Google Scholar] [CrossRef]
  31. Park, C.M.; Goo, J.M.; Lee,H. J.; Kim,M.A.; Lee,C.H.; Mi-Jin Kang,M-J.; Tumors in the Tracheobronchial Tree: CT and FDG PET Features. RadioGraphics 2009, 29, 1. [Google Scholar] [CrossRef]
  32. Gharraf,H. S.; Mehana, S.M.; ElNagar, M.A.; Role of CT in differentiation between subtypes of lung cancer; is it possible?. The Egyptian Journal of Bronchology 2020, 14, 28. [CrossRef]
  33. Song, Y.; Choi, Y.W.; Paik, S.S.; Han, D.H.; Lee, K.Y. ; Endobronchial squamous cell carcinoma presenting as localized, long, continuous bronchial thickening on CT. Eur J Radiol. 2017, 91, 99–105. [Google Scholar] [CrossRef]
  34. Irodi, A.; Ashu Seith Bhalla, A.S.; and all. ; Imaging Recommendations for Diagnosis, Staging, and Management of Lung Cancer- Review Article. Indian Journal of Medical and Paediatric Oncology 2023, 44, 181–193. [Google Scholar] [CrossRef]
  35. Bilaçeroğlu, S.; Kumcuoğlu, Z.; and all. ; CT Bronchus Sign-Guided Bronchoscopic Multiple Diagnostic Procedures in Carcinomatous Solitary Pulmonary Nodules and Masses. Respiration 1998, 65, 49–55. [Google Scholar] [CrossRef] [PubMed]
  36. Ulmeanu, R.; Nedelcu, R. ; The role of autofluorescence bronchoscopy in detecting dysplasia and incipient lung cancer- literature review. Romanian Journal of Rhinology, 2012, 2, 231–234. [Google Scholar]
  37. Kalinke, L.; Thakrar, R.; Janes, S.M. ; The promises and challenges of early non-small cell lung cancer detection: patient perceptions, low-dose CT screening, bronchoscopy and biomarkers – review. Molecular Oncology 2021, 15, 2544–2564. [Google Scholar] [CrossRef]
  38. Sun. J.; Garfield, D.H.; Lam, B.; Yan, J.; Gu, A.; Shen, J.; Han, B.; The value of autofluorescence bronchoscopy combined with white light bronchoscopy compared with white light alone in the diagnosis of intraepithelial neoplasia and invasive lung cancer: a meta-analysis. J Thorac Oncol 2011, 6, 1336–1344.
  39. Inage, T.; Nakajima, T.; Yoshino, I.; and all. ; Early Lung Cancer Detection. Clin Chest Med 2018, 39, 45–55. [Google Scholar] [CrossRef]
  40. Zheng, X.; Xiong, H.; Li, Y.; Han, B.; and Jiayuan Sun, J. ; Application of Quantitative Autofluorescence Bronchoscopy Image Analysis Method in Identifying Bronchopulmonary Cancer. Technology in Cancer Research & Treatment 2017, 16, 482–487. [Google Scholar] [CrossRef]
  41. Daniels, J.M.; Sutedja, T.G. ; Detection and minimally invasive treatment of early squamous lung cancer. Ther Adv Med Oncol 2013, 5, 235–48. [Google Scholar] [CrossRef]
  42. Zaric, B.; Perin, B.; Stojsic, V.; and all. ; Relation between vascular patterns visualized by Narrow Band Imaging (NBI) videobronchoscopy and histological type of lung cancer. Med Oncol 2013, 30, 374. [Google Scholar] [CrossRef] [PubMed]
  43. Lam, S.; Standish, B.; Baldwin, C.; and all. ; In vivo optical coherence tomography imaging of preinvasive bronchial lesions. Clin Cancer Res 2008, 14, 2006–2011. [Google Scholar] [CrossRef] [PubMed]
  44. Gupta, A.; Harris, K.; Dhillon, S.S. ; Role of bronchoscopy in management of central squamous cell lung carcinoma in situ- review article. Ann Transl Med 2019, 7, 354. [Google Scholar] [CrossRef] [PubMed]
  45. Shah, P.L.; Kemp, S.V.; Newton, R.C.; and all. Clinical Correlation between Real-Time Endocytoscopy, Confocal Endomicroscopy, and Histopathology in the Central Airways. Respiration 2017, 93, 51–7. [Google Scholar] [CrossRef] [PubMed]
  46. Rowell, N.P.; Williams, C.J. ; Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable): a systematic review. Thorax 2001, 56, 628–38. [Google Scholar] [CrossRef]
  47. Wang, H.; Liu, S.; Li, F.; Gao,W. ; Lv, N.; Autofluorescence bronchoscope diagnosis for lung nodules and masses. Am J Transl Res 2021, 13, 7775–7782. [Google Scholar]
  48. Nooreldeen, R.; Bach, H. ; Current and Future Development in Lung Cancer Diagnosis Review. Int. J. Mol. Sci. 2021, 22, 8661. [Google Scholar] [CrossRef]
Table 1. Representative articles from the literature specifying the main author and the types of examination researched.
Table 1. Representative articles from the literature specifying the main author and the types of examination researched.
