Topographic and Macroscopic Features
Based on the initial site within the respiratory tract, tumors are divided into three anatomic groups:
- Central (hilar) cancer — arises in large airways: the main, lobar, or proximal segmental bronchi.
- Peripheral cancer — originates from small branches, bronchioles, and presumably alveolar tissue.
- Mixed (massive) cancer — combines features of both locations.
Depending on the direction of growth, the neoplasm may be exophytic (growing into the bronchial lumen, i.e., endobronchial) or endophytic (growing into the bronchial wall or surrounding lung tissue — exobronchial and peribronchial).
Macroscopically, tumors take various forms, including plaque-like, polypoid, nodular, branched, or nodular-branched. Cavitary forms, diffuse endobronchial growth, and a specific pneumonia-like variant also occur.
Histological Types (Classification by Histogenesis)
Microscopic structure determines the histological subtype. The main types include:
- Squamous cell carcinoma — varies in degree of differentiation and cellular architecture.
- Small cell carcinoma — divided into classic (including oat cell, lymphocyte-like, and intermediate cell variants) and combined types.
- Adenocarcinoma — a glandular tumor presenting in acinar, papillary, solid, and lepidic variants, as well as papillary bronchioloalveolar carcinoma and solid forms with mucin production. When well-differentiated, hematoxylin and eosin-stained sections clearly demonstrate glandular structures.
- Large cell carcinoma — includes giant cell and clear cell variants.
- Adenosquamous carcinoma.
- Carcinoid tumor.
- Bronchial gland carcinoma — e.g., adenoid cystic or mucoepidermoid carcinoma.
The Role of Microscopy and Immunohistochemistry (IHC)
Current WHO standards mandate the use of immunohistochemistry. Without IHC, the risk of misdiagnosis reaches 40%. The universal marker for all types of pulmonary carcinomas is the expression of cytokeratins. Detection of p53 protein accumulation (e.g., via immunoperoxidase staining in large cell carcinoma) is also utilized.
Routine light microscopy does not always reveal the true cellular nature:
- In large cell carcinoma, light microscopy shows large cells without clear differentiation; however, electron microscopy and histochemistry reveal hidden glandular or squamous epithelial features.
- In small cell carcinoma, small undifferentiated cells demonstrate squamous, glandular, or most commonly neuroendocrine differentiation at the ultrastructural level.
Neuroendocrine Tumors and Clinical Classification
Tumors with neuroendocrine differentiation are now classified as a distinct group encompassing three grades of malignancy:
- Well-differentiated carcinoma (typical, benign carcinoid).
- Moderately differentiated (atypical carcinoid).
- Poorly differentiated (small cell lung cancer with neuroendocrine features).
In clinical practice, due to differences in morphology, symptoms, chemotherapy response, and prognosis, all histological forms are grouped into two major categories:
- Small cell lung cancer (SCLC) — characterized by an aggressive clinical course and, along with large cell carcinoma, the poorest prognosis.
- Non-small cell lung cancer (NSCLC) — includes all other histological types.