Lung cancer diagnostic study of choice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]Kim-Son H. Nguyen M.D., Cafer Zorkun, M.D., Ph.D. [3]. Rim Halaby, M.D. [4], Michael Maddaleni, B.S.

Overview

Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include a solitary pulmonary nodule, centrally located masses, mediastinal invasion CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases such as adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the tumor, demonstrating proximity to the nearby structures, and deciphering whether lymph nodes are enlarged in the mediastinum.

Diagnostic Study of Choice

Study of Choice

Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include:^[1]

Solitary pulmonary nodule
Centrally located masses
Mediastinal invasion
Peripherally situated lesions invading the chest wall
A ground-glass opacity
Consolidation
Mixed density or pure ground glass nodules
Mixed density or pure ground glass consolidation

Common radiological appearances of lung cancer. Centrally located mass with mediastinal invasion (arrow, A), peripherally situated mass abutting the pleura (arrow, B), mass with smooth, lobulated margins (arrow, C) and with spiculated, irregular margins (arrow, D), via <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F1/>^[1]	Lung cancers with atypical radiological pattern. Squamous cell cancer presenting as a cavitating mass (arrow, A). Adenocarcinoma presenting as dense consolidation (arrow, B). Bronchoalveolar carcinoma (adenocarcinoma in situ) presenting as ground-glass opacity (arrow, C) and mixed density, solid (arrow), and ground-glass nodules (arrowhead) in D via <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F2/>^[1]
Stage T1 and T2 tumors. Stage T1 tumor due to size < 3 cm (arrow, A). Stage T2 endobronchial tumor (arrowhead) causing pneumonitis restricted to the upper lobe (arrow) in B. T2a tumor > 3 cm but < 5 cm (arrow, C). T2b tumor > 5 cm but < 7 cm (arrow in D) via <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F3/>^[1]	Stage T3 tumors. T3 tumor due to size > 7 cm in size (arrow, A), eroding the ribs (arrow, B), infiltrating the mediastinal pleura but not the vessels (arrow, C), and causing atelectasis of the entire lung (arrowhead, D via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F4/>.^[1]
Stage T4 tumors. T4 tumor due to invasion of pulmonary artery (arrow, A), descending aorta (arrow, B), vertebral body (arrow, C), superior vena cava with thrombus (arrow, D)via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F5/>^[1]	Superior sulcus tumor. Axial (A) and coronal (B) CT scans show a large mass in the apex of the right lung causing destruction of the first and second ribs (arrows) with erosion of the right half of the vertebral body (arrowheads) suggestive of a superior sulcus tumor, via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F16/>^[1]

Spiral CT Perfusion Imaging

Spiral CT perfusion study can be used as a diagnostic method for peripheral pulmonary nodules.
Spiral CT perfusion study provides non-invasive method for the quantitative assessment of blood flow patterns of peripheral pulmonary nodules.
Spiral CT perfusion imaging is analyzed and evaluated for:^[2]
- TDC (time density curve)
- Perfusion parametric maps
- The respective perfusion parameters
- Immunohistochemical findings of microvessel density (MVD) measurement
- VEGF expression

(A-H) Poorly differentiated adenocarcinoma found in the apicoposterior segment of superior lobe of the left lung of a 56 year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) typeI parametric maps, PS value is higher (30.883). (G) CD34 staining shows many immature tumor microvessels (× 200). (H) VEGF expression is strong positive (× 400) via, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474637/figure/F6/.^[2]	(A-H) (A-H) Well differentiated squamous cell carcinoma found in the posterior basal segment of inferior lobe of the right lung of a 61-year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) TypeII parametric maps, PS value is higher (27.051). (G) CD34 staining shows many immature tumor microvessels (× 200). (H) VEGF expression is strong positive (× 400). via, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474637/figure/F3/.^[2]

CT Findings of Metastatic disease

CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases such as adrenal glands, liver, and brain.
The benefits of CT scan in lung cancer patients are the following:^[3]
- Provides anatomical detail to locate the tumor
- Demonstrates proximity to nearby structures
- Deciphers whether lymph nodes are enlarged in the mediastinum

Metastatic disease. Bilateral pleural effusions-M1a (arrow, A), lung metastases-M1a (arrows, B), adrenal metastasis-M1b (arrow, C), vertebral metastasis-M1b (arrow, D), brain metastasis-M1b (arrow, E), liver metastases-M1b (arrows, F)via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F10/>This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.^[1]	Adrenal adenoma versus metastasis. Enhancing solid adrenal nodule on CT scan in a case of lung cancer (arrow, A) suggestive of metastatic deposit. Unenhanced CT scan shows fatty attenuation within the nodule with an HU value of 0 suggesting the possibility of an adenoma (arrow, B). FDG-PET/CT shows no tracer concentration in the nodule, confirming the diagnosis of adenoma. Enhancing solid adrenal nodule on CT scan in another patient of lung cancer (arrow, D), which is indeterminate in nature. FDG-PET/CT shows abnormal focal tracer concentration in the nodule (arrow, E) highly suggestive of a metastatic deposit via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F11/>^[1]	Brain metastases in asymptomatic patient, CT scan versus MRI. MRI brain in a patient of lung cancer shows multiple tiny enhancing foci scattered in the parenchyma bilaterally (arrows in A and B) suggestive of metastatic lesions. Corresponding contrast CT scan sections of the brain show no obvious lesions (C and D). Note the beam hardening effects due to bone, leading to a loss of resolution on the CT images (C and D)via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F12/>^[1]