NR REF AUTHOR NR PATIENTS STUDY TYPE DIAGNOSTIC YELD SENSITIVITY SPECIFICITY CT BRONHOSCOPY/ AFB BRONHOSCOPY/NBI Clinic TUMOR MERKER
1 3 Saibin Wang 531 retrosp 95% 95% 95% 0 95% 0 CLINIC unspec
2 5 Xiaochuan Zhang 366 retrosp 91,40% 9, 14% 92,4% CT unspec 0 CLINIC unspec
3 7 Wei Zhao 135 retrosp 91,30% 0 0 0 unspec 0 0 MARKER
4 8 Suofu Ye 1922 retrosp 90,20% 82,50% 81,30% 0 unspec 0 0 MARKER
5 9 Tatsuya Imabayashi 1021 retrosp 75,9 - 95% 95% 95% CT AFB 0 0 unspec
6 10 Camelia Bădescu 156 prosp 84% 84% 84% 0 AFB 0 0 unspec
7 11 Zheng Liu 708 retrosp 89,30% 95,70% 89,30% 0 AFB 0 0 unspec
8 12 Urska Janzic 54 observ 72% 0 0 0 0 0 0 MARKER
9 18 Linjie Liu 2097 observ 65,93% 81,63% 65,93% 0 0 0 0 MARKER
10 19 Zhong-qing Chen 693 observ 65,93% 0 0 0 0 0 0 MARKER
11 20 Rafael Molina 3,144 observ 0 88,50% 82,00% 0 0 0 0 MARKER
12 27 Viorel Biciușcă 38 descrip 0 0 0 0 AFB 0 CLINIC 0
13 33 Yoonah Song 5 retrosp 0 0 0 CT AFB 0 0 0
14 35 Semra Bilaçeroğlu 92 prosp 68% 68% 68% CT AFB 0 0 0
15 38 Jiayuan Sun 232 meta-anal 95% 95% 95% 0 95% 95% 0 0
16 40 Xiaoxuan Zheng 218 retrosp 92,10% 92,10% 87,30% 0 AFB 0 0 0
17 42 Bojan Zaric 65 descrip 0 0 0 0 0 mucosal wich tortuous blood vessels were identified in 72 % 0 0
18 44 Ankit Gupta 0 review 95% 95% 95% 0 95% mucosal wich abnormal vascular patterns include increased vessel growth, tortuous vessels, dotted vessel, and spiral or screw-type vessels 0 0
19 47 Hongling Wang 38 descri 93,4% 93,4% 93,4% 0 AFB 0 0 0
Table 2. The representative scientific studies that we analyzed for tumor markers alone or in groups, with significance for squamous cell carcinoma.
Table 2. The representative scientific studies that we analyzed for tumor markers alone or in groups, with significance for squamous cell carcinoma.
REFERENCES 7 8 12 18 19 20
AUTHOR Wei Zhao Suofu Ye Urska Janzic Linjie Liu Zhong-qing Chen Rafael Molina
NR PATIENTS 135 1922 54 2097 693 3144
STUDY TYPE retrospective retrospective observational observational observational observational
DIAGNOSTIC YELD 91,30% 90,20% 72% 65,93% 65,93% unspecified
SENSITIVITY unspecified 82,50% unspecified 81,63% unspecified 88,50%
SPECIFICITY unspecified 81,30% unspecified 65,93% unspecified 82%
SCC-Ag 59,60% unspecified unspecified 36,68% 39,80% 4,80%
CYFRA21-1 unspecified 51% unspecified 61,15% 88,60% 12,60%
CEA 55,80% 33,80% unspecified 21,55% 23,50% 8,20%
TrxR unspecified 71,60% unspecified unspecified unspecified unspecified
NSE unspecified 21,30% unspecified 7,51% unspecified 17,20%
bFGF 65,40% unspecified unspecified unspecified unspecified unspecified
CEA+SCC-Ag+bFGF 91,30% unspecified unspecified unspecified unspecified unspecified
CA19-9 unspecified 18,80% unspecified unspecified unspecified unspecified
NSE+ Cyfra21-1 +CA19-9+ CEA+ TrxR unspecified 83% unspecified unspecified unspecified unspecified
NSE + Cyfra21-1 +CA 19-9 unspecified 52,50% unspecified unspecified 5,54% unspecified
PD-L1 unspecified unspecified 72% unspecified unspecified unspecified
ProGRP unspecified unspecified unspecified 8,27% unspecified 32,00%
CA125 unspecified unspecified unspecified 20,05% 28,90% unspecified
CEA +CYFRA21-1 + SCC-Ag + ProGRP + CA 125 unspecified unspecified unspecified 65,93% unspecified unspecified
CEA +CA125 +CA15-3 +CA19-9 +CA72-4 +CYFRA21-1 + SCC-Ag unspecified unspecified unspecified unspecified unspecified unspecified
CA72-4 unspecified unspecified unspecified unspecified 16,90% unspecified
CA 15-3 unspecified unspecified unspecified unspecified 9% 26,60%
CA15.3 +CEA +CYFRA 21-1 +NSE + ProGRP unspecified unspecified unspecified unspecified unspecified 88.50%
Table 3. Representative scientific research analyzed for the specific elements of CT examinations.
Table 3. Representative scientific research analyzed for the specific elements of CT examinations.
REFERENCES 5 9 33 35
AUTHOR Xiaochuan Zhang Tatsuya Imabayashi Yoonah Song Semra Bilaçeroğlu
NR PATIENTS 366 1021 5 92
STUDY TYPE retrospect retrospect retrospect prospect
SENSITIVITY 91.40% 95% unspecif 68%
SPECIFICITY 92.40% 95% unspecif 68%
DIAGNOST YELD 91.40% 95% unspecif 68%
POLIPOID LESSIONS present present unspecif present
FOCAL SESILE LESSIONS present present unspecif present
CT bronchus sign present present present present
Bronchial cutoff sign present present present present
PLATED LESSIONS OF THE WALL present present present present
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