Classification and CT semiotics
From the perspective of diagnostic imaging and prognosis, lung adenocarcinomas are generally divided into several main groups. This classification helps determine patient management tactics.
- Invasive mucinous adenocarcinoma (Invasive mucinous adenocarcinoma). In the modern classification, this type is separated from non-mucinous variants (previously called mucinous bronchioloalveolar carcinoma).
- Adenocarcinoma in situ and minimally invasive adenocarcinoma. They are characterized by an extremely favorable prognosis—disease-free survival reaches 100%. On CT, they appear as areas of pure ground-glass lesion (GGO). These are focal areas of lung tissue opacity against which normal lung anatomical structures remain visible.
- Minimally invasive adenocarcinoma (Minimally invasive adenocarcinoma). Characterized predominantly by lepidic growth. The total size of the nodule does not exceed 3 cm, and the invasive (solid) component is no more than 5 mm. On CT, this appears as a subsolid nodule.
- Invasive adenocarcinoma (Invasive adenocarcinoma). Includes solid, acinar, papillary, micropapillary, and predominantly lepidic subtypes. The prognosis for this form heavily depends on the specific histological structure.
Management of part-solid nodules
Since minimally invasive forms grow very slowly, international societies (such as the Fleischner Society and BTS) recommend prolonged follow-up—up to 5 years.
The main marker of tumor progression (growth) is the appearance of a new solid component within the nodule or an increase in the existing one. If such changes are detected on CT, the patient requires immediate further evaluation and a decision on initiating treatment.
Pericystic tumors
Special attention should be paid to pericystic tumors (Pericystic Tumours). These are malignant nodules (most commonly adenocarcinomas) that begin to grow in the walls of pre-existing cystic lesions of the lung. Fibrotic cavities, bronchiectasis, subpleural blebs, or emphysematous bullae can serve as a basis for them.
The diagnostic challenge lies in the fact that the soft-tissue component of the tumor is very thin in the early stages, making it difficult to spot, which leads to late diagnosis. Furthermore, due to the small size of this component, performing a percutaneous or bronchoscopic biopsy is technically difficult and carries high risks for the patient. Although these tumors are being detected more frequently thanks to screening programs, there are still no specific clinical guidelines for their management.
Nodule evaluation: contrast enhancement and PET/CT
To differentiate indeterminate pulmonary nodules, methods assessing their vascularization and metabolism are used.
- Assessment of contrast enhancement. Malignant nodules typically enhance with contrast media. If there is no enhancement, the probability of cancer is extremely low. However, this method is applicable only to soft-tissue nodules; it does not work for calcifications, cavities, or ground-glass opacities. Dual-energy CT (Dual-energy CT) allows for the creation of virtual non-contrast images, reducing radiation exposure. Today, this method has largely been superseded by PET/CT.
- 18F-FDG PET/CT. It is the main tool for cancer staging and evaluating suspicious nodules. The method is based on the fact that tumor cells actively uptake the radiopharmaceutical (glucose labeled with the radioactive isotope fluorine-18). The SUV (standardised uptake value) is used to assess metabolic activity.
Limitations of PET/CT:
- The method is not used for nodules smaller than 6 mm.
- For nodules up to 1 cm, there is a high risk of false-negative results (especially in poorly differentiated adenocarcinomas).
- False-positive results are possible in sarcoidosis and inflammatory (granulomatous) processes.
Briefly: answers to topical questions
What target mutations need to be tested for in invasive lung adenocarcinoma?
In invasive lung adenocarcinoma, genetic aberrations of EGFR, ALK, ROS1, and BRAF are routinely tested.
- EGFR — activating mutations are sensitive to tyrosine kinase inhibitors.
- ALK — gene fusions are often responsible for the signet-ring cell subtype of adenocarcinoma.
- ROS1 and BRAF — are part of the recommended testing panel and serve as targets for oral kinase inhibitors.
How is the stage of lung adenocarcinoma classified using the TNM system?
Staging of lung adenocarcinoma using the TNM system is based on assessing the primary tumor, lymph nodes, and metastases.
- T criterion (tumor) — assesses size and extent: T1 (up to 30 mm, including T1mi for minimally invasive), T2 (31–50 mm or pleural/bronchial involvement), T3 (additional nodule in the same lobe), T4 (nodule in a different lobe of the ipsilateral lung).
- N criterion (nodulus) — lymph node involvement: from N0 (no involvement) to N3 (contralateral or supraclavicular).
- M criterion (metastasis) — presence of distant metastases (M1).
Additionally, prefixes (cTNM, pTNM, iTNM, yTNM, rTNM) are used to indicate the method of assessment.
What biopsy methods exist for peripheral lung lesions?
To verify peripheral lung lesions, percutaneous, surgical, and transbronchial methods are used, as biopsy via standard endoscopic techniques is extremely problematic.
- Percutaneous fine-needle or cutting-needle biopsy (cutting-needle biopsy) — an accurate method for confirming malignancy under imaging guidance.
- Transthoracic needle biopsy — a crucial tool for indeterminate nodules.
- Transbronchial lung biopsy — one of the tissue acquisition options.
- Surgical lung biopsy — used depending on the diagnostic yield versus procedure risk ratio.
Class and exam questions
What is the ground-glass opacity (GGO) sign on CT?
This is a focal increase in lung density through which normal structures (vessels, bronchi) are clearly visualized. It is characteristic of non-invasive or minimally invasive adenocarcinomas.
Which radiopharmaceutical is used in lung PET/CT?
18F-fluorodeoxyglucose (FDG) is used — a glucose analog labeled with radioactive fluorine-18. Malignant cells actively uptake this agent.
Why are pericystic tumors difficult to diagnose?
The soft-tissue tumor component grows within the cyst wall; it is very thin in early stages and difficult to distinguish on CT. For this reason, performing a safe biopsy is also extremely challenging.
At what nodule size is PET/CT impractical?
PET/CT is not recommended for nodules less than 6 mm in diameter, and for lesions less than 1 cm, results are interpreted with great caution due to the risk of false-negative findings.
What else to study on this topic
- Histological subtypes of invasive adenocarcinoma (lepidic, acinar, solid)
- Dual-energy CT: physical principles and virtual non-contrast images
- Differential diagnosis of causes of false-positive FDG uptake on PET/CT
- Comparison of Fleischner Society and BTS guidelines for the management of pulmonary nodules
- Maximum intensity projection (MIP) in PET/CT imaging
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