Unfortunately, research has shown that there are a number of false positives associated with CT scanning because CT scan alone cannot determine malignancy.
A positive result for a tumor using CT scan is typically followed up with a biopsy for confirmation.

Staging

The following is 2017 TNM classification of lung cancer.^[4]^[5]^[6]

T: Primary Tumor

T	Description
TX	Primary tumor cannot be assessed. OR Tumor is demonstrated by the presence of malignant cells in bronchial washings or sputum, but is not visualized by imaging or bronchoscopy.
T0	There is no evidence of primary tumor.
Tis	Carcinoma in situ
T1	The tumor has the following characteristics: T1a: Tumor ≤ 1 cm in the largest diameter. T1b: Tumor > 1 cm, but ≤ 2 cm in the largest diameter. T1c: Tumor > 2 cm, but ≤ 3 cm in the largest diameter. AND The tumor is surrounded by lung or visceral pleura AND The tumor does not extend to the main bronchus as demonstrated by the absence of bronchoscopic evidence of invasion more proximal than the lobar bronchus.
T2	The tumor has the following characteristics: T2a: Tumor > 3 cm, but ≤ 4 cm in the largest diameter. T2b: Tumor > 4 cm, but ≤ 5 cm in the largest diameter. The tumor involves the main bronchus, 2 cm or more distal to the carina. OR The tumor invades the visceral pleura. OR There is evidence of atelectasis or obstructive pneumonitis that extends to the hilar region without the involvement of the entire lung.
T3	Tumor > 5 cm, but ≤ 7 cm in size. AND It directly invades any of the following: Chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium. OR The tumor is localized in the main bronchus at a distance less than 2 cm distal to the carina but without the involvement of the carina. OR There is evidence of associated atelectasis or obstructive pneumonitis of the entire lung.
T4	Tumor > 7 cm in size. The tumor invades any of the following: Mediastinum, heart, great vessels, trachea, esophagus, vertebral body, and carina OR There is/are separate tumor nodule(s) in the same lobe. OR The tumor is associated with malignant pleural effusion.

N: Regional Lymph Nodes

T	Description
NX	Regional lymph nodes cannot be assessed.
N0	There is no evidence of regional lymph node metastasis.
N1	Metastasis in ipsilateral peribronchial and/or ipsilateral hilum or intrapulmonary lymph nodes N1a: Invasion of 1 lymph node. N1b: > 1 lymph node affected.
N2	There is metastasis in the ipsilateral mediastinal and/or subcarinal lymph node(s). N2a1: One lymph node affected without lymph node involvement of an N1-defined lymph node station. N2a2: One lymph node affected with a lymph node of an N1-defined lymph node station N2b: > 1 lymph node affected
N3	There is metastasis in the contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).

M: Distant Metastasis

T	Description
MX	Distant metastasis cannot be assessed.
M0	There is no evidence of distant metastasis.
M1	There is evidence of distant metastasis which includes the presence of separate tumor nodule(s) in a different lobe (ipsilateral or contralateral). M1a: Tumor foci separated from the primary tumor in a contralateral lung lobe; tumor with pleural metastases or malignant pleural or pericardial effusion M1b: Single metastatic lesion in an organ M1c: Multiple metastases in one organ or one or more metastases in more than one organ

Classification of Lung Cancer by Staging

Stage	T	N	M
Occult carcinoma	TX	N0	M0
Stage 0	Tis	N0	M0
Stage IA1	T1(mi)/T1a	N0	M0
Stage IA2	T1b	N0	M0
Stage IA3	T1c	N0	M0
Stage IB	T2a	N0	M0
Stage IIA	T2b	N0	M0
Stage IIB	T1a	N1	M0
	T1c	N1	M0
	T2a	N1	M0
	T2b	N1	M0
	T3	N0	M0
Stage IIIA	T1a	N2	M0
	T1b	N2	M0
	T1c	N2	M0
	T2a	N2	M0
	T2b	N2	M0
	T1a	N2	M0
	T1b	N2	M0
	T1c	N2	M0
	T2a	N2	M0
	T2b	N2	M0
	T3	N1	M0
	T4	N0	M0
	T4	N1	M0
Stage IIIB	T1a	N3	M0
	T1b	N3	M0
	T1c	N3	M0
	T2a	N3	M0
	T2b	N3	M0
	T1a	N3	M0
	T1b	N3	M0
	T1c	N3	M0
	T2a	N3	M0
	T2b	N3	M0
	T3	N2	M0
	T4	N2	M0
Stage IIIC	T3	N3	M0
Stage IIIC	T4	N3	M0
Stage IVA	Any T	Any N	M1a
Stage IVA	Any T	Any N	M1b
Stage IVB	Any T	Any N	M1c

Procedures for Staging Lung Cancer

There are currently multiple different procedures available to stage lung cancer.

