Classification of lung cancer

Topographic and macroscopic picture

Depending on which part of the respiratory tract the tumor initially originates from, three anatomical groups are distinguished:

• Central (root) cancer — forms in the large airways: the main, lobar, or proximal segmental bronchus.
• Peripheral cancer — originates from small branches, bronchioles, and, presumably, alveolar tissue.
• Mixed (massive) — combines features of both locations.

Depending on the direction of growth, the neoplasm can be exophytic (growing into the lumen of the bronchus, i.e., endobronchial) or endophytic (growing into the thickness of the bronchial wall or extending into the surrounding lung tissue — exobronchial and peribronchial).

Macroscopically, the tumor assumes a wide variety of shapes. It can be plaque-like, polypoid, nodular, branched, or nodular-branched. Cavitary forms, endobronchial diffuse growth, and a specific pneumonia-like variant are also encountered.

Histological types (classification by histogenesis)

The microscopic structure determines the tumor's belonging to one of the histological variants. The main types include:

1. Squamous cell carcinoma — varies in degree of differentiation and cellular architecture.
2. Small cell carcinoma — divided into classical (including oat cell, lymphocyte-like, and intermediate cell variants) and combined.
3. Adenocarcinoma — a glandular tumor. Presented by acinar, papillary, solid, lepidic variants, as well as papillary bronchioloalveolar carcinoma and a solid form with mucin production. In well-differentiated tumors on hematoxylin and eosin-stained sections, glandular structures are clearly defined.
4. Large cell carcinoma — includes giant cell and clear cell variants.
5. Adenosquamous carcinoma.
6. Carcinoid tumor.
7. Bronchial gland carcinoma — for example, adenoid cystic or mucoepidermoid carcinoma.

The role of microscopy and immunohistochemistry (IHC)

Modern WHO standards require the mandatory use of immunohistochemistry. Without IHC, the risk of misdiagnosis reaches up to 40%. The universal marker for all types of pulmonary carcinomas is the expression of cytokeratins. Detection of p53 protein accumulation (e.g., by the immunoperoxidase method in large cell carcinoma) is also used in diagnosis.

Conventional light microscopy does not always reflect the true nature of the cells:

• In large cell carcinoma, light microscopy simply reveals large cells without distinct differentiation. However, electron microscopy and histochemistry reveal hidden features of glandular or squamous epithelium in them.
• In small cell carcinoma, small undifferentiated cells at the ultrastructural level demonstrate squamous, glandular, or, most frequently, neuroendocrine differentiation.

Neuroendocrine carcinomas and clinical division

Tumors with neuroendocrine differentiation are now distinguished into an independent group that includes three grades of malignancy:

• Well-differentiated carcinoma (typical, benign carcinoid).
• Moderately differentiated (atypical carcinoid).
• Poorly differentiated (small cell carcinoma with neuroendocrine features).

In clinical practice, considering the differences in morphology, symptoms, response to chemotherapy, and prognosis, all histological forms are combined into two global groups:

1. Small cell lung cancer (characterized by an extremely aggressive course and, along with large cell carcinoma, has the worst prognosis).
2. Non-small cell lung cancer (includes all other histological types).

Class and exam questions

What else to study on this topic

• Features of macroscopic forms (from plaque-like to pneumonia-like)
• Subtypes of adenocarcinoma (lepidic, solid, acinar) and their morphology
• Ultrastructural features of neuroendocrine differentiation
• Mechanism of mutant p53 protein accumulation in cancer cells
• Rare forms: bronchial gland carcinoma (adenoid cystic, mucoepidermoid)

Other topics in the "Lung Diseases" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.