They can be broken down into two overarching categories, invasive and minimally invasive.

Invasive

Minimally Invasive

EBUS-FNA (endobronchial ultrasound guided fine needle aspiration)
EUS-FNA (esophageal endoscopic ultrasound guided fine needle aspiration)

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 ^1.8 ^1.9 Purandare, NilenduC; Rangarajan, Venkatesh (2015). "Imaging of lung cancer: Implications on staging and management". Indian Journal of Radiology and Imaging. 25 (2): 109. doi:10.4103/0971-3026.155831. ISSN 0971-3026.
↑ ^2.0 ^2.1 ^2.2 Ma, Shu-Hua; Le, Hong-Bo; Jia, Bao-hui; Wang, Zhao-Xin; Xiao, Zhuang-Wei; Cheng, Xiao-Ling; Mei, Wei; Wu, Min; Hu, Zhi-Guo; Li, Yu-Guang (2008). "Peripheral pulmonary nodules: Relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression". BMC Cancer. 8 (1). doi:10.1186/1471-2407-8-186. ISSN 1471-2407.
↑ Gerard A. Silvestri, Lynn T. Tanoue, Mitchell L. Margolis, John Barker, Frank Detterbeck.11/30/11.The Noninvasive Staging of Non Small-cell Lung Cancer. Chestpubs. http://chestjournal.chestpubs.org/content/123/1_suppl/147S.full/
↑ Mountain, CF (2003). A Handbook for Staging, Imaging, and Lymph Node Classification. Charles P Young Company. Retrieved 2007-09-01. Unknown parameter |coauthors= ignored (help)
↑ Collins, LG (Jan 2007). "Lung cancer: diagnosis and management". American Family Physician. American Academy of Family Physicians. 75 (1): 56–63. PMID 17225705. Retrieved 2007-08-10. Unknown parameter |coauthors= ignored (help)
↑ Harms, A.; Kriegsmann, M.; Fink, L.; Länger, F.; Warth, A. (2017). "Die neue TNM-Klassifikation für Lungentumoren". Der Pathologe. 38 (1): 11–20. doi:10.1007/s00292-017-0268-y. ISSN 0172-8113.

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[PurandareRangarajan2015-1] 1.0 ^1.1 ^1.2 ^1.3 ^1.4 ^1.5 ^1.6 ^1.7 ^1.8 ^1.9 Purandare, NilenduC; Rangarajan, Venkatesh (2015). "Imaging of lung cancer: Implications on staging and management". Indian Journal of Radiology and Imaging. 25 (2): 109. doi:10.4103/0971-3026.155831. ISSN 0971-3026.

[MaLe2008-2] 2.0 ^2.1 ^2.2 Ma, Shu-Hua; Le, Hong-Bo; Jia, Bao-hui; Wang, Zhao-Xin; Xiao, Zhuang-Wei; Cheng, Xiao-Ling; Mei, Wei; Wu, Min; Hu, Zhi-Guo; Li, Yu-Guang (2008). "Peripheral pulmonary nodules: Relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression". BMC Cancer. 8 (1). doi:10.1186/1471-2407-8-186. ISSN 1471-2407.

[Silvestri-3] Gerard A. Silvestri, Lynn T. Tanoue, Mitchell L. Margolis, John Barker, Frank Detterbeck.11/30/11.The Noninvasive Staging of Non Small-cell Lung Cancer. Chestpubs. http://chestjournal.chestpubs.org/content/123/1_suppl/147S.full/

[4] Mountain, CF (2003). A Handbook for Staging, Imaging, and Lymph Node Classification. Charles P Young Company. Retrieved 2007-09-01. Unknown parameter |coauthors= ignored (help)

[Collins-5] Collins, LG (Jan 2007). "Lung cancer: diagnosis and management". American Family Physician. American Academy of Family Physicians. 75 (1): 56–63. PMID 17225705. Retrieved 2007-08-10. Unknown parameter |coauthors= ignored (help)

[HarmsKriegsmann2017-6] Harms, A.; Kriegsmann, M.; Fink, L.; Länger, F.; Warth, A. (2017). "Die neue TNM-Klassifikation für Lungentumoren". Der Pathologe. 38 (1): 11–20. doi:10.1007/s00292-017-0268-y. ISSN 0172-8113.

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